2013 Neonatal Handbook
2013 Neonatal Handbook
2013 Neonatal Handbook
saturation 88 to 92%
Avoid over-ventilation.
CO
C for oxyhood.
5. Infants who have chronic oxygen needs will require orders for the provision of blended oxygen during the
performance of activities of daily living (when in oxyhood and nipple feeding, the infant may need a nasal
cannula during feeding to provide a continuous, uninterrupted source of blended oxygen).
6. Increase and decrease the blended oxygen concentration delivered based on the oxygen saturation monitoring
device.
Standard Protocol:
a. Saturation > 92% oxygen
b. Saturation < 85% oxygen
7. Oxygen saturation alarms must be set and on while the infant is on blended oxygen therapy.
a. High Saturation 94%
b. Low Saturation 80%
8. Oxygen saturation and concentration may vary based on the infants diagnosis or the physicians/neonatal
nurse practitioners orders.
9. Blood gases will be monitored per policy and procedure NC-SN-15 Blood Sampling, Arterial/Venous,
Assisting With.
D. Documentation
1. In emergency, chart interventions taken to sustain life in detail. Chart the physician/neonatal nurse
practitioner called and the time so that medical supervision of the emergency is noted.
2. Place on the Patient Care Plan the method to determine the amount of blended oxygen needed during those
times when interruptions of standard delivery methods are necessary (i.e. nasal cannula for feeding or
interventions).
3. Chart oxygen concentration hourly, along with the method of delivery.
4. Document alarm limits on each shift.
E. Special Instructions
This policy will not apply when specific orders are written for exceptional infants.
A patient who has orders for comfort measures only (CMO) on the chart may have oxygen adjusted according to the
patient-monitoring device or a blood gas if the hypoxia is iatrogenic in nature (i.e. procedure). The blended oxygen
will be weaned back to pre-procedure status as soon as possible. Other changes in the method of respiratory support
will be ordered by the physician/neonatal nurse practitioner.
References:
Pediatrics Vol. 118 No. 6 December 2006, e1798-1804.
Pediatrics Vol. 111 No. 2 February 2003, pp 339-345.
Biology of The Neonate 2005; 87:27-34.
Neonatology 2008; 94:176-182.
Neonatal Resuscitation Check List
Nursing/Physician/NNP
Radiant Warmer on High & OR Temperature and L&D Thermostat Set at 73F
Turn bed off if anticipating an asphyxiated term infant
Plastic Bag & Port-A-Warmer if <30 Wks and /OR 1.5 Kg
Suction & Catheter connected to With Suction at 100 mmHg
8 FR for Preterm and 10 FR for Term
Meconium Aspirator Attached If MEC Stained Fluid
Respiratory Therapist/Physician/NNP
Working Laryngoscope and Appropriate Sized Blade & ET Tube
(2.5 <1.0 Kg/3.0 <2.0 Kg/3.5 <3.0 Kg/4.0 >4.0 Kg)
Attached and Infant Bag with Appropriate Sized Masks
Oxygen Source Attached To Blender Set On 30% FIO2
O2 Pox Sensor Attached To Right Hand on Preterm OR any Term Infant Requiring Resuscitation
00 Miller blade for infants <1500 G. 0 Miller blade for infants >1500 G. 1 Miller blade for Infants >3Kg
Revised 7/11/2013 Page 52 of 123
L&D Oxygen Delivery Guidelines by Gestational Age
(RT to place POx Sensor and Wean FIO2)
Remember infants are BLUE in-utero. Do not be frightened by initial cyanosis. Heart rate is initially a more sensitive indicator
of successful oxygenation.
Preterm Infant 32 Weeks:
Place Pox Sensor on Right Hand After Birth
Start 30% FIO2 @ 5L Flow via Blender adjust O2 To Keep Satuarations
70-75% First 2 Minutes
80-85% First 2-5 Minutes
5 Minutes 85-92%
Infants > 32 Weeks:
Place Pox Sensor On Right Hand If Starting Resuscitation
Start 21% FIO2 @ 5L Flow via Blender
Adjust to Keep Sats Same as Preterm Once O2 Initiated
70-75% First 2 Minutes
80-85% First 2-5 Minutes
5 Minutes 85-92%
NUTRITION:
Caloric needs for the preterm vary individually but are around 120140 cal/kg/day for enteral feeds and 100 cal/kg/day if given IV.
The goal is a weight gain of 1- 2% of the present weight per day or 15 gm/kg/day (mimicking intrauterine weight gain).
Caloric needs at term are less at 100-120 cal/kg/day enterally and 80-100 cal/kg/day IV.
To follow growth rate in the SCN a growth chart adapted from known intrauterine growth rate needs to be followed weekly. The
best time is the same day of nutrition labs on Wednesday. The process for this is noted at the end of the nutrition section and
should be adhered to.
SUGGESSTED GUIDELINES FOR THE INITIATION OF PARENTERALNUTRITION:
TPN (parenteral nutrition) should be initiated ASAP postnatally (Early TPN stock solution) in infants less than 1,500 g.
Infants >1,500 gms can start TPN the day after birth.
Cycling TPN is used with infants requiring prolonged TPN and will be handled on a case by case basis.
EARLY AMINO ACID INFUSION FOR VLBW INFANTS:
Postnatal growth of ELBW infants remains poor and does not come close to approximating rates of in utero growth. There is
good evidence that early deficiencies in protein may be an important contributor to the poor growth and neurologic outcomes observed
in this population. Providing intravenous amino acids to sick premature infants in early postnatal life can improve protein balance and
can increase protein accretion, even at low caloric intakes.
Several controlled studies have demonstrated the efficacy and safety of amino acids initiated within the first 24 hours after birth. No
recognizable metabolic derangements, including hyperammonemia, metabolic acidosis or abnormal aminograms, were observed.
Early parenteral nutrition with amino acids minimizes the abrupt postnatal deprivation of amino acid supply and meets the following
goals:
1. Prevention of protein catabolism
2. Prevention of a decrease in growth-regulating factors such as insulin and down-regulation of glucose transporters
3. Prevention of hyperglycemia and hyperkalemia
Based on available evidence, providing ELBW with 2.5 to 3.5g/k/day of intravenous amino acid as soon as possible after birth is a
reasonable recommendation.
EL PASO CHILDRENS HOSPITAL EARLY PN SOLUTION PROTOCOL
The hospital pharmacy will prepare a stock amino acid and dextrose solution that will be readily available for use 24 hours a day.
This solution will consist of either 7.5% dextrose, 4% amino acids, 200mg Ca gluconate/100mL and 0.5units/mL heparin or 5%
Revised 7/11/2013 Page 53 of 123
dextrose, 4% amino acids, 200mg Ca gluconate/100mL and 0.5units/mL heparin.
The early PN solution will be initiated within the first hours of life in critically ill VLBW (<1500g) newborns at a maximum rate of
60ml/kg/day to deliver 2.4g/kg/day amino acids.
Other fluids can be co-infused with the stock solution to meet the changing individual needs for glucose homeostasis, electrolyte
balance and total fluid requirements.
If the solution is not immediately available, start D5W or D10W at a rate of 80-100ml/k/day or higher depending on patient
requirement. Early PN solution will then be started as soon as available at a maximum rate of 60ml/k/day with proper rate adjustment of
the other IV fluid to make up for the remainder of the total fluid requirement for the day.
Precautionary measures to prevent hyperglycemia:
1. Do not start early PN solution if serum glucoses are 120mg/dL and higher.
2. If serum glucoses are between 100-119 mg/dL, use D
5
Early PN solution.
3. If D7.5 Early PN is used, decreased rate to ~30ml/kg/day and give the rest of the fluid requirement as D5W. Gradually increase
Early PN rate to goal of 60ml/kg/day if serum glucoses are 100mg/dL and lower
Please allow time to warm the solution before starting infusion.
Type Early TPN in Cerner and choose the appropriate early PN. It is advisable to inform Pharmacy ahead of time if the delivery of a
VLBW infant is anticipated. Early PN should commence no later than 4 hours after delivery.
The tables provide essential calculations of calorie and protein intake depending on administration rate.
Glucose concentration Rate (ml/k/day) Non-protein calories
(kcal/kg/day)
Gram protein/kg/day
7.5% 40 10.2 1.6
7.5% 60 15.3 2.4
7.5% 80 20.4 3.2
7.5% 100 25.5 4
Glucose concentration Rate (ml/k/day) Non-protein calories
(kcal/kg/day)
Gram protein/kg/day
5% 40 6.8 1.6
5% 60 10.2 2.4
5% 80 13.6 3.2
5% 100 17.0 4
Please make sure to document Early PN solution in the Site of Care note as an event.
References:
1. David H. Adamkin. Nutrition Management of the Very Low-birthweight Infant: I. Total Parenteral Nutrition and Minimal Enteral
Nutrition
NeoReviews, Dec 2006; 7: e602 - e607.
2. Scott C. Denne. Evidence supporting early nutritional support with parenteral amino acid infusion. Semin Perinatol. 2007
Apr;31(2):56-60. Review.
3. Tsang RC, Uauy R, Koletzko B, Zlotkin SH eds. Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines.
Cincinnati, OH: Digital Educational Publishing;2005
TPN COMPOSITION:
Carbohydrate
Major source of energy during parenteral nutrition and should provide 35-55% of the total caloric intake.
o 1 gram CHO provides 4 kcal.
Source used in PN is mostly glucose. Dextrose is a form of glucose.
o 1 gram of glucose provides only 3.4 kcal because glucose crystals are weighed in the hydrated state.
Revised 7/11/2013 Page 54 of 123
Infants <1,000g have glucose needs but may not handle glucose well.
Initial glucose infusion rates (GIR) is based on endogenous production of glucose.
o Term newborns: 3 5 mg/kg/min
o Extremely premature infants: 8 to 9 mg/kg/min
However, ELBW infants are susceptible to hyperglycemia in the first few days of life. Suggested initial glucose
delivery rates are 6-8 mg/kg/minute initially and gradually advance to maximum of 12 mg/kg/min.
D5W-D7.5W at 80-120 ml/kg/day usually meets this need.
o Glucose delivery should not increase greater than 2 mg/kg/minute per day.
Goal is a glucose range of 50-120 mg/dl, treating glucoses >150 mg/dl.
Do not exceed 18 gm/kg/day glucose.
o Excessive glucose 18 g/kg/day or 13 mg/kg/min or 60 kcal/kg/day as glucose may interfere with respiratory gas
exchange and induce lipogenesis, which increases energy expenditure.
Goal is to maximize protein, intralipid and carbohydrate deliver y to provide 105 -115 kcal/kg/day (including at least 3.5
gram/kg/day of protein) or weight gain of 1-2% per day.
Calculate GIR as follows:
For example: A patient receiving TPN with D
10
at a volume of 100 ml/kg/day will have a GIR of (0.1 x 100) divided by 1.44 =
6.9 mg/kg/min.
There are several ways to calculate GIR. In the Glucose Metabolism Section you will find another method of calculating GIR.
Protein
The rationale for routine administration of amino acids during parenteral nutrition is to provide nitrogen for protein synthesis and
growth.
Amino acids can also be oxidized as substrate for energy source and should provide 7-15% of total kilocalories.
1 gram protein provides 4 kcal.
Use specially formulated amino acid solution for neonates (Trophamine) that contains a larger percentage of total nitrogen as
essential amino acids and branched chain amino acids, and have a balanced amount of non-essential amino acids instead of a single
amino acid concentration
Use of Trophamineresults in plasma amino acid levels that are similar to breastfed infant and improve weight gain and nitrogen
balance
Recommended intakes of IV amino acids vary with gestational age.
o FT infants: 2.5g/kg/day. PT infants: 3-4 g/kg/day.
Amino acids should be provided as soon after birth as possible at a minimum of 1.5 g/kg/day. Infants not receiving amino acids
during first days lose 1% of endogenous protein stores or 1 gm/kg/day.
Our practice is to begin Early PN immediately after birth for VLBW infants (<1500g) using a standard solution of D
5
W or D
7
.
5
W
and 4% AA.
o When infused at maximum of 60ml/kg/day, 2.4 g/kg/day of AA is provided.
o After the first 24 hours, an individualized TPN solution is ordered with an initial AA concentration of 2-2.5g/kg/day.
o AA intake is advanced to 3-3.5g/kg/day within the first few days of life.
For infants with BW >1500g, AA is initiated at 2g/kg/day and advanced to 3g/kg/day the following day.
If concerns regarding significant renal ischemia or dysfunction exist, a less aggressive approach is used.
Daily lytes or BMPs (if clinically indicated) should be followed in VLBW (those infants less than 1,500 g) while advancing TPN.
Intralipids
Major advantages of intravenous lipids: 1. Source of essential fatty acids, 2. high caloric density, and 3. low osmolality.
Revised 7/11/2013 Page 55 of 123
Fats should provide 30-50% of total daily calories.
1g Fat provides 9 kcal (for 20% intralipid solution: 1mL = 2 kcals)
Lipid emulsions consist of vegetable oil triglycerides, emulsified with egg yolk phospholipid and glycerol to achieve isotonicity.
We use 20% intralipid in this nursery.
o It contains reduced content of phospholipids per gram triglyceride compared to 10% lipid solution improved lipid
clearance.
o More energy dense allows for smaller infusion volume prevents fluid overload.
Intralipid (IL) can be added approximately 1-2 days after birth - helps stabilize serum glucose in certain instances.
Initial starting rate is 0.5 gm/kg/day advancing by 0.5 gm/kg/day daily (max 3.0 g/kg/day)
Triglyceride levels should be checked the morning after initiating intralipid then after each two increases of 0.5 gm lipid each
day
o Preterm infants have a limited ability to hydrolyze triglycerides (TG)
o Elevated serum TG levels are more frequently observed with decreasing GA, infection, surgical stress, malnutrition, and
SGA infants
Reasons to decrease or stop IL infusion:
o Triglyceride >150 mg/dL or evidence of IL intolerance
o Suspected clinical sepsis or documented bacteremia
Discuss with attending about IL infusion during this period
Until infection controlled some attendings stop or the infusion rate
o Serum bilirubin rising quickly or close to exchange levels
Lower infusion to 1.0 g/kg/day or less until bilirubin controlled.
Please discuss this with your attending.
o Evidence of cholestasis
An elevated direct bilirubin (DB) is early evidence of PN-associated hepatocellular damage
DB > 1.5 2.0 mg/dl or,
DB that is 40% of the total bilirubin concentration
Alkaline phosphatase and gammglutamyl transferase (GGT) levels may be elevated but are less specific
compared to DB
Calcium (Ca) and Phosphorus (P)
TPN amounts are often lower than recommended levels.
Difficult to administer both at high concentrations because of the increased risk of precipitation.
Because of insufficient amounts risk of decreased bone mineralization with prolonged parenteral nutrition.
Goal is to maximize amount of Ca/Phos in TPN (avoiding precipitation) at ratio allowing max retention of both minerals. Ratio of
1.3:1 to 1.7:1 Ca to P by milligram weight or a 1:1 molar ratio should be obtained.
Conversion table
Element mEq/dL mmol/dL mg/dL
Calcium 1 0.5 20
Phosphorus - 1 31
Maximum safe Ca/Phos delivery
>120 ml/kg/day TPN: 90 mg/kg/day (4.5 meq/kg/day) Ca & 60 mg/kg/day (2 mM/kg/day) of P if on 2-3 mg/kg/day protein and 40
mg/day cysteine
This quantity of protein with the cysteine the pH the solubility of these minerals in solution.
100-120ml/day TPN: decrease the Ca to 60 mg/kg/day (3 meq/kg/day) and P to 45 mg/kg/day (1.5 mM kg/day)
<100ml/kg/day limit Ca to 40 mg/kg (2 meq/kg) and P to 31 mg/kg/day (1 mM/kg) until TPN no longer used.
Do not deliver >3 meq/kg/day of Ca peripherally. Higher concentrations should be administered via central line (PICC, Broviac,
CL or UVC) only.
TF (ml/kg/day) Ca Phos Ratio (by weight)
>120 90 mg/kg/day
4.5 mEq/kg/day
2.2 mM/kg/day
60 mg/kg/day
2 mM/kg/day
1.5:1
100-120 60 mg/kg/day
3 mEq/kg/day
1.5 mM/kg/day
45 mg/kg/day
1.5 mM/kg/day
1.3:1
Revised 7/11/2013 Page 56 of 123
<100 40 mg/kg/day
2 mEq/kg/day
1 mM/kg/day
31 mg/kg/day
1 mM/kg/day
1.3:1
Cysteine
Unstable in solution and easily oxidized to the insoluble form cystine
o Most commercially available AA solutions contain very low or no cysteine
Cysteine supplementation in PN is provided in the form of cysteine hydrochloride
o Also improves delivery of soluble Ca and P by lowering pH of PN solution
o Metabolic acidosis can occur due to the hydrochloride provided from the cysteine salt. Each mmol of cysteine (175 mg)
provides 1 mEq chloride and 1 mEq of hydrogen ion.
o Maximum dose: 100-120 mg/kg/day
Dose: 30-40 mg/ gram of protein
Carnitine
Plays an essential role in the oxidation of fatty acids for energy
o Facilitates transfer of long-chain fatty acid (LCFA) across the mitochondrial matrix for oxidation
Evidence for its use in PN remains unclear. However, most neonatologist would consider adding carnitine to PN if an infant
requires prolonged TPN >10-14 days
Dose: 10-20 mg/kg/day ( <34 weeks =10 mg/kg/day)
Other Electrolytes
Individualize need for each patient.
o Sodium
Usually added on day 2 of life
Diuretic therapy may require moresodium
For premature infants <1000 g: calculate total Na load from all sources
i.e. TPN, IV infusion via UAC, flushes
Under NO circumstances can the sodium content of TPN exceed 154 mEq/L. If the patient requires more
sodium, it should be through a separate infusion.
o Potassium
Do not add potassium to TPN until urine output has been established
Conditions that require less potassium
Oliguria or anuria (i.e. renal disease, cardiogenic shock)
Hyperkalemia (i.e. adrenal insufficiency)
Patients receiving a lot if insulin
Refeeding syndrome
Diuretic therapy may warrant more potassium
Under NO circumstances can potassium exceed 80 mEq/L of TPN for central line and 40 mEq/L for peripheral
line
o Calculate maintenance +deficit as needed
o Do not add magnesium initially if the mother received magnesium
Recommended daily requirements
Element mEq/kg/day
Sodium 2 - 4
Potassium 2 - 4
Magnesium 0.25 0.5
Vitamins
Manufactured as a multi-ingredient solution (MVI)
Essential component of a patients daily PN regimen because they are necessary for normal metabolism and cellular function
TPN vitamin D in the vitamin additives is adequate.
Fat-soluble vitamins can be absorbed into the storage bag (~80% of Vitamin A is lost).
Amounts can vary with light (Vitamin A is light sensitive), O2 and heat. (TPNs are dispensed from pharmacy in opaque bags)
Dose according to weight:
o < 1 kg: 30% (1.5 ml) of a single full dose (5 ml). Do not exceed this daily dose.
o 1-3 kg: 65% (3.25 ml) of a single full dose (5 ml)
o 3 kg: 5 ml/day added to TPN or 100 ml of appropriate solution
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Trace elements
Manufactured as a multi-ingredient solution
Often present: zinc, copper, manganese, chromium, selenium
Cofactors essential for the proper functioning of several enzyme systems
Dose: 0.2 ml/kg ( max: 4 ml)
Certain conditions predispose to trace element toxicity due to impaired ability to excrete these substances. Administration in PN
should therefore be limited.
o Cholestasis: DB 2 mg/dL
Delete or limit copper (Cu) and manganese (Mn)
Add trace elements to TPN only 2x/week
Provide zinc (Zn) daily
o Renal insufficiency
Delete or limit selenium (Se), chromium (Ch), molybdenum (Mo)
Condition that require additional supplement of Zn
o Ostomy losses
o Trace element solution dosed at 0.2 ml/kg/day provides 300 mcg/kg/day of zinc.
Recommend daily requirements (mcg/kg/day)
MINERAL PRETERM TERM
Zinc 400 250 <3 months
100 >3 months
Copper 20 20
Selenium 2 2
Chromium 0.2 0.2
Manganese 1 1
Molybdenum 0.25 0.25
Iodide 1 1
Osmolarity
Maximum osmolarity in PN solution is determined by the type of vascular access
o Peripheral line:
Neonates: 900 mOsm/L ( max: 1000 mOsm/L)
Pediatric: 1100 mOsm/L
o Central line:
No limit
It is important to inform Pharmacy what type of vascular access the patient has (select either peripheral or central during TPN
order entry.
TPN Pearls:
NICU Clinical Pharmacist and Registered Dietitian are available during day time hours for questions and/or help regarding TPNs.
TPN is costly and is associated with complications. If the gut works, use it.
Usual TPN volumes: 80 140 ml/kg/day.
Avoid TPN volumes <50 ml/kg/day as they are likely to be super concentrated. Let TPN expire and use IV fluids until full feeds
are achieved.
If TPN is turned off, it must be weaned to avoid hypoglycemia. Decrease infusion rate by half for 30 minutes and they by half again
for 30 minutes then discontinue.
Limits:
o PIV: D
12.5
W KCl =40 mEq/L Ca 13.5 mEq/L or 2.4 mEq/kg Osmolality 900 mOsm/L
o Central: D
25-30
W KCl =80 mEq/L
TPN Weaning Guidelines:
PN COMPOSITION
TOTAL TPN
VOLUME
(ML/KG/DAY)
ENTERAL FEED
VOLUME
(ML/KG/DAY)
EBM/FORMULA
CONCENTRATIO
N
(KCAL/OZ)
GIR (MG/KG/MIN)
PROTEIN
(GM/KG/DAY)
LIPIDS
(GM/KG/DAY)
12 3.5 3 100-140 0-49 20
10 2.5 2 70-90 50-74 20
8 2 1.5 55-65 75-99 20
8 2 1 55 100-120 22
None None N/A None 120-150 22-24
None None N/A None 150-160 24
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ALL TPN ORDERS ARE DUE BY 1300
o Make sure you add patients MRN number on the TPN form
o Sign and print your name and the date on the order form
o Select the correct line type central vs peripheral
Sources of calories in PN
Carbohydrates ( Dextrose) 3.4 kcal/gram
Lipids (20% Intralipid) 10 kcal/gram
(Fat: 9 kcal, glycerol: 1 kcal)
Protein 4 kcal/gram
Cycling TPN (Cyclic TPN)
Cyclic TPN refers to providing parenteral nutrition over less than 24 hours. While the TPN is off, the central line is heparin-
locked or infused with a cycling fluid. Intermittent administration of TPN can help minimize the long-term adverse effects of
chronic TPN, such as liver complications. The exact etiology of parenteral nutrition associated liver disease (PNALD) is
unknown, but likely multifactorial. Infants who receive TPN >60 days have an 80% likelihood of developing cholestasis.
Dextrose, amino acids, and lipids may all contribute to PNALD. Cycling TPN gives the liver a break from continuously
metabolizing macronutrients. Cyclic TPN is not without risk, especially risk of hypoglycemia due to limited glycogen stores
and high requisite glucose needs. To reduce the risk of hypoglycemia, the TPN rate must be ramped up and ramped down.
This allows the pancreas time to respond to the change in glucose load and alter the endogenous production of insulin.
Cyclic TPN should be used for:
o TPN induced hepatic dysfunction/failure that is imminent or already present
o Chronic TPN patient to allow period of time off an infusion pump
Cyclic TPN is not appropriate for:
o Patients on short term TPN (<2 weeks)
o Patients who have an unstable hemodynamic or metabolic status
o Patients requiring exogenous insulin
o Patients who have poor weight gain
o Patients that do not have central venous access
Cyclic TPN is not recommended for patients who are septic or immediately post-op
o If a patient becomes septic, hemodynamically or metabolically unstable, cyclic TPN should be discontinued until the
patient is stable
o Cyclic TPN should be temporarily stopped when a patient has surgery and resumed a few days post-op
TPN must be tapered off prior to the end of the TPN time and change of lines
o Decrease hourly rate by 50% x 60 minutes, THEN by another 50% x 30 minutes, THEN off
TPN must be tapered on after a new bag is started
o Increase hourly rate by 25% x 30 mins, THEN by another 25% x 60 mins, THEN to full hourly rate
Maximum time off TPN for neonate =4 hours (start with 1 hour and advance by 1 hour until reach max of 4 hours). Time off
TPN may be >4 hours if cycling fluid is infused when the TPN is off
Check blood glucose 30 minutes after TPN is stopped and again 2 hours has elapsed since TPN was stopped. Glucoses should
be checked until the patient has had 2 weeks of stable glucoses during cyclic TPN
References:
1. Samour P, King K. Pediatric Nutrition. J ones & Bartlett Learning: 2012; 53-69.
2. Collier S, Crouch J , Hendricks K, et al. Use of cyclic parenteral nutrition in infants less than 6 months of age. Nutrition in Clinical Practice. 1994;
9:65-8.
3. Bendof K. Glucose response to discontinuation of parenteral nutrition in patients less than 3 years of age. Journal of Parenteral and Enteral
Nutrition. 1996; 20:120-2.
4. Suita S, Masumoto K, Yamanouchi T, et al. Complications in neonates with short bowel syndrome and long-termparenteral nutrition. Journal of
Parenteral and Enteral Nutrition. 199; 23:S106-9.
5. Dell Childrens Medical Center Protocol for Cycling TPN. 2009.
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General Nutrition Labs For Infants BW <1500g and other infants on prolonged TPN)
Monitoring Growth in SCN
The nurses document the head circumference and weight daily and the length every Wednesday. Board lengths are
available so make sure it is being used to measure lengths.
Please enter these measurements into the Site of Care notes.
Infants who stay in SCN longer than one week should have a growth chart plotted. Cerner will plot growth curves if the initial
anthropometrics measurements are saved. Follow these steps in Cerner: Ad Hoc General AssessmentChoose the applicable
growth chart: Term or pretermenter the values and gestational ageclick the save iconrefresh.
o This should be done each Wednesday as nutrition labs are done that day.
o Nutrition rounds are done every Thursday at 8:30 AM. Residents and intern are expected to calculate weekly weight gain,
nonprotein and protein calories for the NICU patients.
Adjusted age should be calculated by the post menstrual age (Site of Care does this).
Documentation of nutrition
Caloric intake and source should be well documented daily in Site of Care allows data analysis for quality improvement and
research purposes
Caloric intake from TPN and enteral feeds should be documented individually.
Quantity of TPN in ml/kg/day, Glucose, Protein and IL in g/kg/day should be entered daily in Site of Care
Glucose Routinely done on all infants while on IVF
Electrolytes < 1000g: Follow q12 hours until stable then q24 hours until TPN fully advanced and
infant stable.
> 1000g: Follow q24 hours until stable.
BMP <1500g/<34 wks: Consider BMP or CBG to follow CO2 at >72 hours.
HCO3 loss in the urine with high FENa due to renal immaturity.
Suspect if excess weight loss/poor weight gain despite adequate calories in the 1
st
week of life.
Some recommend BMP qWed/Sat or weekly until >1500g
In the growing preterm a BUN <10 mg% may indicate need for a higher protein intake
in the form of the high protein preterm formula or fortification of human milk with
Beneprotein.
Ca, Mg, P <1250g: iCa should be monitored q24 hours until stable, then Q Wednesday while on
TPN.
All other infants: Every Wednesday while on TPN.
T&D bili <1500g and other infants on prolonged TPN
Every Wednesday while on TPN.
DB is the first lab to become elevated in TPN cholestasis.
If elevated LFTs +GGT need to be followed every other week.
If cholestasis identified follow direct bili even off TPN until <2 mg/dL
Alkaline
phosphatase
<1500g and other infants on prolonged TPN
Every other Wednesday starting 2
nd
week of life.
Markedly elevated before changes noted on x-ray in osteopenia.
Abnormal if >500 U/L.
Follow every other Wednesday until <350 U/L on preterm formula.
Spun
HCT/retics
Every Wednesday. Order reticulocyte count Q Wednesday after 3 weeks of age.
Triglyceride After the first 24 hours on intralipid 24 hours after each total increase of 1 g/kg/day
until stable on 3g/kg/day.
Other
considerations
Fluid delivery should be based on Na and weight changes.
Urine output in the preterm infant is not a good indicator of hydration status
<1,250 g will continue to have brisk urine output despite significant fluid losses.
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INITIATION OF ENTERAL FEEDS:
Important concepts
Even under the best circumstances, it takes a substantial amount of time to achieve full enteral feeds in premature neonates.
Based on currently available evidence, providing minimal volume feeds for some period of time seems reasonable.
Minimal enteral feeds, also known as trophic feeds, are typically defined as low-volume feeds that do not provide sufficient calories
for growth but rather help promote the maturation of the structure and function of the premature intestinal tract.
BW 500-1000g or GA < 28 weeks
May start feeds as bolus or drip.
Full strength human milk preferable but preterm 20 cal formula with iron can be used.
Feeds initiated when infant clinically stable after discussion with the attending.
Feeds can be started as early as DOL #1 but usually by day 2 of life.
Trophic feeds started initially at 5-10 ml/kg/day or 1-2 ml q 6 hours.
When infants tolerate trophic feeds for ~2-3 days advance 10ml/kg/day if <1,000 g.
When 100-120 ml/kg/day of PO feed reached feeds fortified by changing preterm formula to 22 calories 24 calories.
o Breast milk fortifier is added after reaching 100-120ml/kg/day, by adding 1 packet per 50 ml one day 2 packets per
50ml the next day.
o When increasing concentrations do not advance volume of feeds that day.
o If powdered HMF is not tolerated Similac Special Care 30 can also be used as a human milk fortifier (Note that
nutritional values are somewhat less than those provided by HMF powder). When human milk is mixed with Similac
Special Care 30 in ratios 2:1, 1:1 or 1:2 resulting fortified human milk provides 23, 25 or 27cal/oz.
Other considerations
Although human milk is considered to be the optimal source of primary nutrition for premature infants, human milk does not
completely meet the nutritional needs of premature infants.
Human milk fortifiers should be used in premature infants fed human milk with BW <1500g and considered in those with BW <
2000g.
Preterm formulas are designed for use in-hospital as the sole source of nutrition for preterm infants who are not breastfed and may
be used to supplement breastfeeding if supply is inadequate.
o Preterm formula has increased protein, less lactose than term formula and increased Ca, P, and Vitamins.
o It can be initiated on any infant <37 weeks.
BW 10001250g or GA 28 30 weeks
Same feeding suggestions as above but advancing feeds 15-20 ml/kg/day.
Trophic feeds should be considered.
BW 12501500 g or GA 30-32 weeks
Trophic feeds usually are not needed.
Start at 20ml/kg/day and fortify breast milk or formula when at 100-120ml/kg/day.
BW 1500-2500 g or GA 33-36 weeks
Start Full Strength preterm formula or HM at 30ml/kg/day advancing 30ml/kg/day.
Preterm formula may be used up to 35-36 weeks.
Preterm formulas are not needed after 36 weeks unless infant is an ELBW preterm.
GA 35 weeks
If healthy, the infant may be started on a term 20 calorie formula
Start at 10 ml/feed advancing 3 ml/feed if 2,500 g
Start at 15 ml/feed advancing 5ml/feed if >2,500 g
Initially advance to fluid goal which on the first day of life is usually 60 ml/kg/day.
If the infant does well, after the first day of life feeds may be advanced 3-5ml/feed to the fluid goal for that day or if healthy ad
libitum (ad lib) (usually 20-30 ml/kg/day).
o These feeding advances should be reserved only for healthy infants.
Infants with feeding difficulty, any feeding intolerance or neonatal depression should be initiated and advanced in a tailored
conservative manner based on the infants clinical presentation and problems.
Infants with any suspicion of NEC should have feeds initiated after a period of NPO;
o Start at 10-20ml/kg/day
o Advance no more than 20ml/kg/day unless discussed with an attending.
o Human milk or preterm formula (<36 wks) or term formula ( 37 weeks) may be used initially unless discussed otherwise.
o If there is a strong suspicion of short gut then a more elemental formula may be started.
Revised 7/11/2013 Page 61 of 123
Initiation of iron therapy
AAP recommends 2-4 mg/kg/day of enteral iron daily depending of the degree of prematurity, once on full feeds beginning
between 2 weeks and 2 months after birth and or 2 weeks after the last transfusion.
Premature infants should be maintained on iron even after discharge.
Formula fed infants may also benefit from additional iron at 1mg/kg.
Infants on rhEpo will require more iron, dose of 4-6mg/kg.
Fer-in-sol or MVI with Fe may be used.
o Fer-in-sol: 15 mg of elemental Fe/ml
o Poly-vi-sol with Iron: 10 mg of elemental Fe/ml
o Tri-vi-sol: 10 mg of elemental Fe/ml
MVI with Fe has 10mg /ml and the dose restricted to 0.5ml QD if the infant is <2 kg.
Do not give Fe with HM.
Use of MVI
MVI not indicated for infants on preterm formulas unless they have osteopenia.
The preterm infant formulas may not have enough vitamin D to meet the 400 IU/day requirement for osteopenia.
MVI with Fe is recommended for infants on HM remembering that some HM fortifier has some MVI & Fe fortification.
o Infants 1-2 kg should be started on 0.5ml per day, dividing the dose as 0.25ml BID
o Infants over 2 kg may take 1 ml/day.
POST DISCHARGE NUTRITION
Preterm infants are in a state of suboptimal nutrition at the time of discharge from the hospital and beyond.
Improving this situation would be beneficial both in the short-term and potentially for longer-term health and development.
Nutrient-enriched formula for preterm infants after hospital discharge (post-discharge formula [PDF]) is generally intermediate in
composition between preterm and term formulas.
Compared with term formula (TF), PDF contains
o Increased amount of protein with sufficient additional energy to permit utilization
o Contains extra calcium, phosphorous, and zinc, necessary to promote linear growth
o Additional vitamins and trace elements to support the projected increased growth
For ELBW 24 cal preterm formula or fortified HM is suggested until 42 weeks.
For ELBW >42 wks, VLBW/LBW: Preterm 22 calorie formula (Enfacare, Neosure) can be used.
o PDFs are approved for ELBWs until 9-12 months corrected age.
o A WIC form needs to be filled out for special formulas prior to discharge.
For breastfed infants, formula powder can be used to increase caloric density of human milk. See table below.
Fortification of Human Milk for Home Use
C Ca al lo or ri ic c a am mo ou un nt t B Br re ea as st t M Mi il lk k
2 24 4 c ca al l 1 1 t ts sp p f fo or rm mu ul la a p po ow wd de er r t to o 9 90 0 m ml l E EB BM M
2 26 6 c ca al l 1 1 t ts sp p f fo or rm mu ul la a p po ow wd de er r t to o 9 90 0m ml l E EB BM M
Potential formulas: Enfacare, Neosure, Enfamil Lipil, Similac Advance
Other preparation: 1 tsp Neosure advance +75 ml water (24 cal )
HELPFUL HINTS
20cal/oz formula (any kind) 0.68 kcal/ml (same for HM overall)
22cal/oz 0.74 kcal/ml
24 cal/oz 0.81 kcal/ml
26 cal/oz 0.87 kcal/ml
27 cal/oz 0.90 kcal/ml
30 cal/oz 1.00 kcal/ml
Additives:
Corn oil 8.30 kcal/ml
MCT oil 7.70 kcal/ml
Safflower oil 8.00 kcal/ml
BRC ( 3.5 g/tbsp = 1.16 g/tsp) 4.24 kcal/ml
Beneprotein ( 1.3 g protein/tsp or 4 cal/g) 5.20 kcal/ml
Polycose 3.80 kcal/ml
Revised 7/11/2013 Page 62 of 123
REFERENCE TABLES
ENERGY REQUIREMENT ESTIMATES FOR GROWING PREMATURE INFANTS
KCAL/KG/DAY
Resting Metabolic Rate
Energy of activity
Thermoregulation
50
5
10
Total Energy Expenditure 65
Energy excreted 15
Energy stored 30-50
Recommended Energy Intake 110-130
REVISED ADVISABLE PROTEIN RECOMMENDATION FOR GROWING PRETERM INFANTS*
Without need for catch-up growth With need for catch-up growth
26 30 wks PCA: 16 18 g/kg/day LBM
14 % protein retention
3.8 - 4.2 g/kg/day
PER: 3.0
4.4 g/kg/day
PER: 3.3
30 36 wks PCA: 14 15 g/kg/day LBM
15 % protein retention
3.4 3.6 g/kg/day
PER: 2.8
3.6 - 4.0 g/kg/day
PER: 3.0
36 40 wks PCA: 13 g/kg/day LBM
17 % protein retention
2.8 3.2 g/kg/day
PER: 2.4 2.6
3.0 3.4 g/kg/day
PER: 2.6 2.8
PCA: postconceptual age; LBM: lean body mass; PER: protein:energy ratio
* Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Desci T, et al. Enteral nutrient supply for preterm infant. A comment of the
ESPHAGN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010;50(1): 85-91.
Revised 7/11/2013 Page 63 of 123
EBM and INFANT FORMULA SPREADSHEET:
Amanda Timmerman
DIETARY EVALUATION/CONSULT POLICY:
High risk neonatal infants identified at nutritional risk will receive an initial nutrition assessment to identify the need for care, the type
of care to be provided and the need for further reassessment.
A. Neonatal infants identified to receive an initial assessment include the following:
Neonates admitted into ICN >48 hours
All neonates 1500 grams
All infants on parenteral nutrition
Neonates on specialized formula
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B. The interdisciplinary staff is also recommended to notify Clinical
Nutrition Services if the following criteria occur
Initiation of parenteral nutrition support
Significant change in medical condition negatively impacting nutritional status
Slow weight gain
PROCEDURE
A. An order for nutritional consult will be placed in Cerner.
B. The unit clerk will place the order for the nutrition consult via established process
C. Upon received order for consult, nutritional services will complete a nutrition assessment within 24-48 hours of notification.
D. Neonates will be followed by nutrition services until:
a. Patient reaches full feeds
b. Growth adequate
Nutritional risk/problem resolved; no longer at nutritional risk
INITIAL FLUID AND ELECTROLYTE MANAGEMENT IN THE NEONATE:
o Appropriate fluid and electrolyte management during the first week of life requires anticipation of fluid and electrolyte losses that
are likely to occur.
o Intakes must be individualized and evaluation of fluid and electrolyte balance must be periodically evaluated so that fluid and
electrolyte intake can be appropriately adjusted.
o Fluid needs in first 24 hours depend on insensible losses (evaporative), respiratory losses, stool losses (minimal), and urine output.
o At term, insensible losses are minimal due to mature skin barrier, especially if in an isolette which minimizes these losses further.
o Preterm (34 weeks or less) however has an immature epidermis and under a radiant warmer with no plastic protective barrier and no
previous antenatal steroids to mature the skin, the preterm <1,000 g can have losses up to 7-9 ml/kg/hr.
o Serial weights on the same scales and electrolytes are the easiest tools to measure fluid needs in the newborn in the first 2-3
days of life.
Please weigh all infant <1,500 g upon admission to the ICN on the same scale they will be weighed on each day. The following
information is only a guideline to follow in the initial management of fluids in the newborn
Term to 35 weeks
o First 24 hours starting fluid is D
10
W at 60 ml/kg/day
o No Na+or K+is required the first 24 hours
o At 24 hours fluid is changed to D
10
NS (2-3 mEq/kg/Na/day) if good urine output established
o If normal diuresis at 48 hours of life and K+normal start K+2 mEq/100 ml IVF (2 mEq/kg/day)
o Exception is in HMD, add Na only after diuresis and Na <135
o Advancing fluids each day depends on weight change, serum Na and urine output
o Most term infants tolerate advancing IVF 20 ml/kg/day unless
Inadequate urine output, Na <135, gained weight and not diuresing
o Term infants should lose 1-2% of birth weight per day (weigh on same scale) and maintain serum Na of 135-140.
o Normal urine output is 1-4 ml/kg/day.
o Some term infant, on the first 24-48 hours may have UO <1.0 ml/kg/day due to ADH output at delivery or ischemia.
o If no sepsis or asphyxia, they should start urinating >2ml/kg/day by 24-48 hours of life.
o Hypoglycemic infants may have glucose needs.
o Frequently D
10
or D
12.5
is advanced above the usual fluid goal in the first 24-48 hours putting the infant at risk for dilutional
hyponatremia.
o If infant needs more than 100 ml/kg/day IVF in the first 24-48 hours consider a UVC or central line for D
15
or greater to fluid
intake and avoid hyponatremia.
o DISCUSS THE INFANT WITH AN ATTENDING PRIOR TO PLACING A CENTRAL LINE FOR
HYPOGLYCEMIA.
o If the term infant is to be NPO >72 hours consider TPN.
Preterm infant 34 weeks or less
o Due to gestation and heat source, fluid needs are higher but these infants frequently are unable to handle over 4-6 mg/kg/minute
glucose.
The following are guidelines.
o ALL INFANT <32 WEEKS SHOULD BE PLACED IN A GIRAFFE OMNIBED. IF NONE IS AVAILABLE, INFANTS
SHOULD BE COVERED BY PLASTIC WRAP IF UNDER A RADIANT WARMER AND INTUBATED (insensible losses may
be reduced by 30-50 ml/kg/day).
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o IF NOT INTUBATED THEY NEED TO BE IN AN ISOLETTE.
Fluid Requirement First 24 hours
All preterm infants <1500g should be started on early PN solution shortly after birth if stable.
< 800 g 100-120ml/kg/day
o varies in Versalet vs radiant warmer
o consider Aquaphor TP q 12 hours x 3 days
D5W or more
800-1000 g 80-100 ml/kg/day D5W
1,000 -1,500 g 80 ml/kg/day D7.5-D10W
1,500-2,500 g 60-80 ml/kg D10W
Term 60 ml/kg D10W
Suggested management after the first 24 hours
Sodium o Introduced at 48-72 hours if weight loss has occurred and the serum Na <140.
o Started at 2-3 meq/kg and adjusted based on needs to keep Na 135-140.
o Remember urinary fractional excretion of Na (FENA) can be high, excreting ~NS in the urine
and worse if on caffeine, aminophylline or diuretics.
Potassium o Placed in the IVF at 48-72 hours (1-2 meq/kg/day) if serum K normal (3.5-4.5 central and 3.5-6.0
capillary) and urine output is adequate.
Calcium o Initially there will be no electrolytes in the TPN or early PN solution except Ca Gluconate.
o Introduced to IVF at 0-48 hours to avoid the excess nadir of serum Ca that occurs in preterm
infants.
Total fluids o Fluid needs may still be in flux so 80 ml/kg TPN can be written for allowing extra fluid or
glucose needs to be met by changing out or adding additional fluid.
GLUCOSE METABOLISM IN THE NEWBORN:
At birth, the maternal glucose supply is acutely interrupted and the neonate accommodates by increasing glucagon levels within
minutes after birth Decreasing insulin production Increasing catecholamine secretion increase glycogenolysis,
gluconeogenesis, lipolysis and ketogenesis.
Glucose concentration is lowest at 30-90 minutes after birth in full term infant.
Glucose production in full-term infant is ~4-6mg/kg/min, premature infant often with higher glucose production.
HYPOGLYCEMIA
Definition
There is no general consensus defining a blood level diagnostic of hypoglycemia.
In our NICU, regardless of gestation a serum glucose < 40 mg/dL is hypoglycemia.
A serum glucose <45 mg/dL if symptomatic will be treated as a hypoglycemia.
Etiology
Limited glycogen supply (prematurity, perinatal stress)
Hyperinsulinism (infant of diabetic mother, SGA, LGA, discordant twin, Beckwith-wiedemeann syndrome, pancreatic
adenoma, erythroblastosis fetalis)
Hormone abnormalities (panhypopituitarism, growth hormone deficiency, cortisol deficiency 21 hydroxylase deficiency,
adrenal hemorrhage)
Hereditary abnormalities (galactosemia, glycogen storage disease, hereditary fructose intolerance, MSUD, propionic
acidemia, fatty acid oxidation defect etc)
Others (hypothermia, sepsis, polycythemia)
Signs and symptoms
Apnea, bradycardia, cyanosis, diaphoresis, jitteriness, lethargy, limpness, poor feeding, seizures, tachypnea, temperature
instability, tremors
Monitoring
All infants admitted to the SCN will be screened for hypoglycemia on admission.
Serum glucose monitoring as follows:
o q 30 min after intervention until stable
o then q 3-6 hour if on IVF only
o or ac (pc if borderline) for the first 24 hrs or beyond until stable
Diagnosis
If cause of hypoglycemia is clearly self-limited (such as IDM, LGA infants) then complete diagnostic testing may not be
needed.
If the etiology is not clear or in cases of prolonged, severe hypoglycemia, the history, physical examination and laboratory
findings should be used together to make the diagnosis.
o Plasma should be obtained for the critical blood measurements at the time of hypoglycemia: lactate, free fatty acids,
Revised 7/11/2013 Page 66 of 123
ketones, insulin, cortisol and growth hormone.
o Additional tests of pituitary function should be included of pituitary deficiency is suspected.
o Obtain urine sample for urine organic acid as indicated.
o Glucagon stimulation test may also provide useful diagnostic information: At the time of hypoglycemia, 0.5 to 1 mg
IV glucagon is given. A rise in serum glucose of >30mg/dL suggests inappropriate preservation of liver glycogen
stores (hyperinsulinism, panhypopituitarism).
Treatment
If not clinically contraindicated and glucose is >30 mg/dL, the infant can be fed if the baby is in the well baby nursery.
If oral feeds fail to resolve hypoglycemia, glucose <30 mg/dL or unable to feed secondary to respiratory distress or is already
admitted in SCN/IMCN
o Glucose bolus is given at a dose of 200 mg/kg (2 ml/kg of D10W)
o Glucose infusion is started with D10W at a rate of 85 ml/kg/day (GIR 6 mg/kg/min)
o GIR can be increased by increasing either the fluid rate to max of 100ml/k/day or by increasing the dextrosity of
the IV glucose solution.
o Concentrations >D12.5% are sclerosing to veins and should only be administered via a central line (UV or PICC).
If glucoses remain unstable despite continuous glucose infusion, the decision to continue feeds should be discussed with the
neonatologist.
After the serum glucose has stabilized and enteral feedings have been initiated, taper IV fluids by glucose protocol.
Glucose protocol
o If the serum glucose is stable and the infant is feeding well, then determinations will be made by checking ac
glucoses.
o If the serum glucose >60 mg/dL, the IV fluids will be weaned by 2 ml/hr.
o If serum glucose >50 mg/dL, wean by 1 ml/hr.
o If you are not able to wean the IVF do not advance enteral feeds.
o Once the IV is discontinued, then glucose determinations are done ac x 2.
Specific therapies such as diaxoxide or somatostatin (octreotide) may be indicated after appropriate diagnostic evaluation.
Glucocorticoid should not be used for non-specific treatment of hypoglycemia in neonates.
HYPERGLYCEMIA
Definition
Serum glucose >125 mg/dL in term infants and >150 mg/dL in preterm infants.
Etiology
Excess glucose administration (>8 mg/kg/min), sepsis, hypoxia, hyperosmolar formula, transient neonatal diabetes mellitus,
medications, and stress
Signs
Physiologic concerns with high glucose levels include osmotic diuresis, dehydration, and weight loss.
Non-specific symptoms may be related to the cause.
Clinical studies suggest increased mortality, IVH and major handicaps in infants with hyperglycemia.
Monitoring
Serum glucose q 1 hr until <150 mg/dL then q 4 hrs until normoglycemic
Treatment
If serum glucose >150 mg/dL.
Reduce glucose infusion rate (GIR) 2 mg/kg/min by decreasing total fluids.
If total fluids cannot be decreased, decrease glucose concentration or Y-in lower dextrose concentration to maintain total fluids
constant.
IV human regular insulin administration (0.1unit/kg IV) if reducing the GIR is not effective or is not possible.
Continuous insulin infusion starting at 0.01 units/kg/hour increasing gradually to 0.05 to 0.1units/kg/hour may sometimes be
indicated.
This treatment should only be undertaken after consulting the neonatologist. There is no standard glucose monitoring policy to
follow insulin administration so you need to order glucose 30 minutes after the bolus then q 30 minutes if glucose >150 mg/dL
or <100 mg/dL then q 1 hour until stable.
Additional policy regarding monitoring glucoses
Certain infants not on IVF are at risk for hypoglycemia and need monitoring the first 24 hours of life.
These include LGA and SGA infants, Polycythemic infants, Infants of diabetic mothers and others at risk.
o They should be monitored hourly on IVF or ac and pc during transition then q 3-6 hours ac as the admit policy
suggests x 24 hours.
All infants with infusions of IV glucose require periodic monitoring.
These include infants receiving infusions for fluid requirements as well as caloric requirements.
After any change in glucose concentration or increase in rate of infusion, monitor 30 minutes later.
All infants with infusions of D10W or TPN with normal serum glucose need glucose determinations q 6 hrs.
Infants with heparin locks previously documented to be normoglycemic and feeding well do not require glucose
Revised 7/11/2013 Page 67 of 123
monitoring.
Normoglycemic infants who are feeding well and on IV therapy at a rate <4 ml/hr do not need glucose monitoring unless
otherwise ordered.
GIR calculation
Glucose infusion rate: rate (ml/hr) x dextrose infusion (D10) x 0.167 (constant)
Wt in Kg
Example: A 3 kg baby on D10W at 80 ml/kg/day (rate of 10ml/hr)
o GIR =10 x 10 x 0.167 =5.5 mg/kg/min
3
APPROACH TO SEPSIS IN THE NEWBORN:
This guideline will only address the recognition and emergent management of early-onset bacteremia (less than
72 hours of age).
Maternal Risk Factors:
1. Onset of premature labor and delivery
2. Prolonged rupture of membranes (more than 18 hours)
3. Maternal chorioamnionitis
temperature greater than 37.5C
uterine tenderness
foul smelling amniotic fluid
fetal heart rate greater than 160 beats per minute
bacteria and white blood cells (WBC) in the amniotic fluid
4. Manipulative operative delivery
5. Maternal GBS colonization
Neonatal Risk Factors:
1. Perinatal asphyxia
2. Low birth weight
3. Prematurity
4. Invasive procedures
5. Presence of open congenital anomalies
Clinical Signs in the Neonate:
1. Respiratory distress
a. grunting, retractions, tachypnea, cyanosis, apnea
b. Lung is most common site of infection in the neonate
2. Temperature instability
a. Hyperthermia more common in term
b. Hypothermia more common in preterm
3. Cardiovascular
a. Poor perfusion
b. Tachycardia
c. Hypotension
d. Shock
e. Acidemia
4. Gastrointestinal
a. Poor feeding
b. Abdominal distention
c. Emesis, increased spits
d. Ileus
5. Neurologic
a. Seizures
b. Lethargy, decreased activity
c. Poor feeding
d. hyptonia
6. Skin
a. Poor perfusion
b. Petechiae; purpura
c. Pallor
7. Metabolic
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a. Glucose instability
b. Metabolic acidosis
Investigations
General investigations include parameters important in assessment of general well being of the infant eg blood gases, true blood
glucose
Infection related tests
Non-specific markers e.g. C-reactive protein (CRP), Full Blood Examination
CRP rises approximately 12 hours after onset of sepsis and returns to normal within 2 to 7 days of successful treatment. If the
CRP remains elevated or rises after initial improvement, care must be taken to look for possible collections, including
endocarditis (particularly if 'long-lines' have been used) or fungal infection. CRP is raised in 85 % of episodes of confirmed
sepsis with a specificity of 90%. It can, therefore, be normal in cases of true sepsis and should be used in conjunction with
clinical signs and culture results.
FBE -The Polymorphonucleocyte (PMN) count can be normal in 1/3 of cases of confirmed sepsis, but can also be elevated in
the absence of infection. Neutropenia in the face of confirmed sepsis can indicate that the baby is extremely unwell. A raised
immature to total white cell ratio (I:T ratio >0.3) is about 85 % sensitive and specific - particularly for early onset sepsis.
Tests to identify the infective organism
Early onset sepsis
Blood culture (mandatory)
Lumbar puncture (LP) should be performed where the 'index of suspicion' of meningitis is high i.e. abnormal conscious state or
seizures. LP may need to be delayed until after the infant's condition has stabilised sufficiently to tolerate the procedure and
abnormalities of coagulation status have been controlled. If the initial blood culture is positive. LP must be performed to
exclude meningitis since the presence of meningitis alters the length of antibiotic treatment as well as prognosis.
There is little to be gained from performing urine aspiration for culture, as hematogenous spread is the mechanism behind
positive urine cultures in the first few days of life
Indications for early onset Sepsis workup (BC x 2 always and LP if clinically indicated):
1. Chorioamnionitis
2. >72 hours PROM
3. Symptoms such as emesis, temperature instability, poor feeding, unexplained apnea,
respiratory distress etc.
Blood Cultures (aerobic and anaerobic):
a. Obtain from a peripheral vessel or as first specimen from a central line
b. Minimum two separate blood cultures sets from two separate sites
c. Minimum blood requirement 0.5 ml (preferably 1.0-2.0 ml per culture)
d. For late onset sepsis send cultures from all central lines and a peripheral culture
Cerebral Spinal Fluid (CSF):
Many centers elect to defer the lumbar puncture (LP) in rule out sepsis evaluations in asymptomatic
neonates being evaluated for early onset sepsis.
a. If the neonate is symptomatic, a LP is indicated
b. It may be deferred if the neonate is clinically unstable or if it causes clinical deterioration.
c. If an LP is done after the initiation of antibiotics, interpretation of results might
be difficult; although inflammatory changes may persist.
Urine:
Urine cultures are of little use in the diagnosis of early-onset bacteremia so not obtained on the initial
workup after birth
but very necessary if > 72 hours.
a. Urine culture is part of a routine work-up on sepsis suspected in infants >72 hours of life.
b. Bagged urine specimens for culture are not reliable thus not acceptable.
c. A suprapubic tap is the preferred method to obtain urine followed by a catheterized specimen.
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Tracheal aspirates:
a. Cultures and gram stains useful when obtained via the ETT of neonates requiring positive pressure ventilation at
admission if suspected having of sepsis.
b. They only reflect colonization of the upper airway after the initial intubation.
Other Cultures:
Amniotic fluid, gastric aspirate, ear canal, skin cultures and gram stains identify the
flora of the fetal environment but do not confirm neonatal sepsis so are not routinely done.
X-rays:
Chest and abdominal x-rays should be obtained in neonates who have respiratory and or GI symptoms
Further lab evaluation:
Leukocyte profiles:
a. 1st CBC has poor predictive value.
b. Initial CBC is drawn followed by a 24 and 48 hour CBC.
c. Total WBC <5,000/mm3 (helpful if no maternal preeclampsia).
d. Absolute neutrophil count less than 1,000/mm3.
e. Bands/bands +polymorphoneuclear ratio (I:T ratio) greater than 0.2.
f. These profiles have the highest predictive accuracy and sensitivity for bacteremia.
g. Leukocytosis may be a stress reaction and not indicative of sepsis.
Thrombocytopenia:
a. Platelet count of less than 100,000 may be associated with bacteremia.
b. If low platelet count; a venipuncture should be done to confirm.
c. May need DIC Panel
Arterial blood gases: Look for acidemia and hypoxia if infant has respiratory distress or cardiovascular instability.
Late onset sepsis
Blood cultures (mandatory)
SPA specimen of urine should be obtained, as a primary UTI is not uncommon as a cause of sepsis after 5 days of age
The role of LP in late onset sepsis is controversial and depends on the clinical setting
Non-NICU infants suspected of being septic - LP should be performed to exclude CNS infection. If there is a high clinical index of
CNS infection, appropriate treatment should be instituted early even if the LP is delayed until the baby is stable enough to tolerate
the procedure.
Infants in NICU - The role of LP is limited since the commonest organism causing sepsis is the Coagulase Negative Staph (CONS).
CONS rarely cause CNS infection unless a Ventriculoperitoneal shunt is present. LP when CONS is isolated from blood culture is
reserved for infants who are not following the expected clinical course despite appropriate antibiotics. LP is performed when the
infant's condition is suggestive of meningitis or blood culture identifies an organism other than CONS.
ETT cultures and skin swabs are of limited value for babies in NICU situations. Their value is as a guide to the profile and
sensitivity of organisms in the nursery, particularly Staphylococcus aureus.
Inflammatory mediators:
1. ESR or C-reactive protein
a. Not always a reliable test of infection in the neonate, particularly <24 hours.
Might be useful in conjunction with other tests.
b. These mediators are not elevated until 6-8 hours after the onset of bacteremia.
c. CRP is used here at 24 and 48 hours in conjunction with the 24 and 48 hour CBC.
d. Look for changes in the CRP. Levels below 10 are considered normal
e. Check maternal cultures before and after delivery and notify appropriate pediatric personnel.
f. Bacterial antigen identification: Latex agglutination or counter immune electrophoresis (CIE)
may not be reliable. These screening tests can be performed rapidly on serum, urine, or
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amniotic fluid but infrequently used at this institution.
Treatment:
Supportive:
1. Neutral thermal environment (Refer to Neonatal Guidelines of Care: Thermoregulation)
2. Intravenous fluids, glucose and electrolytes (Refer to Neonatal Guideline of Care: Maintenance Fluid and
Electrolyte Therapy)
3. Adequate oxygenation and ventilation
a. Oxygen and assisted ventilation based upon arterial blood gas analysis
Capillary blood gases may be highly inaccurate in neonates with shock syndromes due to poor
Peripheral circulation. (Refer to Neonatal Guidelines of Care: Respiratory Distress in the Neonate
and Basic Guidelines for Administration of Oxygen).
b. Continuous cardio-respiratory monitoring and pulse oximetry
4. Maintenance of tissue perfusion:
a. Volume expanders, such as normal saline, fresh blood and plasma
b. Use of isotropic drugs for improved cardiac contractility as necessary.
(Refer to Neonatal Guidelines of Care: Hypotension and Shock).
Antibiotic choice
Given the usual causative organisms the following regimes are recommended initially. Antibiotic choice can then be rationalised on the
basis of culture results and clinical course.
Early onset sepsis
Ampicillin- 50mg/kg IV 12 hr
100mg/kg/dose 12 hr if meningitis suspected
Gentamicin see table for weight and gestational age.
Note: both can be given IM if IV access is not possible
If history or clinical appearance suggests the possibility of Listeria, ampicillin 50mg/kg IV 12hourly can be used instead of penicillin
(although data indicating that this is superior is lacking).
For treatment of meningitis (until sensitivities are known)
Cefotaxime - 50mg/kg/dose 12 hourly for preterm babies or term babies in the first week of life, 8 hourly after that time
Ampicillin - 50mg/kg/dose 12 hourly for preterm babies or term babies in the first week of life, 8 hourly after that time
Late onset sepsis
Vancomycin and Tobramycin are the usual first choice antibiotics
In meningitis use Ampicillin and Cefotaxime.
For necrotizing enterocolitis use Ampicillin, Gentamicin, & Metronidazole
Doses of antibiotics need to be adjusted for age of the baby and on the basis of levels in the case of gentamicin and vancomycin.
An aminoglycoside other than gentamicin may be used in some hospitals at times depending on the profile of prevalent organisms.
When to stop Antibiotics
Duration of antibiotic treatment depends upon the clinical condition of the infant and the organism identified on culture.
where the likelihood of infection is low, with a baby in good condition and infective indices negative, antibiotics can be ceased
if cultures are negative after 48 hours
sepsis strongly suspected, despite negative blood culture at 48 hours. It is advisable to repeat blood culture and continue
antibiotics for at least 5 days providing infective indices have normalised. Another approach is to continue antibiotics for 48
hours after indices have normalised
proven gram negative bacteraemia, with clear CSF, treat for 10 days, antibiotics can be rationalised in the face of culture and
Revised 7/11/2013 Page 71 of 123
sensitivities
proven GBS bacteraemia, with clear CSF, 10 days treatment should be sufficient
meningitis, treat for 14 days for GBS and 21 days for gram negative organisms. In some centres, 48-hourly LPs are performed
in cases of gram negative meningitis, with treatment continuing for 14 days after the first negative culture - in practice this
usually equates with a 21 day treatment course
UTI - treat with IV antibiotics for at least 5 days, a total of 10 days treatment is needed. The infant can be managed with
appropriate oral antibiotics for the latter half of the treatment course if clinical condition is satisfactory. Ongoing prophylactic
antibiotics will be needed until renal investigations (ultrasound and/or MCU) are completed
Special Circumstances
The GBS colonised mother
At delivery approximately 15% of women are colonised with GBS. Up to 70% of infants born to colonised women are themselves
colonised. Infection occurs in 1% of colonised infants. 75% of early onset GBS disease in neonates occurs in term babies. The incidence
of GBS disease varies, with the rate being 3 per 1000 live births in the USA, compared to 0.3 per 1000 in Australia and the UK. The risk
is 3 times higher in the Aboriginal community.
Screening for GBS remains the subject of heated debate, but it is known that intrapartum administration of antibiotics (penicillin or
amoxycillin) reduces neonatal colonisation by 90%, and early onset GBS disease by 90%.
The CDC in the USA recommends that all women be screened with anorectal and vaginal swabs at 35 -37 weeks' gestation.
Intrapartum antibiotics are given according to the following strategies
if screening is performed administer to
o GBS colonised women
o Non-colonised women with risk factors present
if screening is not performed administer to women with risk factors
o Preterm onset of labour (<37weeks)
o ROM for >18 hours
o Maternal fever (>38C)
o Previous baby with invasive GBS disease
o GBS bacteriuria this pregnancy
Use of the CDC guidelines is estimated to result in around 27% of women receiving antibiotics, with an associated reduction in early
onset GBS disease of around 85%. The disadvantages of such an approach are the risk of maternal complications (anaphylaxis), and the
cost (GBS rates of >0.5 per 1000 live births are needed to justify such an approach on a cost-effectiveness basis).
Intrapartum chemoprophylaxis consists of penicillin 1.2gms IV statim, then 0.6gms 4hrly (erythromycin can be used in cases of
penicillin allergy). Should the infant be delivered before prophylaxis has been administered to the mother, or within 4 hours of the initial
dose, the infant should be observed closely in hospital for 48 hours. Some workers recommend giving a single intramuscular injection of
100mg penicillin, IM, to such an infant while others recommend taking an FBE and blood culture prior to observation. Occasional
treatment failure has been associated with the single IM dose regime.
If the infant is initially (or becomes) symptomatic, or if significant prematurity (<35 weeks gestation) is present, the infant
should undergo a septic evaluation and treatment with intravenous antibiotics despite maternal intrapartum prophylaxis.
Prolonged Rupture of Membranes (PROM)
The majority of women will come into labour within 24 hours of rupture of the membranes; however, this may be delayed in up to 4%
of cases. PROM for greater than 18 hours may lead to increased risk of infection in mother and baby - particularly if the mother is GBS
positive or undergoes repeated vaginal examinations. In practice, the risk is greatest for preterm infants, but 75% of early onset GBS
sepsis occurs in term babies. Since there is a lack of evidence from trials available there is debate as to the role of prophylactic
antibiotics in PROM. Obstetric staff will need to consider signs of possible maternal sepsis, as well as risk factors such as GBS
colonisation in deciding to administer antenatal antibiotics. Babies born with a background of PROM need to be viewed as potentially at
Revised 7/11/2013 Page 72 of 123
risk of sepsis.
Preterm infants, particularly those <35 weeks, are usually screened for sepsis and treated with IV antibiotics until infection in the baby
has been excluded.
Term infants
if there are no risk factors, apart from the PROM, the infant is usually observed closely and treated only if symptoms develop
if there is a risk factor present in addition to PROM, such as GBS positive mother, maternal intrapartum fever or suspected
chorioamnionitis that infant should be treated as potentially septic, even if completely asymptomatic
any symptomatic baby needs septic evaluation performed and treatment for infection regardless of the presence or absence of
risk factors
Fungal sepsis
Generally seen in VLBW infants in NICU. Risk factors include multiple courses of IV antibiotics, presence of central lines and
extensive areas of skin breakdown. Consideration of fungal sepsis is particularly necessary when such infants deteriorate whilst
receiving antibiotics. Empirical treatment with Amphotericin until cultures are reported as clear for fungal organisms is appropriate.
SPA of urine must be performed prior to starting Amphotericin as bag specimens will often be contaminated with Candida colonising
the skin. If fungal sepsis is confirmed, then the addition of a further antifungal (e.g. fluconazole mg/kg stat, then 2mg/kg 48hrly) may be
useful. Duration of treatment depends upon the site of infection but generally ranges from 3 to 6 weeks. Ultrasound of the kidneys and
formal fundoscopy should be performed.
Antimicrobial Therapy: Intravenous antibiotic therapy should be initiated as soon as possible
in neonates suspected of sepsis.
1. Maternal antenatal treatment of suspected infection begins treatment of the fetus.
2. Empiric therapy pending the results of bacterial cultures usually consists of penicillin and an
Aminoglycoside. (Ampicillin and Gentamycin).
3. Third generation cephalosporin antimicrobials (Cefotaxime) may replace (or be used in conjunction with
amninoglycosides) the preceding regimen for treatment of neonatal Gram negative bacilli sepsis and/or
meningitis. They are not routinely used as the first line due to risk of multi-drug resistant organisms.
Immunotherapy:
1. Exchange transfusion, granulocyte transfusion, granulocyte colony stimulation factor (Neupogen) and
intravenous (IV) immunoglobulin (IG) is still considered investigational therapies for neonatal sepsis.
2.These interventions may offer increased survival for rapidly deteriorating neonates. Such neonates should
be cared for in the NICU.
Prevention:
The empiric therapy of neonates born after premature and/or prolonged rupture of membranes remains controversial. Some investigators
have offered a scoring system to guide therapy.
1. Term neonates with prolonged rupture of membranes (greater than 18 hours) who are asymptomatic
need only be carefully observed.
2. Neonates who have risk factors for infection should have blood cultures and neutrophil profiles obtained.
Antimicrobial therapy may be indicated for these neonates pending bacteriologic results.
3. Maternal antibiotic therapy of the mother following premature or prolonged rupture of membranes
may lower the incidence of neonatal group B streptococcal (GBS) bacteremia.
4. Penicillin prophylaxis in the neonate has also prevented subsequent GBS infection when given shortly after
birth.
5.The CDC has set forth (2010) guidelines for the care of neonates exposed to Group B Strep.
(Refer to Neonatal Guidelines of Care: Isolation and Infection Control).
Revised 7/11/2013 Page 73 of 123
Areas of Uncertainty in Clinical Practice
1.The role of antigen tests for GBS is controversial
Urine specimens for GBS antigen can be positive when babies are colonised, even when a SPA specimen is taken. If a bag
specimen is used, then contamination with skin GBS colonisation will result in a positive test.
Antigen tests are more sensitive and specific for CSF specimens, but cannot be relied upon to exclude infection. Antigen
testing results need to be viewed from the point of view of adding supplementary evidence of possible infection, but cannot be
relied upon to prove or disprove GBS infection, and are thus of limited value. Similar limitations exist in testing for other
bacterial antigens.
2.Antifungal prophylaxis
A recent Cochrane review failed to demonstrate a reduction in fungal colonisation among patients receiving prophylactic oral
nystatin compared to placebo. All patients in these trials were immuno-compromised but beyond the neonatal period.
A RCT of intravenous fluconazole compared to placebo during the first 6 weeks of life in 100 infants of less than 1000gm
birthweight showed a reduction in fungal colonization and invasive fungal infection.
3.Treatment with Granulocyte Colony Stimulating Factor (G-CSF)
G-CSF has been shown to increase PMN counts in VLBW babies, but the effect on sepsis reduction or mortality from sepsis
has not been demonstrated.
4.Intravenous immunoglobulin (IVIG)
Studies involving IVIG show a possible improvement in mortality in babies given IVIG as part of the treatment of sepsis.
However, larger trials are needed to examine the role of IVIG in neonates with sepsis.
Other ancillary treatments that have been used include exchange transfusion and neutrophil transfusions, but insufficient data is
available to recommend their use.
Further Reading
Isaacs D, Moxon ER. Handbook of Neonatal Infections - a practical guide. WB Saunders, London. 1999.
Remington J S, Klein J O. Infectious Diseases of the Fetus and Newborn Infant 5Th Ed. WB Saunders, Philadelphia. 2000.
CDC (Center for Diseases Control). Prevention of perinatal group B streptococcal diseases: a public health perspective. MMWR 1996:
45(RR-7).
Smaill, F. Intrapartum antibiotics for Group B streptococcal colonisation. Cochrane Pregnancy and Childbirth Group. The Cochrane
Library.
Flenady, V. King, J . Antibiotics for prelabour rupture of membranes at or near term. [Protocol] Cochrane Pregnancy and Childbirth
Group. The Cochrane Library.
References available from Dr. G. Levin, M.D.
Revised 7/11/2013 Page 74 of 123
ADMINISTRATION SCHEDULE FOR GENTAMICIN (2010):
Present Antibiotic
Gentamicin Dosing Schedule:
Gestation Age Dose Interval
29 weeks 0-7 days
8-28 days
29 days
5 mg/kg q 48h
4 mg/kg q 36h
4 mg/kg q 24h
30-34 weeks 0-7 days
8 days
4.5 mg/kg q 36h
4 mg/k q 24h
35 weeks all ages 4 g/kg q 24h
Routine monitoring of Gentamicin (this includes all aminoglycosides) is usually not necessary if treating only for
48 hours while ruling out sepsis. For those infants being treated for >48 hours routine monitoring should be done
obtaining levels around the 3
rd
dose (trough 30 minutes before the third dose and peak 30 minutes after the 3
rd
dose). Monitoring may
be done sooner in case of renal dysfunction, birth asphyxia, symptomatic PDA needing indomethacin, and altered perfusion.
Desired peak level: 5-12 mcg/ml. Desired trough level: 0.5-1 mcg/ml
After the first week of life, give a dose of 4 mg/kg and measure the peak in 30 minutes after infusion and another level 24 hours later to
determine dosing interval.
Reference: NeoFax 2009
Antibiotic Administration for Ampicillin and Vancomycin
Ampicillin:
Neonate:
<7 Days: > 7 Days:
<2 kg: 100 mg/kg/24 hr /IV-Q12 hr <1.2kg: 100mg/kg/24hr - Q12hr/IV
>2 kg: 100 mg/kg/24 hr /IV-Q8 hr 1.2-2kg: 100mg/kg/24hr - Q8hr/IV
>2kg: 100mg/kg/24hr - Q6/IV
Vancomycin Dosing and Monitoring in the NICU
Dosing and Interval Chart by postnatal age and GA (gestational age) by PMA (post-menstrual age).
Neofax 2009
Gestational Age by PMA
(weeks)
Postnatal Age (days) Interval
(hours)
29 0 to 14
>14
18
12
30-36 0 to 14
>14
12
8
37-44 0 to 7
>7
12
8
45 ALL 6
This chart uses starting doses:
15 mg/kg/dose for suspected meningitis/deep infections such as osteomyelitis
10 mg/kg/dose for simple bacteremia.
Dosing and Interval based on Creatinine (for immaturity or renal impairment).
Capparelli et al. J Clin Pharmacol 2001; 41:927-934.
Creatinine based dosing (considers clearance decreased with decreased GFR).
Revised 7/11/2013 Page 75 of 123
Creatinine (mg/dl) Dose (mg/kg/dose) Interval (hours)
1.7 15 48
1.3-16 10 24
1.0-1.2 15 24
0.7-0.9 20 24
0.6 15 12
Monitoring: Trough should be done 30 minutes before the 3
rd
dose. Although peaks are not routinely
necessary, if choosing to do a peak it should be done 30 minutes after the 3
rd
dose. Peak levels should
be between 30 to 40 mcg/ml if treating meningitis and 20-40 mcg/ml for other infections.
Because vancomycin exhibits time-dependent bacterial killing, effectiveness may be compromised if trough concentrations fall below
the minimum inhibitory concentration (MIC) for prolonged periods. If initially concerned about obtaining therapeutic troughs rapidly,
levels for above graphs can be done at the first dose
and dose adjusted based on first dose pharmacokinetics, especially if dosed every 18-24 hours.
Crumby et al. Am J Health-Syst Pharm; Vol 66, Jan 15, 2009.
Follow-up troughs after the 1
st
dose adjustment should be done before the next dose of the new time
interval. Consider reassessing the trough weekly if on vancomycin for longer than 7 days. Troughs
are affected by indocin and dopamine.
Due to the diverse population and disease states found in the NICU, nomograms should be cautiously
applied and dose adjusted after troughs obtained.
MANAGEMENT OF INFANTS BORN TO HERPES SIMPLEX VIRUS POSITIVE MOTHERS:
1. Care of infants born vaginally to a mother with active genital ulcerative lesions. Primary 1
st
episode of HSV
infection or known recurrent lesion or status unknown:
A. Asymptomatic Infant
1. Obtain HSV cultures (conjunctiva, nasopharynx, mouth, stool or rectal swab, urine)
24-48 hours after delivery. Cultures are delayed to distinguish between viral replication
vs transient colonization.
2. Observe carefully for signs and symptoms, vesicular scalp or skin lesions, RDS, seizures,
or other signs and symptoms of sepsis.
3. Initiate IV acyclovir only if HSV cultures are positive. Obtain a CSF analysis, culture,
blood and CSF PCR for HSV prior to initiation of therapy.
4. If this is presumed or proven maternal primary HSV infection, initiate therapy at birth after
cultures are obtained.
5. Infants who develop a vesicular rash or unexplained clinical signs and symptoms of sepsis
should be evaluated immediately and managed similar to the asymptomatic infant with
possible HSV infection.
B. Symptomatic infant S/S of HSV infection or non-specific for sepsis, vesicular skin or scalp lesions
1. HSV cultures (skin lesions +all of the above) immediately after birth
2. Initiate IV Acyclovir immediately after cultures are obtained
2. Care of the infant born via C/S to a mother with active genital ulcerative lesions (primary, recurrent or
unknown)
1. Observe the infant carefully for the development of scalp or skin lesions or S/S of HSV infection
or sepsis
2. Obtain HSV cultures as above
3. Initiate IV Acyclovir if cultures are positive
4. Initiate therapy immediately after birth or at onset of clinical S/S and obtain HSV cultures
if neonatal HSV infection is strongly suspected: S/S of sepsis, scalp or skin lesion, or
ROM >6 hours.
Revised 7/11/2013 Page 76 of 123
3. Care of the infant born to a mother with a history of HSV infection and no active lesions at delivery.
1. Neither HSV cultures nor empiric therapy with IV Acyclovir are indicated
2. No isolation necessary.
4. Diagnostic tests for HSV
1. HSV Culture: HSV culture remains the Gold Standard for HSV detection. Specimens for
HSV culture should be obtained from skin vesicles (if present), nasopharynx, conjunctiva,
stool or rectum, urine, blood and CSF. A positive culture obtained from surface culture >48
hours after birth indicates viral replication suggestive of infant infection rather than
colonization after intrapartum exposure.
3. HSV PCR: This is a very sensitive detection method for HSV encephalitis. HSV CSF culture
is not very sensitive.
4. Rapid diagnostic test: Direct fluorescent staining (DFA) of vesicle scraping or enzyme
immunoassay detection of HSV culture. In general, HSV serology is not reliable.
If TORCH titers are sent, you must request IGM titers. The Tzank test has low
sensitivity and is not recommended as a rapid diagnostic test.
5. Treatment for HSV infection:
1 Acyclovir 20 mg/kg/dose q 8 hours for 14-21 days (SEM+14 days, disseminated disease
or CNS disease =21 days of treatment). The drug should be infused over 1 hour (the interval
should be increased for premature infants <34 wks PMA or in patients with renal
impairment of hepatic failure).
2 Topical ophthalmic therapy is used for ocular involvement in addition to IV therapy. 1-2% trifluridine, 1%
iododeoxyuridine or 3% vidarbine along with IV Acyclovir. Consider
evaluation with the ophthalmologist. Topical corticosteroids are contraindicated.
3 Complications of Acyclovir: Phlebitis, transient renal dysfunction, crystaluria.
Less common complications: bone marrow suppression, elevated LFTs, skin rash,
CNS symptoms (seizures, lethargy).
4 Monitor urinalysis, BUN, creatinine during the course of therapy. Consider
monitoring liver enzymes and CBC.
6. Other recommendations
1. Delay elective or ritual circumcision for 1 month after birth of infants at highest risk of disease.
2. Neonatal HSV infection can occur as late as 6 weeks after delivery, although most infected infants are
symptomatic by 4 weeks of age. Any rash or other symptoms that may be caused by HSV must be
evaluated carefully.
7. Isolation
1. Managed in private room when possible or strict contact precautions for the duration of the illness.
2. Strict contact precautions should be maintained for all infants perinatally exposed to HSV.
3. Women with active lesions should be managed with strict contact precautions. Careful hand
washing is recommended. Mothers with cold sore or stomatitis should wean surgical masks when
touching their newborn infant until the lesions are crusted and dried. She should not kiss or nuzzle
her newborn until the lesions have cleared.
4. Breastfeeding is acceptable if no lesions are present on the breast and if active lesions elsewhere are
covered.
CANDIDATES FOR RSV PROPHYLAXIS:
Prior to discharge all infants meeting the following AAP guidelines will receive Synagis 15 mg/kg IM. This is a monoclonal antibody
immunization prophylaxis for the ameliorization of RSV bronchiolitis.
AAP guidelines for Synagis (as per Red Book, 2009):
1. Infants born at 28 weeks gestation up to one year of age at the onset of RSV season.
2. Infants born at 29-31 6/7 weeks gestation up to six months of age at the onset of RSV season.
3. Infants 24 months or younger with hemodynamically significant cyanotic and acyanotic congenital heart disease.
4. Infants 24 months or less with CLD who have required medical therapy (supplemental oxygen, bronchodilators,
diuretic or steroid therapy) for CLD within 6 months before the anticipated start of the RSV season.
5. Infants born at 32 0/7-34 6/7 weeks gestation with 2 or more of the following risk factors for severe RSV disease.
These risk factors are not absolute. Managed care companies need to approve these factors.
Risk factors include:
Day care attendance.
Revised 7/11/2013 Page 77 of 123
School age siblings.
Exposure to environmental air pollutants (smoking can be controlled and
is not considered a risk factor however the family needs to be educated
and counseled and this needs to be documented).
Severe neuromuscular disease.
Congenital abnormalities of the airways.
Condition
Max
Number of
Doses
Age (in months) at Onset of RSV Season
0 to < 3 3 to < 6 6 to < 12 12 to < 24 > 24
Hemodynamically significant Congenital Heart
Disease (CHD) 2,3
Infants/children requiring medication to control
congestive heart failure (CHF)
Infants/children with moderate to severe pulmonary
hypertension
Infants/children with cyanotic heart disease
5 Yes Yes Yes Yes No
Chronic Lung Disease (CLD) formerly called
Bronchopulmonary dysplasia defined as:
For infants <32 weeks: Oxygen requirement at 36
weeks gestational age or at discharge
For infants >32 weeks: Oxygen requirement at age 28
days or greater at discharge
Infants/Children who have received treatment for
CLD within 6 months of the anticipated onset of the
season with Oxygen
Bronchodilators
Diuretics and/or steroids
5 Yes Yes Yes Yes No
Premature infants <28 weeks, 6 days gestational age
OR
Infants with a significant congenital abnormality of
the airway or neuromuscular condition that
compromises handling of respiratory secretions
5 Yes Yes Yes No No
Premature infants >29 weeks, 0 days; <31 weeks, 6
days, gestational age
5 Yes Yes No No No
Premature infants >32 weeks, 0 days; <34 weeks, 6
days with one of the following two risk factors:4
Child care attendance 5
Sibling <5 years of age
3 Yes No No No No
Infants of 35 weeks, 0 days and older gestational age
(without CLD or Hemodynamically Significant CHD)
6,7,8
0 No No No No No
Additional Notes:
1. If an infant receiving Synagishas a breakthrough RSV infection during the season, Synagisshould continue to be given for a
maximum of 3 doses for the 32 to <35 week infant category (until they reach 90 days of life) and for a maximum of 5 doses for the
other high risk categories.
2. High-risk CHD patients receiving Synagiswho undergo heart surgery with the use of cardio-pulmonary bypass should receive a
dose of Synagispost-op as soon as medically stable.
3. Patients with CHD who are NOT candidates for Synagisinclude:
o Hemodynamically insignificant heart disease
o Secundum ASD
o Small VSD
o Pulmonic stenosis
o Uncomplicated aortic stenosis
o Mild coarctation of the aorta
o Patent ductus arteriosus (PDA)
Revised 7/11/2013 Page 78 of 123
4.Infants with corrected surgical lesions unless they continue to require medication for CHF
5.Infants with mild cardiomyopathy who are not receiving medical therapy
6. Premature infants 32 35 weeks should only receive prophylaxis until they turn 3 months old (maximum of 3 doses many
will require only 1 or 2 doses). Prophylaxis is not recommended after 3 months of age.
10. Participation in child care (two or more unrelated infants/children for more than 4 hours per week) should be
restricted during
the RSV season for high-risk infants whenever feasible. Parents should be instructed on the importance of careful hand
hygiene.
8. All high risk infants and their contacts should be immunized against influenza beginning at 6 months of age.
9.. Limited studies have suggested that some patients with cystic fibrosis may be at risk of RSV but it is not known whether RSV
exacerbates the chronic lung disease in CF patients and there is insufficient data to determine the effectiveness of Synagisin
this population. Therefore there is no recommendation for routine prophylaxis for cystic fibrosis.
11. Synagishas not been evaluated in randomized trials in immunocompromised children. However, children
with severe
immunodeficiencies (such as severe combined immunodeficiency syndrome or advanced AIDS) may benefit from prophylaxis.
Reference:
Red Book 2012 Report of the Committee on Infectious Diseases, 27 Edition, Elk Ridge Village, IL, 2006.
American Academy of Pediatrics. Policy Statement Modified Recommendations for Use of Palivizumab for Prevention of
Respiratory Syncytial Virus Infections. Pediatrics Vol. 124 December 2009, pp 1694-1701. Academy of Pediatrics
RECOMMENDATIONS FOR HEPATITIS C VIRUS (HCV) EXPOSED INFANTS:
Transmission Modes:
60-90% seropositive people have history of exposure to blood such as IV drug users.
Can be sexually transmitted but that is not the major route of transmission.
In US 1-2% of pregnant women are thought to be seropositive.
HCV infection in infants born to HCV+, HIV neg. moms is 5-6% (range: 0-25%)
Infection rates born to moms co-infected with HCV & HIV, 14% (range: 5-36%)
Consistent factor associated with transmission is HCV RNA in mom at birth
There is an association between virus titer and transmission of HCV.
Transmission via breast milk not documented but due to the theoretical risk breast feeding is not recommended if nipples are
cracked or bleeding. Discuss with mom.
Screening recommended in moms with a history of:
blood or blood product transfusions before J uly 1992
organ transplants before July 1992
persistently abnormal ALT levels
IV drug use or hepatitis
Detection of exposed infants and their follow-up:
Screening test is the HCV IgG antibody. No IgM test available.
If HCV antibody status on the mother not available check infants HCV antibody.
If infants HCV antibody is positive and the mother has not been tested inform the
mothers obstetrician.
Infant should be followed with the mother in Dr. Handals Infectious Disease Clinic.
Seroprevalence among pregnant women in the United States has been estimated at 1% to 2%. The risk of perinatal transmission
averages 5% to 6%, and transmission occurs only from women who are HCV RNA positive at the time of delivery. Maternal co-
infection with HIV has been associated with increased risk of perinatal transmission of HCV, which depends in part on the serologic
concentration of HCV RNA in the mother. Serum antibody to HCV (anti-HCV) and HCV RNA have been detected in colostrum, but
the risk of HCV transmission is similar in breastfed and bottle-fed infants.
All people with HCV-RNA in their blood are considered to be infectious.
The incubation period for HCV disease averages 6 to 7 weeks, with a range of 2 weeks to 6 months. The time from exposure to
development of viremia generally is 1 to 2 weeks.
DIAGNOSTIC TESTS: The 2 major types of tests available for laboratory diagnosis of HCV infections are immunoglobulin (Ig) G
antibody enzyme immunoassays for HCV and NAA tests to detect HCV RNA. Assays for IgM to detect early or acute infection are not
Revised 7/11/2013 Page 79 of 123
available. The third-generation enzyme immunoassays are at least 97% sensitive and more than 99% specific. False-negative results
early in the course of acute infection can result from the prolonged interval between exposure and onset of illness and seroconversion.
Within 15 weeks after exposure and within 5 to 6 weeks after onset of hepatitis, 80% of patients will have positive test results for serum
anti-HCV antibody. Among infants born to anti-HCV-positive mothers, passively acquired maternal antibody may persist for up to 18
months.
Food and Drug Administration (FDA)-licensed diagnostic NAA tests for qualitative detection of HCV RNA are available. HCV RNA
can be detected in serum or plasma within 1 to 2 weeks after exposure to the virus and weeks before onset of liver enzyme abnormalities
or appearance of anti-HCV. Assays for detection of HCV RNA are used commonly in clinical practice to identify anti-HCV-positive
patients who have HCV infection, for identifying infection in infants early in life (ie, perinatal transmission) when maternal antibody
interferes with ability to detect antibody produced by the infant, and for monitoring patients receiving antiviral therapy. However, false-
positive and false-negative results can occur from improper handling, storage, and contamination of test specimens. Viral RNA may be
detected intermittently, and thus, a single negative assay result is not conclusive. Quantitative assays for measuring the concentration of
HCV RNA are available but are less sensitive than qualitative assays. The clinical value of these quantitative assays appears to be
primarily as a prognostic indicator for patients undergoing or about to undergo antiviral therapy.
TREATMENT: Patients diagnosed with HCV infection should be referred to a pediatric hepatitis specialist for clinical monitoring and
consideration of antiviral treatment. Therapy is aimed at inhibiting HCV replication, eradicating infection, and improving the natural
history of disease. Therapies are expensive and can have significant adverse reactions. Interferon-alfa or peginterferon-alfa alone and
peginterferon-alfa in combination with ribavirin are approved by the FDA for treatment of chronic HCV infection in adults. Response to
treatment varies depending on the genotype with which the person is infected. Combination therapy with pegylated interferon-alfa and
ribavirin is the preferred treatment and results in sustained virologic response, defined as undetectable HCV RNA concentrations 6 or
more months after treatment cessation. A sustained viral response occurs in 40% to 45% of treated adult patients infected with genotype
1 and approximately 80% in patients with genotypes 2 or 3. The FDA has approved use of both nonpegylated interferon-alfa-2b in
combination with ribavirin and pegylated interferon-alfa-2b combined with ribavirin for treatment of HCV infection in children 3 to 17
years of age. As in adults, pegylated interferon in combination with ribavirin is the preferred treatment with sustained virologic response
documented in 55% of pediatric patients infected with HCV genotypes 1 and 4 following 48 weeks of therapy and in 96% of patients
infected with HCV genotypes 2 and 3 following 24 weeks of therapy. The few studies of combination therapy in children suggest that
children have fewer adverse events compared with adults; however, all treatment regimens are associated with adverse events. Major
adverse effects of combination therapy in pediatric patients include influenza-like symptoms, hematologic abnormalities,
neuropsychiatric symptoms, thyroid abnormalities, ocular abnormalities including ischemic retinopathy and uveitis, and growth
disturbances. Of 107 patients 3 to 17 years of age in a clinical trial of pegylated interferon-alfa-2b plus ribavirin, severely inhibited
growth velocity (<3rd percentile) was observed in 70% of the subjects during treatment. Of subjects experiencing severely inhibited
growth, 20% had continued inhibited growth velocity (<3rd percentile) after 6 months of follow-up after treatment. Education of
patients, their family members, and caregivers about adverse effects and their prospective management is an integral aspect of
treatment.
A number of new direct-acting antiviral drugs (DAAs) are in development for treatment of chronic HCV infection. Preliminary results
of studies conducted in adults with telaprevir or boceprevir in combination with pegylated interferon-alfa and ribavirin suggest that rates
of sustained virologic responses with these new DAAs dramatically are higher, especially in adults with genotype 1 than with current
standard of care. In addition, adults with HCV genotype 1 and evidence of rapid virologic response within the first 4 to 8 weeks of
treatment may be successfully treated with shorter durations of DAAs plus standard of care therapy. Trials of these oral agents in
pediatric patients, in combination with standard therapy, now are starting. All patients with chronic HCV infection should be immunized
against hepatitis A and hepatitis B because of the very high rate of severe hepatitis in patients with chronic liver disease from HCV who
become co-infected with hepatitis A or B virus.
DIAGNOSTIC TESTS: The 2 major types of tests available for laboratory diagnosis of HCV infections are immunoglobulin (Ig) G
antibody enzyme immunoassays for HCV and NAA tests to detect HCV RNA. Assays for IgM to detect early or acute infection are not
available. The third-generation enzyme immunoassays are at least 97% sensitive and more than 99% specific. False-negative results
early in the course of acute infection can result from the prolonged interval between exposure and onset of illness and seroconversion.
Within 15 weeks after exposure and within 5 to 6 weeks after onset of hepatitis, 80% of patients will have positive test results for serum
anti-HCV antibody. Among infants born to anti-HCV-positive mothers, passively acquired maternal antibody may persist for up to 18
months.
Food and Drug Administration (FDA)-licensed diagnostic NAA tests for qualitative detection of HCV RNA are available. HCV RNA
can be detected in serum or plasma within 1 to 2 weeks after exposure to the virus and weeks before onset of liver enzyme abnormalities
or appearance of anti-HCV. Assays for detection of HCV RNA are used commonly in clinical practice to identify anti-HCV-positive
patients who have HCV infection, for identifying infection in infants early in life (i.e., perinatal transmission) when maternal antibody
interferes with ability to detect antibody produced by the infant, and for monitoring patients receiving antiviral therapy. However, false-
Revised 7/11/2013 Page 80 of 123
positive and false-negative results can occur from improper handling, storage, and contamination of test specimens. Viral RNA may be
detected intermittently, and thus, a single negative assay result is not conclusive. Quantitative assays for measuring the concentration of
HCV RNA are available but are less sensitive than qualitative assays. The clinical value of these quantitative assays appears to be
primarily as a prognostic indicator for patients undergoing or about to undergo antiviral therapy.
TREATMENT: Therapy is aimed at inhibiting HCV replication, eradicating infection, and improving the natural history of disease.
Therapies are expensive, can cause significant adverse reactions, and are effective in approximately half of people treated. Response to
treatment varies depending on the genotype with which the person is infected. The few studies of combination therapy in children
suggest that children have increased sustained virologic response rates and fewer adverse events compared with adults, but The FDA
has not approved use of (nonpegylated) interferon-alfa-2b in combination with ribavirin for treatment of HCV infection in neonates.
Reference:
Red Book 2012 Report of the Committee on Infectious Diseases, 27 Edition, Elk Ridge Village, IL, 2006.
APPROACH TO HIV EXPOSED NEONATES:
Diagnostic tests for infants born to HIV infected mothers:
1. HIV DNA PCR is presently the preferred virologic method for diagnosis in the neonate and should be drawn within the first 48
hours after birth. Cord blood should not be used.
2. The second sample should be drawn at 1-2 months in Dr. Handels ID clinic. This can also be done at 14 days to help decide
antiretroviral therapy at an early age if the first sample is positive.
3. The third sample should be drawn at 2-4 months of age. Any time an infant tests positive, testing should be repeated on a
second blood sample as soon as possible to confirm the diagnosis.
4. An infant is considered HIV infected if two separate HIV DNA PCRs are positive. Infection can be excluded when 2 HIV
DNA PCR assays performed at or beyond 1 month of age, and a third performed on a sample obtained at 4 months of age or
older, are negative.
In the United States, the preferred test for diagnosis of HIV-1 infection in infants is the HIV-1 DNA polymerase chain reaction (PCR)
assay. Approximately 30% to 40% of HIV-1-infected infants will have a positive DNA PCR assay result in samples obtained before 48
hours of age. A positive result by 48 hours of age suggests in utero transmission. The DNA PCR assay routinely can detect 1 to 10 DNA
copies of proviral DNA in peripheral blood mononuclear cells. Approximately 93% of infected infants have detectable HIV-1 DNA by
2 weeks of age, and approximately 95% of HIV-1-infected infants have a positive HIV-1 DNA PCR assay result by 1 month of age. A
single HIV-1 DNA PCR assay has a sensitivity of 95% and a specificity of 97% for samples collected from infected infants 1 to 36
months of age. Detection of the p24 antigen (including immune complex dissociated) is substantially less sensitive than the HIV-1 DNA
PCR assay or culture. An additional drawback is the occurrence of false-positive test results in samples obtained from infants younger
than 1 month of age. This test generally should not be used, although newer assays have been reported to have sensitivities similar to
HIV-1 DNA PCR assays. Plasma HIV-1 RNA assays may be used to diagnose HIV-1 infection. However, a false-negative test result
may occur in neonates receiving ARV prophylaxis. Diagnostic testing with HIV-1 DNA or RNA assays is recommended at 14 to 21
days of age, and if results are negative, repeated at 1 to 2 months of age and again at 4 to 6 months of age. Viral diagnostic testing in the
first few days of life (eg, less than 48 hours of age) is recommended by some experts to allow for the early identification of infants.
**Management of infants born to mothers with Western blot/DNA PCR positive:
1. Zidovudine (AZT) a nucleoside analogue reverse transcriptase inhibitor
Must be started 6-12 hours after birth until 6 weeks of age
Dosage: 2 mg/kg orally q 6 hour or 1.5 mg/kg IV over 1 hour q 6 hours
(preterm infants <2 weeks of age to be given q 12 hours then at 2 weeks q 6 hours).
Breastfeeding is contraindicated.
If complete HIV testing is pending after birth and the mom is Eliza positive with the Western Blot pending then breast
feeding should not be initiated until the Western Blot has been reported negative.
This should be discussed with the mother by the pediatrician.
All infants born to mothers who are HIV positive should be followed in the Infectious
Disease Clinic and the initial consult should be initiated while the infant is in the
nursery.
Read J S; American Academy of Pediatrics, Committee on Pediatric AIDS. Diagnosis of HIV-1 infection in children younger
than 18 months in the United States, Pediatrics. 2008;120(6):e1547-e1562. Available at:
http://pediatrics.aappublications.org/cgi/content/full/120/6/e1547
Revised 7/11/2013 Page 81 of 123
PREVENTION OF PERINATAL HBV INFECTION:
Perinatal transmission of HBV infection can be prevented in ~95% of infants born to
HbsAg-positive mothers by early active and passive immunoprophylaxis of the infants.
The infants (including preterms) should receive the initial dose of hepatitis B vaccine within 12 hours of birth and HBIG
(0.5ml) IM given concurrently at a different site.
The complete three vaccines should be completed by 6 months.
In preterm infants the first vaccine should not be counted as one of the 3 serial immunizations.
Four doses are recommended in this circumstance.
Follow-up of Exposed Infants
Infant born to moms who are Hep B +should have an ID consult and follow-up in ID clinic in one month.
The infants should then be tested serologically for anti-HBs and HBs Ag 1-3 months after completion of the immunization
series.
Testing for HbsAg identifies infants who become chronically infected and helps in long-term medical management.
Pregnant women whose HbsAg status is unknown at delivery should undergo testing ASAP. If the results are not back within 12 hours
of delivery please refer to the chart below obtained from the Red Book 2012 with attention to the preterm and low birth weight infants <
2.0 kgs.
All infant born to mothers who are Hepatitis B positive should have an Infectious Disease consult and follow-up in the Infectious
Disease clinic 1 month after discharge.
References: Red Book 2012 American Academy of Pediatrics, 27
th
edition.
Revised 7/11/2013 Page 82 of 123
Maternal Status Infant 2000 g Infant < 2000 g
HbsAg
positive
Hepatitis B vaccine + HBIG
(within 12 h of birth)
Immunize with 3 vaccine doses at
0, 1, and 6 mo of chronologic age
Check anti-HBs and HBs Ag at 9-15
mo of age.
If infant I HbsAg and anti-HBs
negative, re-immunize with 3 doses
at 2-mo intervals and retest.
Hepatits B vaccine + HBIG (within
12 h of birth)
Immunize with 4 vaccine doses at 0, 1, 2-3,
and 6-7 mo of chronologic age.
Check anti-HBs and HbsAg at 9-15 mo. of
age.
If infant is HbsAg and anti-HBs negative,
re-immunize with 3 doses at 2-mo intervals
and retest.
HbsAg status
unknown
Hepatitis B vaccine (by 12 h)
+ HBIG (within 7 days) if mother tests
HbsAg positive.
Test mother for HbsAg
immediately.
Hepatitis B vaccine + HBIG (by 12 h).
Test mother for HbsAg within 12 h of birth and if
unavailable, give infant HBIG.
HbsAg Negative Hepatitis B vaccine at birth preferred
Immunize with 3 doses at 0-2, 1-4,
and 6-18 mo of chronologic age.
May give hepatitis B-containing
combination vaccine beginning at
6-8 wk of chronologic age.
Follow-up anti-HBs and HbsAg
testing not needed.
Hepatitis B vaccine dose 1 at 30 days of chronologic age if
medically stable, or at hospital discharge if before 30 days
of chronologic age.
Immunize with 3 doses at 1-2, 2-4, and 6-18
Mo of chronologic age.
May give hepatitis B-containing combination
Vaccine beginning at 6-8 wk of chronologic
age.
Follow-up anti-HBs and HbsAg testing not
needed.
El Paso Childrens Hospital Policy: PH-D-34
Department of Pharmacy Effective Date: 05/2012
Hepatitis-B Vaccination Procedures (Newborn):
HEPATITIS-B VACCINATION PROCEDURES (NEWBORN)
All newborns will be administered the Hepatitis-B vaccine.
For the Neonatal Intensive Care (NICU) and Intermediate Care Nursery (IMCN), administration of vaccines will be
based on weight and risk status.
The RN will notify the pediatrician if the mothers Hb
S
Ag results are positive.
The Physician or Neonatal Nurse Practitioner will order the Hepatitis-B vaccine and/or Hepatitis-B Immune Globulin
(HBIG).
RESPONSIBLE:
Physicians
Neonatal Nurse Practitioners (NNPs)
Registered Nurses
Licensed Vocational Nurses
Registered Pharmacists
Pharmacy Technicians
LITERATURE REFERENCE:
CDC: MMWR Recommendations and Reports: A Comprehensive Immunization Strategy to Eliminate Transmission of
Hepatitis B Virus Infection in the United States. December 23, 2005/ 54(RR16); 1-23.
Pickering LK. (2009). Red Book: Report of the Committee on Infectious Diseases. 28
th
ed. Elk Grove Village, IL:
American Academy of Pediatrics.
Revised 7/11/2013 Page 83 of 123
DEFINITIONS:
Low-Risk Infants: All newborn infants not otherwise designated as high-risk infants
High-Risk Infants: Newborns at high risk of developing Hepatitis-B infection, including:
- Newborns of IV substance abusers whose Hepatitis-B status is not known at delivery
- Newborns of Hepatitis-B surface Ag positive mothers as documented in mothers medical record
PROCEDURE:
A. Vaccine Administration
1. For the Neonatal Intensive Care (NICU) and Intermediate Care Nursery (IMCN), administration of vaccines will
be based on weight and risk status.
2. Vaccine Administration for Infants >2 kg:
i. Infants >2kg born to known positive HBsAg mothers:
1. Will receive Hepatitis B vaccine and HBIG as soon as possible, but within 12 hours of birth
2. The Registered Nurse (RN) will notify pediatric provider at birth to order the appropriate stat
medications
3. If parents refuse administration of HBIG and/or Hepatitis B vaccine, RN will document and
notify the attending physician as soon as possible
ii. Infants >2 kg born to mothers with unknown HBsAg status:
1. Should receive Hepatitis B vaccine as soon as possible, but within 12 hours of life
2. If the mother is found to be HBsAg positive, the infant will receive HBIG as soon as possible
but within 7 days of life
3. If the maternal status is unknown at the time of discharge or at 7 days (whichever is first), the
infant will receive HBIG
4. If maternal HBsAg status is unknown and parents refuse vaccine administration, RN will
document and notify the attending physician as soon as possible
iii. Medically stable infant >2 kg whose mother is HBsAg negative:
1. Will receive Hepatitis B vaccine by 12 hours of life
2. If parents decline vaccination, document and notify the attending physician to ensure mothers
HBsAg-negative status is appropriately documented in the infants medical record
3. Vaccine Administration for Infants <2 kg:
i. Infants <2 kg born to mothers with known positive HBsAg:
1. Will receive Hepatitis B Vaccine and HBIG as soon as possible after birth, but within 12 hours
2. RN will notify physician at birth to order the appropriate stat medications
3. This first dose of Hepatitis B vaccine will not count toward the required three-dose schedule
4. If parents refuse administration of HBIG and/or Hepatitis B vaccine, RN will document and
notify the physician as soon as possible
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ii. Infants <2 kg born to mothers with unknown HBsAg status:
1. Will receive Hepatitis B vaccine as soon as possible, but within 12 hours of life
2. If maternal HBsAg status is found to be positive or will be unknown by 12 hours of life, give
HBIG as soon as possible, but within 12 hours of life
3. This first dose of Hepatitis B vaccine will not count toward the required three-dose schedule
4. If parents refuse administration of HBIG and/or Hepatitis B vaccine, RN will document and
notify the physician as soon as possible
iii. Infants <2 kg born to mothers with known negative HBsAg:
1. Will receive first dose of Hepatitis B vaccine at 1 month of chronological age or at the time of
discharge if medically stable and exhibiting consistent weight gain
2. If parents decline vaccination, document and notify the physician to ensure mothers HBsAg-
negative status is appropriately documented in the infants medical record
4. Newborn infants with household contacts or primary caregivers with acute HBV infection require protection and
should receive Hepatitis B vaccine and HBIG prior to discharge from the hospital
5. The Hepatitis B Vaccine dose is 0.5ml IM for both preterm and term infants of Recombivax HB. The same
dose is used regardless of maternal HBsAg status
6. Infanrix(diphtheria and tetanus toxoids, and acellular pertussis) combination vaccine will not be used for the
initial Hepatits-B vaccination dose
7. HBIG dose is 0.5ml IM (given at a separate site than that used for Hepatitis B Vaccine).
Recommendation Summary
Maternal HBsAg Status Birth Weight >2 kg Recommendation Birth Weight <2kg Recommendation
Positive Hepatitis B Vaccine within 12 hours of
birth
HBIG within 12 hours of birth
Hepatitis B Vaccine within 12 hours of
birth
HBIG within 12 hours of birth
Hepatitis B Vaccine does not count
towards 1
st
in series
Unknown Hepatitis B Vaccine within 12 hours of
birth
HBIG within 7 days or prior to discharge
Hepatitis B Vaccine within 12 hours of
birth
HBIG within 12 hours of birth
Hepatitis B Vaccine does not count
towards 1
st
in series
Negative Hepatitis B Vaccine prior to discharge Hepatitis B Vaccine at 1 month
chronological or age or at discharge if
infant medically stable and gaining
weight
8. Upon receiving the physicians or NNPs order indicating Hepatitis-B vaccination, the licensed nurse will follow
the below administration procedures:
i. Ask the mother/guardian to read form C-106 Important Information About Hepatitis-B and Hepatitis-B
Vaccine at the time of admission, when the newborn is first brought to the mother, or by 12 hours of life.
ii. Complete theVaccine Administration Record form and have the mother or guardian sign the form after
answering any questions they may have.
iii. After verifying that the Vaccine Administration Record form has been completed, obtain the vaccine
(Recombivax HB 0.5 ml or Engerix 0.5 ml) from In-Patient Pharmacy.
Revised 7/11/2013 Page 85 of 123
iv. Administer the vaccination intramuscularly and complete an immunization card for the newborn. Place
the immunization card with the newborns flow chart.
v. If administering both Hepatitis-B vaccine and HBIG, the registered nurse will give in opposite thighs.
vi. Document the following information in the Electronic Medical Record (eMAR):
Site of administration
Date of administration
Vaccine lot number
Vaccine manufacturer
Vaccine expiration date
5. The parent/guardian will be provided with the immunization card upon discharge.
B. Immune Globulin Administration
1. Upon receiving the physicians or NNPs order indicating Hepatitis-B Immune Globulin, the licensed nurse will
follow the below administration procedures:
i. Obtain Hepatitis-B Immune Globulin from Inpatient Pharmacy
ii. Administer 0.5mL I.M. in the anterolateral aspects of the upper thigh or the deltoid muscle.
iii. May be administered at the same time as the hepatitis vaccine. Do not administer the hepatitis vaccine
and HBIG in the same limb (vaccine will be neutralized).
C. Control/Handling
1. Each Nursing unit will keep an acceptable inventory level as determined by the nurse manager of each area.
The inventory will be monitored through use of the Pyxisdevice.
2. Pharmacy will re-stock the Pyxisinventory daily, as needed.
3. The registered nurse responsible for the patient must report all positive Hepatitis-B-antigen surface results to the
Texas Department of Health.
APPROACH TO SUSPECTED CONGENITAL SYPHILIS:
Congenital syphilis in newborns:
Infant RPR titers>1:4 are suspect and should be evaluated for possible treatment.
What is important in interpreting any titer (even 1:1) is the history.
Even when the maternal RPR is low if the maternal confirmatory test (TPPA) is positive, the infants receive treatment.
Mothers are adequately treated if they receive three doses of Penicillin IM >one month prior to delivery.
Positive Maternal RPR and MHATP:
Thorough History & PE
Quantitative nontreponemal serologic test of serum (RPR on mother & infant)
VDRL test of CSF
Long bone radiograph (when clinically indicated)
CBC and platelet count
Other tests (when clinically indicated) ( e.g. CXR and LFTs)
Treatment:
Recommended treatment is 10-14 days of aqueous penicillin G or procaine penicillin G. In Most cases treatment for 10 days
is adequate.
Aqueous crystalline penicillin G is recommended if congenital syphilis is proved or highly suspected.
Presently there has been a shortage of Penicillin G so we use Procaine Penicillin.
While Procaine Penicillin (50,000 U/kg IM) has been recommended as an alternative to treat congenital syphilis, but adequate
Revised 7/11/2013 Page 86 of 123
CSF concentration may not be achieved consistently so follow up is imperative.
Further Outpatient Care:
Follow congenital syphilis at ages 1,2,4,6, and 12 months in Dr. Handals ID clinic.
Obtain nontreponemal titers at ages 3, 6, and 12 months after conclusion of treatment.
Nontreponemal antibody titers should decline by age 3 months and negative by age 6 months
Consider re-treatment for patients with persistently stable titers, including low titers.
Infants treated for congenital neurosyphilis should undergo repeat clinical evaluation and CSF examination at 6-month
intervals until their CSF examination result is normal.
A positive CSF VDRL result at age 6 months is an indication for re-treatment.
Follow-up early-acquired syphilis with a quantitative nontreponemal test at 3, 6, and 12-month intervals after conclusion of
treatment.
Patients with syphilis for more than 1 year also should undergo serologic testing 24 months after treatment.
Pregnant patients who have received treatment should have quantitative serologic testing monthly for the remainder of their
pregnancy.
Congenital Syphilis
Clinical Manifestations
75% of infants with early congenital syphilis will be asymptomatic
If symptomatic, symptoms develop between the 3
rd
and 14
th
week of life and include:
IUGR
Hepatosplenomegaly (most common)
Snuffles (Syphilitic rhinitis)
Maculopapular rash- Start as pink, oval macules, then become coppery brown and desquamates.
Pemphigus syphiliticus- vesiculobullous eruptions on the palms and soles.
J aundice
Elevated liver enzymes, leukocytosis, thrombocytopenia, or leukopenia.
Diagnosis
A positive nontreponemal test (i.e. VDRL and RPR) and, if positive, treponemal testing for confirmation.
An RPR titer in the infant, more than fourfold the Mothers, is a strong indication of infection rather than just passive transfer
of antibodies via the placenta
Evaluation of the infant to include CBC, CSF exam and VDRL, and, when indicated, long bone x-rays, ophthalmologic exam,
and LFTs.
Treatment
1. Maternal RPR is reactive, but TP-PA or FTA-ABS is nonreactive
OR
If the infants RPR is reactive, but less than fourfold the Mothers, the infants physical exam is normal, and the Mother was
treated during pregnancy:
THEN: no treatment required
2. Maternal RPR and TP-PA/FTA-ABS are reactiveand infants RPR is nonreactive
OR
If the infants RPR is reactive, but less than fourfold the Mothers, physical exam is normal, and the Mother was treated more
than 4 weeks before delivery:
OR
If the infants RPR is reactive, but less than fourfold the Mothers, the infants physical exam is normal, and there is no
documentation of treatment during pregnancy, treatment was with a non-penicillin drug, treatment was less than 4 weeks prior
Revised 7/11/2013 Page 87 of 123
to delivery, or there is evidence of relapse of infection in the Mother, and the CBC, CSF, VDRL, and long bones are normal in
the infant
THEN: Treat with a single IM injection of benzathine penicillin 50,000 units/kg
3. If the infants RPR is more than fourfold the Mothers, the infants physical exam is abnormal, there is no documentation of
treatment during pregnancy, treatment was with a non-penicillin drug, treatment was less than 4 weeks prior to delivery, or
there is evidence of relapse of infection in the Mother, or the CBC, CSF, VDRL, or long bones are abnormal
THEN: Treat with aqueous penicillin G 50,000 units/kg IV every 12 hrs (if less than 1 week old) or every 8 hours (if more than 1
week old) or procaine penicillin G 50,000 units/kg IM daily for 10 days.
Follow Up
Follow up in the form of nontreponemal testing should be performed every 2-3 months until the test is either nonreactive or the titer has
decreased fourfold.
Due to the devastation syphilis can cause if left inadequately treated, any infant who you feel may not receive adequate follow up
should be treated with the full 10 day course as outlined in #3 above.
References
Pickering L.K., Baker C.J ., Kimberlin D.W., Long S.S., (eds). (2009). Red Book: 2009
Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics
Sati, K.F., Ali, S.A., & Weitkamp, J .H. (2010). Congenital infections part 2: Parvovirus,
listeria, tuberculosis, syphilis, and varicella. NeoReviews, 11; e681. doi: 10.1542/neo.11-12-e681
Revised 7/11/2013 Page 88 of 123
Revised 7/11/2013 Page 89 of 123
Systemic Candidiasis:
1
Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious
Diseases Society of America. Clin Infect Dis. 2009; 48(5):503-535
Invasive Disease. Treatment of invasive candidiasis in neonates and nonneutropenic adults should include prompt removal of any
infected vascular or peritoneal catheters and replacement, if necessary, when infection is controlled. Avoidance or reduction of systemic
immunosuppression also is advised when feasible. Immediate replacement of a catheter over a wire in the same catheter site is not
recommended.
Amphotericin B deoxycholate is the drug of choice for treating neonates with systemic candidiasis; if urinary tract involvement and
meningitis are excluded, lipid formulations can be considered. Echinocandins should be used with caution in neonates, because dosing
and safety have not been established. Treatment for neonates is at least 3 weeks. In nonneutropenic and clinically stable children and
adults, fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) is the recommended treatment; amphotericin B
deoxycholate or lipid formulations are alternative therapies (see Drugs for Invasive and Other Serious Fungal Infections, p 835). In
nonneutropenic patients with candidemia and no metastatic complications, treatment is 2 weeks after documented clearance of Candida
from the bloodstream and resolution of clinical manifestations associated with candidemia.
In critically ill neutropenic patients, an echinocandin or a lipid formulation of amphotericin B is recommended because of the fungicidal
nature of these agents when compared with fluconazole, which is fungistatic. In less seriously ill neutropenic patients, fluconazole is the
alternative treatment for patients who have not had recent azole exposure, but voriconazole can be considered. The duration of treatment
for candidemia without metastatic complications is 2 weeks after documented clearance of Candida organisms from the bloodstream
and resolution of neutropenia.
Most Candida species are susceptible to amphotericin B, although C Lusitania and some strains of C glabrata and C krusei have
decreased susceptibility or resistance. Among patients with persistent candidemia despite appropriate therapy, investigation for a deep
focus of infection should be conducted. Short-course therapy (i.e., 7-10 days) can be used for intravenous catheter-associated infections
if the catheter is removed promptly, there is rapid resolution of candidemia once treatment is initiated, and there is no evidence of
infection beyond the bloodstream. Lipid-associated preparations of amphotericin B can be used as an alternative to amphotericin B
deoxycholate in patients who experience significant toxicity during therapy. Published reports in adults and anecdotal reports in preterm
infants indicate that lipid-associated amphotericin B preparations have failed to eradicate renal candidiasis, because these large-
molecule drugs may not penetrate well into the renal parenchyma. Flucytosine is not recommended routinely for use with amphotericin
B deoxycholate for C albicans infection involving the central nervous system because of difficulty in maintaining appropriate serum
concentrations and the risk of toxicity.
Fluconazole may be appropriate for patients with impaired renal function or for patients with meningitis. However, data on fluconazole
use for Candida meningitis are limited. Fluconazole is not an appropriate choice for therapy before the infecting Candida species has
been identified, because C krusei is resistant to fluconazole, and more than 50% of C glabrata isolates also can be resistant. Although
voriconazole is effective against C krusei, it is often ineffective against C glabrata. The echinocandins (caspofungin, micafungin, and
anidulafungin) all are active in vitro against most Candida species and are appropriate first-line drugs for Candida infections in severely
ill or neutropenic patients (see Echinocandins, p 830). The echinocandins should be used with caution against C parapsilosis infection,
because some decreased in vitro susceptibility has been reported. If an echinocandin is initiated empirically and C parapsilosis is
isolated in a recovering patient, then the echinocandin can be continued. Echinocandins are not recommended for treatment of central
nervous system infections.
Ophthalmologic evaluation is recommended for all patients with candidemia. Evaluation should occur once candidemia is controlled,
and in patients with neutropenia, evaluation should be deferred until recovery of the neutrophil count.
Chemoprophylaxis. Invasive candidiasis in neonates is associated with prolonged hospitalization and neurodevelopmental impairment
or death in almost 75% of affected infants with extremely low birth weight (ELBW [less than 1000 g]). The poor outcomes, despite
prompt diagnosis and therapy, make prevention of invasive candidiasis in this population desirable. Four prospective randomized
controlled trials and 10 retrospective cohort studies of fungal prophylaxis in neonates with birth weight less than 1000 g or less than
1500 g have demonstrated significant reduction of Candida colonization, rates of invasive candidiasis, and Candida-related mortality in
nurseries with a moderate or high incidence of invasive candidiasis. Besides birth weight, other risk factors for invasive candidiasis in
neonates include inadequate infection-prevention practices and injudicious use of antimicrobial agents. Adherence to optimal infection
Revised 7/11/2013 Page 90 of 123
control practices, including "bundles" for intravascular catheter insertion and maintenance and antimicrobial stewardship, can diminish
infection rates and should be optimized before implementation of chemoprophylaxis as standard practice in a neonatal intensive care
unit. On the basis of current data, fluconazole is the preferred agent for prophylaxis, because it has been shown to be effective and safe.
Fluconazole prophylaxis is recommended for ELBW infants cared for in neonatal intensive care units with moderate (5%-10%) or high
(10%) rates of invasive candidiasis. The recommended regimen for ELBW neonates is fluconazole administered intravenously during
the first 48 to 72 hours after birth at a dose of 3 mg/kg, twice a week, for 4 to 6 weeks, or until intravenous access no longer is required
for care. This dosage and duration of chemoprophylaxis has not been associated with emergence of fluconazole-resistant Candida
species.
Fluconazole can decrease the risk of mucosal (eg, oropharyngeal and esophageal) candidiasis in patients with advanced HIV disease.
However, an increased incidence of infections attributable to C krusei (which intrinsically is resistant to fluconazole) has been reported
in non-HIV-infected patients receiving prophylactic fluconazole. Adults undergoing allogenic hematopoietic stem cell transplantation
had significantly fewer Candida infections when given fluconazole, but limited data are available for children. Prophylaxis should be
considered for children undergoing allogenic hematopoietic stem cell transplantation during the period of neutropenia. Prophylaxis is
not recommended routinely for other immunocompromised children, including children with HIV infection.
Intravenous Oral Intravenous or Oral
Caspofungin,
a
Micafungin,
a,b
or
Disease Amphotericin B Anidulafungin
a,b
Flucytosine Itraconazole
a
Fluconazole
a
Voriconazole
a
Posiconazole
a
Aspergillosis A A ... M ... P ...
Blastomycosis P ... ... M M ... ...
Candidiasis:
Chronic,
mucocutaneous
Oropharyngeal,
esophageal
A A ... A P A A
P (severe cases) P ... A P A
Systemic P
c
P S ... P, M A
Coccidioidomycosis P ... ... P, M P, M ... ...
Cryptococcosis P,S ... S ... A,M ... ...
Fusariosis A ... ... ... ... P . ..
Histoplasmosis P ... ... P,A A,M ... ...
Mucormycosis
(zygomycosis)
P ... ... ... ... ... ...
Paracoccidioidomycosis P
d
... ... P,M ... ... ...
Pseudallescheriasis ... ... ... M ... P ...
Sporotrichosis P ... ... M ... ... ...
P indicates preferred treatment in most cases; A, efficacy less well established or alternative drug; M, for mild and moderately severe cases; S,
combination recommended if infection is severe or central nervous system is involved.
Efficacy has not been established for children.
Approved by the Food and Drug Administration for adults.
Preferred treatment in neonates; alternate treatment for children and adults.
Usually in combination with itraconazole or a sulfonamide.
2012 by the American Academy of Pediatrics. All rights reserved.
Table 4.6. Drugs for Invasive and Other Serious Fungal Infections
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IMMNUNIZATION OF PRETERM INFANTS IN THE NURSERY:
Preterm infants should be immunized at the usual chronologic age.
Some studies suggest reduced immune response in VLBW infant (<1,500 g) immunized by the usual schedule, additional data
needed to justify changing present schedule.
Vaccine doses should not be reduced for preterm infants.
If the infant is still hospitalized at 2 months the routine immunization schedule should be followed.
This includes DPaT, HIB, Prevnar and inactivated poliovirus (IPV).
The first hepatitis B vaccine should to given upon discharge to all infants >2.0 Kg.
The infants with weights 2 kg whose mothers are hepatitis B surface antigen negative should receive the vaccination (if
thriving and well) at 30 days of age or upon discharge, which ever comes first (even if they weigh less than 2 Kg.).
The exceptions are those infants born to mothers who are HbsAg positive (See hepatitis B exposed infant.).
ROUTINE HEAD SONOGRAM SCREENING FOR PRETERM INFANTS:
Due to several factors related to prematurity, preterm infants are at risk for development of IVH (intraventricular hemorrhages) and PVL
(periventricular leukomalacia). Infants less than 1,000 grams at birth are most likely to have an IVH in the first 72 hours of life with
75% of the IVHs occurring before 3-5 days after birth.
The following schedule is recommended for screening VLBW infant for IVH and PVL:
<1,000 grams DOL 1-3 DOL 7 DOL 14 DOL 28 PTD
1,000 1,250 grams DOL 7 DOL 28 PTD
1,251 1,500 grams DOL 7 PTD
1,501 2,000 grams DOL 7 only if clinically indicated PTD
Follow-ups beyond the above schedule as needed on a case by case basis.
PREVENTION OF INTRAVENTRICULAR HEMORRHAGE BY INDOMETHACIN INPRETERM INFANTS:
Intraventricular hemorrhage (IVH) remains a major problem of preterm neonates. Indomethacin has been shown to reduce the incidence
and severity of IVH in very low birth weight preterm infants. It has also been shown to reduce the incidence of symptomatic PDA and
the rate of surgical ligation for PDA. These short term benefits are not accompanied by any of the adverse outcomes that were possible
that is, important renal side effects, gastrointestinal perforation, and necrotising enterocolitis.
Indication: IVH prevention for LBW preterms, BW <1250g
Dose: Indomethacin 0.1mg/kg q24 hrs for 3 doses, beginning at 6 hours of age
Monitoring:
Monitor urine output, serum electrolytes, glucose, BUN and creatinine, platelet count. BUN/creatinine/platelet count must be obtained
prior to each dose.
Observe for GI bleeding and prolonged bleeding from puncture sites.
Adverse effects/precautions:
If oliguria occurs, observe for hyponatremia, hypokalemia and elevated creatinine (>1.6) and consider prolonging the dosing interval of
indomethacin and other renally excreted drugs such as gentamicin.
Withhold feedings during treatment.
Consider platelet transfusion if platelet count <80,000. May administer indomethacin if platelet count >80, 000 and there is no active
bleeding.
Contraindications: active bleeding, significant thrombocytopenia (<80, 000) or coagulation defects, necrotizing enterocolitis,
significantly impaired renal function, GI perforation.
Other considerations:
Obtain head ultrasound within the first 24 hours. If IVH is present discontinue treatment.
Obtain cardiac echo at the end of treatment to determine presence of significant PDA that requires treatment. For <1500g use neoprofen
for treatment of PDA.
References:
P W Fowlie, P G Davis. Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal
Revised 7/11/2013 Page 92 of 123
Neonatal Ed 2003; 88:F464F466.
Ment L, Vohr B, Makuch T, Westerveld M, Katz K, Schneider K, Duncan C et al. .
Prevention of Intraventricular hemorrhage by Indomethacin in Male Preterm Infants. J Pediatr 2004; 145:832-4.
POLYCYTHEMIA:
Polycythemia is a normal state relative to adults in term infants but when the spun central venous Hct (preferably from the antecubitus)
approaches 65% the viscosity of the blood increases dramatically placing the infant at risk for hyperviscosity syndrome. Hyperviscosity
is when sludging of the RBCs occurs in the capillaries decreasing O2 delivery to the tissues resulting in end-organ ischemia.
Symptoms of hyperviscosity:
temperature instability
feeding problems
plethora
irritability
lethargy
hypoglycemia
respiratory distress
hypoperfusion
Initially a peripheral Hct is obtained to screen infants to evaluate only infants at risk of polycythemia. If the Hct is 65-69% and the
infant is asymptomatic no intervention is warranted. If the peripheral Hct is 70% or greater a central venous Hct needs to be done. If it
is 65-69% and the infant is doing well no further intervention is needed. If it is >70% a partial reduction exchange needs to be
performed. If the infant is symptomatic and the spun Hct is 65% a central venous Hct needs to be done. If the central Hct is 65 %
and the infant is symptomatic a partial exchange reduction needs to be done.
Reduction-Exchange Transfusion for Polycythemia/Hyperviscosity:
Obtain an informed consent from the mother after discussing the polycythemia/hyperviscosity and need for transfer to the SCN
if the infant is in NBN.
The procedure can be done in IMCN or ICN.
The Infant needs to be NPO with IVF D10W at 60-80ml/kg/day if in the first 24 hours or as indicated by need and age.
The infant should be placed on a Cardiac/Apnea and Sat monitor on a radiant warmer with a temp probe attached.
A UVC will be placed under sterile technique with cap, mask, sterile gown and gloves.
A KUB should be done after line placement and before the procedure to check line placement and status of the bowel.
Sterile IV Normal Saline without preservatives will be used to replace blood removed.
Formula for calculating the amount to be reduced and replaced with NS:
Hct observed Hct desired (55%) X Total Blood Volume (85ml) X Wgt(Kg)
Hct observed
The infant will be NPO 4 hours after the procedure. The infant may be fed after the 4 hour period only if clinically stable.
Glucoses will be checked at the end of the procedure and 0.5 hours, 1 hour and hourly until 4 hour after the procedure, then as
per routine for an infant on IVF.
A central venous Hct will be checked 24 hours after the procedure.
SUCROSE ADMINISTRATION FOR PAIN IN INFANTS:
Use 24% Sucrose approximately 2 minutes prior to painful procedures.
Used in conjunction with containment, rocking and swaddling.
Target population is infants from 28-46 weeks PCA
Some benefit in infants up to 4 months of age as well.
Doses range from 0.05 ml to 2.0 ml.
Daily safe doses have not been well established.
Term drip 0.1-0.3 ml on a pacifier and give to infant.
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As hypertonic do not give >2.0 ml to term infants per procedure.
Infants <31 weeks give 0.1-0.5 ml with no repeated doses per procedure.
Sucrose has peak analgesic effect 2 minutes after administration and is effective for 5-7 minutes after a single dose is given.
When Sucrose may be offered:
Heelsticks
Arterial and venous punctures
Lumbar puncture
Gavage tube insertions
Removal of adhesives
IM injections including Vit K and immunizations
In conjunction with more potent analgesia for circumcisions, eye exams, LPs, dressing changes, chest tube and PICC line
placement.
If the patient is on an opioid drip it is appropriate to give sucrose for procedures. Be careful as swallowing could be impaired.
Any other procedure that would be painful to you or your own child!
Side effects:
Increased risk of NEC and hyperglycemia in preterm as the solution is hyperosmolar.
Infants with impaired swallowing may choke if given large volumes of solution.
Most trials did not address the safety and side effects of the sucrose.
Sucrose is an appropriate intervention only for procedural pain.
Infants on respiratory support should be first evaluated for other causes of agitation, i.e. respiratory distress. Is the baby really
crying or grunting?
As sucrose is only effective 5-7 minutes, the infants with persistant pain or lengthy procedures could be exposed to multiple
repeated doses of the medication which may not be safe.
When to use with caution? (0.1-0.3 ml/procedure, no repeated doses)
Infants <31 weeks GA in the first week of life
A baby with any GI condition, especially NEC
A baby with PDA on Indocin
Intubated infants
A baby on paralytics
A baby with poor oral-motor control
RETINOPATHY OF PREMATURITY (ROP):
ROP is a retinal vascular disorder of VLBW preterm infant potentially leading to visual impairment including blindness.
All infants 32 weeks and/or 1,500 g are screened.
First retinal exam is done at 4 weeks after birth for all infant born 32 weeks. These infants have a follow up exam based on
their retinal findings at each exam per the International Classification of Retinopathy of Prematurity.
Ordering initial exams:
It is the residents duty to identify these infants after birth.
Fill out a consult for Dr. Radinovich and call her office; consult to go in front of chart.
At time of 1
st
exam place infants name on list eye exams to be done at the front desk.
Day of the exam the eye drops need to be ordered by the resident.
Cyclomidril ophthalmic solution i-ii drops OU q 3-5 minutes x 2 at least 1 hour prior to the exam.
Parents need to be notified about the first exam, understand the disease we are screening for and the follow up. They also need
to understand the results of all eye exams. It is the resident or nurse practitioners responsibility to do this. The triplicate ROP
Information Form needs to be signed by the parents prior to discharge informing them of the severity of ROP and need for
outpatient follow up. The white copy goes in the chart, yellow to Dr. Radenovichs office and pink to HRC.
Infants that need to be screened:
32 weeks
1,500 g
1,500-2,000 g with an unstable clinical course believed to be at risk for ROP.
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INFANTS OF DRUG DEPENDENT MOTHERS:
These infants may be identified in L&D or mother baby. Until newborn nursery is trained to care for these infants, they may be
transferred to EPCH NICU IMCN for a social service consult, evaluation, and care. The following is the new policy for care of infants
identified with Neonatal Abstinence Syndrome.
Neonatal Abstinence Syndrome (NAS)
Opioids activate opiate receptors in the locus ceruleus (one of the major clusters of noradrenergic cells in the brain). This action
decreases the activity of adenylate cyclase, resulting in a reduction in cAMP production. As a consequence, potassium efflux is
increased and calcium influx into the cell is decreased, resulting in a decrease in nor-adrenaline release. During chronic opiate use, nor-
adrenaline release is gradually increased towards its normal level as tolerance develops. Once the opiates are withdrawn there is loss of
the inhibitory effect and significant increase in nor-adrenaline release to well above normal levels. This increase in noradrenergic
activity coincides with withdrawal symptoms. Administration of opioids results in a reduction in neuronal activity and a decrease in
withdrawal symptoms. Opioids are the best pharmaceuticals to treat neonatal abstinence although Phenobarbital in combination with
opioids has been shown to decrease the time patients may need pharmaceutical treatment. As methadone and morphine have cross
dependence and similar receptors they have been the most successful in most studies to decrease the symptoms of neonatal abstinence
syndrome when non pharmacologic therapy is not successful. The following treatment guideline will first introduce you to the signs
and symptoms of NAS while instructing how to score the severity of NAS with the modified Finnegan scoring system. It will also
discuss the non-pharmacologic treatment of NAS and finally when using the Finnegan scale, how to initiate opioids for treatment of
NAS, when to advance the dose and how to wean.
The Modified Finnegan Neonatal Abstinence Scoring System
This is a 31 item scale designed to quantify the severity of NAS and guide treatment. It is administered every 3 hours. Infants scoring 8
or greater after implementing non- pharmacologic treatment are recommended to receive pharmacologic therapy.
The Assessment of NAS
Excessive Crying: Infants with NAS cry more often and the cry in high pitched. This is scored when the infants discomfort has been
alleviated.
A score of 2 is given to infants that cry more often but are consolable.
A score of 3 is given for non-consolable crying infants.
Sleeping: The amount of time the infant sleeps continuously between feeds. Those infants in a quiet alert state before a feeding can be
considered spending time in sleep. Breast fed infants feeding every 2 hours should have the scale adjusted to their physiologic state.
A score of 3 is given for Infants sleeping less than 1 hour.
A score of 2 is given for those infant sleeping 1-2 hours.
A score of 1 is given for those infants sleeping 2-3 hours.
A score of 0 is given for those infants sleeping 3 or more hours.
Moro reflex:
A score of 1 is given for an exaggerated Moro reflex (hyperactive response with excessive abduction at the shoulder and
extension at the elbow with or without tremors).
A score of 2 is applied for the response above plus marked adduction flexion at the elbow with arms crossing to the midline.
Tremors: These are involuntary movements that are rhythmical in nature and generally of equal amplitude. Tremors that occur in
absence of stimulation are tremors occurring undisturbed. Those occurring with stimulation are tremors that occurred after being
disturbed.
A score of 1 is applied for mild tremors occurring in a fussy or crying state.
A score of 2 is applied for moderate to severe tremors occurring in a drowsy state or often in a quiet alert state and consistently
in a fussy or crying states or consistently and repeatedly in all states. Myoclonic jerks are involuntary rapid muscle
contractions and not part of the scoring for tremors.
Increase muscle tone: Tone is the resistance of parts of the body to passive movement and can be observed with the infant at rest and
assessed by testing the infants motor resistance with gentle handling. The infants arm and legs are passively extended and released to
asses recoil. Hypertonia is increased resistance to extension or flexion; the extremity returns to its prior position spontaneously. Infant
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tone should be evaluated at rest, with gentle handling, in a quiet alert state and mildly fussy state, but not when the infant is rigorously
crying or over stimulated.
A score of 1 is applied for generalized increased resistance to extension or flexion of the limbs (slight flexion or extension is
possible) which is palpable on handling, and head lag on pulling to sit.
As score of 2 is given for exaggerated increased tone, or increased tone visualized without handling, and/or increased
resistance to extension of their limbs with difficulty in straightening or bending the arms with or without head lag (or
alternatively have chin tuck) on pull to sit.
Excoriation: This is redness of the skin or broken/bleeding skin that is the result of rubbing an extremity or face on a linen covered
surface and is generally found on elbows, knees, nose and/or chin due to excessive and uncontrolled movements of the extremities
(tremors) and/or head (rooting). Facial excoriations may occur due to the neonate clawing at his face. Infants with excoriation are
scored for this as long as the excoriation is present. Excoriations in the diaper area from movement should be distinguished from diaper
dermatitis due to loose stools that should not be scored as excoriations.
A score of 1 is applied if the skin is red but intact or healing.
A score of 2 is applied if the skin is broken.
Generalized seizure: Any suspected seizure actively should be brought to the attention of the medical provider. The incidence of
seizures as a symptom of NAS is low, but if present should be given a score of 8.
Hyperthermia: Elevations in body temperature should be assessed by a provider to rule out infection. If no infection is present the
temperature should be scored as long as the fever is present.
A score of 1 is applied for any axillary temperature of 37.3C (99.0F)
Yawning, sweating, nasal stuffiness and sneezing: These symptoms represent alteration in autonomic nervous system regulation.
A score of 1 is applied for an infant yawning 4 times or more within the 3 hour testing period.
A score of 1 is applied if there is dampness of the infants forehead or upper lip, when the environment is not hot or the infant
is not excessively bundled.
A score of 1 is applied for any nasal noise when breathing (avoid aggressive nasal suctioning as this may lead to trauma) and
may or may not be associated with coryza and is not associated with illness.
A score of 1 is applied if the infant sneezes 4 or more times within the 3 hour assessment period, whether individually or
continuously.
Tachypnea: In scoring tachypnea all other medical conditions should be ruled out.
A score of 2 should be given for a respiratory rate >60 at rest and not in a fussy or crying state
Poor feeding: Poor feeding may be present for several reasons. It may be due to suck/swallow in coordination, positioning difficulties
due to hypertonia, sensory integration difficulties, and inefficient suck for maladaptive tongue positioning.
A score of 2 is given when feeding problems are present.
Vomiting: The effortless return of esophageal and/or stomach contents to the mouth. Small amounts of formula or milk lost during
burping (wet burp) does not constitute vomiting. Projectile vomiting may indicate other pathology and should be evaluated for other
than NAS.
A score of 2 is applied to vomiting either a whole feed or two or more times during a feed not associated with burping unless
the infant vomits a large amount with burping.
Loose stool:
A score of 2 is given for a solid liquid stool or liquid stool with or without a water ring on the diaper.
Failure to thrive:
A score of 2 should be given at any time the infants weight is <10% below his/her birth weight. The score should be given at
any time during the scoring period that the infant remains <the 10% below birth weight.
Irritability: Infants with NAS may manifest irritability or fussiness, even with light touch or handling despite attempts to console and
may not cry excessively or at all. Irritability can also be expressed as grimacing or appearing sensitive to touch, light or sound,
displaying symptoms such as gaze aversion, pull down (infant retreats and becomes quiet and non interactive, not feeding and at risk for
failure to thrive) etc. and may or may not occur in conjunction with crying. Dysregulated behaviors in response to any internal or
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external stimuli or rapid changes of state (termed poor state control, defined as moving rapidly between sleep/wake and quiet/fussy
periods with little modulation between states) would constitute irritability.
A score of 1 is given for minor irritability defined as an infant that calms/whose behaviors become more regulated only with
intervention and displays 1 symptoms of irritability.
A score of 2 is applied for an infant the displays 2-3 signs of irritability and is consoled only with intervention after time.
A score of 3 is applied for an infant in whom no amount of consoling reduces the symptoms of irritability.
Non Pharmacologic Treatment
To fully be able to maximize non pharmacologic therapies for infants with NAS it is strongly recommended to read The Opioid
dependent mother and newborn dyad: non-pharmacologic care by Drs. Martha Velez and Laren J ansson (4). These treatment guidelines
stress various responses the care giver can give for various symptoms the infant with NAS may demonstrate. As the following
symptoms are noted, educating the parents is important to help them identify symptoms as a result of NAS and that these symptoms are
not a negative reaction to them as parents but NAS. Once the behavior is pointed out to the parent it is important for the caretaker to
teach the parents how to respond to their infants special needs. .
Reactivity to sensory stimulation and regulatory issues:
For hyper- or under-responsive infant the room should be quiet with dim lighting and the infant handled in a soft, slow manner
Holding/containing techniques
o Holding the newborns hands against her/his chest in a supine or side position
o Providing firm but gentle pressure to the trunk or head
o Swaddling
Pacifier to stimulate a non-nutritive suck and containment of the upper extremities while changing a diaper for an infant
sensitive to touch
Behavioral states and state control:
Respect sleep and wake a newborn slowly only if a feeding is needed
Slow arousal while keeping the environment minimally stimulating and using gentle handling prior to the time of feeding,
bathing and changing (preparing the infant for any interaction).
If overstimulation results in poor eye-to-eye contact adjust the environment by such measures as giving a pacifier, gently and
slowly rocking vertically and containing the arms with gentle pressure may facilitate eye contact and more normal interactions.
Limiting bright colors, using black and white objects that may be less visually stimulating and comfortable preventing
overstimulation. This may facilitate attention by obtaining better control of movements, allowing the infant to focus and
follow.
Motor and tone control:
Gentle handling and containment, positioning, non-nutritive sucking and swaddling (with careful observation of infant
temperature) to treat motor and tone dysregulation manifested as tremors or disorganized motor movements and hypertonicity.
Put the infant on her/his side or back and hold the infants hands. If the infant is on her/his side, the head and hips can be placed
loosely in the fetal position.
o Very gentle pressure or rubbing on head and or trunk
Slow vertical rocking helps with relaxation
Hyperthermic infants that cant be swaddled may do well with a folded blanket across the chest to contain the arms.
Mittens, frequent holding, swaddling and pacifiers may help infants that develop excoriations in attempt to self soothe.
Infants with feeding difficulties due to motor and or tone regulation:
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o Small frequent feeds of high caloric formula (compensates for excessive caloric expenditures).
o Frequent burping (rubbing the back instead of patting)
o Evaluation for signs of stress during feeds at frequent intervals
o Interruption of the feeding if the infant is growing tired
o Some infants may need the pacifier if they become agitated upon removal of the nipple to burp
Autonomic signs of stress: As soon as signs of stress are detected (hiccups, color change, bowel sounds, sneezing, back arching)the
interactions with the infant should be modified to stop the signs and prevent further dysregulation such as spitting up, gagging, excess
stooling or abnormal bowel sounds in response to external changes or demands. There are those infants that exhibit under reactivity
(pull down) and are under recognized but this can result in poor feeding and failure to thrive. The treatment for them is the same.
Avoid vigorous stimulation
Small and frequent feeds
Gentle handling
Quiet environment
Pharmacotherapy Management Guidelines
Pharmacotherapy should be used in combination with supportive therapy measures (swaddling, positioning, holding, minimizing
environmental stimuli, pacifiers, feedings) to reduce the severity of NAS symptoms. Generally, severe irritability interfering with
feeding and sleep, vomiting and diarrhea, temperature instability, tachypnea, and seizures are indications for pharmacological treatment.
The goal of medication therapy is to reduce severity of withdrawal symptoms (Finnegan <8), allowing infants to gain weight, sleep and
interact with caregivers. An opioid is the first-line therapy for NAS in infants with maternal opioid use. In cases that involve polydrug
abuse, phenobarbital should be considered. The following guidelines serve as the basis for treatment.
A. Initiation of Pharmacotherapy (scores based on modified Finegan scoring tool)
1. Infants with score 8, continue to monitor and treat with supportive care only
2. Infants with score >8, rescore in 1 hour
3. Initiate therapy with oral methadone for below criteria:
a. 3 consecutive withdrawal scores 8 or a mean of 3 consecutive scores 8
b. Any 2 scores 12 or mean of 2 consecutive scores 12
4. Methadone Dosing:
a. Initial Doses: Methadone 0.1 mg/kg/dose every 6 hours x 4 doses (24 hours), then methadone 0.05 - 0.1 mg/kg/dose
PO every 12 hours
b. Dose Escalation: Increase methadone dose by 0.05 mg/kg/dose until withdrawal symptoms are controlled (2
consecutive scores <8) or a maximum dose of 0.15 0.3 mg/kg/day has been reached.
i. Use caution during dose escalationmethadone exhibits a long half-life, drug will accumulate and can result
in excessive sedation.
ii. Methadone should be used with caution in patients with congenital QT prolongation, hypokalemia, and
hypomagnesemia.
c. Breakthrough withdrawal symptoms:
i. Morphine 0.05 mg/kg/dose (can be given every 4 hrs) or
ii. Phenobarbital 15-20 mg/kg loading dose followed by 5 mg/kg/day maintenance dose. Order a level after the
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5
th
dose and weekly. Phenobarbital should be stopped 72 hours prior to stopping methadone.
d. Continue to score patient every 3 hours
B. .Weaning Therapy
1. 24-48 hrs after symptoms are controlled, lengthen the dosing interval to every 24 hours
2. Start methadone taper once patient has been stable for 72 hours (Finnegan scores <8 and consistent weight gain).
3. Wean the dose by 10% every 2-3 days as tolerated, continue to score patient
a. If score >8, rescore in 1 hour
b. 2 consecutive scores 8, increase methadone to previous dose
4. If infant tolerates the 10% daily dose wean for 2 consecutive weans, decrease daily dose by 20% every 2-3 days as tolerated
5. The weaning amount is calculated by taking 10-20% of the original dose, not the new lower dose.
6. Discontinue methadone once the daily dose is 0.05 mg/kg
7. Monitor the patient for 24-48 hours after discontinuing methadone
C. Monitoring of Therapy
1. Monitor for resolution of withdrawal symptoms, signs of excessive dosing (bradycardia, lethargy, hypotonia, irregular
respirations, respiratory depression, etc)
2. Continue to score patient every 3 hours during hospital stay
D. Reversal of Adverse Effects Therapy (over-sedation, respiratory distress)
1. To reverse administer Naloxone (Narcan)
2. Dose: 0.01 mg/kg/dose IM, IV, or ETT.
3. If response inadequate, can administer a second dose of 0.01 mg/kg in 2-3 minutes.
E. Other Drugs of Abuse
1. Marijuana
a. Crosses the placenta slowly and is metabolized by the fetus
b. May exhibit signs of nicotine toxicitytremors, tachycardia, irritability, and poor feeding in infants of heavy users
c. No known overt withdrawal
2. Cocaine
a. Manifests on day 2-3 postnatally
b. Vasoconstrictive effects cause neurological complicatiosn (IVH, infarcts, cystic lesions)
c. Exposed infants may exhibit hyperactive Moro reflex, jitteriness, excessive sucking
d. Higher incidence of prematurity, LBW, and placental abruption
e. Association with higher incidence of genitourinary tract and GI anomolies
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f. Short and/or long term neurobehavioral alterations
3. Alcohol
a. May exhibit symptoms within a day or 2 of birth
b. Acute ingestion: hyperactivity, tremors initially, followed by lethargy
c. Chronic ingestion: spectrum of abnormalities (FAS)
Bibliography:
i. AAP Committee on Drugs. Neonatal Drug Withdrawal. Pediatrics 1998; 101: 1079-1088.
ii. J ansson L. et al. The Opioid Exposed Newborn: Assessment and Pharmacologic Management. J Opioid
Manag 2009; 5 (1): 47-55.
iii. Lexi-Comp Online. Available at: https://online.lexi.com/lco/action/home.
iv. Velez M. et al. The Opioid dependent mother and newborn dyad: non-pharmacologic care. J addict Med
2008; September 1 2(3): 113-120.
INITIAL EVALUATION OF THE CYANOTIC NEWBORN:
Jeffrey D. Schuster, M.D.
1. Initial diagnostic evaluation
History
Obstetrical ultrasounds
Fetal echocardiograms
Meconium
GBS
Oligohydramnios
Physical examination
Respirations and air movement
Rhythm and murmurs
Peripheral perfusion
Right hand pulse-ox
Chest X-ray
Lung Fields
Heart size and contour
Vital signs and non-invasive monitoring
2. Oxygen therapy
Head hood up to 100% FiO2
Intubation and ventilation
Failure to respond at all suggests but does not confirm cyanotic heart disease
3. Arterial blood gases
Blue babies are sickput in a UAC for best data
CBGs have no role in the initial evaluation of cyanotic newborns
Pay attention to acid/base status
SECOND STEPS AND DIFFERENTIAL
Respiratory distress suggests lung disease
Quiet respirations without distress suggest cyanotic heart disease
CXR is important in detecting lung disease
Black lung fields can mean pulmonary blood flow or pulmonary hypertension
Small heart and massive pulmonary congestion could be TAPVR
Right hand pulse ox is (almost always) pre-ductal.
Differential pulse oxs (right hand and a leg) indicate one thing:
Right-to-left ductal shunt
Could be left heart obstruction with ductal systemic supply
Could be pulmonary hypertension with supra-systemic PA pressure
Reliable pulse oximetry requires adequate perfusion
Failure to respond to oxygen therapy
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Assess adequacy of ventilation
Most cyanotic heart diseases have normal or near normal pCO2
Elevation of pCO2 suggests lung disease
Proceed to increase tidal volume and rate
Consider oscillatory ventilation
Arterial blood gases
pO2 >250 excludes cyanotic heart diseasebut not other heart diseases
pO2 <50 despite all manipulations suggests heart disease
pO2 persistently in the 30s suggests transposition
Significant improvement in pO2 with oxygen and ventilation suggests lung disease
Tertiary Evaluation
Persistent cyanosis unresponsive to oxygen, ventilation, and correction of acid/base imbalance requires echocardiography to establish
anatomic diagnosis.
Have the clerk call the echo tech. The resident should speak to the tech and convey the information about the cyanotic infant.
STABILIZING TREATMENT
Right Heart Obstruction
Tetralogy of Fallot/ Pulmonary Atresia/ Tricuspid Atresia
Maintain Ductal patency to provide pulmonary perfusion
Oxygen will not make a substantial difference in saturation and should be weaned to close to room air
Left Heart Obstruction
Hypoplastic left heart syndrome/ Interrupted aortic arch/Critical coarctation/ Critical aortic stenosis
Oxygen will vasodilate the pulmonary circulation and steal from the systemic circulation
Oxygen is contraindicated in left heart obstructions
Transposition of the Great Arteries
Maintain ductal patency to increase pulmonary venous return to dilate the left atrium to promote atrial level mixing
Keep volume status high to dilate the left atrium
Oxygen will not significantly effect saturation
MAINTAINING DUCTAL PATENCY
Prostaglandin E1 requires continuous infusion
Initial dose is 0.1 microgram/kg/min
This is standardized by pharmacy so need only write as above (start PGE1 at 0.1 micrograms/kg/minute)
Can start with double dose to open a closed ductus
After good success, dose can be halved and halved again to 0.025 mcg/kg/min
Must be given in a secure IV
UVC
UAC
PIC Line
Peripheral IV (least optimal)
Side Effects:
APNEA
Vasodilation: Hypotension
? Seizures
Diarrhea
OPERATIVE CONSIDERATIONS IN THE NEWBORN:
Donald E. Meier, MD
ABDOMINAL WALL DEFECTS
Omphalocoele is a defect in the abdominal wall at the umbilicus. The protruding viscera are covered by membranes unless the
membranes have ruptured in utero or peripartum. There is a high incidence of associated anomalies including serious abnormalities of
the alimentary, cardiovascular, musculoskeletal, and central nervous systems. Omphalocele is also associated with Beckwith
Wiedeman Syndrome (microglossia, gigantism, and hypoglycemia).
Gastroschisis is a defect in the abdominal wall slightly superior and to the right of an intact umbilical cord. The protruding viscera are
not covered by a membrane and are usually edematous and even fibrotic because of their prolonged in utero exposure to amniotic fluid.
There is a low incidence of associated extra-intestinal anomalies, but a relatively high incidence of associated bowel atresias.
Omphalocoele is more common than gastroschisis in many countries, but omphalocoele is less common in the United States, probably
due to the high rate of voluntary interruption of pregnancy in cases of omphalocoele diagnosed prenatally.
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Management of Gastroschisis and Omphalocoele: Immediate coverage of the intestine is indicated for all newborns with
gastroschisis and for newborns with omphalocoele when the membranes have ruptured. Coverage can usually be achieved by
placement of a spring loaded silo in the delivery room or intensive care nursery without intubation and mechanical ventilation. If
successfully placed, the silo can be gradually shortened over the next few days and then the child can be taken to the operating room
for removal of the silo, closure of the fascia and skin, and placement of a central venous line for parenteral nutrition. If a spring-loaded
silo cannot be adequately placed at birth, the child should be taken to the operating room immediately. Under general anesthesia the
abdominal wall musculature is manually stretched. Options after stretching include: (1) fascia and skin closure, (2) skin closure only,
and (3) use of a silo. The ideal is to close fascia and skin, but this may result in a prohibitive increase in intraabdominal and
henobarbi pressures. Closure of fascia and skin can be accomplished in 80% of cases, but in 20% the best treatment will be
intraoperative placement of a silo. In children with gastroschisis, bowel function does not usually return for several weeks, and
therefore all neonates undergoing gastroschisis repair should undergo placement of a central venous catheter for parenteral nutrition if
PICC line placement has been unsuccessful. If the omphalocoele membranes are intact at the time of birth, non-operative treatment is a
viable option. The membranes are coated with a desiccating agent such as silver sulfadiazine, and over the next few days or weeks the
resultant dry scab serves as a barrier for the peritoneal cavity while the epithelium slowly grows in from the periphery. The end result
is an umbilical hernia that can be more safely repaired at a later date when the child is better able to tolerate general anesthesia and an
increase in intraabdominal pressure.
Inguinal hernias can be a cause of major morbidity and even mortality in the newborn. They are particularly common in premature
infants. Most can be repetitively reduced in the neonatal period until the child is of adequate maturity to tolerate anesthesia. Some,
however, will incarcerate and need urgent operation. In the intensive care nursery it is best to wait until the newborn is ready for
discharge and then repair the hernias a couple of days before the planned discharge.
Exstrophy of the bladder refers to a lower abdominal wall defect associated with pubic diastasis, a deficient or absent anterior
bladder wall, and epispadias. It can also be associated with imperforate anus and cloacal exstrophy. Treatment involves a series of
operations. The initial operation achieves (1) approximation of the pubis, (2) closure of the bladder, and (3) creation of a neourethra.
Further operations involve penile reconstruction at 2 years of age and a urinary continence operation at 4 years.
ESOPHAGEAL ATRESIA AND TRACHEOESOPHAGEAL FISTULA
Esophageal atresia with a distal TEF is the most common (90%) type. Less common types are pure atresia without a fistula and
an H-type fistula without atresia. EA/TEF is suspected in any newborn with respiratory difficulties, excessive salivation, and
vomiting. An orogastric tube is passed, and an X-ray taken. The diagnosis is confirmed by seeing the OG tube coiled in the atretic
pouch and air in the GI tract. The major immediate danger in EA/TEF is pneumonitis secondary to gastric reflux through the TEF. The
patient is best managed with the head of the bed elevated and suctioning of the pouch until operation can be performed. DO
NOT PERFORM ENDOTRACHEAL INTUBATION AND POSITIVE PRESSURE BREATHING UNLESS ABSOLUTELY
NECESSARY FOR A CHILD IN RESPIRATORY DISTRESS. Positive pressure breathing results in distention of the stomach
without a way to decompress it and may to lead to a vicious cycle resulting in death from increased intraabdominal pressure. The
EA/TEF abnormality is best repaired using a 4
th
intercostal space, extrapleural approach, although a transpleural approach is
acceptable. The fistula is ligated, and the distal esophagus separated from the trachea. The proximal esophageal pouch is mobilized
extensively, and a 1-layer primary anastomosis is performed. The minimum acceptable operation for EA/TEF in a very high risk
newborn is ligation of the fistula and placement of a feeding gastrostomy.
Pure esophageal atresia without a TEF, the two ends of the esophagus are usually separated by a long gap, which precludes early
primary anastomosis. With time the two ends may lengthen, and a primary anastomosis can sometimes be performed by 2 months of
age. The initial neonatal operation for this defect involves simple placement of a feeding gastrostomy. Parenteral nutrition is not
needed. Suction for the esophageal pouch is performed continuously. If the two ends do not spontaneously lengthen a thoracotomy can
be performed to apply dynamic traction to both ends of the esophagus followed by another operation to perform an esophageal
anastomosis.
H-type fistula is not associated with atresia. It is suspected in a child who coughs or chokes when feeding or one who has recurrent
bouts of pneumonia. The diagnosis is made by a skilled pediatric radiologist carefully performing an esophageal contrast study with
fluoroscopy or by a pediatric bronchoscopist. These techniques are available only in the most sophisticated centers, and this diagnosis
is therefore readily missed. The treatment for an H-type fistula is ligation of the fistula and separation of the trachea and esophagus
using a right supraclavicular incision.
CONGENITAL DIAPHRAGMATIC HERNIA (CDH)
CDH results from incomplete fusion of the various components of the fetal diaphragm at 8 weeks of gestation. The bowel returning
from the umbilical cord takes the path of least resistance up into the chest cavity, and the resultant increase in intrathoracic pressure
causes hypoplasia of the lung. The incidence is 1 in 5000 births, and it is more common on the left than right. Many CDHs in the US
are diagnosed by antenatal ultrasound. Children with CDH usually develop respiratory distress soon after birth. The diagnosis is made
by chest X-ray. Treatment involves passage of an orogastric tube to decompress the stomach and orotracheal intubation and ventilation
to prevent hypoxia, hypercarbia, and acidosis. The immediate cause of death in these children is usually hypoxemia secondary to
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persistent fetal circulation with pulmonary artery constriction causing blood to shunt around the lung through the ductus arteriosus.
ExtraCorporeal Membrane Oxygenation (ECMO) is the usual next step in the US if ventilator therapy is unsuccessful. Emergency
operation does not decrease mortality. One third of children will do well no matter what is done, and one third of children (those with
severe pulmonary hypoplasia) will die no matter what is done. The middle third of children are the ones who may benefit from heroic
measures in neonatal centers of expertise. Without availability of ECMO the best survival rate is probably in the 50% range.
INTESTINAL ATRESIAS
Atresias can occur anywhere in the gastrointestinal tract. The most common anomaly associated with an intestinal atresia is another
intestinal atresia. Therefore when an atresia is repaired a tube must be passed or saline instilled throughout the rest of the intestinal
tract to assess for other atretic segments.
Duodenal atresia, duodenal stenosis, and annular pancreas are all interrelated. One third of children with duodenal atresia have
Down syndrome. In the US the diagnosis is often made by antenatal ultrasound performed for polyhydramnios. In other cases the
presentation is characterized by feeding intolerance and vomiting (usually bilious) within a few hours of birth. The epigastrium appears
full, but the rest of the abdomen is not distended. The classic X-ray picture is a double bubble. Operation is performed through a
right upper quadrant transverse incision, and a duodenoduodenostomy is performed using a diamond anastomosis. No resection is
performed since this may damage the pancreatic and biliary ducts.
Jejunal and ileal atresias present with bilious vomiting. The time interval from birth to vomiting and the amount of abdominal
distention are directly related to the distance of the atresia from the Ligament of Treitz. An abdominal Xray shows dilated bowel
proximal to the atresia. Treatment is resection of the atretic segment with a 1 layer end-to-oblique anastomosis.
MALROTATION
Malrotation is a spectrum of intraperitoneal abnormalities resulting from incomplete or abnormal rotation of the bowel when it
reenters the peritoneal cavity in-utero. Children with malrotation: (1) may be asymptomatic; (2) may present with malnutrition from
chronic vomiting caused by Ladds bands obstructing the duodenum; or (3) may present catastrophically with a midgut volvulus. The
diagnosis must be emergently considered in any child (especially a neonate) with bilious vomiting. The diagnosis is best made by a
pediatric radiologist using a fluoroscopically guided contrast upper GI series. The treatment is emergent operation to prevent
strangulation from a midgut volvulus. The operative procedure (Ladds procedure) involves a transverse right supraumbilical incision
with: (1) complete lysis of Ladds bands; (2) widening of the base of the small bowel mesentery; (3) appendectomy; and (4)
intraperitoneal placement of the bowel in the position of nonrotation, with the cecum and colon in the left side of the abdomen and the
small bowel on the right. In a rural hospital without UGI capabilities and without the capability for rapid referral to a major medical
center, laparotomy may be indicated without radiologic confirmation. A negative laparotomy for suspected midgut volvulus is far
better than a positive autopsy.
MECONIUM ILEUS
Meconium ileus is a form of intraluminal obstruction of the bowel resulting from abnormally thick meconium. Meconium ileus is
almost always associated with cystic fibrosis. Typically a term neonate presents with abdominal distension and bilious vomiting and
fails to pass meconium, not at all unlike the presentation of neonates with bowel obstruction from other causes. If meconium ileus is
suspected, contrast studies can confirm the diagnosis and can also provide treatment by irrigating out the obstructing meconium pellets.
If, however, meconium ileus cannot be differentiated radiographically from other causes of obstruction, or if the inspissated meconium
cannot be cleared with intestinal washouts, then laparotomy is indicated. Meconium ileus is divided into two categories: uncomplicated
and complicated. In complicated cases the meconium ileus has caused an in-utero volvulus, perforation, or atresia with formation of a
giant pseudocyst secondary to the perforation. Operation for complicated meconium ileus involves resection of the atretic area or
pseudocyst and exteriorization using a procedure such as a Bishop-Koop procedure. At operation for simple meconium ileus the pellets
are mechanically evacuated out the rectum if possible and on-the-table, transrectal irrigations performed. If the meconium obstruction
cannot be cleared with irrigations, an enterotomy is performed and converted to a Bishop-Koop or similar exteriorization procedure.
HIRSCHSPRUNGS DISEASE
Hirschsprungs Disease (HD) is aganglionosis of the colon, which results from failure of caudal migration of neural crest cells. The
defect proceeds from distal to proximal. Therefore, the distal rectum is always involved and the proximal extent may go all the way
into the proximal small bowel, but there are no skip lesions. The diagnosis is often made in the US in the newborn nursery when there
is delayed passage of meconium. Any term child in the US who does not pass meconium in the first 48 hours deserves a barium
enema and a suction rectal biopsy. If the diagnosis is definitively made, the newborn can undergo a one stage pull-through
procedure, often laparoscopically. If the expertise is not locally available for histopathologic diagnosis, or if the surgical expertise is
not available for a pull-through procedure, then the best form of urgent treatment for HD is a colostomy performed in the dilated colon
proximal to the transition zone. This allows for a more elective workup and definitive treatment.
ANORECTAL MALFORMATIONS
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The term anorectal malformations (ARMs) encompasses a wide spectrum of abnormalities. Children with ARMs tend to have
multiple congenital abnormalities as evidenced by the VACTERRL complex (Vertebral, Anorectal, Cardiac, TracheoEsophageal,
Renal, Radial, and Limb abnormalities). The ARM is usually the most pressing problem and is the one that the surgeon is first
consulted to manage. When a child is born with an ARM, the surgeon needs to decide within 24 hours if this is a high lesion or a low
lesion. The first step is to look well at the perineum. If meconium is visible in the perineum or along the scrotal raphe, this is a low
lesion and can be managed by an anoplasty, which is basically an incision and drainage in the area where you suspect the sphincter to
be. If there is a well-established fistula tract, you can follow this tract back to the sphincter muscle complex. It is important when you
do the anoplasty to place some sutures (absorbable preferably) between the anorectal mucosa and the anal skin.
Unfortunately most ARMS are high lesions. In females the most common fistula is into the vestibule of the vagina. This needs to be
considered a high lesion for management purposes. In males the most common fistula site is the urethra. ALL high lesions need to have
a colostomy in the neonatal period and a definitive procedure later by someone who knows how to do a proper Posterior Sagittal
AnoRectoPlasty, an operation popularized by Dr. Pena. The colostomy should be performed in the proximal to mid sigmoid colon, not
in the distal sigmoid since a distal colostomy tethers the colon and prevents if from being pulled down at a later operation. I use a left
lower quadrant transverse incision, take down a bit of the mesocolon, transect the colon, and bring out the two ends of the colon
through opposite ends of the incision. The colon needs to be secured to the fascia to minimize stomal herniation. The fascia and skin
between the two ends of the colon are closed, thereby providing a divided or separated or double barrel colostomy.
NECROTIZING ENTEROCOLITIS
Necrotizing Enterocolitis (NEC) of the neonate is the most common operative emergency and the most common gastrointestinal
emergency in the neonatal intensive care unit (NICU). Ninety percent of cases are premature or low birth weight infants. The clinical
signs of NEC are those of intestinal ischemia including abdominal distention, lethargy, feeding intolerance, bilious vomiting, and rectal
bleeding. The early manifestations are indistinguishable from those of neonatal septicemia. Abdominal radiographs may show
pneumatosis intestinalis, portal venous gas, or free air from bowel perforation. The first line of treatment for NEC is medical, including
cardiovascular support, control of sepsis, and close observation for gangrene. One-half to two-thirds of infants survive with medical
management alone. The only absolute indication for operation in NEC is intestinal perforation. A relative indication, however, is
continued deterioration of a child on maximum medical therapy. The best monitors of ongoing sepsis in NEC children are
thrombocytopenia and persistent acidosis. Premature infants who are too ill to undergo operation may benefit from bedside placement
of intraperitoneal drains. If the child can undergo operation, the principles of operation for NEC are: (1) excision of the gangrenous
bowel; (2) exteriorization of the marginally viable ends; (3) preservation of as much intestinal length as possible. If the gangrenous
segment is short, resection with exteriorization of the ends is advisable. If resection of all non-viable bowel results in leaving less than
30-cm of viable intestine, resection should not be performed and the child should be managed expectantly. If there is an extensive
amount of bowel of questionable viability, diverting stomae should be performed and a second look operation anticipated to determine
if there are specific segments that have progressed to obvious gangrene. The stomae can be closed when the child is free of all infection
and in an anabolic state. A contrast study of the distal small bowel and colon should be performed prior to stomae closure to locate
strictures that should be resected at the time of stomal closure. Children who survive non-operative treatment for NEC may develop
bowel strictures in the area of previously inflamed bowel. Contrast studies may be needed to determine the location, number of
strictures, and need for operative intervention.
INABILITY TO FEED AND GASTROESOPHAGEAL REFLUX
Many neonates are unable to feed properly because of anatomical or physiological abnormalities. These children can be temporarily
fed with oro- or naso-gastric tubes, but for long-term treatment a gastrostomy tube is preferred. Gastrostomy tubes can be placed either
by a PEG technique (using a gastroscope) or by an open technique. Prior to insertion of a gastrostomy tube by either technique, an
Upper GI Series should be performed to be sure that there is no gastric outlet obstruction (duodenal stenosis, malrotation) and to assess
for reflux. If the child has any reflux on UGI series, the child will have a lot of reflux after placement of a gastrostomy tube unless an
antireflux operation is also performed.
Gastroesophageal reflux is a major cause of morbidity in children, and in a number of childrens hospitals reflux-related operations are
the most common intraabdominal procedures performed. Infants normally have some degree of emesis ranging from a wet burp to
regurgitation of a significant amount, if not all, of a recent feeding. Children with pathologic GER, however, regurgitate larger volumes
more frequently. Symptoms related to gastroesophageal reflux include vomiting, repeated respiratory infections, or poor feeding due to
repetitive bouts of reflux esophagitis or stricture formation. The emesis with GER is usually non-bilious and typically occurs during a
feeding or just after. If the GER is severe, there will be weight loss and failure to thrive. Aspiration of gastric contents into the
tracheal/bronchial tree can cause apnea, pneumonia, bronchitis and asthma.
A contrast esophagogram is an excellent screening test with a sensitivity of approximately 85%. Monitoring of pH for a continuous 24
hours is quite specific and quite sensitive, but it is much more difficult to perform. A radionuclide scan can also be used to identify the
presence of GER and to provide physiologic information regarding the efficacy of gastric emptying.
Non-operative treatment of GER is successful in at least 80% of children, particularly in those with mild to moderate reflux. There
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appears to be physiologic maturation of the lower esophageal sphincter during the first 4 to 6 months of age. The major medical
components of GER treatment include upright positioning, frequent and low volume feedings, thickened feedings, and pharmacologic
treatment with antacids and prokinetic agents. Surgical correction is reserved for those children whose symptoms cannot be controlled
medically or for those with an identifiable, contributing anatomic abnormality. The principles for surgical treatment of GER include
the establishment of an intra-abdominal portion of the esophagus and the development of a lower esophageal sphincter that resists the
passage of gastric contents from the stomach to the esophagus. After an anti-reflux procedure, an increase in intragastric pressure
temporarily causes the portion of the stomach positioned around the intra-abdominal esophagus to act as a one-way valve. As soon as
intragastric pressure decreases, the infolded stomach around the esophagus collapses and does not impinge on the esophagus. A floppy
Nissen fundoplication is the most commonly performed procedure, but many recommend a partial anterior (modified Thal) or a partial
posterior (Toupet) antireflux procedure. All of these procedures can be performed open or laparoscopically. Each procedure has its
proponents. Gas bloat syndrome is more likely with the Nissen wrap, but recurrence rates are probably higher for the partial wraps.
PYLORIC STENOSIS
Pyloric stenosis is not normally seen in the intensive care unit since it usually occurs in 3-6 week-old, previously healthy infants. They
have progressive, projectile vomiting of non-bilious material. The characteristic physical finding is an olive-shaped mass in the
midepigastrium, although the art of feeling olives is disappearing as the use of UGI and ultrasonography is increasing. If the history is
characteristic and a mass is identified, no further diagnostic studies are indicated. However, if there is not a palpable mass an upper GI
series or ultrasonography (preferable) is indicated for definitive diagnosis. In less developed countries these radiographic studies may
not be available, and in this scenario it is acceptable to operate on the basis of a convincing history even in the absence of a palpable
mass. The characteristic fluid and electrolyte abnormality in these infants is volume deficit with a hypokalemic, hypochloremic
alkalosis. Pyloromyotomy is not an emergent operation. Fluid and electrolyte abnormalities should be corrected before performing
pyloromyotomy. A transverse incision is performed through the right rectus abdominis muscle midway between the xiphoid and the
umbilicus. The pylorus is delivered through the wound. A longitudinal incision is performed through the serosa and into the muscularis
from a point just proximal to the vein of Mayo up onto the stomach 1 cm proximal to the palpable hypertrophic area. A pyloric
spreader or hemostat is used to gently separate all of the muscle fibers and allow the mucosa/submucosa to bulge. The most common
mistake is to go too far distally where the duodenal wall is thin and to cut through the mucosa. If this happens the hole should be
precisely closed and a piece of omentum placed over the hole and sutured to the surrounding serosa to hold it in place. After an
uncomplicated operation the child remains NPO for 6 hours and then is allowed to feed. The parents are warned that the child will
probably vomit a few more times before reaching normal feeding status. Pyloromyotomy is now commonly performed
laparoscopically.
BILIARY ATRESIA
Biliary atresia (BA) is a malformation of the intra- or extra-hepatic ducts or both in which the ducts are either absent or only fibrous
cords. Etiology is not defined. The duct obstruction is followed by progressive periportal fibrosis, biliary cirrhosis, portal
hypertension, hepatomegaly, ascites, and death. There are many causes of neonatal jaundice other than BA (physiologic jaundice,
systemic infections, genetic-metabolic disorders, choledochal cyst, neonatal hepatitis, TPN-induced cholestasis, etc). Abdominal
ultrasound is performed to rule out choledochal cyst and to look for a gall bladder (often absent or fibrotic in BA). In BA a technetium
scintiscan with henobarbital pretreatment may show excretion of the isotope without clearance from the liver into the intestine. The
definitive diagnostic test is a laparotomy which should be performed before 8 weeks of life. A cholangiogram is performed through
the gall bladder if present. The surgical treatment for BA is a Roux-en-y hepaticojejunostomy (Kasai procedure). Over-simplified
result assessment: 1/3 do well without transplant, 1/3 do well with late transplant, 1/3 need early transplant (12-16 months).
CHOLEDOCHAL CYST
Choledochal Cysts are cysts of the common bile duct (CBD) occurring in 5 different types. Over 90% are Type I which is cystic
dilatation of the common bile duct itself. Most infants have complete obstruction of the CBD at the pancreatic area, but adults usually
have a small patency of the distal common duct. The most common presentation is jaundice, and ultrasound is the diagnostic modality
of choice. Treatment is excision of the cyst with Roux-en-y biliary drainage. If the cyst is not excised there is a high chance of
malignancy later in life. Treatment in years past was simple choledochal enteric bypass without excision. There are now adults who
are walking around with choledochal cysts that have been bypassed. If you see these patients in practice they should be referred for
excision because of this high incidence of malignancy.
NEWBORN LUNG ANOMALIES
1. Congenital cystic adenomatoid malformations (C-CAMs) are cystic, solid, or mixed intrapulmonary masses that communicate
with the tracheobronchial tree and rarely have an anomalous blood supply. They may present with early respiratory distress when
the lesions are large. Smaller lesions may be asymptomatic or may present with recurrent pulmonary infections.
2. Congenital lobar emphysema is a problem with air trapping, probably secondary to a partial obstruction of a bronchus, usually
the LUL bronchus. These neonates present with progressive respiratory compromise due to the over-expansion of the involved
lobe resulting in compensatory under-expansion of the other lobes and a mediastinal shift. Urgent thoracotomy is often indicated
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to get the affected lobe quickly out of the thoracotomy incision to allow ventilation. Resection of the involved lobe is the proper
treatment.
3. Pulmonary sequestration is abnormal lung tissue that receives an anomalous blood supply and does not have a connection to the
tracheobronchial tree. They are intralobar in 90% and extralobar in 10%. Infants are not usually symptomatic at birth. They are
usually diagnosed after a CT scan is obtained in a child with recurrent pulmonary infections. The treatment is removal.
NECK MASSES
Here are a few neck masses you need to know about:
1. Cystic hygromas usually present as soft, non-tender multicystic masses in the lateral part of the neck. They reside near large
veins and lymphatic ducts. Spontaneous remission is rare and infection of or bleeding into a hygroma is relatively common.
Therefore excision of the hygroma is indicated but radical resection to include important nerves or major vessels is not indicated.
2. Branchial remnants can present as fistulae, cysts, sinuses, or cartilaginous remnants. Fistulae, cysts, and sinuses can become
infected and should be excised prophylactically. Most remnants of the second branchial cleft present along the anterior border of
the sternocleidomastoid muscle. A 2
nd
cleft fistula goes between the branches of the bifurcation of the common carotid artery.
3. Thyroglossal duct cysts result from abnormal descent or closure of the thyroid diverticulum which arises from the foramen
cecum of the tongue and proceeds down the anterior portion of the neck. The cysts are midline, smooth, discrete, and non-tender
(unless infected). The cyst should be excised when it is diagnosed to prevent infection which may lead to initial incision and
drainage followed by a more difficult excision at a later date. Excision is performed by complete excision of the cyst and tract all
the way to the foramen cecum. This involves taking a portion of the medial part of the hyoid bone en bloc (Sistrunk procedure).
4. Torticollis results from fibrosis of the sternocleidomastoid muscle, forming a fibrous mass and shortening of the involved muscle.
Usually a mass is noted in the SCM after 2 weeks of age. The face rotates away from the affected side. Most cases resolve with
passive stretching exercises. If not, operative transection of the middle third of the SCM is indicated.
NEONATAL BLOOD PRODUCT TRANSFUSION GUIDELINES:
Neonatal Crossmatch:
Tests done:
ABO
DAT
Rh
Antibody screen
Specimen requirement:
All neonates <4 months
Plasma preferred
2 (1 ml EDTA plastic lavender top microtainers)
2 (1 ml plastic red top microtainer, no gel)
Turn around time:
Routine 8 hours
STAT 1 hour
PRBC Transfusion:
All blood Type O with correct Rh and antibody negative
All PRBCs are CMV negative leukocyte reduced (or washed) and irradiated.
All PRBC transfusions are IV using a blood filter
Must be transfused 4 hours
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Transfusion guidelines (discuss all transfusions with attending):
Hct Clinical criteria Transfusion
Hypovolemic shock due to blood
loss
Symptoms of shock 20 ml/kg over 1 hour
Hct 35% Mech Vent MAP 8
O2 40%
PRBC 15-20 ml/kg over 2-4
hours
Hct 30% CPAP 6 or mech vent
O2 40% non-vented
Surgery
PRBC 15-20 ml/kg over 2-4
hours
Hct 25% Non-vented, O2 21-40% and
any of following:
HR>180, RR > 80
Poor weight gain
No progress in nippling
Unstable apnea
PRBC 15-20 ml/kg over 4 hours
(may transfuse in 10 ml/kg
aliquots)
Hct 21% No symptoms but retic <2% PRBC 20 ml/kg over 4 hours
(may transfuse in 10 ml/kg
aliquots)
Platelet Transfusions:
Do not have to be ABO compatible though preferred
Unless anticipating multiple transfusions
Transfuse infants with ABO compatible if possible due to small size.
Should be Rh compatible to the recipient
Volume reduction of platelets prior to transfusion not recommended
Filtered during transfusion with 80-260 micron filter
Discuss all transfusions with attending
Guidelines for platelet transfusions (5-10 ml/kg plt ct 50,000-100,000/L):
Platelet Count Clinical criteria Transfusion
30,000 Healthy term newborn 10ml/kg over 1 hour
50,000 Healthy preterm 34 weeks
Any bleeding
Anticipate invasive procedures or
surgery
10 ml/kg over 1 hour
80,000-100,000 Sick preterm 34 weeks 5-10 ml/kg over 1 hour
Fresh Frozen Plasma Transfusion:
Indicated in severely ill infants bleeding or at risk for bleeding
Must be ABO compatible
Transfused 10-15 ml/kg over 1 hour
Transfuse with 80-180 micron filter
Discuss all transfusions with attending
Pediatric Transfusion: A Physician Handbook, 1
st
edition, Bethesda, MD: American Association of B1ood Bank, 2003
Thomason Regional Laboratory Blood Preparation Protocol IH-021
Galel S, Therapeutic Techniques: Selection of Blood Components for the Neonatal Transfusion, NeoReviews Vol. 6 No. 7, J uly 2005.
Ohls RK, Transfusions in the Preterm Infant, NeoReviews, Vol. 8 No.9, September 2007.
Murray NA, Neonatal Transfusion Practice, Arch Dis Child Fetal Neonatal Ed 2004; 89: F101-107.
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FORMULA TO RECONSTITUTE BLOOD FOR EXCHANGE TRANSFUSION:
Garrett S. Levin, M.D.
o Exchange transfusion is generally performed for hyperbilirubinemia and or anemia, usually due to hemolytic disease of the
newborn or prematurity.
o For treating anemia, a single volume (80-100mL/kg exchange is generally adequate.
o For management of hyperbilirubinemia, a double volume exchange (160-200mL/kg) is favored.
o Plasma reduced blood with hematocrit (HCT) of 0.5 - 0.6 is recommended.
Calculation of double volume exchange
Double volume exchange: [Infant's blood volume x weight (kg)] x 2
Blood volume: Term 80-85mL/kg; Preterm: 90-100mL/kg
Example
Exchange volume for a 3.5kg term newborn
Solution: [80mL/kg x 3.5kg] x 2 =560mL
Formula to reconstitute blood for exchange transfusion
*Theoretically, this is the same as for doing a reduction-exchange transfusion except here we are reducing a bag of blood in contrast
to a baby.
For convenience of calculation, one must assume weight =volume.
Therefore a unit bag of blood that weighs 300 grams has 300 milliliters of blood.
Facts Example
1. Weight of bag
2. Weight of bag with blood
3. Hematocrit of blood
4. Desired Hematocrit =55%
1. Weight of bag =35 grams
2. Weight of bag with blood =285 grams
3. Hematocrit of blood =90%
4. Desired Hematocrit =55%
Solution
1. (90 - 55 / 90) (285-35 +X) =X
2. (35 / 90) (250 +X) =X
3. (0.38) (250 +X) =X
4. 95 +0.38X =X
5. 95 =1X - 0.38X
6. 95 =0.62X
7. 95 / 0.62 =X
8. 153 =X
Therefore, we need to add 153mL of Fresh Frozen Plasma (FFP)
to the bag containing 250mL of blood giving 403 mL of blood
with a hematocrit of 55%.
Do not exceed more than 500mL per bag. If a double-volume
exceeds this amount, you will need to prepare several bags.
Always use a Pall filter through a port to filter the blood and
products.
AAP Guidelines Readiness for Hospital Discharge for Discharge Planning
Infant Readiness
1. Sustained pattern of weight gain.
2. Adequate maintenance of normal body temperature in open crib.
3. Competence in breast and bottle feeding.
4. Physiological stability of cardio and respiratory status.
5. Appropriate immunization.
6. Appropriate metabolic screening
7. Stable Hematological status.
8. Nutritional risks assessments completed
9. Hearing test done
10. ROP screening
11. Neurobehavioral and developmental assessment
12. Car seat evaluation
13. Unresolved problems identified and plans of monitoring implemented
14. Home assessment made
Family and Home Environmental Readiness
1. 2 committed family members need to attend the discharge planning classes
2. Parents to demonstrate care for the infant in the rooming in setting
3. Psychological assessment of parents
4. Safety at home
5. Financial resources available
Parental Readiness for Care of the Infant
1. Competence in feeding
2. Basic infant care, bathing, skin, cord care, genital care
3. CPR training
4. Detection of early signs and symptoms of illness
5. Infant safety precautions, sleep safety and car seat safety
6. Safety of equipment and medication use
7. Competence in maintaining tracheostomy, ostomies and other attached devices
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Community and Healthcare System Readiness
1. Primary care provider and a medical home
2. Surgical and medical subspecialties
3. Neurodevelopment follow up provided by high risk follow up clinic
4. Early childhood intervention program
5. Home nursing
6. Lactation support for breast feeding mothers.
INFANTS TO BE FOLLOWED IN SPECIAL CARE CLINIC:
o All infants ventilated 96 hours or iNO therapy
o Infants 32 weeks or <1,500 grams
o Infants with BPD on O2 or medication at discharge
o Infants with complex congenital anomalies
o Infants with uncommon chromosomal abnormalities
o Infants with metabolic disorders
o Infants with apnea requiring a monitor (6 months to one year follow-up unless other criteria met)
o Infants with IVH grade II, hydrocephalous or PVL
o Infants with Stage II NEC
o Asphyxiated infants with: HIE or abnormal neurologic exams or cooling therapy
o Infants born to mothers on psychotropic or anticonvulsant drugs
o Infants exposed to illicit drugs in pregnancy treated for withdrawal symptoms and or presence of abnormal neurologic exams prior
to discharge.
o Infants requiring double volume exchange transfusions
Most SCC patients are followed until 18 months (18 months corrected for premature infants). Follow-up for some patients may be
extended beyond 18 months if needed as determined by the neonatologist. Other patients however may be qualified for earlier
discharge. The above list is not inclusive. Patients who are deemed high risk with diagnoses other than those listed above may be
referred to Special Care Clinic. Those referrals will be reviewed and will be accepted if services needed are within the scope of SCC.
POLICY FOR VITAMIN A ADMINISTRATION TO ELBW INFANTS:
Supplemental Vitamin A administration to ELBW infants has been shown in meta-analysis of clinical trials to decrease the incidence
of BPD as well as mortality.
Patients eligible: All infants 1,000 grams at birth as ordered by the attending physician.
Initiation of therapy: 24-96 hours of age
Drug: Vitamin A preparation 50,000 International Units per milliliter
(Retinyl Palmitate brand name Aquasol A, Astra USA, Westborough, Mass.).
Refrigerate and shield at all times from direct light.
Dose: 5,000 International Units (0.1ml) Monday, Wednesday, Friday for four weeks (total of
12 doses). Same dose used regardless of birth weight as smallest infants have the
highest incidence of chronic lung disease, the lowest vitamin A stores at birth and the
lowest enteral intakes.
Route: IM in a 0.3 ml syringe (Becton Dickinson, Cockeysville, Md)
29-guage needle.
Pain Control: Pacifier and swaddling
Bibliography:
Tyson J E, Wright LL, Oh W, Kennedy KA, Mele L, Ehrnkranz RA, el al. Vitamin A supplementation for Extremely-low-birth-weight
infants: National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 1999: 340:1962-8.
Young TE. Neofax, Manual of Drugs Used in Neonatal Care 2003: 214.
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NEONATAL DOCUMENTATION OF GESTATIONAL AGE ASSESSMENT:
Best obstetrical information will be used.
LMP confirmed US or early prenatal clinical assessment.
o Following prenatal US confirms maternal LMP
Sono 20 wks (+/-) 5-7 days of LMP
Sono >20 wks (+/-) 2 weeks of LMP
If only unsure LMP known then perform a ballard at 24 hours of life.
o If Ballard is (+/-) 2 weeks then use the LMP as the Ballard is not sensitive even in the best examiners hands.
o If Ballard is (+/-) 3 weeks on two separate exams then use the ballard.
o The Ballard should not be used as the sole determiner of GA if OB criteria is available.
For documentation of GA, full completed week of gestational age will be used (if 23 5/7 wks then 23 wks will be documented).
Document method used to assess GA.
NEWBORN SCREENING:
1. Biotinidase Deficiency
Disorder of biotin recycling
Biotin: water-soluble vitamin of the B complex, binds to carboxylases to enhance function
Biotinidase: an enzyme that releases biotin from carboxylases
Clinical Manifestations
Autosomal recessive
Most infants first exhibit clinical symptoms between 3-6 months of age
CNS and skin most commonly affected
Myoclonic seizures, hypotonia, seborrheic or atopic dermatitis, partial or complete alopecia, and conjunctivitis
Other features: developmental delay, sensorineural hearing loss, lethargy, ataxia, breathing problems, hepatosplenomegaly, and coma
Laboratory findings: keto and lactic acidosis, organic aciduria, mild hyperammonemia
Diagnosis
1. Newborn screen: Semiquantitative colorimetric assessment of biotinidase activity performed on whole blood spotted on filter paper
2. Follow-up and Diagnostic Testing
Positive screening result definitive testing quantitative measurement of enzyme activity on a fresh serum sample
Residual enzyme activity determines whether the patient has profound (10% activity) or partial (10%30% activity) biotinidase
deficiency
Treatment
Profound biotinidase deficiency: Carnitine: 520 mg/day
Partial biotinidase deficiency: Consider lower doses of biotin 15 mg/day and/or only during times of metabolic stress
2. Congenital Adrenal Hyperplasia
Newborn screening focuses exclusively on the most common form of CAH - 21-hydroxylase (21-OH) deficiency
21-OH deficiency - autosomal recessive disorder caused by a mutation of the CYP21 gene
Pathophysiology
21-OH deficiency cortisol deficiency +aldosterone deficiency
Cortisol deficiency increased ACTH secretion excess secretion of the precursor steroids 17-OHP hyperplastic changes of the
adrenal cortex
The precursor steroids metabolized by the androgen biosynthetic pathway excess androgen production virilization
Aldosterone deficiency Salt wasting
The increased circulating 17-OHP: diagnostic for 21-OH deficiency
Clinical Manifestations
1. Salt wasting form
Adrenal crisis during the 1st-4th weeks of life: Poor feeding, vomiting, loose stools or diarrhea, weak cry, FTT, dehydration, and
lethargy. If untreated circulatory collapse shock death.
Affected females have ambiguous genitalia (AG) with normal internal reproductive anatomy diagnosis.
In milder cases, females present later with hirsutism, menstrual irregularities, and decreased fertility.
Affected males have no obvious physical signs of CAH. If no salt-wasting, may present later with precocious puberty and advanced
bone age.
2. Simple virilizing form
No adrenal-insufficiency symptoms unless subjected to severe stress but exhibit virilization
Males and some females not diagnosed until later (virilization, precocious pseudopuberty, growth acceleration)
Advanced skeletal age diagnosed late short adult stature
3. Mild 21-OH deficiency
No symptoms at birth and manifests as premature sexual hair, acne, and mild growth acceleration in childhood and hirsutism, excessive
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acne, menstrual disorder, and infertility later in life
Diagnosis
1. Prenatal
Carrier testing for CAH - performed most accurately using CYP21 genotyping
Pregnant women known to be at risk of having a fetus with CAH - First-trimester prenatal diagnosis indicated
An elevated 17-OHP concentration in amniotic fluid (618 ng/mL) is also diagnostic
2. Postnatal
Newborn screen: elevated 17-OHP, ideal to measure after 24 hours, falsely elevated in premature infants
Follow-up and diagnostic testing: Immediate evaluation (serum electrolytes, 17-OHP)
Treatment
1. Prenatal
Indicated for female fetuses with classic virilizing CAH
Maternal dexamethasone therapy at 20 mg/kg per day beginning at 5 to 8 weeks fetal age prevents or reduces AG in most affected
females
2. Postnatal
Replacement of cortisol suppresses increased ACTH, 17-OHP, and androgen secretion
Replacement of aldosterone with an analog of mineralocorticoid (Florinef) for patients with SW CAH
Special medical care is needed in case of stress
In virilized female infants surgical correction generally performed before 1 year of age and, if necessary, again before menarche
3. Congenital Hearing Loss
Defined as permanent and is bilateral or unilateral, is sensory or conductive, and averages 30 dB or more in the frequency region
important for speech recognition
Many etiologies, with at least half associated with genetic risk factors
Pathophysiology
~50% of the cases of CHL are thought to be attributable to environmental factors: acoustic trauma, ototoxic drug exposure
[aminoglycosides], bacterial or viral infections such as rubella or CMV)
Remaining cases are attributable to genetic mutations
Screening - performed before discharge from the nursery
Computerized equipment: automated auditory brainstem response (AABR), distortion product otoacoustic emissions (OAEs), or
transient evoked OAEs
Follow-up:
Infants who do not pass the screening: Re-screen before discharge or give an appointment for re-screening as outpatient
Failure to pass the screening: refer to a qualified audiologist for confirmatory testing for congenital hearing loss
Treatment
Comprehensive pediatric and genetic evaluation
Core personnel: individuals with expertise in the genetics of hearing loss, dysmorphology, audiology, otolaryngology, genetic
counseling. Others: ophthalmology, cardiology, nephrology, neurology
Referral to the state early intervention program and/or the state program for children with special health care needs as appropriate
4. Congenital Hypothyroidism
Thyroid hormone deficiency at birth is one of the most common treatable causes of mental retardation
Inverse relationship between age at diagnosis and neurodevelopmental outcome: the later treatment is started the lower the IQ
Pathophysiology
1. Thyroid dysgenesis (75%) due to thyroid aplasia, hypoplasia or ectopy
2. Thyroid dyshormogenesis (10%) defect in thyroid hormone synthesis due to TSH unresponsiveness, iodide transport,
organification, thyroglobulin abnormality or deiodinase deficiency
3. Hypothalamic-pituitary defect (5%) panhypopituitarism, hypothalamus or pituitary abnormality, isolated TSH deficiency or TH
resistance
4. Transient hypothyroidism (~10%) maternal anti-thyroid medications (PTU crosses placenta) or maternal antibodies (TSH
receptor-blocking antibodies), neonatal iodine exposure
5. Transient hypothyroxinemia of prematurity etiology unknown or may be due to immature hypothalamic-pituitary axis
6. Sick euthyroid acute or chronic illness Abnormal thyroid tests yet normal thyroid function
Clinical manifestations
Most affected infants appear normal at birth
5% are more severely affected have recognizable features at birth (large fontanels, wide suture, macroglossia, distended abdomen
with umbilical hernia, and skin mottling)
As maternal thyroid hormone is excreted and disappears in the first few weeks clinical features gradually become apparent:
Slow to feed, constipated, lethargic, sleep more, hoarse cry, cool to touch, hypotonic with slow reflexes, prolonged jaundice due to
immaturity of hepatic glucuronyl transferase, goiter, common in those with an inborn error of T4 synthesis, if undiagnosed beyond 2 to
3 months of age slow linear growth, if untreated loss of IQ proportionate to the age at which treatment is started
Other long-term neurologic sequelae: ataxia, gross and fine motor incoordination, hypotonia, spasticity, speech disorders, problems
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with attention span, associated sensorineural deafness, strabismus
Some NBS programs also detect secondary or hypopituitary hypothyroidism: associated midline defects: syndrome of septooptic
dysplasia or midline cleft lip and palate; Other pituitary hormones, such as growth hormone, may also be missing
Diagnosis
1. Newborn screening
Majority initially measure T4, if low T4 measure TSH
2. Follow-up testing
Abnormal screening confirmatory serum T4 testing
Measure of thyroid binding proteins (triiodothyronine [T3] resin uptake), free T4 level, TSH
Once diagnosis is confirmed determine etiology (Should never delay onset of treatment)
Thyroid ultrasound or thyroid uptake and scan (technetium 99m pertechnetate or iodine 123)
If evidence of maternal autoimmune thyroid disease measure thyrotropin-binding inhibitor immunoglobulin in the mother and infant
identify those with likely transient hypothyroidism
If iodine exposure or deficiency is suspected measure urinary iodine confirm this etiology
Treatment
Levothyroxine is the treatment of choice: recommended starting dose is 10 to 15 g/kg per day
Treatment goals
Keep T4 (1016 g/dL ) or free T4 (1.2 2.3 ng/dL) in the upper half of the reference range
Thyrotropin in the reference range (6 mU/L)
Laboratory evaluation should be conducted
At 2 and 4 weeks after initiation of T4 treatment
Every 1 to 2 months during the first year of life
Every 3 to 4 months between 1 and 3 years of age
2 to 4 weeks after any change in dosage
5. Cystic Fibrosis
Pathophysiology
Abnormalities in the CF transmembrane conductance regulator (CFTR) protein (Membrane glycoprotein that regulates ion flux at
epithelial surfaces)
cause thick secretions that obstruct pancreatic ductules exocrine pancreatic destruction
in the airway, dehydration of airway surface liquid chronic infection and neutrophil dominated inflammation
bronchiectasis and progressive obstructive lung disease
Inheritance: Autosomal recessive
Mutation F508 accounts for >70% of affected chromosomes
Clinical manifestations
Usually presents in infancy - Meconium ileus occurs in ~17% of infants with CF
Beyond the perinatal period FTT, Hypoelectrolytemia from sweat salt loss, chronic respiratory symptoms: cough, wheeze,
chronic endobronchial infections
Diagnosis
1. Newborn screening: determination of Immunoreactive trypsinogen (IRT) concentrations from dried blood spots
2. Follow-up testing: Two approaches can be taken if the IRT concentration is high
1. Perform mutation analysis from the dried blood spot for a set of CF mutations - a second specimen is not required
2. Persistent elevation of IRT concentration - require a second dried blood spot taken at 2 to 3 weeks of age in infants with a
high concentration on the first specimen
For programs that perform mutation analysis diagnosis of CF can be made if 2 mutations are identified from the dried blood
spot. If only one mutation is identified sweat testing (definitive diagnostic test) should be performed ASAP.
In programs that do not perform mutation analysis sweat testing should be performed within a few days of the repeat IRT
test.
Sweat testing should be performed at >1 week of age. Sweat collection inadequate in preterm infants perform mutation
analysis. Sweat chloride >40 mmol/L required for diagnosis of CF in the newborn. Values >30 mmol/L requires follow-up.
6. Galactosemia
Pathway
Lactose A Galactose +glucose B Galactose 1-phosphate +UDP glucose C UDP galactose +glucose 1
phosphate
A Lactase B Galactokinase C Galactose-1-phosphate-uridyltransferase
Clinical manifestations
Autosomal recessive
Typically presents soon after feeds are introduced: Poor feeding, vomiting. Lethargy, hepatomegaly, liver failure, renal tubular
dysfunction (acidosis, glycosuria, amino aciduria), Cataracts at birth due to fetal exposure to galactose, Increased risk of neonatal
infection E coli sepsis
If mild neonatal symptoms, can present later with FTT
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Older children with learning disabilities despite therapy
Diagnosis
1. Newborn Screening: Test for galactose, galactose 1-phosphate +galactose, or GALT enzyme deficiency - Some laboratories test
for all of these substances
2. Follow-up testing:
Diagnostic studies for classic galactosemia: quantitative analysis of GALT and red blood cell galactose 1-phosphate
Evaluated rapidly for feeding difficulty, signs of sepsis, jaundice, and hepatomegaly
Treatment
Galactose-free formula until diagnostic testing confirms diagnosis
Supportive care: vitamin K, FFP, antibiotics for presumed Gram(-) sepsis, phototherapy for hyperbilirubinemia
Milk and milk products are excluded from the diet indefinitely - Significant ingestion of galactose at any age can be toxic
Regular nutritional evaluation, ensure adequate calcium intake
7. Homocystinuria
Pathway
Methionine A Homocyteine B Cystathionine Cysteine
A Betaine-homocyteine methyltransferase and methytetrahydrofolate-homocyteine methytransferase
B Cystathionine synthase
Cystathionine -synthase (CBS) deficiency (most common defect) high concentrations of serum methionine
Pathophysiology: 2 mechanisms explain most of the clinical symptoms
1. Abnormal (hyper) coagulation because of sticky platelets; and
2. Direct toxicity of homocystine and its metabolites, causing endothelial cell damage
Clinical Manifestations:
Multiple, recurrent thromboemboli
Ectopia lentis, glaucoma, cataracts, developmental delays/mental retardation, seizures, psychiatric disturbances, muscle weakness with
a shuffling gait
Osteoporosis with bone deformities, scoliosis, high palatal arch, and a marfanoid habitus
Diagnosis
1. Newborn Screening: The bacterial inhibition assay (BIA) test - detect increased concentrations of blood methionine
2. Follow-up testing
Quantitative serum or plasma amino acid determination - used for diagnosis of homocystinuria
Plasma amino acids: increased methionine and homocystine, with reduced cystine and absent cystathionine
A urine organic acid profile: may be used to determine the presence or absence of methylmalonic acid
Treatment
1st step: trial of pyridoxine (vitamin B6) - ~50% of patients respond to large doses of this vitamin
Non-responsive patients with CBS deficiency:
Methionine-restricted, cystine supplemented diet
Folic acid and betaine therapy may be helpful
In the disorders of cobalamin metabolism and transport in which methylmalonic acid and homocystine appear in the urine
hydroxycobalamin treatment (vitamin B12, not cyanocobalamin) may be beneficial
Aspirin and dipyridamole decrease the occurrence of thromboembolic phenomena
8. MSUD
Caused by a deficiency in activity of the branched chain -keto acid dehydrogenase (BCKD) complex accumulation of the
branched-chain amino acids (BCAAs) leucine, isoleucine, and valine and the corresponding branchedchain -keto acids (BCKAs)
Clinical Manifestations
Classic MSUD (residual enzyme activity 2%) most severe and most common form
Normal at birth, with symptoms developing between 4 and 7 days
Lethargy and poor sucking with little interest in feeding, weight loss
Abnormal neurologic signs (alternating hypertonia and hypotonia; dystonic posturing of the arms)
Characteristic odor of the urine - smelling like maple syrup, burnt sugar, or curry
Seizures and coma, leading to death (in untreated cases)
Laboratory: increased concentrations of BCAAs, ketosis, acidosis, and occasionally hypoglycemia
Diagnosis
1. Newborn screen: elevated leucine, isoleucine, valine
2. Follow up testing: Blood leucine concentration >4 mg/dL, or a concentration of 3 to 4 mg/dL (305 mmol) in the first24 hours of
life immediate medical follow-up
Plasma amino acid analysis reveals findings diagnostic for MSUD: increased concentrations of BCAAs, low alanine
concentrations, and the presence of alloisoleucine
Treatment
Regulated diet that provides sufficient BCAAs for normal growth and development. The goal of long-term dietary management is
normalization of blood BCAA concentrations while providing nutrition adequate to sustain growth and development in children.
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Dietary therapy should be continued for life.
Natural protein must be limited, a medical food product (BCAA-free) supplement is necessary .
A metabolic team: physician metabolic specialist, metabolic nutritionist
A trial of thiamine supplementation (50300 mg/day for at least 3 weeks) is recommended.
Treatment during acute illnesses should be aggressive dialysis to remove toxic metabolites
9. MCAD Deficiency
Pathophysiology
Disease of hepatic FAO, with the most frequent presentation being episodic hypoketotic hypoglycemia provoked by fasting
The inability to break down fats to ketone bodies for an energy source while fasting hypoglycemia
FA that are not oxidized will be excreted in urine as carnitine esters carnitine deficiency
Encephalopathy due to hypoglycemia and hypoketonemia
Severe acidosis
Diagnosis
1. NBS: MS/MS - measuring octanoylcarnitine (a compound normally not present) on the filter paper blood spot
2. Any child with an octanoylcarnitine concentration of >1.0 mol/L will require definitive diagnostic testing. Follow-up testing:
plasma acylcarnitine analysis, urinary organic acid analysis, and molecular testing.
Plasma acylcarnitine analysis and urinary organic acid analysis will confirm the diagnosis
The molecular analysis should provide guidance regarding prognosis
Brief Overview of Disease Management
Avoidance of fasting
Mildly decreased intake of dietary fat
L-carnitine supplementation
Patients should be treated aggressively even during minor illnesses to avoid a severe episode
10. PKU
Classic phenylketonuria (PKU): when the concentration of Phe is very high (20 mg/dL or 1210 mol/L) and there is accumulation
of phenylketones
Deficiency of activity of a liver enzyme, phenylalanine hydroxylase (PAH) increased concentrations of Phe in the blood and
other tissues
Pathway
Phenylalanine A Tyrosine B Dopamine
A Phenylalanine hydroxylase: produce in the liver, requires BH4
B Tyrosine hydroxylase, requires BH4
Clinical Manifestations
Rarely diagnosed before 6 months of age without newborn screening
Most common manifestation without treatment is developmental delay mental retardation
Microcephaly, delayed or absent speech, seizures, eczema, and behavioral abnormalities
Musty or mousy urine odor (due to phenylacetate) often, normal at birth
Diagnosis
1. Newborn screening: measures whole blood phenylalanine (elevated by 12 -24 hours of age)
2. Follow up testing: Quantitative determination of plasma Phe and tyrosine concentrations
If low or normal tyrosine PKU. If high tyrosine transient tyrosinemia.
Brief Overview of Disease Management
Metabolic control should be achieved as rapidly as possible
Medical foods - medical protein sources low in Phe
Small amounts of Phe must also be provided - use of small amounts of natural protein
Can be given breast milk along with Phe-free formula under the direction of a metabolic dietitian
Monitoring - periodic measurement of blood Phe concentrations, assessment of growth parameters, and review of nutritional intake.
The most commonly reported blood Phe concentration recommendations: 2 to 6 mg/dL for individuals 12 years or younger, 2 to 10
mg/dL for persons older than 12years
Fetuses exposed to increased concentrations of Phe risk of microcephaly, congenital heart disease, and reduced IQ
Woman with PKU - Phe concentrations of <6 mg/dL at least 3 months before conception and maintained between 2 and 6mg/dL
throughout pregnancy
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11. Sickle Cell Disease
Sickle cell disease (SCD) - group of genetic disorders characterized by chronic hemolysis and intermittent episodes of vascular
occlusion recurrent episodes of severe pain and a wide variety of other disease manifestations
Incidence: Overall, SCD occurs in 1 of 2500 to 1 of 2000 US newborns (1 of 346 black infants, 1 of 1114 Hispanic infants in the
eastern US). Highest in persons of African, Mediterranean, Middle Eastern, Indian, Caribbean, and Central and South American
ancestry
Clinical Manifestations
Healthy at birth and become symptomatic later during infancy or childhood
Most common clinical manifestation: musculoskeletal or abdominal pain
Acute manifestations that may rapidly become life-threatening: bacterial sepsis or meningitis, splenic sequestration, acute chest
syndrome, and stroke
Other acute complications: aplastic crises, priapism, and renal papillary necrosis
Chronic manifestations: anemia, jaundice, splenomegaly, hyposthenuria, hematuria, proteinuria, cholelithiasis, and delayed growth and
sexual maturation
Pathophysiology
Sickle hemoglobin is caused by a point mutation in the -globin gene amino acid change that causes hemoglobin to polymerize
when deoxygenated
Sickle red blood cells shortened red cell survival and intermittent episodes of vascular occlusion tissue ischemia and organ
damage
Diagnosis
1. NBS: Isoelectric focusing to separate hemoglobins eluted from dried blood spots. Infants with SCD also show a predominance of
F at birth: FS, FSC, or FSA
2. Follow-up and Diagnostic Testing: Infants with possible SCD (FS, FSC, FSA) confirmatory testing of a second blood sample
accomplished before 2 months of age (isoelectric focusing, HPLC, hemoglobin electrophoresis (cellulose acetate and citrate agar),
and/or DNA-based methods)
3. Family testing to identify carriers, for the purpose of defining an infants diagnosis and/or providing genetic education and
counseling: CBC, hemoglobin separation by electrophoresis, isoelectric focusing, and/or HPLC
Brief Overview of Disease Management
Family and patient education
Health maintenance issues: prophylactic medications, particularly prophylactic penicillin (should be started no later than 2 months of
age), and timely immunizations, especially with the pneumococcal conjugate and polysaccharide vaccines
Periodic comprehensive medical evaluations
Timely and appropriate treatment of acute illness is critical
12. Tyrosinemia
Type I (hepatorenal) tyrosinemia
Liver toxicity increased tyrosine and other metabolites hepatocellular damage
J aundice and increased transaminase concentrations high risk of hepatic cancer
Other features: renal Fanconi syndrome, peripheral neuropathy
Caused by deficiency of the enzyme fumarylacetoacetate hydrolase(FAH)
Type II (oculocutaneous tyrosinemia, also known as Richner-Hanhart syndrome
Corneal lesions and hyperkeratosis of the palms and soles
Caused by deficiency of theenzyme tyrosine aminotransferase (TAT).
Neonatal tyrosinemia
More common in preterm infants
Most common cause of abnormal initial NBS results for tyrosinemia and PKU
Increased concentrations of serum tyrosine that can be detected on newborn screening
Pathophysiology
Type I: Increased concentrations of tyrosine and its metabolites inhibit transport functions and enzymatic activities
Type II: Deficiency of hepatic TAT, the rate-limiting enzyme of tyrosine catabolism. Tyrosinemia, tyrosinuria, and increases in urinary
phenolic acids, N-acetyltyrosine, and tyramine persist for life
Neonatal: Relative deficiency of p-hydroxyphenylpyruvate oxidase stressed by high-protein diets, with resulting high tyrosine and
phenylalanine concentrations. Mild decrease in TAT activity
Diagnosis
1. NBS: The BIA can be used to screen for tyrosinemia using dried blood spots. Abnormal concentrations of tyrosine >6 mg/dL.
Best if measurements are obtained 48 to 72 hours after milk feeding.
2. Follow-up testing: Determination of the concentrations of tyrosine and other amino acids and metabolites in the blood and urine
Brief Overview of Disease Management
Type 1
Dietary therapy, liver transplantation, and pharmacologic agent NTBC
Type II
Therapy with a diet low in tyrosine and phenylalanine is curative in type II tyrosinemia
Neonatal
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May be transient and controlled by reducing the protein intake to 2 to 3 g/kg per day or by breastfeeding
Some patients respond to ascorbic acid supplementation
Evaluation of Inborn Error of Metabolism (IEMs):
Sudden metabolic deterioration after a period of apparent normalcy is highly suggestive of a metabolic disorder but evaluation and
treatment for sepsis and evaluation for CHD need to be done in this metabolic crisis. During this acute period it is crucial to set aside
samples (at least 5 ml plasma and 5 ml urine) before attempting to correct metabolic abnormalities as some metabolic defects are seen
only during the crisis.
Clinical Presentation of Neonates with Inborn Errors of Metabolism
Majority present after 48 hours of age
Consider diagnosis of metabolic disease if:
Family History
Neonatal death of unclear etiology
History of child with neurological deterioration (note: majority of metabolic diseases are AR and thus typically no family history)
History of miscarriages
Consanguinity
Clinical
Decreased oral intake and or vomiting
Lethargy, coma, seizures, changes in tone or reflexes
Cardiomegaly
Hepatosplenomegaly, dysmorphic features
Cataracts
Developmental delay or failure to thrive
Asymptomatic infants who become sick typically have metabolic disorder associated with intoxication effects (e.g. organic
academia, urea cycle defect) while infants who have overwhelming abnormal neurological findings immediately at birth typically
have a metabolic disorder associated with energy deficiencies (e.g. mitochondrial disorder, nonketotic hyperglycinemia)
Laboratory Findings
Infant with hypoglycemia of unexplained etiology
Metabolic acidosis of unexplained etiology (typically increased anion gap)
Respiratory alkalosis (primary)
Abnormal liver function tests
Hyperbilirubinemia that is not consistent with physiologic jaundice or other causes
Ketonuria or ketosis
Abnormal urine odor
Hypearmmonemia
Urine reducing substances
Diagnostic Evaluation in an Infant with a Possible Metabolic Disorder:
Initial Evaluation Secondary evaluation targeted based on results from initial
evaluation
CBC to assess for neutropenia and or thrombocytopenia
Electrolytes and arterial blood gas to assess for
acidosis/alkalosis, increased anion gap
Glucose and presence/absence of urine ketones
Serum ammonia (arterial)
Lactate (arterial) and pyruvate concentration with ratio of
lactate to pyruvate
Liver function tests
Urine ketones
Check newborn screen results , if available
Others: urinalysis, urine reducing substance
Plasma amino acid analysis
Urine organic acid analysis
Plasma carnitine and acylcarnitien profile
Plasma uric acid
CSF amino acid analysis
Peroxisomal function tests
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Key Lab Finding for Neonates with IEM:
Laboratory Findings Metabolic Disease Consideration
Neutropenia, thrombocytopenia OA (propionic, isovaleric, and methylmalonic acidemia)
GSD I
Respiratory chain defects
Hemolytic anemia G6PD, pyruvate kinase
Metabolic acidosis with elevated anion gap OA (propionic, isovaleric, and methylmalonic acidemia)
FA oxidation defects (short, medium, long and very long chain abnormalities), carnitine
deficiency
Congenital lactic acidosis (pyruvate dehydrogenase complex deficiency, pyruvate carboxylase
deficiency, Mito)
Secondary lactic acidosis (hereditary fructose intolerance, GSD I, FAO, biotinidase deficiency,
propionic, methylmalonic and isovaleric acidemias, HMG CoA lyase deficiency)
Others (prematurity, HIE, severe hepatitis, portal venous obstruction, abnormal mitochondrial
oxidation fromhypoxia)
Normal anion gap Diarrhea, RTA, Galac, Tyr, some Mito
Respiratory alkalosis UCD
Plasma amino acids elevated MSUD (increased leucine, isoleucine, valine)
Organic acidemias (increased glycine)
Tyrosinemia (increased methionine and tyrosine)
Arginosuccinic acid sythethase deficiency and argininosuccinic acid lyase deficiency (increased
citrulline)
Hyperammonemia (increased glutamine)
Lactic acidosis (increased alanine)
Prolonged alimentation in premature infants
Ketotic hyperglycinemia Propionate pathway abnormalities
Ketotic hypoglycemia GSD, OA (propionic, isovaleric, and methylmalonic acidemia), short chain acyl-CoA
dehydrogenase deficiency
Hypoketotic hypoglycemia FAO (MCAD, LCHAD, hydroxymethylglutaryl CoA lyase deficiency), Carnitine deficiency
Serumammonia UCD, OA, FAO, PDH, PC
Increased creatinine kinase FAO
Increased serumuric acid GSD I
Decreased serumuric acid Molybdenum cofactor
Plasma acylcarnitine profile FFAO, OA
Plasma (Total&Free) carnitine FFAO, OA
Urine organic acids OA, FAO, Mito, PDH, PC
Urine reducing substances Galac, HFI, Try 1
Urine mucoplysaccharides Lysosomal storage disorder
Urine oligosaccharides Lysosomal storage disorder
7-dehydrocholesterol Smith Lemli Opitz syndrome
Serumtransferring glycoforms CDG
Very long-chain FA Peroxisomal disorders
Legend: CDG (congenital disorder of glycoslylation), FAO (fatty acid oxidation defect), Galac (galactosemia), GSD I (glycogen storage disease type I), G6PD (glucose
6 phospshate dehydrogenase), HFI (hereditary fructose intolerance), Mit (mitochondrial energy metabolismdefects), OA (organic aciduria), PD (pyruvate carbolylase
deficiency), PDH (pyruvate dehydrogenase), Tyr 1 (tyrosinemia type 1), UCD (urea cycle defect), UOA (urine organic acid).
Metabolic Acidosis
Increased anion gap check serumlactate Normal anion gap =hypochloremia
Abnormal bicarb loss, diarrhea,
RTA, Galac, Tyr, Some Mito
High check urine organic acid (UOA) Normal lactate check UOA
Abnormal UAO
Organic acidemia
Abnormal UOA Normal UOA
FAO, OA Check pyruvate & lactate
pyruvate & lactate; normal
pyruvate:lactate ratio check glucose
Normal or pyruvate
pyruvate:lactate ratio
Pyruvate carboxylase deficiency,
some Mito
GSD, fructose
intolerance
Low glucose Normal glucose
Pyruvate DH complex def, pyruvate
carboxylase def, some Mito
Revised 7/11/2013 Page 117 of 123
Algorithm for evaluation of hypoglycemia if IEM suspected:
Algorithm for evaluation of Hyperammonemia:
HYPERAMMONEMIA
No acidosis, no ketonuria Acidosis +ketonuria Acidosis, no ketonuria
FAO Propionic, methylmalonic and isovaleric acidemia,
Lactic academia, Glutamic aciduria, Pyruvate
carboxylase def, B-methylcrotonyl glycinuria
Plasma citrulline
Normal to moderately increased
check urine argininosuccinic acid
Very high Absent or trace check urine erotic
acid
Argininosuccinic acid synthetase def
Low or normal Low or normal
Carbamylphosphate
synthetase def
N-acely glutamate
synthetase def
Ornithine
transcarboxylase def
Absent Present
Check plasma
arginine
Argininosuccinic acid lyase def
Normal or low Elevated
Transient neonatal hyperammonemia
Lysine protein intolerance
Arginase def
HYPOGLYCEMIA assess urine for
non-glucose reducing substances
Present Absent
Galac, hereditary fructose intolerance, Tyr Check for ketones
High Low or absent
FAO (also with abnormal
UOA)
Hyperinsulinism
3OH-MH-CoA lyase def
Other glycosylation d/o
SCHAD (+ketones)
Check serumlactate and UOA Check serumlactate and UOA
Abnormal UOA Normal UOA lactate
GSD, F1-6 biphosphatase def,
phosphoenolpyruvatekinase def
Organic acidemia Potential endocrine etio
Succinyl-Co-A:3-oxoacid-
CoA transferase def
SCHAD (+ketones)
Revised 7/11/2013 Page 118 of 123
IEM Associated with Hydrops Fetalis:
Disorder Test
Hematologic Abnormality
G6PD deficiency
Pyruvate kinase deficiency
CBC with peripheral smear for hemolytic anemia.
Lysosomal Storage Disease
Mucopolysaccharidoses,
sphingolipidoses, mucolipidoses.
Urine screen for mucopolysaccharides and oligosaccharides.
Lysosomal enzyme studies.
Disorders of Steroid Metabolism
Smith-Lemli-Opitz syndrome
Mevalonic aciduria
7-dehydrocholesterol
Urine organic acids
Other
Zellweger syndrome
Congenital disorders of glycosylation
Mitochondrial disorders
Glycogen storage disease type IV
Plasma very long-chain fatty acids
Serum transferring isoforms
Serum lactate
Enzyme studies, liver biopsy
Samples to collect in a dying neonate with undiagnosed suspected IEM:
Samples collected and stored for future testing
Plasma (at least 5 ml) frozen
Urine (at least 5 ml) frozen
Dried blood spot on a newborn screening filter paper card
Postmortem tissue samples (after proper consent):
Skin biopsy in sterile saline or culture medium at room temperature (Caution: povidone-iodine is toxic to cell growth)
Liver tissue unfixed, immediately frozen below -20C
Muscle biopsy, immediately frozen below -20C
Tables from NeoReviews 2008; 9; e291-298.
SPECIAL CARE NURSERY RE-ADMISSION POLICY:
1. The EPCH NICU can accept infants from outside the hospital up to 14 days of age or less.
2. Infants may be accepted for admission if the physician feels that there is no evidence of community acquired or respiratory
infection. This would not pertain to any perinatally acquired newborn infection.
3. These infants may be admitted from another hospital, lay midwife birthing center, home, or ED.
4. This policy does not pertain to infants back-transferred from another hospital at any age unless there is evidence of infection.
5. If there is an admission of an infant who has just been discharged and they are greater than 5 days from discharge, they will
not be re-admitted to the NICU.
J uly 12, 2012
Revised 7/11/2013 Page 119 of 123
Perinatal Hypoxic-Ischemic Encephalopathy (HIE)Total Body Cooling Clinical Practice Guideline:
Adapted from Women and Infants Hospital of Rhode Islands Guidelines
Terminology: Perinatal hypoxia-ischemia is commonly used to describe infants that experience impairment of placental gas exchange
proximate to birth. Asphyxia is a more accurate term for this event and it is important to recognize that asphyxia and hypoxia-ischemia
are not physiologically equivalent. However the term asphyxia carries far greater medical-legal implications than hypoxia-ischemia
and unfortunately these concerns are often inappropriate. Given that asphyxia, hypoxia-ischemia, and ischemia are often used
interchangeably in the literature, it is best that discussions and charting be limited to the use of the term hypoxia-ischemia.
General Considerations: Newborn encephalopathy is characterized by difficulty initiating respirations at birth, and is accompanied
by decreased levels of activity, tone, reflexes, consciousness, and possibly seizures. It is a diagnosis of near-term and term infants and
is usually not considered for preterm infants since neurological features of prematurity can be similar to encephalopathy. Recognition
is typically at birth or shortly thereafter, although symptoms may evolve over the first few days. Encephalopathy is a non-specific
response to multiple different events of which intrapartum hypoxia-ischemia represents one specific type.
Diagnostic Considerations: The challenge for diagnosing perinatal HIE is two fold; first, biochemical abnormalities of placental
gas exchange, as evidenced by fetal acidemia, do not correlate well with clinically important problems(1), and second, perinatal HIE
has etiologic links to neurodevelopmental outcomes such as cerebral palsy (2). Thus, it is difficult to translate a simple physiologic
concept of hypoxia-ischemia into an easily characterized clinical diagnosis. Essential criteria have been formulated by the American
College of Obstetricians and Gynecologists (ACOG), and the International Cerebral Palsy Task Force to define an acute intrapartum
event that is sufficient to cause cerebral palsy(3).
These criteria include:
a) fetal acidemia with a prominent metabolic component (pH<7.0, BE>-12mmol/L),
b) moderate or severe encephalopathy
c) CP of the spastic quadriplegic or dyskinetic type
d) exclusion of other identifiable etiologies as outcomes such as CP can only be linked to perinatal events if moderate or
severe encephalopathy has occurred
These criteria however are focused on establishing links between perinatal events and long term outcome. Previously published criteria
by both ACOG and the AAP are probably better suited for evaluation and clinical management in the immediate neonatal period (4).
These criteria include:
a) profound fetal acidemia (pH<7.0)
b) depression at birth with Apgars of 0-3 for more than 5 minutes
c) evidence of encephalopathy
d) multi-system organ dysfunction
These criteria were also meant to provide links to outcome accounting for the severity of the parameters. More modest alterations
within these categories (eg umbilical artery pH of 7.00-7.10, 10 minute Apgar of 5 with consequent need for ventilation at birth) can
still be accompanied by important organ dysfunction that may impact neonatal management. Organ dysfunction may not be apparent
immediately after birth and the diagnosis is sometimes only established at 48-72 post birth after evolution of neurological findings and
exclusion of other causes of encephalopathy. Thus, a reasonable approach to diagnosis is a step wise sequence in which the history is
suggestive of an acute peri-partum event, followed by the presence of birth depression with fetal acidemia, and accompanied by organ
system dysfunction noted in the first 48 hours following birth. The latter may be non-CNS alone, but if encephalopathy is present, there
will invariably be other organ system dysfunction. Finally exclusion of other causes of encephalopathy is essential.
Surveillance for Organ System Dysfunction and Metabolic Abnormalities:
CNS Injury: The principal manifestation of hypoxic-ischemic cerebral injury is encephalopathy and severity is most easily
characterized using the Sarnat stages (5). This assumes that an acute event has occurred around the time of birth. Neurological
abnormalities reflecting events remote from delivery can usually be differentiated from acute processes; however,
superimposition of acute upon chronic events can be challenging to distinguish. Abnormalities of the neurological examination,
seizures and Sarnat stages are not specific for hypoxia-ischemia. An important observation is that the extent of neurological
finding may progress over the first 12-48 hours following birth. Sarnat stages are often used to provide prognostic information
as follow-up studies indicate that prognosis is very accurate when the maximal extent of encephalopathy is Sarnat stages I or III
(mild or severe) and corresponds to a good or poor outcome for death/disability, respectively. In contrast, there is a variable
outcome for infants in whom the maximal stage of encephalopathy is Sarnat II.
Renal Dysfunction: Assessment of renal function is the simplest means to assess the presence or absence of non-CNS organ
dysfunction (6,7). Parameters that can be assessed include urine output, weight, serum Na, urine analysis, and serum BUN and
creatinine. The latter should be assessed at an interval following delivery (eg, at 24 hours of age) and knowledge of the maternal
creatinine may be necessary depending on the presence of specific maternal diagnoses (eg, advanced diabetes, severe pre-
eclampsia etc).
Revised 7/11/2013 Page 120 of 123
Pulmonary Dysfunction: Persistent pulmonary hypertension of the newborn (PPHN) and meconium aspiration syndrome (MAS)
can be associated with perinatal hypoxia-ischemia. PPHN without MAS will often be self limited and resolves with
improvement in oxygenation, perfusion pressure and correction of metabolic acidemia.
Myocardial Dysfunction: Adverse effects on the myocardium are not common but can include tricuspid insufficiency, and
global ischemia. Suspicion of myocardial dysfunction can reflect obvious inability to maintain perfusion pressure or more
subtle difficulty in resolving metabolic acidemia.
Hematopoietic Abnormalities: Thrombocytopenia can occur following hypoxia-ischemia. Laboratory abnormalities of clotting
function are common but clinically apparent consumption coagulapathy is less frequent.
Hepatic Dysfunction: Biochemical abnormalities supportive of hepatic injury can occur in response to hypoxia-ischemia but
clinical manifestations are rare.
Gastrointestinal Dysfunction: Evidence of bowel hypoxia-ischemia is difficult to assess due to absence of easily monitored
laboratory parameters.
Metabolic Abnormalities: Reductions in serum concentrations of glucose, calcium and magnesium should be actively surveyed.
Changes in glucose concentrations are most common immediately after birth while changes of calcium and magnesium are more
characteristically found between 12-24 hours after birth.
Electrolyte Disturbances: Hyponatremia can occur and may reflect excess free water administration or SIADH. Hypernatremia
secondary to diabetes insipidus occurs but is rare.
Differential Diagnosis: Since the diagnosis of HIE is a composite diagnosis (perinatal events, evidence of impaired placental gas
exchange, respiratory depression at birth, and multi-organ system dysfunction), there can be multiple conditions that mimic the effects
of hypoxia-ischemia. Considerations that should be considered include:
a. Infection
b. CNS malformation
c. CNS vascular event
d. CNS trauma
e. CNS hemorrhagic lesions
f. Drug and anesthetic effects
g. Congenital neuromuscular disorders
h. Inborn errors of metabolism
Brain Imaging: Given the above differential diagnosis, brain imaging is recommended for near term and term infants manifesting
encephalopathy. Recommendations for imaging are as follows; after birth when the infant is unstable a head ultrasound can be done to
rule out hemorrhages in the periventricular area, (realizing that epidural, subdural and subarachnoid abnormalities will not be
visualized well with this imaging study). CT scans were the preferred initial study but risks of radiation exposure have limited routine
use. When the infant is stable a MRI later in the first week can establish the pattern of injury and provide additional prognostic
information for counseling. These recommendations have been endorsed by the American Academy of Pediatrics, American Society
of Pediatric Neuroradiology, and the Society for Pediatric Radiology (8). Infants that are sick enough to warrant brain cooling should
have MRI imaging performed as part of their care.
Initial Stabilization: Like any other acutely ill newborn, priorities for stabilization include securing the airway, effective ventilation,
and supporting the circulation. Of particular importance in the acute stabilization are correction of hypotension, hypoglycemia, and
metabolic acidemia. Both persistent hypotension and hypoglycemia will limit the recovery of cerebral high energy phosphorylated
metabolites (eg, ATP) following acute hypoxia-ischemia (9). The urgency in correction of metabolic acidemia is less clear. Rationale
for rapid correction of acidosis is potential deleterious effects on myocardial function and pulmonary vasomotor tone. Rapid
correction of acidosis has little effect on cerebral tissue acidosis; correction of the latter is largely dependent upon establishment of
adequate perfusion pressure and cerebral blood flow since there is limited passage of exogenous alkali across the blood brain-barrier.
An alternative approach to rapid correction is serial measurements of blood gases and pH to determine the rapidity of self-correction.
The latter may give important information regarding hemodynamic instability; metabolic acidemia is usually rapidly cleared in the
presence of adequate myocardial function.
Therapy: Management and treatment of infants with evidence of hypoxia - ischemia can be considered under categories of supportive
care and brain specific interventions.
Supportive Intensive Care
1. Correct metabolic abnormalities: This will include hypoglycemia, hypocalcemia, hypomagnesaemia, and acidosis.
Consideration can be given to addition of supplemental calcium to the IV fluid given the frequency of hypocalcemia with
moderate/severe HIE.
2. Correct hypotension/hypo-perfusion: Usual management guidelines of volume expansion followed by pressor support
should be used judiciously in these patients, and only when assessments support hypo-perfusion and persistant MAP at
less than the 5%. Consideration can be given to obtaining an echocardiogram to assess myocardial function and fluid
status.
3. Fluid management: In general fluids should be administered judiciously for infants with hypoxia-ischemia once
Revised 7/11/2013 Page 121 of 123
perfusion and blood pressure are stabilized. This approach is based on the associated renal and CNS morbidities that may
be exacerbated with excess free water administration. Consideration can be given to placement of a UVC to facilitate
fluid restriction. This will also allow simultaneous provision of high glucose concentrations to meet glucose
requirements with restricted fluids.
4. Treatment of seizures: The potential of seizures exacerbating brain injury remains a concern but without strong
corroborating human data. However this concern drives the practice of treating clinically detectable seizures; treatment
of electrographic seizures in the absence of clinical evidence is unclear. Phenobarbital and phosphenytoin are the drugs
most commonly used in neonates and have been evaluated better than other agents for effectiveness (10). Consideration
should be given to obtaining EEG studies early if there is an index of suspicion for seizures. In addition the EEG
background activity may provide helpful prognostic information .
5. Bleeding and/or thrombocytopenia: Clinical bleeding from presumed DIC is usually responsive to replacement therapy.
Whether asymptomatic thrombocytopenia secondary to hypoxia-ischemia needs to be treated is uncertain.
6. PPHN and/or MAS: Treatment and management for these conditions should reflect broader approaches to these
conditions irrespective of the etiology.
7. Treatment of cerebral edema: Cerebral edema may be suspected based upon a full/bulging fontanel, or abnormalities on
imaging. There is no evidence that intervention to reduce edema (osmotic diuretics, hyperventilation etc.) change
outcome. Experimental data supports the notion that cerebral edema is a manifestation of injury and occurs beyond the
stage when interventions may be helpful (11).
Brain Specific Therapies
1. Modest brain cooling: The NICHD Neonatal Network randomized trial of modest hypothermia demonstrated that whole
body cooling (esophageal temperature of 33.5
o
C) reduced the incidence of death and disability (moderate to severe in
extent) in near term and term infants with moderate or severe encephalopathy (12). Benefits of this therapy were not
associated with an increase in predefined serious adverse events (13). It is recommended that this therapy be offered only
to infants that fulfill the entry criteria of the above study; evidence of effectiveness and safety of this therapy for infants
who do not meet these criteria is unknown.
2. Other therapies: At this time there are no data to justify the implementation of other potential neuroprotective therapies
(eg, high dose barbiturates, magnesium, and allopurinol). Use of high dose phenobarbital for other indications, eg, control
of seizures, achieving sedation etc, need to be individualized.
Algorithm For Potential Use of Modest Hypothermia:
Inclusion Criteria: Infants will be evaluated in two steps; evaluation by clinical and biochemical criteria (Step A), followed by a
neurological exam (Step B).
Step A: All infants will be evaluated for the following:
1. History of an acute perinatal event (abruptio placenta, cord prolapse, severe FHR abnormality: variable or late
decelerations).
2. An Apgar score <5 at 10 minutes.
3. Cord pH or first postnatal blood gas pH at <1 hour <7.0.
4. Base deficit on cord gas or first postnatal blood gas at <1 hour >-16 mEq/L.
Continued need for ventilation initiated at birth and continued for at least 10 minutes.
IF BLOOD GAS IS AVAILABLE:
IF BLOOD GAS IS NOT AVAILABLE
OR pH between 7.0 and 7.15,
BASE DEFICIT 10 to 15.9mEq/L
A1 A2
Infant should have: (3 or 4 from above) Infant should have: (1 and 2 or 5 from above)
Acute perinatal event and either
Cord pH or first postnatal blood gas within 1
hour with pH <7.0
An Apgar score <5 at 10 minutes
OR OR
Base deficit on cord gas or first postnatal blood
gas within 1 hour at >16 mEq/L
Continued need for ventilation initiated at birth
and continued for at least 10 minutes
If an infant meets either A1 or A2, proceed to the neurological examination.
Step B. The presence of moderate/severe encephalopathy defined as seizures OR presence of signs in 3 of 6 categories in the table
below.
Revised 7/11/2013 Page 122 of 123
Category Moderate Encephalopathy Severe Encephalopathy
1. Level of consciousness Lethargic Stupor/coma
2. Spontaneous activity Decreased No activity
3. Posture Distal flexion Decerebrate
4. Tone Hypotonia (focal, general) Flaccid
5. Primitive reflexes
Suck
Moro
Weak
Incomplete
Absent
Absent
6. Autonomic system
Pupils
Heart rate
Respirations
Constricted
Bradycardia
Periodic breathing
Skew deviation/dilated/non-reactive to light
Variable HR
Apnea
Performance of the examination: The neurological examination should be performed by physician examiners, two attendings
or one attending and the 3rd or 2nd year pediatric resident/NNP. Examinations should be performed independently by attending and
resident/NNP and then jointly discussed. This will provide important training for the residents and NNPs. The decision of eligibility
as per the examination findings and whether to offer the treatment will be based on a joint decision of the resident or NNP and
attending. In cases where the decision to use the therapy is unclear either due to the findings of the examination or specific issues
related to the infant, consultations with other available attendings should be pursued
Timing of the examination: In general there is decreasing efficacy of neuroprotective treatments the further into the
therapeutic window treatment is started. Initial management needs are to prioritize stabilization of the airway if intubated, adjustment
of ventilator support, establishment of intravenous and/or arterial vascular access, correction of acid-base disturbances, insurance of
adequate perfusion pressure, and maintenance of a normal blood glucose concentration. Categorizing neurological findings after birth
is complex given the transitional physiology, maternal medications, evolving neurological abnormalities, and other non-CNS
conditions. Thus, appropriate attention to the above priorities is beneficial to obtaining accurate assessments of the neurological
examination since it prevents detailed judgments in the first 1-3 hours after birth. If examinations are performed too early after birth,
more infants may be needlessly exposed to treatment. Given the uncertainty of duration of the therapeutic window, neurological
examinations and a decision to initiate cooling must be made by 6 hours after birth. If an infant meets criteria A1 or A2 and criteria B
and does not meet exclusion criteria, the infant is eligible for whole body cooling.
Exclusion Criteria
a. Inability to complete the neurological examination by 6 hours of age.
b. Presence of known chromosomal anomaly.
c. Presence of major congenital anomalies.
d. Severe intrauterine growth restriction (weight <1800g).
e. Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist.
Equipment Required
a. Cincinnati Sub-Zero (CSZ) Blanketrol III Hyper-Hypothermia system with hoses
b. Patient probe jack
c. CSZ Esophageal temperature probe, 491B
d. One blanket, 25 x 33 inches
e. Two gallons of sterile or distilled water (not de-ionized)
Equipment (Item Number) Units needed
Blanketrol III, Model 223R 1/unit
Revised 7/11/2013 Page 123 of 123
Hose #286 1/Blanketrol III
Rectal/Esophageal:sterile disposable probe,
#491B
1 carton/center
Reusable Probe Adapter Cable, RJ 11 2/Blanketrol III ( includes 1 backup)
Maxi-Therm Lite Pediatric Blanket #874 (25in
x 33in)
1 Box/center
Operation of the CSZ Blanketrol Unit A separate summary is provided for operation of the cooling unit including salient features
of the system, initiation of cooling, monitoring of cooling, rewarming infants, and an algorithm for trouble shooting problems with the
cooling system.
Monitoring of Temperatures and Vital Signs during Body Cooling
a. During cooling all exogenous heat sources should be off.
b. Temperatures should be recorded from the esophageal and skin probes at 15 min intervals for the first four hours of
cooling to insure that the system is functioning properly. Of note, there is an initial overshoot in esophageal temperature
with the present system (mean sd temperature of 32.70.9
o
C in the hypothermia group of the Network trial with initial
cooling and by 2 hours increased to close to 33.5
o
C; thereafter temperature fluctuated around the set point from 33.0 to
34.0
o
C).
c. Esophageal and skin temperatures should be recorded at hourly intervals from 12 hours until 72 hours, and at hourly
intervals during reheating.
d. Measurement and recording of axillary temperatures and other vital signs should continue as per NICU policy.
Blood Gas and pH Measurements during Body Cooling Blood gases will be temperature corrected while infants are undergoing
whole body cooling. This is an arbitrary recommendation since there is no firm data to drive the decision for or against temperature
correction. Temperature correction of blood gases and pH was performed in the Network trial.
1. Follow-up of Infants with Perinatal Hypoxia-Ischemia: Given the potential link between perinatal hypoxia-ischemia and early
childhood adverse neurodevelopmental outcome, it is recommended that all infants with a moderate or severe encephalopathy of
any duration should be followed-up in the Special Care Clinic in addition to routine pediatric health maintenance. This
recommendation is irrespective of imaging findings, absence of seizures, or normal evaluation at the time of discharge. Infants
with no CNS involvement or encephalopathy limited to stage I Sarnat (mild encephalopathy) do not need follow-up unless there
are unusual findings (eg, abnormalities on MRI imaging etc).
References (available if needed)