NeoReviews August 2024

FEBRUARY
AUGUST 2021
2024
Vol. 22
25 No. 2
8
www.neoreviews.org
ARTICLES
ARTICLES
Gastroesophageal
NonimmuneRefl ux Disease
Hydrops in
Fetalis
Neonates: Facts and Figures
When Life Is Expected to Be Brief:
FetalAHeart
Case-Based Guide Category
Rate Tracing to Prenatal
II:
Collaborative
A �road Category in Need of Stra�fica�Care
on
Understanding Obstetrical Surgical
Maternal Planning
Hematologic Condi�
for the ons and
Pediatrician
Fetal/Neonatal Outcomes of Pregnancy
MATERNAL-FETAL CASE STUDIES
Obesity of
Surgical Management and Pregnancy
Appendicitis
During Pregnancy
COMPLEX FETAL CARE
Fetal Sacrococcygeal Teratoma and the
VISUAL DIAGNOSIS
A Necrotic Ulcer in anof
Development Extremely
Hydrops
Premature Infant
VISUAL DIAGNOSIS
Sudden Onset of a Unilateral Erythematous
Preauricular Mass in a Preterm Infant
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ARTICLES Editor-in-Chief: Dara Brodsky, Boston, MA
Associate Editor, IOS Cases: Elizabeth Schulz, Bethesda, MD
e475 Nonimmune Hydrops Fetalis Associate Editor, IOS Cases: Jayasree Nair, New York, NY
Associate Editor, CME: Santina A. Zanelli, Charlottesville, VA
Shannon B. Dunn, Julie R. Whittington Associate Editor, NeoQuest: Rita Dadiz, Rochester, NY
Associate Editor, Perspectives: Mamta Fuloria, Bronx, NY
e486 When Life Is Expected to Be Brief: A Case-Based Guide to Associate Editor, Maternal-Fetal Medicine: Brett Young, Boston, MA
Associate Editor, Video Corner: Akshaya Vachharajani, Columbia, MO
Prenatal Collaborative Care Assistant Editor, CME: Theodore De Beritto, Los Angeles, CA
Sharen Wilson, Krista Mehlhaff Associate Editor, Complex Fetal Care:
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Carl Backes, Columbus, OH • •
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e497 Understanding Obstetrical Surgical Planning for the
Pediatrician
EDITORIAL BOARD
Jane Brumbaugh, Rochester, MN MOC
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INDEX OF SUSPICION IN THE NURSERY Krithika Lingappan, Houston, TX
Sai Mukthapuram, Cincinnati, OH
e506 A Term Neonate with Congenital Torticollis Zeynep Salih, Carmel, IN
Thomas E. Wiswell, Honolulu, HI
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e511 A Neonate with Epileptic Encephalopathy
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ARTICLE
Nonimmune Hydrops Fetalis

Shannon B. Dunn, MD, FAAP,* Julie R. Whittington, MD, FACOG†‡
*Division of Neonatology, Orlando Health Winnie Palmer Hospital for Women and Babies, Orlando, FL
†
Department of Women’s Health, Navy Medicine Readiness and Training Command Portsmouth, Portsmouth, VA
‡
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD
EDUCATION GAP
The primary cause of hydrops fetalis is nonimmune. Although idiopathic

cases persist, advances in fetal diagnostic techniques have increased the
identification of causes, with nearly 60% diagnosed prenatally and up to
85% including postnatal evaluation. Progress in fetal therapy offers the
potential for in utero intervention, aiming to extend pregnancy and
enhance neonatal outcomes.
OBJECTIVES After completing this article, readers should be able to:
1. Describe the general pathophysiology and common etiologies of

nonimmune hydrops fetalis.
2. Describe advances in antenatal evaluation and in utero management of
hydrops fetalis.
3. Counsel pregnant people about the management, prognosis, and
outcomes of hydrops fetalis.
ABSTRACT
AUTHOR DISCLOSURE Drs Dunn and
Nonimmune hydrops fetalis (NIHF) poses a significant challenge in perinatal Whittington have disclosed no financial
care due to its high mortality rates and diverse etiologies. This comprehensive relationships relevant to this article. This
review examines the pathophysiology, etiology, antenatal diagnosis and article does not contain a discussion of
an unapproved/investigative use of a
management, postnatal care, and outcomes of NIHF. NIHF arises from
commercial product/device. The views
numerous underlying pathologies, including genetic disorders, cardiovascular expressed in this article are those of the
causes, and fetal infections, with advances in diagnostic techniques improving author(s) and do not necessarily reflect
identification rates. Management strategies include termination of pregnancy the official policy or position of the US
Navy, Department of Defense, or the
for severe cases and fetal therapy for selected treatable etiologies, and United States Government.
neonatal care involves assessing and treating fluid collections and identifying
underlying causes. Prognosis depends on factors such as gestational age at
ABBREVIATIONS
diagnosis and the extent of resuscitation needed, with challenges remaining
CDH congenital diaphragmatic
in improving outcomes for affected infants.
hernia
CPAM congenital pulmonary airway
malformation
MCA middle cerebral artery
INTRODUCTION MRI magnetic resonance imaging
Hydrops fetalis is pathologic fluid accumulation in at least 2 extravascular com- NIHF nonimmune hydrops fetalis
PCR polymerase chain reaction
partments. (1) Fluid collections most commonly involve the fetus, including pleu- TTTS twin-to-twin transfusion
ral effusion, pericardial effusion, ascites, and skin edema, but can also present as syndrome
Vol. 25 No. 8 AUGUST 2024 e475

polyhydramnios and placental thickening. (1) Hydrops feta- GENERAL PATHOPHYSIOLOGY
lis is a clinical finding that results from fluid accumulating Hydrops fetalis occurs when fluid accumulates in extravas-
in fetal tissues or body cavities when interstitial fluid pro- cular compartments because of an inability to regulate fluid
duction is greater than the rate of reabsorption by the capil- movement between the vascular and interstitial spaces, ei-
lary and lymphatic circulations. (2) This fluid production ther from an increase in production or a decrease in fluid
and removal imbalance has many potential etiologies, and reabsorption. This balance depends on hydrostatic and on-
the underlying causes are classified as immune and nonim- cotic pressures in the capillaries and interstitial space and
mune. (3) on the integrity of the capillary endothelium. It can, there-
Immune hydrops fetalis occurs secondary to an immune fore, be affected by various pathophysiologic processes that
response in the pregnant person, causing fetal red blood affect 1 or more of these factors and results in hydrops. For
cell hemolysis and fluid imbalances from severe fetal hemo- example, structural heart defects may lead to increased
lytic anemia. Since the advent of Rho (D) immune globulin, right heart pressures, resulting in increased central venous
the incidence of immune hydrops has rapidly declined. As pressure, or severe anemia may lead to high-output cardiac
a result, nonimmune hydrops fetalis (NIHF) now accounts failure and extramedullary hematopoiesis, often with associ-
for almost 90% of cases, with a reported incidence of 1 in ated hepatic dysfunction. (1)
2,000 to 3,000 pregnancies. (3) The most common diagno-
ses associated with NIHF include congenital heart disease, ETIOLOGIES OF NONIMMUNE HYDROPS
cardiac arrhythmia, chromosomal abnormalities, congenital Hydrops fetalis is a clinical finding rather than a final diag-
anomalies, congenital infectious disease, congenital anemia, nosis. NIHF is the physiologic result of many underlying
and twin-to-twin transfusion syndrome (TTTS). (4)(5) De- pathologies, and the hope of identifying the cause in each
spite advances in prenatal testing, the inability to determine unique case often depends on extensive investigative efforts
the etiology of hydrops remains common, and the progno- to establish a diagnosis. (1) A summary of the underlying
sis depends on the underlying diagnosis. pathologies and associated pathophysiologic mechanisms
Unfortunately, NIHF is associated with up to 60% of that contribute to the development of hydrops is provided
neonatal mortality, with the risk of neonatal death increas- in Table 1.
ing with earlier gestational ages and as the number of The most common etiologies of NIHF are genetic disor-
fluid collection sites increases. Significant perinatal mor- ders, including chromosomal abnormalities, monogenic ab-
bidity and implications in the pregnant person may also normalities, and inborn errors of metabolism; cardiovascular
be secondary to polyhydramnios, malpresentation, and causes, including cardiac structural abnormalities and ar-
preterm birth. (4)(6) In this review, we summarize the rhythmias; and fetal infections. Other associated conditions
pathophysiology, etiology, antenatal diagnosis and man- include hematologic abnormalities, TTTS, and fetal malfor-
agement, postnatal care, and outcomes of NIHF. mations, including extracardiac anomalies, particularly those
Table 1. Causes and Mechanisms of Nonimmune Hydrops Fetalis

ETIOLOGY CASES, % MECHANISM(S)
Genetic
Chromosomal abnormalities 45–50 Cardiac anomalies, lymphatic dysplasia, abnormal myelopoiesis
Monogenic disorders (including Multiple mechanisms, including visceromegaly, obstruction of venous return,
inborn errors of metabolism, decreased erythropoiesis and anemia, hypoproteinemia
syndromes)
Cardiovascular 15 Increased central venous pressure
Infection 10 Anemia, anoxia, endothelial cell damage, and increased capillary permeability
Hematologic 5 Anemia, high-output cardiac failure
Extracardiac malformations
Thoracic 5–8 Increased intrathoracic pressure, impaired venous return
Gastrointestinal Impaired venous return, bowel obstruction/infarction, protein loss, and
decreased colloid osmotic pressure
Urogenital Urinary ascites, nephrotic syndrome
Lymphatic dysplasia Impaired venous return
Tumors 2 Anemia, high-output cardiac failure, hypoproteinemia
Fetomaternal hemorrhage 1 Anemia, high-output cardiac failure
Idiopathic 15 Unknown
Modified with permission from Khairudin et al. (10)
e476 NeoReviews

involving the thoracic cavity, (7)(8) lymphatic dysplasia, arte- infectious contacts, travel, and professional exposures, if
riovenous malformations, and fetal tumors. (5)(8)(9)(10) Al- any, to assess the risk of fetal viral infection. In addition, a
though the number of idiopathic cases remains appreciable, detailed family history of metabolic or genetic disorders,
advancements in fetal diagnostic techniques, cytogenetics, consanguinity, developmental delays in other family mem-
and molecular biology have led to a reduction in the inci- bers, childhood or premature adult death, and ethnic ori-
dence of cases classified as idiopathic. (10)(11)(12) It seems gins should be obtained.
that a cause can be identified prenatally in nearly 60% of pa- If not previously obtained as part of routine prenatal
tients with hydrops, and this percentage increases to 85% care, the pregnant person’s blood type and Rh(D) antigen
when postnatal evaluation is added. (7)(8) status should be identified, and an antibody screen (indi-
rect Coombs test) should be performed to distinguish be-
ANTENATAL INVESTIGATION BY ETIOLOGY tween immune and nonimmune etiologies. Additional
Assessing NIHF necessitates a coordinated investigation blood studies in the pregnant person include a complete
involving obstetric, genetic, and laboratory disciplines. The blood cell count with differential indices and infectious
comprehensive evaluation is typically conducted in a ter- serologies.
tiary obstetric facility where the expertise of a maternal- All patients should undergo detailed ultrasonography
fetal medicine specialist, neonatologist, geneticist, pediatric with fetal echocardiography evaluating for anomalies of
cardiologist, pediatric palliative care specialist, pathologist, the fetus, umbilical cord, and placenta, and estimating am-
and social worker is available for consultation and counsel- niotic fluid volume. Several potential etiologies, including
ing for the family. (1) An antenatal investigation is espe- TTTS, cardiac arrhythmias, and structural anomalies, can
cially important to identify potentially treatable conditions be confirmed, or excluded, based solely on ultrasonogra-
or genetic disorders that could recur in future pregnancies, phy findings. If these studies do not reveal structural
guide management of the fetus and newborn, and steer dis- anomalies, further ultrasonography with Doppler interro-
cussions on perinatal outcomes and prognosis. gation of the middle cerebral artery (MCA) should be per-
The trimester during which hydrops is identified should formed to screen for increased flow velocity through this
guide the initial evaluation. In the first trimester, hydrops vessel, a marker of fetal anemia.
fetalis can be presumed nonimmune as a significant trans- Amniocentesis (or chorionic villus sampling if hydrops
placental passage of red blood cell antibodies from the preg- fetalis is identified before 15 weeks’ gestation) should be
nant person does not occur until approximately 13 weeks of offered to evaluate for chromosomal anomalies and con-
gestation. Greater than two-thirds of NIHF cases presenting genital infections regardless of whether a structural anom-
in the first trimester are caused by chromosomal abnormal- aly is identified on ultrasonography. Invasive testing also
ities. Counseling and evaluation at this gestational age facilitates evaluation for lysosomal storage disorders.
should focus on genetic testing. When pleural effusion or abdominal ascites are identi-
Regardless of etiology, in the second and third trimes- fied, ultrasonography-guided thoracentesis or abdominal
ters, identifying hydrops fetalis is a fetal emergency and paracentesis, respectively, can be performed to obtain fluid
should be managed accordingly. In the second trimester, for cytologic analysis.
chromosomal abnormalities remain the leading cause of
NIHF. Hydrops fetalis presenting in the third trimester is Cardiac
more likely to be secondary to cardiovascular causes or Cardiac causes of NIHF include cardiac structural abnor-
monogenic disorders rather than chromosomal abnormali- malities, arrhythmias, and cardiomyopathies. Right-sided
ties. It is also important to recognize that ultrasonography heart defects such as pulmonary valve atresia and tricus-
findings may evolve as the pregnancy progresses and to pid valve abnormalities such as Ebstein anomaly are the
remain vigilant for new information. (10) most common structural abnormalities associated with
NIHF. (2)(13) In cases of NIHF secondary to in utero heart
Overview failure from congenital heart disease, the prognosis is
It is important to elicit details of the pregnant person’s poor, with combined fetal and neonatal mortality reported
medical and obstetric histories, such as history of miscar- to be 92%. (14)
riages or other fetal losses and previous hydropic fetuses/ Tachyarrhythmias, including supraventricular tachycar-
infants, as well as details of the current pregnancy. This dia and atrial flutter, and bradyarrhythmias, as in congeni-
should also include information on recent illnesses, tal heart block, can both lead to NIHF. (5) Although fetal

cardiomyopathy is rare, it has a broad spectrum of intrin- associated with the underlying condition but can occur
sic and extrinsic causes and is overall associated with poor through a variety of the pathophysiologic mechanisms de-
prognosis. (15) scribed. For example, in both trisomy 21 and Turner syn-
Complete fetal echocardiography should be performed, drome, although congenital cardiac disease is commonly
including the use of M-mode, or motion mode, which allows associated, disordered lymphatic drainage and lymphedema
for a precise, rapid assessment of the relationship between or chylothorax may occur in the absence of a cardiac anom-
atrial and ventricular contraction to more accurately assess aly. (2) One systemic review of monogenic etiologies of
heart rate and rhythm. If fetal bradycardia is identified and NIHF found that the mechanism of hydrops can be linked
congenital heart block is suspected, autoantibody screening to fetal anemia, cardiovascular defects, neuromuscular dys-
in the pregnant person for anti–Sjogren syndrome–related function, lymphatic malformation, or skeletal dysplasia. (12)
antigen A (anti-Ro) and anti–Sjogren syndrome–related anti- Whether ultrasonography suggests a specific etiology of
gen B (anti-La) should be performed to evaluate for systemic hydrops, initial genetic testing, including fetal karyotype and/
lupus erythematosus and other autoimmune disorders or chromosomal microarray analysis, should be offered. Even
known to cause congenital heart block. (2) in the setting of severe fetal anemia as a potential explanation
for the development of hydrops fetalis, genetic testing is en-
Genetic couraged to elucidate the underlying pathology further. For
Current literature suggests that genetically transmitted dis- example, anemia may be the result of transient abnormal
orders are the most frequent cause of NIHF, accounting myelopoiesis in a fetus with trisomy 21. (17)
for nearly 75% of cases identified in the first trimester and Because genetic disorders account for many hydrops
25% to 40% of cases identified later in pregnancy. (10) cases, further evaluation is often indicated when initial ge-
Genetic disorders include chromosomal abnormalities and netic testing is normal. Further history obtained from the
monogenic disorders such as inborn errors of metabolism patient may elicit a personal or family history of genetic
and skeletal dysplasias. (10) Aneuploidy, predominantly disorders, an obstetric history of previous miscarriage, and
Turner syndrome (45, X) and trisomy 21, is the single larg- an assessment for consanguinity. It is also important to
est diagnostic category of NIHF, especially when diag- consider structural anomalies on ultrasonography because
nosed early in gestation. (1) NIHF is also associated with these may help guide the selection and interpretation of
trisomies 13 and 18 and triploidy. Other genetic syndromes further genetic tests.
associated with NIHF include Noonan syndrome, tuber- As new tests and technologies become available, there is
ous sclerosis, myotonic dystrophy, and skeletal dysplasias debate in the literature about the best use of next-generation
such as achondroplasia, achondrogenesis, osteogenesis sequencing to elucidate a genetic cause of NIHF. Norton
imperfecta, osteopetrosis, thanatophoric dysplasia, short- et al(18) compared whole exome sequencing and targeted
rib polydactyly syndrome, and asphyxiating thoracic dys- gene panels and concluded whole exome sequencing to be
plasia. (2)(5) superior in evaluating NIHF. Since becoming available,
Inborn errors of metabolism associated with NIHF in- this technology is thought to be responsible for identifying
clude mitochondrial disorders, sterol biosynthesis disorders, a specific cause of hydrops in an additional one-third of
congenital disorders of glycosylation, fatty acid oxidation previously unexplained cases. (10) However, others sug-
disorders, glycogen storage disease, peroxisomal disorders, gest a more nuanced approach guided by ultrasonography
and lysosomal storage diseases such as mucopolysacchari- findings. Specifically, targeted gene panels may be pre-
dosis type VII, Gaucher disease, GM1 gangliosidosis, and ferred for analyzing limited variants that have suspected
Niemann-Pick disease. (12)(16) As new genetic testing tech- associations with disease because they provide a higher
nologies emerge, many idiopathic NIHF cases have been depth of evaluation with fewer variants of uncertainty in a
reclassified as inborn errors of metabolism, such as lysoso- shorter turnaround time with relatively lower cost associ-
mal storage disorders and congenital disorders of glycosyla- ated. In the case that anemia is suspected by elevated
tion. (12) In fact, 1 review concluded that lysosomal storage MCA peak systolic velocity or a specific genetic condition
diseases occurred in 5% of all patients with NIHF and in is suspected based on ultrasonography findings, targeted
nearly 30% of idiopathic NIHF cases after a comprehensive gene panels may be the more appropriate next step in
evaluation for these conditions. (16) evaluation. (19) Current guidelines of the National Health
The development of hydrops fetalis in genetic disorders is Service in England recommend rapid prenatal exome se-
commonly secondary to congenital cardiac malformations quencing, R21 testing in the National Health Service
e478 NeoReviews

Genomic Test Directory, in all fetuses with NIHF and a Infections
normal microarray. (20) Congenital infections associated with hydrops fetalis in-
Lysosomal enzyme testing should be considered to eval- clude parvovirus B19, syphilis, cytomegalovirus, and toxo-
uate for lysosomal storage disorders, especially in racial plasmosis. Parvovirus is the most reported infectious
and ethnic groups with a higher incidence of these inborn cause of NIHF, with the highest risk to the fetus occurring
errors of metabolism or in patients with recurrent hydrops with infection in the early second trimester. (24) A high
fetalis. (21) If peritoneal fluid is obtained through in utero suspicion for syphilis is also important, particularly with
paracentesis, evidence of vacuolated lymphocytes in the the resurgence of congenital syphilis in recent decades,
fluid suggests glycogen storage diseases. (10) and it is important to note that serologies may be falsely
negative due to the prozone phenomenon, an immuno-
Hematologic Disorders logic phenomenon in which exceedingly high levels of
Fetal anemia can result in immune hydrops fetalis if caused antibodies interfere with the formation of the antigen-
by blood group alloimmunization but can also lead to NIHF antibody complex necessary for a positive test result,
when anemia is secondary to a variety of other causes, such seen during primary and secondary syphilis. (25)
as hemolysis, hemorrhage, or failure of red blood cell produc- If suspected by the pregnant person’s history and/or con-
tion. Causes of fetal anemia include inherited hemoglobinop- stellation of findings, serum immunoglobulin levels should be
athies, acute fetomaternal hemorrhage, TTTS, or hemorrhage obtained and compared with previous baseline levels if avail-
into arteriovenous malformations or other fetal tumors. Tran- able. If an initial rapid plasma reagent test for syphilis is nega-
sient myeloproliferative disorders or congenital leukemia may tive, nontreponemal testing should be repeated using serum
also result in anemia and fetal hydrops. (2) The most common dilutions to ensure the accuracy of results. (25) If amniotic
hemoglobinopathy associated with NIHF is a-thalassemia, an fluid is obtained through amniocentesis, it is recommended
autosomal recessive disorder seen predominantly in Southeast that PCR studies for parvovirus, toxoplasmosis, and cytomega-
Asian populations. (22) lovirus infection be performed. (1) One case report describes
Initial screening for fetal anemia is performed through the use of magnetic resonance imaging (MRI) to uncover early
ultrasonography with Doppler interrogation of the MCA. fetal neurologic involvement of cytomegalovirus infection in a
Increased peak systolic velocity through the MCA, a fetus with hydrops. (26)
marker for anemia, should prompt further evaluation, in-
cluding amniocentesis or fetal blood sampling, with the Malformations and Tumors
latter preferred if simultaneous intrauterine transfusion is Malformations present at birth often complicate NIHF, with
planned. Additional testing to investigate the etiology of certain cases involving cardiac anomalies contributing to the
anemia should include karyotype and viral polymerase onset of hydrops. Extracardiac anomalies associated with
chain reaction (PCR) studies. NIHF may be thoracic, gastrointestinal, urogenital, and/or lym-
The parents of the infant may also be screened via com- phatic. (10) Fetal thoracic abnormalities, including congenital
plete blood cell counts with indices specifically focusing on diaphragmatic hernia (CDH), congenital pulmonary airway
the mean cell volume, as a value less than 80 fL may sug- malformation (CPAM), and bronchopulmonary sequestration,
gest thalassemia carrier status and prompt a-thalassemia are among the most common malformations associated with
DNA testing. (1) If there is concern for fetomaternal hem- NIHF. Chylothorax, secondary to lymphatic obstruction or mal-
orrhage, a Kleihauer-Betke test should be performed to formation, is the most common etiology of an isolated effusion
evaluate for the presence of fetal cells in the peripheral leading to NIHF. (1)
blood of the pregnant person; the test is considered posi- Gastrointestinal malformations reported to be associated
tive when greater than 0.1% fetal red blood cells are de- with NIHF include diaphragmatic hernia, midgut volvulus,
tected. Flow cytometry can be used to more accurately gastrointestinal obstruction, jejunal atresia, malrotation of the
estimate the degree of fetal blood loss. (23) If the etiology intestines, and meconium peritonitis. (27) Intra-abdominal
of anemia is still unclear after this stepwise evaluation, masses may cause hydrops through obstruction of venous re-
consider hemoglobin electrophoresis and testing for turn, and hepatic disorders such as cirrhosis, cholestasis, and
glucose-6-phosphate dehydrogenase deficiency, pyruvate biliary atresia can cause NIHF secondary to hypoproteinemia.
kinase deficiency, and other red blood cell enzymes on fe- (28) Urogenital abnormalities associated with NIHF include
tal blood obtained through percutaneous umbilical blood ruptured bladder or renal collection system, polycystic kidney
sampling. (1) disease, and congenital nephrotic syndrome. (27) Fetal

tumors, including cystic hygromas of the neck and chest, gestational age the NIHF presents. When available and
lymphangiomas, hemangiomas, sacrococcygeal, mediastinal, medically appropriate, termination of pregnancy, should be
and pharyngeal teratomas, and neuroblastomas have been as- offered to families, particularly at lower gestational ages,
sociated with the development of NIHF. given the universal poor prognosis of NIHF and prematu-
Arteriovenous malformations involving the fetus or the rity regardless of the underlying etiology. (1) If pregnancy is
placenta have also been linked to NIHF. (1) Hemangiomas desired and continued, pediatric palliative care specialists
and other vascular tumors in the fetus can lead to NIHF, should be involved early to help guide parental goals and
likely secondary to severe anemia, hypoproteinemia, and/or decision-making on desired medical interventions and treat-
extramedullary erythropoiesis. TTTS is the result of a pla- ment limitations.
cental arteriovenous malformation in a twin pregnancy that Fetal therapy may be considered for selected etiologies of
can lead to NIHF in 1 or both fetuses and most commonly NIHF when the cause of hydrops is known, an informed de-
affects the recipient twin. Placental chorioangiomas are an- cision has been made to continue the pregnancy, and a mul-
other placental lesion that can lead to hydrops, with large tidisciplinary team including a procedurally competent
lesions acting as high-volume arteriovenous shunts. De- perinatologist has determined that a favorable outcome is
tailed anatomic ultrasonography may be all that is needed achievable. Before intervention, extensive counseling should
to diagnose some malformations, including TTTS, placental include a discussion of potential risks, benefits, and alterna-
chorioangioma, CDH, and CPAM. Advanced fetal imaging tives that accounts for the specifics of each unique case, in-
through MRI can help confirm and further characterize cluding the severity of the underlying condition and
congenital lymphatic malformations, although this has not anticipated response to intervention. Fetal therapies may in-
shown much added benefit for hemangiomas. (29) MRI clude initiation of antiarrhythmic drugs for fetal arrhythmias,
may also be useful for surgical planning in the case of fetal corticosteroids or needle drainage of CPAM, laser ablation of
tumors, CDH, CPAM, and other malformations. TTTS, or intrauterine transfusion for fetal anemia (Table 2).
Special tests on pleural or ascitic fluid, when obtained In addition, in the case of severe polyhydramnios,
through ultrasonography-guided fetal procedures, may help which can cause significant discomfort to the pregnant
elucidate the etiology of NIHF. Considerations should be person from uterine distention and prompt preterm labor
made to send pleural fluid for virology, protein concentra- and delivery, amnioreduction may be performed for both
tion, and cell count to differentiate between exudate and palliation and prolongation of pregnancy. (30)
transudate. Peritoneal fluid can also be sent for protein con- The optimal delivery timing has not been determined,
centration, cell counts, and liver function testing. Lymphoid- and there are no management trials on which to base rec-
predominant cell counts suggest chylous fluid in either cav- ommendations. In addition, considering the wide spec-
ity. Elevated g-glutamyl transferase in the peritoneal fluid trum of etiologies and severity of NIHF, it is best to
suggests bowel perforation, whereas low total protein level evaluate each case individually. Experts generally agree
suggests urinary ascites secondary to rupture of the bladder that if NIHF develops or worsens around 34 weeks of ges-
or renal collecting system. (10) tation, it is reasonable to consider delivery. In the absence
of clinical decline or other reasons for earlier intervention,
Idiopathic delivery between 37 and 38 weeks’ gestation is recom-
Although still appreciable, the incidence of idiopathic mended. If preterm delivery is indicated or if fetal therapy
NIHF is decreasing as our understanding of cytogenetics is planned between 24 and 34 weeks’ gestation, the ad-
and molecular biology increases. Yet, despite technological ministration of antenatal corticosteroids for fetal lung ma-
progress enabling diagnosis in more cases of hydrops feta- turity should be considered. In some cases, drainage of
lis, ongoing research is necessary to devise methods for fetal pleural effusions and/or ascites may be required to
early detection of a prodromal stage of NIHF. This would relieve intrathoracic or intra-abdominal pressure and facili-
enable timely, condition-specific therapeutic interventions tate delivery, ideally allowing for improved spontaneous
before catastrophic fetal hydrops ensues. breathing effort and delaying the need for assisted ventila-
tion and emergency thoracentesis or paracentesis in the
IN UTERO MANAGEMENT delivery room.
The cornerstone of counseling and management for NIHF In certain circumstances, prompt delivery may be indi-
is a thorough assessment of the underlying etiology, specifi- cated for pregnancy-related reasons, as is recommended in
cally whether a treatable cause is identified and at what the setting of mirror syndrome in the pregnant person, a
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Table 2. Fetal Therapies Considered for Specific Etiologies in Nonimmune Hydrops Fetalis
ETIOLOGY THERAPY
Cardiac Cardiac tachyarrhythmia (eg, supraventricular Administration of antiarrhythmic medications to the
tachycardia, atrial fibrillation, or atrial flutter) pregnant person or transplacentally (ie, intra-amniotic)
Critical aortic stenosis with evolving Fetal aortic valvuloplasty
hypoplastic left heart syndrome
Pulmonary atresia with intact ventricular Fetal pulmonary valvuloplasty
septum
Thoracic Hydrothorax, chylothorax 1/- Needle drainage of effusion
bronchopulmonary sequestration, or Possibility of repeated thoracentesis or thoracoamniotic
macrocystic congenital pulmonary airway shunt in severe progressive cases to minimize the risk
malformation of pulmonary hypoplasia resulting from intrathoracic
compression
If advanced gestational age, consider needle drainage
before delivery
Microcystic congenital pulmonary airway Administration of corticosteroids to a pregnant person
malformation
Urinary tract Megacysts with normal renal function Vesicoamniotic shunt or fetal cystoscopy
suggested by urinary electrolytes
Hematologic Fetomaternal hemorrhage or parvovirus B19 Fetal blood sampling followed by intrauterine blood
causing fetal anemia transfusion
Tumors Chorioangioma, teratoma In utero resection, radiofrequency ablation, targeted laser
Head and neck Ex utero intrapartum treatment procedure
Infection Cytomegalovirus, herpes simplex, Toxoplasma Antibiotics or antivirals to pregnant person
gondii, Treponema pallidum
Genetic or metabolic Thalassemia, lysosomal storage disorders In utero enzyme replacement therapy, stem cell therapy,
gene therapy
Monochorionic Twin-to-twin transfusion syndrome Fetoscopic laser ablation of placental anastomoses or
twin pathology selective termination
Twin anemia polycythemia sequence Fetoscopic laser ablation, selective termination, or fetal
exchange transfusion/transfusion
Twin reversed arterial perfusion sequence Targeted intrafetal laser or radiofrequency ablation
Modified with permission from Khairudin et al. (10)
rare but significant pregnancy complication of NIHF in an underlying cause if one has not yet been detected. Chest
which the pregnant person develops hypertension, pro- radiography to evaluate for pleural effusions and pulmonary
teinuria, and generalized edema, essentially mirroring the hypoplasia is an important first step. Skeletal anomalies asso-
edema of the fetus. (10) ciated with genetic syndromes may also be identified on
plain radiographs. Lung ultrasonography or MRI can also
NEONATAL AND PALLIATIVE CARE help characterize effusions or further evaluate an existing
Antenatal consultation with neonatal and pediatric palliative intrathoracic anomaly such as CPAM. Cranial and abdomi-
care specialists should be arranged to discuss the family’s in- nal ultrasonography will evaluate structural anomalies and
dividualized birth vision and goals of care, including delivery should include Doppler studies to assess for arteriovenous
planning and the potential for redirection in the delivery malformations. Drained ascitic or pleural fluid should be
room or later in the NICU stay if an underlying life-limiting sent for culture and viral PCR studies, total protein and al-
cause is identified. If a trial of resuscitation is appropriate, bumin levels, and cell counts. If possible, blood should be
and desired by the parents, a skilled neonatal resuscitation obtained for complete blood cell count and reticulocyte
team should be prepared to perform advanced resuscitative count, blood typing, serum total protein and albumin levels,
measures in the delivery room. Often, it is necessary to re- immunoglobulin studies, fetal chromosome studies, hemo-
move fluid from the pleural space and/or abdomen to im- globin electrophoresis, and newborn metabolic screening
prove ventilation. If fetal anemia is present, placement of an before receipt of any blood products. In addition, it is im-
umbilical venous line for an emergency blood transfusion portant to monitor fetal blood gases closely throughout the
may be necessary. Once resuscitation is complete, a thor- initial period of stabilization.
ough physical examination should be conducted for evidence Examination of the placenta after delivery can provide di-
of fetal anomalies to further guide the postnatal evaluation. agnostic information, including identification of pathologies
Postnatal evaluation should focus on identifying treatable such as chorioangioma or vascular abnormalities that may
fluid collections and other pathologies, as well as identifying be the primary cause of NIHF. A postnatal echocardiogram

should be performed to evaluate cardiac structure and func-
and targeted gene panels, many idiopathic NIHF
tion, including chamber size and myocardial contractility.
cases have been reclassified as monogenic
Electrocardiography can help further evaluate for disorders
disorders, most commonly inborn errors of
of cardiac rate and rhythm. Moreover, genetic consultation,
metabolism, such as lysosomal storage disorders
and additional testing if available and indicated, is an im-
and congenital disorders of glycosylation.
portant consideration of postnatal evaluation.
• Fetal therapy, including initiation of
PROGNOSIS AND OUTCOMES antiarrhythmic drugs for fetal arrhythmias,
corticosteroids or needle drainage of congenital
Unfortunately, the identification of NIHF has serious implica-
pulmonary airway malformation, laser ablation of
tions for perinatal morbidity and mortality, regardless of the
twin-to-twin transfusion syndrome, or intrauterine
gestational age at diagnosis. However, outcomes are much
transfusion for fetal anemia, may be considered
more guarded the earlier in pregnancy NIHF is identified,
for selected etiologies of NIHF. When indicated,
with 1 retrospective cohort study reporting miscarriage or later
fetal intervention has been associated with lower
in utero demise in 2 of every 3 pregnancies with NIHF identi-
perinatal mortality.
fied during the first trimester, half of the cases identified dur-
ing the second trimester, and 1 in 6 cases identified during • Consultation with neonatal and pediatric palliative
the third trimester. (31) Among infants who survived to deliv- care specialists should be arranged antenatally
ery, 4 of 10, 2 of 10, and one-quarter died during the neonatal whenever possible. Postnatal evaluation should
period when NIHF was identified in the first, second, and focus on identifying treatable fluid collections and
third trimesters, respectively. (31) other pathologies, as well as identifying an
Various factors have been suggested to affect prognosis. underlying cause if one has not yet been
Studies have suggested that factors affecting prognosis in- detected.
clude the underlying etiology of NIHF, the gestational age • As technological advances allow for diagnosis in a
at detection and delivery, Apgar scores at birth, extent of larger number of hydrops fetalis cases, further
resuscitation required in the delivery room, greater than research is still needed to develop techniques for
or equal to 2 serous cavity effusions, presence of pleural early identification of impending NIHF to allow for
effusion, and a serum albumin level less than 2 g/dL timely intervention before hydrops occurs.
(<20 g/L). (14)(32)(33) Interestingly, although a close cor-
relation between serum albumin concentration and sever-
ity of hydrops fetalis has been suggested in the literature,
aggressive albumin transfusion in the postnatal period has
not been proved to be effective. (32)
American Board of Pediatrics
Summary Neonatal-Perinatal Content
• Hydrops fetalis is a clinical finding that is the Specification
result of fluid accumulating in fetal tissues or body • Know the differential diagnosis and the plan of evalua-
tion and management of a fetus with nonimmune
cavities when the production of interstitial fluid
hydrops.
exceeds the rate of reabsorption by the capillary
and lymphatic circulations.
• The most common etiologies of nonimmune
hydrops fetalis (NIHF) are genetic disorders, References
including chromosomal abnormalities, monogenic
1. Norton ME, Chauhan SP, Dashe JS; Society for Maternal-Fetal
abnormalities, and inborn errors of metabolism; Medicine (SMFM). Society for maternal-fetal medicine (SMFM)
cardiovascular causes, including cardiac structural clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet
Gynecol. 2015;212(2):127–139
abnormalities and arrhythmias; and fetal infections.
2. Murphy JH. Nonimmune hydrops fetalis. NeoReviews. 2004;5(1):
• With the advent of new genetic testing e5–e15
technologies, such as whole exome sequencing 3. Santolaya J, Alley D, Jaffe R, Warsof SL. Antenatal classification of
hydrops fetalis. Obstet Gynecol. 1992;79(2):256–259
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4. Tolia VN, Hunter Clark R Jr, Perelmuter B, et al. Hydrops fetalis- 19. Han J, Li DZ. Further genetic testing in prenatal cases of
trends in associated diagnoses and mortality from 1997–2018. nonimmune hydrops fetalis with a normal array: a targeted panel or
J Perinatol. 2021;41(10):2537–2543 exome? Am J Obstet Gynecol. 2022;226(2):276–277
5. Abrams ME, Meredith KS, Kinnard P, Clark RH. Hydrops fetalis: a 20. Hill M, Ellard S, Fisher J, et al. Optimising Exome Prenatal
retrospective review of cases reported to a large national database Sequencing Services (EXPRESS): a study protocol to evaluate rapid
and identification of risk factors associated with death. Pediatrics. prenatal exome sequencing in the NHS Genomic Medicine Service.
2007;120(1):84–89 NIHR Open Res. 2022;2:10
6. Yeom W, Paik ES, An JJ, et al. Clinical characteristics and perinatal 21. Sheth J, Mistri M, Shah K, Chaudhary M, Godbole K, Sheth F.
outcome of fetal hydrops. Obstet Gynecol Sci. 2015;58(2):90–97 Lysosomal storage disorders in nonimmune hydrops fetalis (NIHF):
an Indian experience. JIMD Rep. 2017;35:47–52
7. Santo S, Mansour S, Thilaganathan B, et al. Prenatal diagnosis of
non-immune hydrops fetalis: what do we tell the parents? Prenat 22. Suwanrath-Kengpol C, Kor-anantakul O, Suntharasaj T, Leetanaporn
Diagn. 2011;31(2):186–195 R. Etiology and outcome of non-immune hydrops fetalis in southern
Thailand. Gynecol Obstet Invest. 2005;59(3):134–137
8. Bellini C, Hennekam RC, Fulcheri E, et al. Etiology of nonimmune
hydrops fetalis: a systematic review. Am J Med Genet A. 2009; 23. Wylie BJ, D’Alton ME. Fetomaternal hemorrhage. Obstet Gynecol.
149A(5):844–851 2010;115(5):1039–1051
9. Bellini C, Hennekam RC. Non-immune hydrops fetalis: a short 24. Enders M, Klingel K, Weidner A, et al. Risk of fetal hydrops and
review of etiology and pathophysiology. Am J Med Genet A. non-hydropic late intrauterine fetal death after gestational parvovirus
2012;158A(3):597–605 B19 infection. J Clin Virol. 2010;49(3):163–168
10. Khairudin D, Alfirevic Z, Mone F, Navaratnam K. Non-immune 25. Berkowitz K, Baxi L, Fox HE. False-negative syphilis screening: the
prozone phenomenon, nonimmune hydrops, and diagnosis of
hydrops fetalis: a practical guide for obstetricians. Obstet Gynaecol.
syphilis during pregnancy. Am J Obstet Gynecol. 1990;163(3):975–977
2023;25(2):110–120
26. Salmaso R, Franco R, de Santis M, et al. Early detection by magnetic
11. Wei X, Yang Y, Zhou J, et al. An investigation of the etiologies of
resonance imaging of fetal cerebral damage in a fetus with hydrops
non-immune hydrops fetalis in the era of next-generation
and cytomegalovirus infection. J Matern Fetal Neonatal Med.
sequence—a single center experience. Genes. 2022;13(12):2231
2007;20(7):559–561
12. Quinn AM, Valcarcel BN, Makhamreh MM, Al-Kouatly HB, Berger
27. Randenberg AL. Nonimmune hydrops fetalis part I: etiology and
SI. A systematic review of monogenic etiologies of nonimmune
pathophysiology. Neonatal Netw. 2010;29(5):281–295
hydrops fetalis. Genet Med. 2021;23(1):3–12
28. Hutchison AA, Drew JH, Yu VY, Williams ML, Fortune DW,
13. Machin GA. Hydrops revisited: literature review of 1,414
Beischer NA. Nonimmunologic hydrops fetalis: a review of 61 cases.
cases published in the 1980s. Am J Med Genet. 1989;34(3):
Obstet Gynecol. 1982;59(3):347–352
366–390
29. Crivelli L, Millischer AE, Sonigo P, et al. Contribution of magnetic
14. Randenberg AL. Nonimmune hydrops fetalis part II: does etiology
resonance imaging to the prenatal diagnosis of common congenital
influence mortality? Neonatal Netw. 2010;29(6):367–380 vascular anomalies. Pediatr Radiol. 2021;51(9):1626–1636
15. Pedra SR, Smallhorn JF, Ryan G, et al. Fetal cardiomyopathies: 30. Dickinson JE, Tjioe YY, Jude E, Kirk D, Franke M, Nathan E.
pathogenic mechanisms, hemodynamic findings, and clinical Amnioreduction in the management of polyhydramnios
outcome. Circulation. 2002;106(5):585–591 complicating singleton pregnancies. Am J Obstet Gynecol.
16. Gimovsky AC, Luzi P, Berghella V. Lysosomal storage disease as an 2014;211(4):434.e1–434.e7
etiology of nonimmune hydrops. Am J Obstet Gynecol. 2015;212(3): 31. Sileo FG, Kulkarni A, Branescu I, et al. Non-immune fetal hydrops:
281–290 etiology and outcome according to gestational age at diagnosis.
17. Malin GL, Kilby MD, Velangi M. Transient abnormal myelopoiesis Ultrasound Obstet Gynecol. 2020;56(3):416–421
associated with Down syndrome presenting as severe hydrops 32. Huang HR, Tsay PK, Chiang MC, Lien R, Chou YH. Prognostic
fetalis: a case report. Fetal Diagn Ther. 2010;27(3):171–173 factors and clinical features in liveborn neonates with hydrops
18. Norton ME, Ziffle JV, Lianoglou BR, Hodoglugil U, Devine WP, fetalis. Am J Perinatol. 2007;24(1):33–38
Sparks TN. Exome sequencing vs targeted gene panels for the 33. Meng D, Li Q, Hu X, et al. Etiology and Outcome of non-immune
evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. Hydrops Fetalis in Southern China: report of 1004 cases. Sci Rep.
2022;226(1):128.e1–128.e11 2019;9(1):10726

NEOREVIEWS QUIZ
NEO
QUIZ
CME QUIZ
1. Hydrops fetalis is defined as the pathologic accumulation of fluid in at least

2 extravascular compartments. Hydrops fetalis is typically categorized as
immune and nonimmune hydrops, with nonimmune hydrops fetalis (NIHF)
now representing more than 90% of cases. Hydrops fetalis regardless of
etiology is associated with significant morbidity and mortality. What is the
overall neonatal mortality associated with NIHF?
A. 20%.
B. 30%.
C. 40%. REQUIREMENTS: Learners can
D. 50%. take NeoReviews quizzes and
E. 60%. claim credit online only at:
https://publications.aap.org/
2. Hydrops fetalis is a clinical diagnosis based on the presence of fluids in 2 or neoreviews.
more extravascular compartments, most commonly pleural effusions, ascites,
To successfully complete 2024
and skin edema. Multiple underlying pathologies can lead to hydrops fetalis,
NeoReviews articles for AMA PRA
and identifying the cause is important to optimize the care of these complex Category 1 Credit™, learners
patients. With advancements in diagnostic evaluations, the incidence of must demonstrate a minimum
hydrops fetalis classified as idiopathic has decreased significantly. Which one performance level of 60% or
of the following statements regarding the identification of a cause for higher on this assessment. If
you score less than 60% on the
hydrops fetalis is CORRECT?
assessment, you will be given
A. Prenatal evaluations lead to the identification of a cause in 40% of additional opportunities to
answer questions until an
patients with hydrops fetalis.
overall 60% or greater score is
B. Overall, a cause is identified in 85% of patients with hydrops fetalis. achieved.
C. Overall, 40% of patients with hydrops fetalis remain classified as
idiopathic. This journal-based CME activity
D. A combination of prenatal and postnatal diagnostic testing results in is available through Dec. 31,
2026, however, credit will be
the identification of a cause in 60% of patients with hydrops fetalis.
recorded in the year in which
E. When whole exome sequencing is performed, a cause of hydrops fetalis the learner completes the quiz.
is identified in 90% of patients.
3. Multiple conditions can lead to NIHF, including cardiovascular causes,
genetic disorders, congenital infections, congenital anemia, and twin-to-twin
transfusion syndrome. According to the current literature, what is the most
common cause of NIHF?
2024 NeoReviews is approved
A. Genetic disorders. for a total of 10 Maintenance of
B. Congenital heart diseases. Certification (MOC) Part 2
C. Congenital infections. credits by the American Board
of Pediatrics (ABP) through the
D. Cardiac arrhythmia.
AAP MOC Portfolio Program.
E. Fetal anemia. NeoReviews subscribers can
claim up to 10 ABP MOC Part 2
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go to: https://publications.aap.
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e484 NeoReviews

4. You are taking care of a 39 weeks’ gestational age neonate with NIHF. Initial
diagnostic evaluations reveal a normal cardiac echocardiogram and cardiac
rhythm, the absence of anemia, and no dysmorphic features or associated
congenital anomalies. In addition, prenatal whole exome sequencing was
unrevealing. You suspect a congenital infection. Which one of the following
congenital infections is the most commonly reported cause of NIHF?
A. Syphilis.
B. Toxoplasmosis.
C. Parvovirus B19.
D. Cytomegalovirus.
E. Hepatitis C.
5. NIHF is associated with high mortality in the newborn period. Multiple
factors affecting the prognosis of NIHF have been identified. All of the
following factors have been shown to negatively affect the prognosis of
patients with hydrops fetalis EXCEPT:
A. Earlier detection in pregnancy.
B. Presence of a pleural effusion.
C. Lower gestational age at birth.
D. Serum albumin level less than 1.5 g/dL (<15 g/L).
E. Need for significant resuscitation in the delivery room.

ARTICLE
When Life Is Expected to Be Brief:

A Case-Based Guide to Prenatal
Collaborative Care
Sharen Wilson, DO,* Krista Mehlhaff, DO†
*Department of Neonatology and
†
Department of Maternal-Fetal Medicine, University of Maryland Medical Center, Baltimore, MD
EDUCATION GAPS
A perinatal palliative care program can be created at any institution to

ensure quality, compassionate, and equitable care to the pregnant person
carrying a fetus with a life-limiting condition.
1. Describe the role of palliative care in pregnancies where the life of the
fetus is expected to be short.
2. Apply palliative care concepts to prenatal counseling, birth planning,
and postnatal care planning.
3. Be able to assist the family in creating a birth plan when the life of the
fetus is expected to be short.
4. Provide case-based examples of the application of a palliative care program
during delivery and postnatal care.
ABSTRACT
Advances in fetal health detection and neonatal care have improved outcome
predictions but have outpaced the development of treatments, leaving some
families facing the heartbreaking reality of their baby’s short life expectancy.
Families with a fetus that has a life-limiting condition must make tough
AUTHOR DISCLOSURES Drs Wilson and decisions, including the possibility of termination, perinatal palliative care
Mehlhaff have disclosed no financial options, and the extent of newborn resuscitation. Access to abortion services
relationships relevant to this article. This
is crucial in decision-making, underscoring the significance of palliative care as
commentary does not contain a
discussion of an unapproved/ an option. Perinatal palliative care programs offer vital support, honoring the
investigative use of a commercial baby and family throughout pregnancy, birth, and death. They provide
product/device.
compassionate care for pregnant individuals, partners, and newborns,
integrating seamlessly into standard pregnancy and birth care. Successful
ABBREVIATIONS
programs prioritize families’ desires, goals, and personal priorities, whether
HELLP hemolysis, elevated liver through a dedicated team or an organized system.
enzymes, and low platelets
LLFC life-limiting fetal condition “Regardless of the length of a baby’s life or duration of illness, it is their
PPC perinatal palliative care lifetime. The infant and family deserve skilled and compassionate attention to
e486 NeoReviews

their plight; a safety net throughout the experience; a palliative care approach emphasizing living fully those days,
hours, and even moments.” (1)
INTRODUCTION fetus A with cervical myelomeningocele, and a large ompha-

“Healthy mom, healthy baby” is a catchphrase occasionally locele in the shared torso (involving liver and bowel). The
used during labor and delivery counseling. However, expe- pregnant patient had a surgical history significant for 1 previ-
rienced obstetricians and neonatologists know that this ous low transverse cesarean delivery due to breech presenta-
saying does not apply to all birthing individuals. During tion at term. The family expressed that their goals were to
the past 70 years, advances in neonatal care and fetal meet the babies alive (if possible), dignity for their babies in
health detection have significantly improved the prediction birth and death, for the infants not to suffer unnecessarily,
of neonatal outcomes. Unfortunately, the ability to diag- and for their other child to meet the twins. The pregnant pa-
nose fetal conditions has outpaced the development of tient wanted to carry the pregnancy as long as possible and
treatments, leaving some families facing the devastating declined termination. The palliative care team’s goals were to
ensure that the family had a clear understanding of the com-
knowledge that their baby will not survive long after deliv-
plexity of fetal conditions, to prioritize maternal health and
ery. In such situations, families have a difficult choice, in-
safety during the pregnancy and delivery, to coordinate
cluding termination, continuation of the pregnancy with
multidisciplinary delivery plans due to the complexity of
newborn resuscitation attempts, or perinatal palliative care
fetal conditions, and to meet the family’s goals.
(PPC). Access to termination services plays a critical role
The delivery plan was formulated after meetings with
in decision-making, making palliative care an increasingly
the multidisciplinary team, including the obstetrician, neo-
vital option for many pregnant individuals. PPC programs
natologist, anesthesiologist, nursing, palliative care special-
offer essential support, honoring the baby and the family
ist, social worker, and family. The plan was for cesarean
throughout the pregnancy, birth, and death. These programs
delivery with vertical hysterotomy, attempt en caul delivery
provide compassionate care for pregnant individuals, part-
to minimize manipulation of exposed organs during deliv-
ners, and newborns and can be integrated into pregnancy
ery, and have the neonatology team scrubbed at the table
and birth care with flexibility based on the patient’s needs.
to provide immediate pain assessment and management
Whether with a small, dedicated team or an organized sys-
as indicated. A transition table (ie, a Mayo stand with a
tem, successful programs prioritize families’ and pregnant
sterile cover) was used to place the babies on after delivery
individuals’ desires, goals, and personal priorities.
for the neonatologist to perform a quick assessment of the
We present 2 cases illustrating the application of a pal-
twins and ensure that there were no signs of distress. The
liative care framework in a low-volume hospital setting
neonates would then be placed in a polyethylene plastic
(1,000 deliveries per year).
bag to cover their lower extremities and thoracoabdominal
regions due to the omphalocele. They would then be swad-
CASE 1
dled with dark towels to mask any serosanguinous fluid
A 30-year-old gravida 2 para 1 woman was diagnosed as for the family’s comfort. In addition, based on best-estimated
having thoracopagus conjoined twins at 14 weeks’ gesta- fetal weights, morphine was prepared ahead of the delivery in
tion. She had low-risk noninvasive prenatal testing. The the event of perceived imminent distress, per NICU guide-
couple met with genetics, who recommended additional lines for palliative care support. Multiple factors contributed to
genetic testing, but the family declined. The couple was the shared decision to deliver at 32 weeks’ gestation, including
counseled regarding complex anomalies resulting from minimizing potential complications in the pregnant patient
conjoined twin anatomy, including an anomalous shared with advancing gestational age, accommodating parental goals
heart. In consultation with a conjoined twin specialist at a of meeting the infants alive, having additional family support
tertiary referral center, the fetal anomalies were incompatible (traveling from out-of-town), and the desire to continue the
with surgical separation and likely to result in an inability to pregnancy as long as possible.
survive long after birth. Fetal anatomic challenges included Cesarean delivery was conducted, as planned. Addi-
complex congenital heart disease, shared liver, the umbilical tional support for the family included ambient tranquil
cord of 1 fetus was directly inserted into the shared liver, music and an otherwise serene and quiet room during de-
short umbilical cord (6 cm), suspected limb body wall defect, livery. A chaplain and a photographer were present, at the

family’s request, and the infants were transferred to the suffering after birth, and having dignity for their infant. Pro-
father soon after birth. A chair was set up next to the vider goals included ensuring that counseling regarding
mother, and the anesthesia team positioned her head to al- treatment options and prognosis was understood, informed
low her to see and touch her twins. The infants survived decisions were being made, and the family’s goals were be-
for 20 minutes after birth and were baptized, according to ing met. Prenatal care was focused on monitoring the fe-
parental wishes. After delivery, a child life specialist, the tus’s well-being, alternating between frequent visits with
family, and the parents’ older son (2 years old) returned to pediatric cardiology and maternal-fetal medicine for fetal
the postpartum recovery room for further visitation and to echocardiograms, and serial growth ultrasonography.
create memories. The family bathed the babies with assis- The pregnant patient chose to wait for the onset of
tance from the nursing team. The crib was kept in the room spontaneous labor. The patient arrived in active labor at
for the family to spend additional time with the twins there- 39 weeks’ gestation and had an uncomplicated vaginal de-
after. The infants were dressed in clothing selected by the pa- livery. Postdelivery care was provided by obstetric nurses
rents and covered in blankets. After discharge, the mother with experience in palliative care, neonatology, and the ob-
followed up with her obstetrician and a social worker within stetric team, and the neonate was frequently monitored by
1 week. The palliative care team members provided imme- neonatology to ensure that comfort goals were being met.
diate postpartum grief support for the parents, and psy- The parents held and comforted their baby as memories
chologists provided ongoing support. The patient received were created with family members and accommodations
preconception counseling 3 months after giving birth, and were made to have their other children spend time with their
she returned 1 year later for prenatal care and the uncom- sister. The mother had postpartum care with her obstetrician
plicated delivery of a full-term singleton. and dedicated preconception counseling 3 months after deliv-
ery. She declined a psychology referral and sought counsel-
CASE 2 ing through her community. She returned 1 year later for
A 32-year-old gravida 6 para 5 woman with a prenatal diag- prenatal care and had an uncomplicated delivery of a term
nosis of hypoplastic left heart syndrome and intact atrial infant.
septum was diagnosed at a detailed anatomic survey at
20 weeks’ gestation. Initial counseling was conducted with a PRENATAL DIAGNOSIS
pediatric cardiologist and a maternal-fetal medicine physician. Approximately 1 in 33 infants born in the United States
The patient’s obstetric history included 1 low transverse cesar- annually are affected by birth defects. (2)(3) Birth defects
ean delivery with her second pregnancy, followed by 3 subse- are a leading cause of neonatal deaths, accounting for ap-
quent vaginal births after cesarean delivery. At 28 weeks’ proximately 20% of all infant deaths. (4) Life-limiting fetal
gestation, the pregnant patient was referred to a specialty conditions (LLFCs) include fetal conditions for which
surgical consultation for consideration of an experimental there is little or no prospect of long-term ex utero survival
in utero surgery. After evaluation, it was determined that without severe morbidity or extremely poor quality of life
she was not a candidate for the experimental procedure. At and for which there is no cure. (5) An LLFC may be evident
32 weeks’ gestation, secondary pulmonary lymphangiectasia from fetal imaging or genetic testing, but this diagnosis
(nutmeg lungs) was observed on fetal magnetic resonance often requires interdisciplinary input from maternal-fetal
imaging. Pediatric cardiology met with the couple again medicine specialists, geneticists, or pediatric subspecial-
and noted that the prognosis was now extremely poor and ists. (5) Prenatal diagnosis is an ever-evolving science
the infant was unlikely to survive, even with a postnatal with continued advances in technology and medical treat-
septostomy. The family elected for no invasive neonatal ments both in utero and postnatally. Although the techni-
care (ie, declined postnatal septostomy and intubation). cal ability to diagnose an LLFC prenatally is high, it is an
After extensive counseling with a multidisciplinary team, imperfect science. (7) One retrospective analysis of a pre-
including pediatric cardiology, neonatology, maternal- selected group of patients who were referred for counseling
fetal medicine, nursing, and social work, the family due to a suspected prenatal diagnosis of an LLFC (n 5 49)
elected for a trial of labor without continuous fetal moni- found that postnatal diagnosis was confirmed in 45 infants.
toring and palliative care after birth. The family’s goals (5) The 4 surviving infants with discrepancies between pre-
included meeting their baby alive and spending as much natal and postnatal diagnosis had substantial comorbid con-
time as possible with the baby, having a strong desire ditions. (5) In addition, there also have been case reports of
for their other children to meet their daughter, limiting prenatal genetic diagnoses that were not as phenotypically
e488 NeoReviews

severe as anticipated, which highlights the need to ac- The process often begins at the onset of an LLFC diagno-
knowledge prognostic uncertainty that may exist and sis. These diagnoses are an ever-moving target as advances
seek out postnatal confirmation of the diagnosis, when in intrauterine therapies, gene therapies, and postnatal care
appropriate. (5) evolve (Table 1). The palliative care team may consist of so-
LLFCs are unique in medical decision-making because cial workers, registered nurses, child life specialists, genetic
2 patients, the pregnant person and the fetus, may have counselors, neonatologists, clinical psychologists, obstetri-
competing best interests. Termination should be offered, cians, midwives, maternal-fetal medicine specialists, spiritual
but terminating a desired pregnancy for LLFCs can be dif- leaders as requested by family, doulas, and, if available, a pal-
ficult for many pregnant persons. (8) In addition, access liative care–trained physician. Importantly, this list may in-
to such services has become increasingly limited for many clude additional members who can aid the patient, family,
in the United States. (9) Factors that have been identified and team based on the conditions and further desires of the
include hope, morality, and potential implications on their family. Increasingly, teams are seeking specialized training
own and others’ quality of life. (10) Ultimately, approxi- in palliative care. Similar to other multidisciplinary groups,
mately half of the pregnant people with an LLFC decide to maintaining a shared mental framework, documenting plans
continue their pregnancy. (1)(11) in a shared location (eg, in the electronic medical record or
on a shared drive that is compliant with current Patient Pri-
PERINATAL PALLIATIVE CARE vacy Act standards), and continued team communication at
The history of PPC can be traced back to the early 1980s, regular chronologic intervals are helpful to ensure that all
when health-care professionals began to recognize the members are abreast of changes in real-time.
need for specialized support for families facing the loss of
an infant. (12) Only recently has it been accepted that pain BIRTH PLANNING
and discomfort can affect newborns and fetuses, despite Birth planning is an essential aspect of prenatal care for
the fact that attention has been drawn to the issue for all birthing individuals. However, it is paramount when
many years. (13) PPC encompasses more than just tradi- the life of the fetus is expected to be short. This planning
tional medical care. Rather, it is a holistic approach that should occur during routine prenatal care and should be-
focuses on providing counseling and support to pregnant gin as early as possible to provide adequate time for the
persons, building relationships with the expectant parents, family to consider their desires, as able, during the birth-
and providing resources and support, as well as prenatal ing process and for the team to ensure that the family’s
and birth planning. Each of these approaches contributes desires can be met or whether additional resources may
toward the ultimate goals of prioritizing quality of life be needed. For birthing individuals, birth planning pro-
and providing an experience for the family that offers vides a structure to contemplate their pending labor and
space, time, and resources to care for a neonate with a birth, helps them understand what choices are available,
life-limiting condition. allows them to gain insight into valued experiences, and
PPC as a part of a family-centered fetal care offers op- aims to decrease their anxiety. For the health-care clini-
portunities for exploring goals of care for the remainder of cians involved in the delivery and care of the newborn,
the pregnancy, during delivery, and in the neonatal period. birth planning offers insight into the family’s needs and
(14) Furthermore, despite advances in technology and di- desires, ensuring that all parties have the same shared
agnostics, it can sometimes be impossible to have a high mental framework and, ultimately, providing a structure
degree of certainty about the prenatal diagnosis or predict to plan for the delivery of the neonate. The vital compo-
an infant’s course after delivery. Therefore, the planning nents of a palliative care birth plan are provided in Table 2
is focused on the known aspects of the fetal condition and and should include developing goals of care, establishing
the family’s wishes. Thus, establishing care goals around expected timing for delivery, discussing options for intra-
their preferences and values is imperative. Neonatal clini- partum fetal and uterine monitoring, discussing indications
cians should remember that palliative care does not ex- for cesarean delivery, appropriately treating and discus-
clude life-sustaining measures, but these actions are not sing impacts of maternal medical conditions, discussing
expected to be curative. The approach to pregnancy and and determining desires for lactation, discussing immedi-
delivery room care needs to be in line with the family’s ate neonatal care (including potential pain management),
goals of care for their child and, of course, the life and and selecting location and desires for ongoing neonatal
health of the person carrying out the pregnancy. palliative care.

Table 1. Partial List of Fetal Conditions that May Be Life-Limiting
ORGAN SYSTEM FETAL CONDITIONS
Neurologic Brain
Lobar holoprosencephaly
Anencephaly
Encephalocele
Spine
Myelomeningocele
Otolaryngology Neck
Mass
Severe microretrognathia
Pulmonary/cardiac Thorax
Congenital diaphragmatic hernia, severe
Pulmonary hypoplasia
Acardiac twin
Hydrops fetalis
Hypoplastic left heart with intact atrial septum
Musculoskeletal Lethal skeletal dysplasia
Limb body wall complex
Amniotic band syndrome, lethal form
Gastrointestinal Short gut syndrome
Biliary atresia
Total aganglionosis of the bowel
Multivisceral organ transplant requirements
Genitourinary Second-trimester anhydramnios
Bilateral renal agenesis
Bilateral multicystic dysplastic kidney
Genetics Aneuploidy (eg, trisomy 13, trisomy 18)
Other Infections (previable chorioamnionitis, congenital herpes simplex virus, etc)
Antepartum complications
Previable delivery
Intrauterine stroke, severe
Severe growth restriction in the periviable period
Developing Goals of Care neonatal death to survival longer than 5 years. (15) For di-
Initiating the conversation and maintaining an open, con- agnoses that have an overall poor prognosis, offering re-
sistent, and compassionate line of communication is the suscitation may be against institutional policy. Therefore,
most essential aspect of care and is often the most chal- it is vital to present medical care options to the family that
lenging for health-care professionals. This communication are reasonable and clear depending on the institutional
begins with attempting to clarify facts about a medical di- standard of care. Occasionally, a consultation with the in-
agnosis, predicting an expected natural course based on stitutional ethics committee may be part of this process.
what is known in the current medical literature, and how
any interventions may alter the natural course of that dis- Timing of Delivery
ease. Due to the high risk of many of these conditions for Expectant parents should be allowed shared decision-mak-
the pregnant person and fetus, it is crucial to clarify goals ing regarding the timing of delivery. Patient autonomy is
and birth plans as early as possible. After this, it is impor- vital, and the pregnant patient’s perceived control over
tant to establish the families’ core values and define the their delivery can have a varying psychological impact.
acceptable and probable outcomes. It is also important to There are limitations to this decision based on complica-
help families understand the ethical choices and how pa- tions in the pregnant person and fetus. Pregnancies with
rental authority and patient autonomy intersect. When LLFC are at higher risk for mid-trimester labor, cervical di-
necessary, parents should be helped to realize that paren- lation, or rupture of membranes. (16) Furthermore, preg-
tal authority has limitations. Some medical interventions nant persons are more likely to have preeclampsia and
may be unreasonable because they create more significant other complications (eg, hemolysis, elevated liver enzyme
harm than benefit. Furthermore, these decisions may vary levels, and low platelets [HELLP] syndrome), which may
widely among clinicians and centers, and based on geo- necessitate earlier delivery for the sake of the pregnant
graphic regions. For example, infants with trisomies 13 person’s health. (16) For some families, having a sched-
and 18 have broad ranges of outcomes spanning from uled delivery may be perceived as choosing the day their
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Table 2. Guide for Labor and Birth Planning
Understanding parents’ When and how did you learn of the fetal condition?
awareness of the fetal What is your understanding of the fetal condition?
condition What is your understanding of how this will impact your child’s ability to survivie during and after
delivery?
What is your understanding of how the baby will look when born?
How do you feel about the circumstances? How are you coping?
Understanding previous Have you had any fertility issues? How did conception occur?
experiences Number of previous pregnancies?
Close family or friend experience with miscarriage or neonatal loss?
What spiritual beliefs or ethnic traditions do you want us to honor?
Do you have other relevant information to share?
Understanding the support Who is your support network? What are their names and where do they live?
network Who do you want present during labor? Do you want these support persons in the delivery room at
time of birth?
For friends and family not present, how would you like to communicate with them?
Do you wish to have clergy or a spiritual advisor present?
Do you want a doula or other labor support person present?
Pregnant person’s health What is the history and outcome of previous pregnancies?
considerations Preexisting health conditions? Mental health conditions?
What health conditions have occurred in this pregnancy?
What surgeries have you had that may impact the delivery?
Desires for labor What fears or concerns do you or your support person have?
Have you taken childbirth classes?
Do you want photographs or video of the birth? (consider hospital policies if limiting)
What comfort measures would you like during labor? Music, soft lights, etc?
What pain management are you interested in?
Desires for birth Who do you want present at the birth?
Do you want coaching during pushing? Mirror?
Fetal monitoring?
Considerations for cesarean delivery? What feelings do you have about cesarean delivery?
Whom do you want to hold the baby immediately after the birth? Special receiving blankets?
Wishes after birth Who do you want in the room after delivery?
Ethnic, religious, or family traditions you would like to honor?
Would you like religious personnel to be present? Immediately after the birth?
When and how do you want additional family, friends to be notified?
Other important wishes?
Considerations if the baby is Who should go with the baby to the NICU?
going to the NICU Items you may want to send to the NICU
Preferences for updates and photographs of the baby’s condition?
What expectations of care do you have?
What is your undertanding of the goals of care and how do you want changes in your baby’s condition
to be discussed?
If the baby has died or is Directives for your baby’s comfort?
expected to die Preferences for photographs and mementos?
Special gowns, blankets, or items?
Experiences and memories you may want to create?
Considerations for oral comfort measures if the baby cannot suck or breastfeed?
This guide aims to facilitate open and compassionate communication between the hospital staff and expectant parents, ensuring a person-
alized and supportive experience during pregnancy, labor, birth, and beyond.
baby will die. In contrast, others may prefer to schedule the accreta), cesarean delivery poses a greater risk of morbidity
date of their delivery. Last, it is essential to remember that de- to the pregnant patient compared with vaginal delivery. (17)
pending on the geographic region and institutional policies, Therefore, labor and delivery teams aim for most intrapar-
there may be limitations or laws that govern what options are tum patients to achieve a vaginal delivery. The American
available at various gestational ages. A compassionate induc- College of Obstetricians and Gynecologists has guidelines
tion of labor may be an option and should be discussed with for obstetric clinicians regarding indications for cesarean de-
the palliative care team and ethics committee, as applicable. livery. (17) However, when a pregnancy involves an LLFC,
the decision for a cesarean delivery may be altered based on
Mode of Delivery the family’s goals and the unique fetal condition. Childbirth
In the absence of certain obstetric complications (eg, pla- classes may help the pregnant person understand parturi-
centa previa, vasa previa, uterine rupture, and placenta tion, prepare for the birthing process, and develop plans and

goals for the delivery. We believe that these patients may vital. In addition, it is critical to screen pregnant people for
benefit from a one-on-one lesson with an instructor to focus preexisting mental health conditions and for health-care pro-
the teaching on their circumstances, when possible. In addi- fessionals to be aware of the inherent risk of depression and
tion, doulas provide an excellent resource for birth planning, anxiety in these situations and, if preexisting, may be exacer-
support, ongoing resources, and comfort for birthing individ- bated by the diagnosis of an LLFC. Mental health services,
uals throughout prenatal care, labor, and postpartum. Na- prepartum and postpartum, are crucial in the care of these
tionwide, many bereavement doulas specialize in supporting patients.
families through miscarriage, birth where the life of the fetus
is expected to be short, stillbirth, and neonatal loss. Lactation
Depending on the goals of care and the infant’s life expec-
Fetal Monitoring tancy, establishing a lactation plan is imperative and can
The physiologic processes of labor can compromise blood provide empowerment during a time of grief. Options
flow to the fetus or the delivery process of a malpositioned should be offered for breastfeeding, pumping, and/or sup-
fetus. Likewise, other birth-related complications can re- pression, depending on the patient’s desires and stage of
sult in the intrapartum death of a fetus with an LLFC. The care. Some may find comfort in donating to a milk bank.
indication for fetal monitoring is to evaluate the intrapar- Many see milk donation as a way to acknowledge their
tum fetal status with the goal of intervening appropriately motherhood, reduce physical discomfort, and find mean-
(eg, position changes, fluid management, and discontinua- ing during bereavement. (21) Others may not, as the lacta-
tion of uterotonic medications in the pregnant person) or tion process can be stressful and exacerbate feelings of
to expedite delivery, if indicated, for signs of fetal distress. loss. Pharmacologic assistance from the medical team may
Pregnant patients must be counseled that there is a risk of be pertinent to minimize lactogenesis. Lactation specialists
fetal compromise during labor. This is an understood risk are experts in this area and can provide a valuable resource
for some patients who do not desire fetal monitoring in la- for all the needs that may arise.
bor. However, in a pregnancy with an LLFC, fetal monitor-
ing can be offered and used depending on the goals of care. Immediate Neonatal Care
Case studies have shown that some patients may want to Delivery room neonatal care should be focused on the pre-
know if their fetus’ heart has stopped beating and may regret viously discussed goals for comfort care and creating a bal-
not knowing. (16) For others, fetal monitoring can be a point ance among stabilizing the infant (to allow for postnatal
of anxiety, and they may elect not to monitor. (16) confirmation of diagnosis if needed), providing immediate
resuscitation and care within reasonable parameters (to al-
Conditions of the Pregnant Person low for the baby and family to meet), and performing only
Although much of the focus may be on the fetus with an procedures and interventions in line with the previously
LLFC, considerations of the pregnant person or fetus may discussed goals of care. Often, clinicians will default to of-
lead to further complications for the pregnant patient re- fering everything versus nothing, but it is necessary and
quiring close monitoring, treatments, and the potential for appropriate to tailor interventions based on their profes-
intervention or even early delivery. Examples include poly- sional knowledge and opinion.
hydramnios (which can cause respiratory or vascular com-
promise in the pregnant person), malpresentation, cord Pain Management
prolapse, preterm contractions, premature rupture of mem- Among many areas that have evolved in PPC, understand-
branes, and preterm labor. (18) Gestational diabetes may also ing of the pain experience has grown exponentially but re-
complicate fetal growth velocity and increase the risk of com- mains one of the most challenging areas to manage due
plications for the pregnant person. (19) Conditions such as to differences in perception and expression of pain. (22)
severe preeclampsia and HELLP syndrome may become life- As recently as the 1970s, neonates were believed to not ex-
threatening to the pregnant person, and early delivery is rec- perience pain due to immaturity of the central nervous
ommended. (20) Medical conditions in the pregnant person system; thus, symptomatic care was limited even when
are vital to the conversation about delivery planning and may completing major surgeries. (12) In the NICU today, most
include saving the pregnant person’s life and altering birth pain management is assessed and managed by the bedside
plans. Appropriate prenatal care and treatment of medical nursing staff. Guidelines for pain management planning
conditions that may impact the pregnant person’s health is include anticipating daily procedures and care practices,
e492 NeoReviews

minimizing painful procedures when possible, anticipat- References
ing pain management needs and frequently assessing for
1. Sumner LH. Taking palliative care into pregnancy and perinatal
pain using standardized and validated tools, considering
loss: a model for community collaboration. National Perinatal
nonpharmacologic interventions, and choosing the appro- Association Bulletin. Autumn 2003;23(4). Accessed July 23, 2023
priate pain scale for the setting/gestational age. 2. Centers for Disease Control and Prevention (CDC). Update on
overall prevalence of major birth defects–Atlanta, Georgia, 1978-
Location for Continued Neonatal Palliative Care 2005. MMWR Morb Mortal Wkly Rep. 2008;57(1):1–5
As previously discussed, limitations exist in prenatal diag- 3. Vaz M, Erickson E, Rajegowda B. Review of birth defects in a community
hospital over a ten-year period. Obstet Gynecol Int J. 2016;5(2):264–266
nosis and the ability to indisputably predict neonatal con-
4. Ely DM, Driscoll AK. Infant mortality in the United States, 2020:
ditions after birth. Therefore, it is essential to discuss with
data from the period linked birth/infant death file. Natl Vital Stat
patients their options for continued neonatal palliative care Rep. 2022;71(5):1–18
based on hospital capabilities. For some facilities, care com- 5. Perinatal Palliative Care: ACOG COMMITTEE OPINION, Number
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room, whereas at other facilities, an infant may require trans- 6. Parravicini E, Lorenz JM. Neonatal outcomes of fetuses diagnosed
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7. Kidszun A, Linebarger J, Walter JK, et al. What if the prenatal
tal model for what their desired level of neonatal care may
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The institution of a PPC program may be accomplished at
11. Kersting A, Reutemann M, Ohrmann P, et al. Grief after
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termination of pregnancy due to fetal malformation. J Psychosom
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ponents of the program are universal. knows a fetus is expected to die: palliative care in the context of
prenatal diagnosis of fetal malformations. J Palliat Med.
2017;20(9):1020–1031
13. Balaguer A, Martın-Ancel A, Ortigoza-Escobar D, Escribano J,
Argemi J. The model of Palliative Care in the perinatal setting: a
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19. ACOG Practice Bulletin No. 190: gestational diabetes mellitus. 21. Limbo R, Wool C, Carter B, eds. Handbook of Perinatal and Neonatal
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20. ACOG Committee on Obstetric Practice; American College of Professionals. New York, NY: Springer; 2020
Obstetricians and Gynecologists. ACOG practice bulletin. Diagnosis 22. Mathur VA, Morris T, McNamara K. Cultural conceptions of
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e494 NeoReviews

NEOREVIEWS QUIZ
NEO
QUIZ
CME QUIZ
1. On a 20-week anatomic ultrasonographic image, a fetus is diagnosed as

having hypoplastic left heart syndrome. Appropriate counseling is
performed, and a guide for labor and birth planning is created. What is the
approximate number of infants affected by birth defects in the United
States?
A. 1 in 10.
B. 1 in 20.
C. 1 in 30.
D. 1 in 40. REQUIREMENTS: Learners can
E. 1 in 50. take NeoReviews quizzes and
claim credit online only at:
2. Life-limiting fetal conditions are diagnoses that carry little or no prospect of https://publications.aap.org/
long-term extrauterine survival. These conditions are associated with severe neoreviews.
morbidity and poor quality of life, and often have no cure. What percentage
To successfully complete 2024
of infant deaths are related to these birth defects?
NeoReviews articles for AMA PRA
A. <1%. Category 1 Credit™, learners
B. 5%. must demonstrate a minimum
performance level of 60% or
C. 10%.
higher on this assessment. If
D. 15%. you score less than 60% on the
E. 20%. assessment, you will be given
additional opportunities to
3. Perinatal palliative care is a holistic approach that focuses on providing
answer questions until an
counseling and support to pregnant persons. These teams provide family- overall 60% or greater score is
centered fetal care and help to develop goals for pregnancy, delivery, and achieved.
the neonatal period. In which decade was the importance of perinatal
This journal-based CME activity
palliative care recognized?
is available through Dec. 31,
A. 1950s. 2026, however, credit will be
B. 1960s. recorded in the year in which
the learner completes the quiz.
C. 1970s.
D. 1980s.
E. 1990s.
4. A fetus is diagnosed as having anencephaly on prenatal ultrasonography,
and the palliative care team recommends the creation of a guide for labor
and birth planning. This guide helps to facilitate open and compassionate 2024 NeoReviews is approved
communication among all individuals involved in the care of the expectant for a total of 10 Maintenance of
Certification (MOC) Part 2
family. When should this guide be enacted?
credits by the American Board
A. At birth. of Pediatrics (ABP) through the
B. At diagnosis. AAP MOC Portfolio Program.
NeoReviews subscribers can
C. During hospital admission.
claim up to 10 ABP MOC Part 2
D. On admission to the NICU. points upon passing 10 quizzes
E. On discharge. (and claiming full credit for
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can start claiming MOC credits
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learn how to claim MOC points,
go to: https://publications.aap.
org/journals/pages/moc-credit.

5. Understanding the pain experienced in neonates has been an area of
exponential growth. As recently as the 1970s, neonates were believed to not
experience pain, and symptomatic care was limited, even in the setting of
major surgery. Which one of the following statements regarding neonatal
pain is INCORRECT?
A. Neonates experience less pain due to an immature central nervous system.
B. Pain should be managed and assessed by bedside nursing staff.
C. Painful procedures should be minimized whenever possible.
D. Providers should consider nonpharmacologic interventions whenever
possible.
E. Standardized pain scales should be appropriate to each setting and
gestational age.
e496 NeoReviews

ARTICLE
Understanding Obstetrical Surgical

Planning for the Pediatrician
Amelia Q. Schuyler, MD, MPH,* Frances R. Koch, MD,† Christopher G. Goodier, MD‡
*Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL
†
Department of Neonatology and ‡Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC
PRACTICE GAPS
1. Understanding cesarean delivery indications, preoperative considerations,

and clinical decision-making regarding various surgical techniques is
important for providers who care for the pregnant person–infant dyad.
2. Cesarean deliveries have both short- and long-term effects on the
pregnant person–infant dyad.
1. Summarize current cesarean delivery epidemiologic data.

2. Describe indications in the pregnant person and fetus for cesarean
delivery.
3. Explain cesarean surgical techniques and the clinical decision-making for
the variety of laparotomy and hysterotomy incisions.
4. Describe common maternal and neonatal complications after cesarean
delivery.
ABSTRACT
Cesarean deliveries are common in the United States, occurring in
approximately one-third of deliveries in 2021. Given this high rate of
cesarean deliveries, it is important for all clinicians caring for the pregnant
person–infant dyad to be educated about cesarean deliveries. In this
review, we describe the indications for cesarean delivery, the evidence-
based practices of preoperative planning to ensure safe deliveries, and the
clinical decision-making behind various cesarean incisions. In addition, we
discuss the most common complications of cesarean deliveries for the
pregnant person–infant dyad.
AUTHOR DISCLOSURE Drs Schuyler,

BACKGROUND Koch, and Goodier have disclosed no
During the past 50 years, the rate of cesarean deliveries, defined as the percent- financial relationships relevant to this
article. This commentary does not
age of cesarean deliveries out of all births each year, has increased dramatically
contain a discussion of an unapproved/
in the United States. (1)(2) Much like the overall cesarean delivery rate, there investigative use of a commercial
has been a substantial increase in the primary cesarean delivery rate, denoting product/device.

the percentage of cesarean deliveries among women with- 2020 and 2021, the rate began to rise again. (1) In 2021, the
out previous cesarean births. Although cesarean delivery rate of overall cesarean deliveries increased to 32.1% and the
can be lifesaving in certain situations for the fetus and the rate of primary cesarean deliveries increased by 2%, to 22.3%.
pregnant person, the rapid increase in the rate without evi- (1) Low-risk cesarean deliveries, defined as those among nul-
dence of concomitant decrease in morbidity and mortality liparous pregnant persons with a term (ie, $37 weeks’
in the birth parent or neonate has raised concern that ce- gestational age), singleton, cephalic-presenting fetus also
sarean delivery is overused, especially in low-risk popula- increased by 2%, to 26.3%. (1) Conversely, there was a
tions. (3) In 2014, the American College of Obstetricians continued increase in the rate of vaginal births after cesar-
and Gynecologists and the Society for Maternal-Fetal Med- ean deliveries among pregnant persons, with an increase of
icine authored “Safe Prevention of the Primary Cesarean 2%, to 14.2%. (1)
Delivery,” a consensus statement aimed to safely lower the The observed rise in cesarean deliveries is influenced
rate of primary cesarean deliveries given this substantial
by many factors, including delayed childbirth associated
increased incidence. (4)
with advanced age in the pregnant person and an in-
For pregnancies deemed low risk, cesarean deliveries
creased proportion of births among nulliparous persons.
pose significant morbidity and mortality compared with
(7) Similarly, the rise in assisted reproductive technology
vaginal deliveries. Although cesarean deliveries can be life-
and rates of obesity in the general population have both
saving in specific cases, the significant risk of morbidity
been shown to increase the risk of cesarean delivery.
and mortality underscores the crucial need to prioritize efforts (8)(9) Additional considerations include request for cesar-
aimed at preventing unnecessary cesarean procedures. (5)(6) ean delivery as well as the obstetrician’s fear of litigation
In this review, we describe the indications for cesarean deliv- due to poor obstetrical outcomes for the pregnant person–
ery, the evidence-based practices of preoperative planning to infant dyad. (10)(11) Recommendations favoring a trial of
ensure safe deliveries, and the clinical decision-making be- labor after cesarean delivery began in the 1970s with accu-
hind various cesarean incisions. In addition, we discuss the mulating safety data in select populations. As a result,
most common complications of cesarean deliveries for the rates of vaginal birth after cesarean delivery increased by
pregnant person–infant dyad. approximately 5%, to 28%, in 1996, which coincided with
a concomitant decrease in the cesarean delivery rate. (12)
EPIDEMIOLOGY
The rate of cesarean deliveries has increased dramatically, INDICATIONS FOR CESAREAN DELIVERY
with the incidence rising in the United States from 4.5% Through data collected by the Consortium of Safe Labor,
in 1970 to 20.7% in 1996. (1)(2) Thereafter, the rate of ce- Boyle et al(13) published a large retrospective study revealing
sarean deliveries in the United States increased annually that the most common indications for primary cesarean de-
until peaking at 32.9% in 2009. (1) Subsequently, the rate of livery included failure to progress (35.4%), nonreassuring fe-
cesarean deliveries decreased in 2018 and 2019; however, in tal heart tones (27.3%), and abnormal fetal presentation
Figure. Hysterotomy incisions. A, Low transverse; B, Low vertical incision; C, Classical incision; D, J incision; E, T. Illustrator: Dr. Frances R. Koch, MD.
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Table 1. Common Indications for Cesarean Deliveries
INDICATIONS IN THE PREGNANT
PERSON FETAL INDICATIONS OBSTETRIC INDICATIONS
Previous uterine scar Fetal distress (18) Cephalopelvic disproportion (23)
Previous cesarean delivery Fetal malpresentation (19) Arrest of dilation
Myomectomy Suspected fetal macrosomia (infant >5,000 g in pregnant Uterine rupture
Placenta accreta spectrum persons without diabetes and >4,500 g in pregnant Umbilical cord prolapse
Placenta previa (14) persons with diabetes) (20) Placental abruption (24)
Vasa previa Congenital anomalies (21) (22) Shoulder dystocia
History of shoulder dystocia Chorioamnionitis
Preeclampsia
Eclampsia
Multiple gestation (15)
Human immunodeficiency virus or herpes
simplex virus (16)
History of pelvic trauma or deformity
Patient request (17)
(18.5%). Other common indications are listed in Table 1 and complications, (29) and several studies report potential
can be classified according to indications related to the preg- harm with drain placement. (30)(31)
nant person, fetus, or labor, although there is considerable The American College of Obstetricians and Gynecolo-
overlap in these categories. gists additionally recommends pneumatic compression
stockings for venous thromboembolism prophylaxis before
PREOPERATIVE PLANNING surgery with continued use until the patient is ambulatory
Most of the current standardized perioperative care for ce- postoperatively. (32) Given the risk of perioperative hypo-
sarean deliveries is based on recent Enhanced Recovery thermia, the latest evidence supports active body surface
After Surgery (ERASV R ) recommendations composed of warming, including the use of forced-air warmers, heated
evidence-based knowledge and consensus guidelines detailing mattresses, and warming blankets. Not only has active
preoperative fasting, surgical site preparation, intraoperative body surface warming been shown to help maintain normo-
antibiotic administration, anesthetic management, and preven- thermia, but there is also additional evidence to support a de-
tion of intraoperative hypothermia. (9) Per these guidelines, crease in wound infections and blood transfusions with its
delivering individuals are made nil per os and solid intake is use. (33) The delivering patient should be positioned in a left
withheld at least 6 hours before surgery due to the risk lateral tilt for uterine displacement until delivery, to decrease
of aspiration. A preoperative laboratory evaluation that in- the risk of aortocaval compression, hypotension, and fetal
cludes hematocrit, blood type, and antibody screen is obtained compromise. Other preoperative considerations include opti-
to ensure that compatible blood products are available during mizing other comorbidities that can affect wound healing
the procedure in the event of excessive blood loss or intrao- and postoperative recovery, particularly glycemic control in
perative hemorrhage. diabetic patients, and, if able, addressing any modifiable risk
Studies investigating hair removal at the incisional site factors, such as smoking. (9)
have not shown a decrease in surgical site infections; how-
ever, in the case of obfuscating hair at incisional sites or
anatomic landmarks, current recommendations implicate DELIVERY TYPES AND INCISIONS
hair clipping instead of removal with shaving. (25) Clean- A cesarean delivery is composed of a laparotomy (ie, an in-
ing the skin with chlorhexidine, in addition to strict adher- cision entering the abdomen), followed by a hysterotomy
ence to all sterile procedures, including standard patient (ie, an incision of the uterus after the peritoneum has been
draping, has been shown to prevent surgical site infections. entered), with subsequent delivery of the fetus. A laparotomy
(26) Studies have also revealed that preincision antibiotic is achieved via a suprapubic transverse incision (eg, Pfannen-
prophylaxis with a cephalosporin or extended-spectrum stiel, Maylard, Joel-Cohen, or modified Joel-Cohen/Misgav-
penicillin and azithromycin, especially for patients in labor Ladach incisions) or a vertical incision (ie, midline vertical or
or with ruptured membranes, have reduced postoperative paramedian incision). Transverse incisions are typically pre-
infections. (27)(28) Furthermore, intraoperative subcutane- ferred over vertical incisions for a laparotomy given that they
ous drain placement has not been shown to reduce wound provide a more favorable cosmetic result, have lower rates of

Table 2. Common Incisions Used in Laparotomy and Hysterotomy
INCISION TYPE SUBTYPE DESCRIPTION
Laparotomy
Suprapubic transverse Pfannenstiel incision A curved, transverse incision is made 3 cm above the superior border of
incision the pubic symphysis at the level of the pubic hairline and is laterally
extended 12–15 cm with subsequent sharp dissection of the
subcutaneous tissue. A midline incision is made at the underlying
fascia and extended laterally. The rectus sheath is separated at the
midline to reveal the transversalis fascia, which is dissected to expose
the peritoneum.
Maylard incision Similar to the Pfannenstiel but the rectus abdominis muscles are
transected to extend the available operating space.
Joel-Cohen incision This incision is a straight, transverse incision made 3 cm below an
imaginary line connecting the anterior superior iliac crests followed by
a medial subcutaneous incision to expose the underlying fascia and a
subsequent transverse fascial incision. Blunt dissection is used to
separate the rectus sheath and underlying peritoneum.
Misgav-Ladach incision Similar to the Joel-Cohen but noted blunt dissection is used to open the
fascia.
Midline vertical incision Incision is made several centimeters above the public symphysis in the
midline and extended caudally 12–15 cm followed by sharp dissection
of the subcutaneous tissue.
Paramedian incision Incision is made several centimeters above the pubic symphysis and
several centimeters lateral to the midline.
Hysterotomy
Low transverse incision Munro Kerr or Kerr incision (Fig A) Small transverse incision made in the lower myometrium
Low transverse incision J incision (Fig D) Extension of 1 corner of the low transverse uterine incision cephalad into
extension the contractile portion of the uterus.
U incision Extension of the low transverse uterine incision bilaterally, from both
corners of the uterine incision superiorly.
T incision (Fig E) Extension of the low transverse uterine incision superiorly in the midline.
Vertical incision Low vertical uterine incision (Fig B) A vertical incision made in the lower, acontractile myometrium of the
uterus.
Classical incision (Fig C) A vertical incision that extends into the upper, contractile myometrium
to the level of the round ligament insertion.
incisional hernias, and can be associated with less postopera- contains the superficial epigastric vessels on either side of the
tive pain. (34) midline, which sometimes necessitate coagulation before en-
A hysterotomy is performed by making a low transverse tering the fascia. A midline incision is made at the level of the
incision (eg, Munro Kerr or Kerr incision) or a vertical inci- 2 fascial layers, the aponeurosis of the external oblique and
sion, including a low vertical incision (eg, Kronig, DeLee, or the fused aponeuroses of the internal oblique and transversus
Cornell incision) or a classical incision. For a hysterotomy, abdominis muscles. (9)
low transverse incisions are favored over vertical incisions, The fascial incision is extended laterally, and care is
particularly classical vertical incisions, given the increased taken to avoid the inferior epigastric arteries, which can be
risk of uterine rupture in subsequent pregnancies with clas- found at the lateral border of the rectus abdominis
sical incisions that involve the upper, contractile portion of muscles and will require ligation or coagulation. (9) Once
the myometrium (see A, B, and C in the Fig) (Table 2). (9) the midline fascial incision is made, the inferior fascia is
elevated and the fascial sheath is separated from the rectus
Laparotomy: Suprapubic Transverse Incision abdominis muscles underneath, either bluntly or sharply,
The most frequently performed suprapubic transverse in- until reaching the superior border of the pubic symphysis.
cision is the Pfannenstiel incision. This curved, transverse The superior fascia is then elevated, and the superior fascial
incision is made 3 cm above the superior border of the pu- sheath is separated from the rectus abdominis muscles. The
bic symphysis at the level of the pubic hairline and is lat- rectus abdominis muscles are then separated at the midline,
erally extended 12 to 15 cm to facilitate delivery of the revealing the transversalis fascia. This fascia and any interven-
fetus. (9) Once through the skin, sharp dissection with a ing fat are dissected to expose the underlying peritoneum. (9)
scalpel continues through the full length of the subcutaneous The peritoneum is entered carefully toward the cephalad por-
tissue to the abdominal fascia below. This subcutaneous tissue tion of the abdominal incision to avoid underlying structures
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such as bowel or bladder. The vesicouterine interface is iden- there is thought to be less stress on the scar and, therefore,
tified, and the peritoneum is dissected to separate the urinary these are felt to be stronger scars than midline scars. (37)
bladder from the lower uterine segment. (9) Care is taken to Compared with transverse incisions, vertical incisions
ensure adequate space for a hysterotomy. can often be performed more quickly and are often chosen
Another variation of the suprapubic transverse incision when emergency entry is necessary. (38) Other considera-
is the Maylard incision in which the skin, subcutaneous tions for a vertical laparotomy include obesity in the preg-
tissue, and fascia are entered similarly as in the Pfannen- nant person, anticipation of significant intra-abdominal
stiel approach. With this technique, however, the rectus adhesive disease, or for needed exposure due to cases of
abdominis muscles are transected to extend the available placenta accreta. However, compared with transverse skin
operating space. (9) This approach requires careful liga- incisions, vertical skin incisions have an increased risk of
tion of the inferior epigastric arteries that are located lat- wound complications, a higher amount of blood loss, in-
eral to the rectus abdominis muscles. Disadvantages of creased operative time, and a greater need for classical
this technique include greater bleeding risks with possible hysterotomy incisions, especially in obese patient popula-
involvement of the inferior epigastric arteries and concerns tions. (39)
for decreased abdominal strength postoperatively given the
transection of the rectus abdominis muscle beds. (9) Hysterotomy: Low Transverse Cesarean Incision
The Joel-Cohen incision is a straight, transverse inci- (Munro Kerr incision or Kerr incision)
sion made 3 cm below an imaginary line connecting the The low transverse cesarean incision, or the Kerr incision,
anterior superior iliac crests (and is therefore higher on was first described by Dr John Munro Kerr in 1921, and it
the abdomen than the Pfannenstiel incision). After mak- remains the most common hysterotomy technique. (40)(41)
ing the skin incision, a small (3-cm), medial subcutaneous This incision is made in the noncontractile lower uterine
segment and is, therefore, easier to repair and is the least
incision is made to expose the underlying fascia. A small
likely uterine scar to rupture in subsequent pregnancies. It is
transverse incision is then made medially in the fascia,
the best choice for patients planning another pregnancy and
with subsequent extension laterally. Blunt dissection is
can allow for a trial of labor after cesarean delivery. The vis-
used to separate the rectus abdominis muscles and to
ceral peritoneum in the lower uterine segment is manipu-
open the peritoneum. (35)(36) There have been multiple
lated with forceps and is subsequently incised transversely
modifications of the Joel-Cohen technique (eg, the Misgav-
with scissors and then extended laterally. The inferior perito-
Ladach technique), which are characterized by the utiliza-
neum, near the bladder, is elevated and bluntly or sharply
tion of blunt dissection when opening the fascia.
dissected to move the bladder away from the lower uterine
segment. (9) The uterus is palpated to distinguish between
Laparotomy: Midline Vertical Incision and the upper, contractile portion of the uterus and the lower,
Paramedian Incision acontractile portion. A small transverse incision is made in
The midline vertical incision is made several centimeters the lower myometrium by making small, shallow strokes
above the public symphysis in the midline and extended with a scalpel to prevent laceration of the fetal head or fetal
caudally 12 to 15 cm. (9) Once the skin is incised, the un- parts (Fig A). This incision is extended to create an opening
derlying subcutaneous tissue is dissected sharply. The un- adequate for delivery of the fetus. (42) If unsuccessful in ex-
derlying anterior rectus sheath is opened by making a tension of the incision with blunt dissection, scissors can be
small incision in the upper portion of the linea alba, to used to extend the incision in a lateral, cephalad direction,
best prevent entry into the bladder. Two fingers are placed with care taken to prevent fetal injury. The use of blunt exten-
under the opened fascia to facilitate the safe, precise place- sion compared with the use of scissors is associated with less
ment of scissors to extend the incision superiorly and inferi- unintended incision extension and less blood loss. (43)(44)
orly to expose the rectus abdominis muscles. (9) Entering If the Kerr incision is unintentionally overextended into
the peritoneum, after separating the rectus sheath, is per- the lower uterine segment laterally, there is a risk of enter-
formed in a similar fashion as described previously with the ing the uterine vessels. Unexpected extension downward,
Pfannenstiel incision. or inferiorly, can enter the cervix or vagina. (45) A major
The paramedian incision is made several centimeters disadvantage of the Kerr incision is that despite using the
above the pubic symphysis and several centimeters lateral to methods described previously herein to adequately extend
the midline. Given this location away from the midline, the initial incision in the myometrium, it can occasionally

remain too small for effective delivery of the fetus, requir- on clinical examination, on imaging with ultrasonography,
ing further extension of the myometrial incision superi- or even on histologic examination, it can be challenging to
orly into the contractile portion of the uterus. These definitively determine whether low vertical incisions are
extensions are made caudally into the contractile portion truly low and confined to the acontractile myometrium, an
of the uterus because further lateral extension confers a important consideration for the safe trial of labor in future
greater risk of bleeding with involvement of uterine vessels. pregnancies.
It is important to understand that all extension techniques Classical incisions are vertical incisions that extend into
result in a weaker uterine scar given the involvement of the the upper, contractile myometrium to the level of the
contractile myometrium and a consequent increased risk of round ligament insertion (Fig C). Compared with low ver-
uterine rupture in subsequent pregnancies. (46) tical or transverse hysterotomies, these incisions have a
The “J” incision is performed by extending one corner higher rate of uterine rupture in subsequent pregnancies
of the uterine incision cephalad into the contractile por- (4%–9% compared with 0.2%–1.5%). (50)
tion of the uterus (Fig D). (47) A “U” incision is made by
extending the incision bilaterally, from both corners of the COMPLICATIONS IN THE PREGNANT PERSON
uterine incision superiorly. A “T” incision can be made by Mortality of the delivering patient is greater after cesarean
extending the incision superiorly in the midline, giving delivery than after vaginal delivery; however, it is also im-
the appearance of an inverted letter “T” (Fig E). (48) portant to note that this increased mortality can be due, in
part, to the underlying indication for cesarean delivery.
Hysterotomy: Vertical Incisions (51) For example, studies have shown that increased length
Despite the risks of an unintended extension or a needed of the first stage of labor increases the risk of cesarean de-
extension with Kerr incisions, these incisions are preferred livery in the pregnant person. (52) It should be noted that
over vertical incisions given the risk of uterine rupture an increased length of the first stage of labor was also
with vertical, specifically classical hysterotomy, incisions. shown to have an increased risk of fever and compositive
There are, however, several indications for vertical inci- maternal morbidity in addition to higher risk of cesarean
sions, including a morbidly adherent bladder to the lower delivery. (52) In addition to mortality, morbidity is also
uterine segment precluding transverse incision and entry, noted to be higher in cesarean deliveries, with increased
lower uterine pathology (eg, cervical cancer, leiomyomas, risk of uterine rupture, (53) placental abruption, (54) ab-
anterior placentation with placenta previa, or accreta), diffi- normal placentation, (55)(56) and obligate preterm birth.
culty exposing the lower uterine segment, anticipated fetal (57) Other common complications include increased rates
macrosomia or anomalies with a risk of needing extension of infection, hemorrhage, and venous thromboembolism
of transverse incisions to deliver the fetus, an underdevel- in the delivering patient. (58) Complications from anesthe-
oped lower uterine segment (in the case of extremely pre- sia are also higher in those delivering by the cesarean
term infants where Osmundson et al (49) noted that 50% of technique compared with those undergoing vaginal deliv-
women at 23 to 26 weeks’ gestation who undergo cesarean ery. (59) Cesarean deliveries also carry a risk of damage to
delivery have a classical vertical hysterotomy), or certain fetal surrounding organs in the pregnant person, most often
presentations with anticipated excessive uterine manipula- the bladder and ureters. (60) Interestingly, cesarean deliv-
tion required for delivery. ery is noted to have lower rates of pelvic organ prolapse
A low vertical uterine incision is made in the lower, and urinary incontinence than vaginal delivery. (61)
acontractile portion of the uterus similar to the Kerr inci- Importantly, patients who have undergone cesarean de-
sion (Fig B). As such, it has a lower risk of uterine rupture livery are at an increased risk for repeated cesarean deliv-
compared with classical incisions, which involve the con- eries in subsequent pregnancies. The risk of morbidity in
tractile myometrium. However, low vertical incisions have the delivering patient is compounded by repeated cesarean
a higher risk of unintended extension of the incision supe- deliveries, with noted increased rates of abnormal placen-
riorly into the contractile myometrium or inferiorly to the tation and greater incidence of infection, organ injury, and
cervix, vagina, and bladder during delivery. It does not bleeding. (62)(63)(64)
have the same risk of unintended lateral extension and A Cochrane review by Hofmeyr et al (65) comparing
subsequent uterine vessel involvement as the Kerr inci- cesarean techniques noted that Joel-Cohen–based techni-
sion. Furthermore, given that it is difficult to determine ques had several advantages over Pfannenstiel techniques,
the distinction of the upper and lower uterine segments with lower rates of blood loss and fever, a shorter operating
e502 NeoReviews

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Gynecol. 2011;205(3):262.e1–262.e8 2020;17(21):8031

INDEX OF SUSPICION IN THE NURSERY
A Term Neonate with Congenital

Torticollis
Abhilasha Kumari, MD,* Prashanth Ranya Raghavendra, DM,* Sruthi Nair, DrNB,* Tehsin Abdul Patel, MD,*
Anitha Haribalakrishna, MD, FRACP*
*Department of Neonatology, Seth G.S. Medical College and King Edward Memorial Hospital, Mumbai, India
PRESENTATION
A 38-week term boy weighing 3,010 g (50th–90th percentile per the modified Fen-
ton chart) is born by cesarean delivery to a 22-year-old primigravida woman. The
neonate cries immediately after birth and has his face and chin tilted to the right
side. The mother is diagnosed as having gestational diabetes mellitus at 28 weeks,
which is well controlled with oral hypoglycemic agents. The antenatal scans are
normal, with normal growth and no oligohydramnios or fetal anomalies.
Detailed examination in the delivery room shows left-sided torticollis with limited
painless range of movement in the horizontal and vertical planes. The left sternocleido-
mastoid muscle is tight, without a palpable mass or tenderness. The face is symmetrical
while the neonate is quiet; however, on crying, the right corner of the mouth draws right
and downward, and the left corner does not move. Bilateral nasolabial folds and forehead
wrinkling are normal, suggestive of left absent depressor anguli oris (Fig 1A). There is
scoliosis with bilateral dynamic congenital talipes equinovarus deformity. The posterior
neckline appears normal, with no short neck or positional plagiocephaly or any other
dysmorphic features. The remainder of the examination findings, including hip and
other systems, are normal.
DISCUSSION
Differential Diagnosis
• Congenital muscular torticollis
• Klippel-Feil syndrome
• Craniocervical vertebral anomalies
• Atlantoaxial rotatory instability/dislocation
• Posterior fossa tumors
• Grisel syndrome
In the NICU, the midline position of the head is maintained, and manipula-
tion and handling of the head and neck are avoided. The further evaluation of
AUTHOR DISCLOSURE Drs Kumari,
congenital torticollis is shown in Table 1.
Raghavendra, Nair, Patel, and
Haribalakrishna have disclosed no
financial relationships relevant to this Actual Diagnosis
article. This commentary does not
Congenital torticollis with atlantoaxial rotatory dislocation (AARD) with multiple
investigative use of a commercial spinal hemivertebrae, congenital kyphoscoliosis with bilateral congenital talipes
product/device. equinovarus, and congenital hypoplasia of the depressor anguli oris muscle.
e506 NeoReviews

Figure 1. A. Radiograph of the spine shows thoracic hemivertebra with scoliosis (arrow). B. Radiograph of the spine shows lumbar hemivertebra with kyphosis
(arrow). C. Magnetic resonance imaging of the cervical spine shows hyperintensity (arrow) in the sternal head of the sternocleidomastoid muscle.
Congenital torticollis refers to contracture or fibrosis of the paired alar ligaments connecting the tip of the dens
the sternocleidomastoid muscle on 1 side, leading to ipsilat- to the occipital condyles, stabilizes this joint.
eral inclination and contralateral rotation of the face and The presence of ligamentous laxity, robust synovia,
chin. Being the third most common congenital orthopedics and increased malleability makes the C1-C2 junction
anomaly, its incidence varies between 0.3% and 1.9%, with prone to AARD even with minor trauma. (7) The cervical
a male/female ratio of 3:2. (1) AARD is defined by a loss of hemivertebrae, as in the index case, can act as a wedge
stability between the atlas and axis (C1 and C2) joint charac- in the vertebral column, causing a curvature and further
terized by osseous abnormalities or ligamentous laxity. increasing the risk of instability of the joint at the level
(2) Most AARD cases are diagnosed in the pediatric popula- of the abnormal vertebrae. (8) Because of the spine's
tion, with 68% being younger than 12 years(3)(4) and the ability to compensate for a postural imbalance in the ax-
youngest infant being 7 months old and presenting with ial skeleton, compensatory lumbar curvature causing
AARD secondary to infection. (5) scoliosis in the setting of congenital torticollis is a
The C1-C2 vertebral junction accounts for 60% of the known association. (9)
total rotation in the craniocervical region. (6) The hall- AARD has been categorized into traumatic and non-
mark structure of the C2 vertebra is its odontoid process traumatic. (10) Genetic conditions (Down syndrome,
(the dens), which is embryologically the body of the C1 skeletal dysplasia, Morquio syndrome) and inflamma-
and serves as the principal attachment for stabilizing tion (Grisel syndrome) are the 2 main causes of non-
the articulation. (6) The apical dental segment does not traumatic AARD. (10) In this case of congenital
get fused to the basal dens of the membranous C2 verte- torticollis, there is uncertainty in the etiology of AARD
bra until 6 to 9 years of age and is fully formed only by considering the normal fetal ultrasonography findings,
age 12 years. (6) Until then, the transverse ligament, early clinical presentation, and absence of other signifi-
which holds the dens to the anterior arch of the C1 and cant clinical/radiologic features other than congenital
Table 1. Investigations Performed in the Index Neonate with Congenital Torticollis

INVESTIGATION FINDINGS
Radiography of the spine (Fig 1) Congenital kyphoscoliosis with multiple thoracic hemivertebrae and lumbar hemivertebra
(Fig 1).
MRI of the neck and spine (Fig 1C) Hyperintensity in the left sternocleidomastoid muscle with normal spinal ligaments.
MRI of the brain Normal
Computed tomography of the Multiple cervical hemivertebrae with rotation of the atlas in relation to the axis,
neck and spine (Fig 2) suggestive of atlantoaxial dislocation with no evidence of fracture
Brainstem auditory evoked response Normal
Fundus examination Normal
Radiography of the hip Normal
MRI5magnetic resonance imaging.
Vol. 25, No. 8 AUGUST 2024 e507

Figure 2. A and B. Computed tomography (sagittal and coronal) of the cervical spine shows multiple cervical hemivertebrae (circled). C. Computed to-
mography (axial) of the cervical spine shows rotation of the C1-C2 (atlantoaxial rotatory dislocation) (arrow).
talipes equinovarus and congenital hypoplasia of the instability (atlantoaxial dislocation leading to sagittal im-
depressor anguli oris muscle, suggestive of any genetic balance or unilateral facet block and arthritis) and with
disorder. Although the index neonate has radiologic neurologic deficits need stabilization (anterior/poste-
features of type 1 AARD, the most common type, and rior) with atlantoaxial arthrodesis. With these measures,
has remained neurologically normal (Table 2), in the there is 97% improve if treatment starts before 6
absence of major trauma there is a need for longer fol- months of age. (16)(17)
low-up in ascertaining the definitive etiology, although
there are case reports in older children presenting with Patient Course
AARD without identifiable causes. (11) The neonate is given multidisciplinary care involving a
In those at risk for neurologic deficits, alternate imag- neonatologist, orthopedician, and occupational therapist.
ing such as magnetic resonance imaging aids in ruling A specially designed facilitation device made of rigid poly-
out traumatic and destructive processes involving the ethene, foam, and rivets is used for the establishment of
C1-C2 junction(12) and helps in deciding treatment, which breastfeeding, which is achieved by day 10 of age (Fig 3).
also depends on the cause, type of AARD, and matura- Early intervention therapy using a custom-made modified
tional stage of the infant. (11)(13) cervical collar made of soft cotton cloth, foam, and strips
For those without neurologic signs, the mainstays of of tough moldable cardboard is initiated to prevent the
treatment are early intervention therapy with age-appro- risk of neural impingement during activities of daily han-
priate active and passive range of motion of the neck; dling, such as changing diapers, changing clothes, and
developing symmetry of the face, head, and neck; and sponging (Fig 4). Hip ultrasonography is planned for
avoiding contractures; and in newborns, the establish- follow-up.
ment of proper breastfeeding position, prevention of ob- Considering the early age of presentation and the pau-
structive apnea, and safe handling. These are addressed city of definitive clinical or radiologic features suggestive
using facilitation devices such as cervical collars and of any syndrome and the neonate being otherwise hemo-
halter traction. (14)(15) Those with a risk of mechanical dynamically stable and neurologically normal, for now,
Table 2. Fielding and Hawkins Classification of Traumatic AARD(12)

TYPE OF AARD ABNORMALITY NEUROLOGIC DEFICITSa
I Pure rotation of the atlas in relation to the axis and normal ADI Nil
II Pure rotation of the atlas in relation to the axis and ADI of 3–5 mm Nil
(mild dysfunction of the transverse ligament)
III Pure rotation and anterior dislocation with ADI >5 mm (complete Present
dysfunction of the transverse ligament)
IV Pure rotation and posterior dislocation of the atlas with ADI >5 mm Present
(complete dysfunction of the transverse ligament)
AARD5atlantoaxial rotatory subluxation, ADI5atlantodens interval.

a
Quadriparesis, quadriplegia, bladder bowel dysfunction, or spasticity of limbs secondary to spinal cord compression.
e508 NeoReviews

Figure 3. A specially designed facilitation device made of rigid polyethyl-
ene, foam, and rivets.
genetic testing is deferred after taking a geneticist’s opin-

ion and is planned on follow-up. He is currently 4 months
old and on regular follow-up with significant improvement
in the torticollis and continues to be neurodevelopmentally
normal (Fig 5).
Lessons for the Clinician

• Atlantoaxial rotatory dislocation (AARD) is to be sus-
pected in a neonate with congenital torticollis with no Figure 5. Figure of the infant at 4 months of follow-up.
history of traumatic delivery or difficult extraction.

• The presence of cervical hemivertebrae increases the
propensity of an AARD, increasing the risk of neural
compression and neurologic deficits. Neonatal-Perinatal Content
• Early use of custom-made cervical collars and facilitation Specification
devices aids in the establishment of breastfeeding and • Know the diagnosis, clinical and imaging features,
better and safe handling during daily activities in these management, and outcome of spinal cord injury.
neonates.
Figure 4. A. Clinical image showing congenital torticollis at birth. B. Early intervention with facilitation device. C. Modified cervical collar made of soft
cotton cloth, foam, and strips of tough moldable cardboard.
Vol. 25, No. 8 AUGUST 2024 e509

Acknowledgments 9. Kim JH, Yum TH, Shim JS. Secondary cervicothoracic scoliosis
We thank Dr Sangeeta Ravat, Dean, Seth G.S. Medical in congenital muscular torticollis. Clin Orthop Surg. 2019;11(3):
College and King Edward Memorial Hospital, Mumbai, 344–351
India, for granting permission for publication. 10. Yang SY, Boniello AJ, Poorman CE, Chang AL, Wang S, Passias
PG. A review of the diagnosis and treatment of atlantoaxial
dislocations. Global Spine J. 2014;4(3):197–210
References 11. Chu ECP, Chakkaravarthy DM, Lo FS, Bhaumik A. Atlantoaxial
1. Kuo AA, Tritasavit S, Graham JM Jr. Congenital muscular torticollis rotatory subluxation in a 10-year-old boy. Clin Med Insights Arthritis
and positional plagiocephaly. Pediatr Rev. 2014;35(2):79–87, quiz 87 Musculoskelet Disord. 2020;13:1179544120939069
2. Neal KM, Mohamed AS. Atlantoaxial rotatory subluxation in 12. Gubin A. General description of pediatric acute wryneck condition.
children. J Am Acad Orthop Surg. 2015;23(6):382–392 In: Chung KJ, ed. Spine Surgery. London, England: IntechOpen;
2012:121–134
3. Khodabandeh M, Shakiba S, Alizadeh S, Eshaghi H. Grisel’s
syndrome associated with tonsillitis. IDCases. 2018;15:e00470 13. Fielding JW, Hawkins RJ. Atlanto-axial rotatory fixation. (Fixed
rotatory subluxation of the atlanto-axial joint). J Bone Joint Surg Am.
4. Gourin CG, Kaper B, Abdu WA, Donegan JO. Nontraumatic atlanto-
axial subluxation after retropharyngeal cellulitis: Grisel’s syndrome. 1977;59(1):37–44
Am J Otolaryngol. 2002;23(1):60–65 14. Marchand AA, Wong JJ. Conservative management of idiopathic
5. Richard SA, Lan ZG, Yang X, Huang S. An infantile alantoaxial anterior atlantoaxial subluxation without neurological deficits in an
dislocation with patent foramen ovale managed with titanium 83-year-old female: A case report. J Can Chiropr Assoc. 2014;58(1):
cabling and allogenic bone grafts. Pediatr Rep. 2018;10(1):7339 76–84
6. Kaiser JT, Reddy V, Launico MV, Lugo-Pico JG. Anatomy, head and 15. Ciftdemir M, Copuro glu C, Ozcan M, Ulusam AO, Yalnõz E.
neck: cervical vertebrae. In: StatPearls. Treasure Island, FL: Non-operative treatment in children and adolescents with
StatPearls Publishing; 2019 [Internet], Available at https://www.ncbi. atlantoaxial rotatory subluxation. Balkan Med J. 2012;29(3):
nlm.nih.gov/books/NBK539734 277–280
7. Powell EC, Leonard JR, Olsen CS, Jaffe DM, Anders J, Leonard JC. 16. Boyko N, Eppinger MA, Straka-DeMarco D, Mazzola CA. Imaging
Atlantoaxial rotatory subluxation in children. Pediatr Emerg Care. of congenital torticollis in infants: a retrospective study of an
2017;33(2):86–91 institutional protocol. J Neurosurg Pediatr. 2017;20(2):191–195
8. Hefti F. [Congenital anomalies of the spine]. [in German] Orthopade. 17. Emery C. The determinants of treatment duration for congenital
2002;31(1):34–43 muscular torticollis. Phys Ther. 1994;74(10):921–929
e510 NeoReviews

A Neonate with Epileptic

Encephalopathy
Trusha More, MD,* Prashanth Ranya Raghavendra, DM,* Sruthi Nair, DrNB,* Anitha Haribalakrishna, MD, FRACP*
*Department of Neonatology, Seth G.S. Medical College and King Edward Memorial Hospital, Mumbai, India
PRESENTATION
A female neonate born by the vaginal route to a primigravida mother (noncon-
sanguineous couple) at 39 weeks of gestation with a birthweight of 2,400 g is
admitted to the NICU for management of neonatal seizures.
At 30 hours of age, she is noted to have uprolling of eyeballs with tonic postur-
ing of all 4 limbs lasting for 30 seconds and subsiding without additional inter-
vention. This is soon followed by multiple episodes of seizures with varying
semiology, with tonic, clonic, and myoclonic spasms occurring with increasing
frequency of up to 30 to 40 episodes per day. Antiepileptic agents are sequentially
started as levetiracetam (60 mg/kg per day), phenytoin (8 mg/kg per day), and so-
dium valproate (40 mg/kg per day) without any clinical response, with new semi-
ology of seizures occurring at variable intervals of 1 to 3 hours. These seizures
were not stimulus-sensitive and did not last for more than 1 minute. Given the re-
fractory seizures, the neonate was started on midazolam infusion on day 2 after
birth, and these episodes persisted till day 5 with no significant improvement.
On reevaluating the history, the mother has no significant medical or obstet-
ric illness. Antenatal scans are suggestive of late-onset fetal growth restriction at
33 weeks of gestation with no Doppler abnormality; the cause of the same was
not evaluated. She had cried immediately after birth, with a normal Apgar score,
and was well in the first 30 hours of exclusive breastfeeding.
Examination in the interictal phase shows normal vital parameters. Her head
circumference is 13.6 in (34.5 cm) and her length is 20.7 in (52 cm) (both in the
10th–50th percentile of the modified Fenton growth chart). The remainder of
the physical examination, including the head examination, findings are normal.
There are no neurocutaneous markers. Neurologic examination shows moderate
stupor, with a poor repertoire of spontaneous limb movements, with axial and
appendicular hypotonia. The neonatal reflexes could not be elicited well consid-
ering the stuporous sensorium. The deep tendon reflexes are also just elicitable.
Other systemic examination findings are within normal limits.
AUTHOR DISCLOSURES Drs More,
Raghavendra, Nair, and Haribalakrishna
DISCUSSION have disclosed no financial relationships
relevant to this article. This commentary
Differential Diagnosis
does not contain a discussion of an
• Pyridoxine-dependent seizures. unapproved/investigative use of a
• Early infantile epileptic encephalopathy (Ohtahara syndrome). commercial product/device.

Figure. Electroencephalogram showing asynchronous burst (red arrow) and attenuation of the epileptiform activity (blue arrow). Background showing
generalized epileptiform activity.
• Early myoclonic epilepsy syndrome. activity have an effect on the cognitive and behavioral state
• Benign familial epilepsy. of the affected person. (1) Most patients have a genetic eti-
• Benign nonfamilial neonatal seizures. ology. (2) Neonatal-onset DEEs caused by mutations in
• Lennox-Gastaut syndrome. SCN2A, KCNQ2, and STXBP1 may cause profound impair-
• Nonketotic hyperglycinemia/glycine encephalopathy. ment in the affected individual. (3) DEE-11 occurs due to a
• Hypoxic ischemic encephalopathy. heterozygous missense mutation in exon 6 of the SNCA 2
Despite multiple antiepileptic drugs, there is no adequate sei- gene, resulting in the amino acid substitution of alanine
zure control. Considering a diagnosis of pyridoxine-dependent for valine at codon 208, with the exact electrophysiologic
seizures, oral pyridoxine (100 mg/d) is added and the neonate is mechanisms causing refractory seizures still unknown in
evaluated for refractory seizures, as summarized in the Table. these patients. DEE-11 results in the onset of refractory
seizures of various types: tonic, clonic, generalized, or
Actual Diagnosis myoclonic. Affected individuals can have microcephaly,
Clinical exome sequencing revealed a heterozygous mis- hypotonia, movement disorder, global developmental de-
sense variant in exon 6 of the SNC2A gene (chr2: lay, and severe intellectual impairment, with a heightened
g.165309369T>C; Depth: 147x), resulting in amino acid risk of autism spectrum disorder. (4)
substitution of alanine for valine at codon 208 (p.Val208Ala; Ohtahara syndrome is a form of developmental and ep-
ENST00000375437.7), classified as variant of uncertain sig- ileptic encephalopathy with seizure onset occurring within
nificance for the disorder developmental and epileptic en- the first 3 months after birth. (5) Classically, the seizures
cephalopathy-11 (DEE-11). are myoclonic spasms that occur in clusters, but they can
also be of varied types (partial or generalized tonic). (5) It
The Condition is characterized by a burst suppression pattern on an elec-
The term developmental and epileptic encephalopathy (DEE) troencephalogram (EEG). Ohtahara syndrome is associated
is used when developmental impairment and epileptic with SCN2A mutations in 16% of the clinical cases. (6)
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Table. Evaluation for Refractory Seizures
Laboratory Investigation Patient Value Reference Range
Complete blood cell count
Hemoglobin (gm/dL) 17.4 13.4–23.7
Total leukocyte count (/lL [×109/L]) 15,500 (15.5) 5,000–20,000 (5.0–20.0)
Platelet count (X103/lL) 250 150–470
Blood glucose (mg/dL [mmol/L]) 110 (6.11) 60–125 (3.33–6.94)
Blood gas (venous)
pH 7.37 7.35–7.45
PCO2 (mm Hg [kPa]) 38 (5.05) 35–45 (4.66–5.99)
PO2 (mm Hg [kPa]) 65 (8.64) 50–70 (6.65–9.31)
Bicarbonate (mEq/L [mmol/L]) 21 (21) 18–24 (18–24)
CSF examination
Cells (/mm3) 00 Up to 20
Polymorphs (cells/cumm) 00 00
Lymphocytes (cells/cumm) 00 00
Protein (g/dL) 0.038 Up to 0.15
Glucose (mg/dL [mmol/L]) 63 (3.5) 2/3 of the blood glucose
CSF culture No growth NA
Ionized calcium (mg/dL [mmol/L]) 4.8 (1.2) 4.0–6.0 (1.0–1.5)
Serum magnesium (mg/dL [mmol/L]) 2.12 (0.87) 1.6–2.4 (0.66–0.99)
Serum ammonia (lg/L) 138 70–150
Serum lactate (mg/dL[mmol/L]) 9.91 (1.1) 4.5–19.82 (0.5–2.2)
TMS and GCMS profile Normal NA
Plasma pipecolic acid (lmol/L) 0.12 <5
a-Amino adipic semialdehyde (lmol/L) 0.60 0–1.0
Cranial ultrasonography Normal NA
MRI of the brain Normal NA
Electroencephalography (Fig) Asynchronous burst with background
showing generalized epileptiform activity NA
(burst suppression)
CSF5cerebrospinal fluid, GCMS5gas chromatography–mass spectrometry, MRI5magnetic resonance imaging, NA5not applicable, TMS5tandem
mass spectrometry.
A study of 71 new patients and a review of 130 established carbamazepine is added (400 mg/d). The frequency of seiz-
patients (34 patients with neonatal onset of seizures) with ures, which initially occur 30 to 40 times a day, reduces to
SCN2A mutation showed that individuals with early onset 8 to 10 episodes per day during the next week and later to
had gain-of-function mutations responding to sodium channel 2 to 3 episodes per day with the prominent semiology being
blockers, including carbamazepine, whereas those with late tonic seizures followed by infantile spasms. The repeated
onset may have loss-of-function mutations whose detrimental EEG shows a reduction in the seizure burden with persis-
effect would be exacerbated by sodium channel blockers. (4) tence of burst suppression. The neonate continues to be neu-
Early initiation of antiepileptic drugs may lead to improved rologically abnormal with exaggerated deep tendon reflexes.
cognitive outcomes. Our neonate had early-onset seizures of Oromotor incoordination is managed by a multidisciplinary
varied types that eventually changed to myoclonic spasms with team of neonatologists, occupational therapists, and lactation
hypotonia and responded to carbamazepine therapy. Although counselors, and she is transitioned to spoon feeds by 28 days
the genetic report of our patient showed a variant of uncertain of age. Early intervention therapy with the promotion of ac-
significance, the clinical phenotype fits into the description of tive movements is initiated, and she is discharged on day 40
the disease in question. Confirmatory testing with the parent’s of age after genetic counseling of the parents. The neonate is
sample could not be performed due to financial constraints. currently 4 months old and is microcephalic with a head cir-
The outcome is usually not favorable, with this mutation in cumference of 14.4 in (36.5 cm). The Hammersmith Infant
SCNA2 leading to global developmental delay and develop- Neurological Examination score is 44, suggestive of a 96%
ment of movement disorders, including dystonia and chorea. risk of developing cerebral palsy(7) and global developmental
Mortality can be seen in 15% of patients by 20 years of age. (6) delay with no head control, unable to reach objects, and non-
vocalizing. Brainstem auditory evoked response testing on
Patient Course follow-up is normal, and a visual evoked potential test is
On diagnosis of Ohtahara syndrome and evaluation of the planned. Compliance with antiseizure medications is satisfac-
EEG in consultation with a pediatric neurologist, oral tory, and regular follow-up is occurring.

Lessons for the Clinician India, for granting permission for publication and Dr S.
• In neonates with refractory seizures, a genetic evaluation for Chandrakala, professor and head of department, Depart-
neonatal epilepsy leads to better management of seizures ment of Hematology, Seth G.S. Medical College and
King Edward Memorial Hospital, for the hematology
and prediction of prognosis. SCN2A–related developmental
images.
and epileptic encephalopathy (DEE) can manifest with varied
semiology of convulsions and occurs multiple times a day.
• Early-onset DEE due to SCN2A mutation responds to References
carbamazepine therapy with better seizure control. 1. Scheffer IE, French J, Hirsch E, et al. Classification of the epilepsies:
• Global developmental delay in DEE requires early interven- New concepts for discussion and debate-Special report of the ILAE
Classification Task Force of the Commission for Classification and
tion and multidisciplinary care from the neonatal period. Terminology. Epilepsia Open. 2016;1(1–2):37–44
2. Nakamura K, Kato M, Osaka H, et al. Clinical spectrum of SCN2A
mutations expanding to Ohtahara syndrome. Neurology. 2013;81(11):
992–998
3. Shellhaas RA, Wusthoff CJ, Tsuchida TN, et al; Neonatal Seizure
American Board of Pediatrics Registry. Profile of neonatal epilepsies: Characteristics of a prospective
US cohort. Neurology. 2017;89(9):893–899
Neonatal-Perinatal Content 4. Wolff M, Johannesen KM, Hedrich UBS, et al. Genetic and phenotypic
Specifications heterogeneity suggest therapeutic implications in SCN2A-related
disorders. Brain. 2017;140(5):1316–1336
• Understand the differential diagnosis and evaluation
of neonatal seizures. 5. Beal JC, Cherian K, Moshe SL. Early-onset epileptic encephalopathies:
Ohtahara syndrome and early myoclonic encephalopathy. Pediatr
• Understand the management of neonatal seizures, in-
Neurol. 2012;47(5):317–323
cluding the role of neurophysiologic monitoring.
6. Howell KB, McMahon JM, Carvill GL, et al. SCN2A encephalopathy:
• Understand the prognostic significance of electroen-
A major cause of epilepsy of infancy with migrating focal seizures.
cephalographic patterns, such as burst suppression.
Neurology. 2015;85(11):958–966
7. Romeo DM, Cioni M, Scoto M, Mazzone L, Palermo F, Romeo MG.
Neuromotor development in infants with cerebral palsy
Acknowledgments investigated by the Hammersmith Infant Neurological
We thank Dr Sangeeta Ravat, dean, Seth G.S. Medical Examination during the first year of age. Eur J Paediatr Neurol.
College and King Edward Memorial Hospital, Mumbai, 2008;12(1):24–31
e514 NeoReviews

Newborn with In Utero Lead Toxicity

Cyndee Jocson, MD,* Babina Nayak, MD, FAAP†
*Department of Pediatrics, Harlem Hospital Center, New York, NY
†
Division of Neonatology, Department of Pediatrics, Harlem Hospital Center, New York, NY
PRESENTATION
A female infant is born at 40 weeks 2 days gestational age to a 29-year-old grav-
ida 7, para 1 mother via vaginal delivery with Apgar scores of 9 and 9 at 1 and
5 minutes. Routine steps are performed at birth, and the infant is admitted to the
newborn nursery. Findings from the infant’s physical examination, including a
detailed neurologic examination, are normal.
The antenatal history is significant for threatened abortion at 14 weeks’ gesta-
tional age and pica, which began during the first trimester, resulting in inges-
tion of paint chips at home. Maternal blood lead levels (BLLs) remained elevated
throughout pregnancy, with the highest level during the third trimester (range,
16–42 mg/dL [0.77–2.03 mmol/L]).
Mother had a similar habit during adolescence, but she claims to have none during
her previous pregnancies and denies any neurodevelopmental or behavioral disorders
in her only living child. She had 5 spontaneous abortions before her successful preg-
nancies. The case was further escalated to the Department of Health (DOH) by her
obstetrician during the first trimester antenatal visits, and necessary measures were
taken by the DOH, including a thorough inspection and repainting of the house.
At birth, the infant’s screening test is remarkable for a capillary lead level of
32 mg/dL (1.54 mmol/L) (newborn reference values, <3.5 mg/dL [<0.17 mmol/L]).
Additional evaluations for the infant, including complete blood cell count and
iron studies, are obtained, and the results are within normal limits for age.
Screening head ultrasonography is performed and is reported to have normal
findings. A lead poisoning specialist is consulted for recommendations on further
management of the patient. The infant is advised to have close monitoring with
serial follow-up for repeated BLLs, and no chelation therapy is recommended at
the time. Also, no further neuroimaging studies or a skeletal survey is recom-
mended. However, following the Centers for Disease Control and Prevention
(CDC) guidelines to defer human milk with maternal BLLs of 40 mg/dL or greater
($1.93 mmol/L), the mother is advised not to breastfeed the infant at the time. (1)
AUTHOR DISCLOSURE Drs Jocson and
After an uneventful nursery stay, the infant is discharged on the second day Nayak have disclosed no financial
after birth. A routine health supervision appointment with the primary care pe- relationships relevant to this article. This
diatrician, a lead clinic appointment, and an early intervention program referral commentary does not contain a
discussion of an unapproved/
were made before discharge. As per local DOH protocol, a venous lead level is investigative use of a commercial
collected on the infant in the primary care clinic after 1 week, which is product/device.

remarkable for a BLL of 28 mg/dL (1.35 mmol/L), followed levels in pregnancy have been associated with gestational
by a repeated level of 30 mg/dL (1.45 mmol/L) collected in hypertension, spontaneous abortion, low birthweight, and
the lead clinic after 2 weeks. Thereafter, serial testing for preterm labor. (1) Lead readily crosses the placenta via pas-
follow-up BLLs in the infant at 2, 4, 8, and 11 months are sive diffusion, thus the fetal lead level is the direct reflection
19 mg/dL (0.92 mmol/L), 21 mg/dL (1.01 mmol/L), 14 mg/dL of the concentration of lead in the maternal blood. Lead lev-
(0.68 mmol/L), and 8 mg/dL (0.39 mmol/L), respectively. els in human milk also increase with increases in maternal
Currently, the infant is 12 months old and continues to lead levels (Fig). (1)(3) In this case, the child was never
follow up in the lead clinic and has regular health supervi- breastfed by the mother during the first year after birth.
sion visits in the primary care clinic; she requires close Children with lead toxicity may be completely asymp-
neurodevelopmental monitoring, with no active concerns tomatic. Acute lead toxicity should be suspected in chil-
to date. In addition, she is being followed by an early in- dren presenting with gastrointestinal symptoms such as
tervention program. She is up to date on immunizations, constipation or obstipation, vomiting, or anorexia and neu-
growing appropriately for age, achieving milestones on rologic changes such as lethargy, irritability, or hyperactiv-
time, and shows no developmental delays. Her most re- ity. Physical examination findings may include evidence of
cent lead level is 8 mg/dL (0.39 mmol/L). increased intracranial pressure or pallor resulting from se-
vere anemia. (4)
DISCUSSION Lead is known to interfere with synaptogenesis, thus
Lead poisoning is a type of poisoning caused by the highly negatively impacting fetal brain cells in the developing
toxic metal lead in the body. It is a cumulative toxicant brain. It substitutes for calcium and zinc as a second mes-
that affects multiple body systems and is particularly senger, which in turn interferes with stimulated neurotrans-
harmful to infants and growing children. Due to its struc- mitter release at synapse, disrupting cell differentiation,
tural similarity to calcium, lead competes with calcium for myelination, and organization of synaptic connections. (2)(5)
absorption in the gastrointestinal tract and is primarily The permeable nature of the fetal blood-brain barrier makes
stored in bones and teeth. (2) Lead stored in bones has a the fetal brain cells more sensitive to lead. Because there is
longer half-life (20–30 years) and can be mobilized into less bone tissue in the fetus for sequestering lead, the devel-
blood and soft tissues during periods of heightened bone oping central nervous system becomes considerably vulnera-
turnover, such as pregnancy and lactation. Elevated lead ble to lead toxicity. (1)(6)
Figure. Major lead exposure pathways from mother to infant. Reprinted from the CDC Guidelines for the Identification and Management of Lead Expo-
sure in Pregnant and Lactating Women. (1)
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Children exposed to lead in utero have been widely requiring chelation therapy. (12) The inhibition of heme
demonstrated to have poor cognition, learning difficulties, synthesis leads to the accumulation of excess porphyrins.
behavioral issues, and attention problems even at levels The level of erythrocyte protoporphyrin, which is assayed as
below the upper limit of the reference value of 5 mg/dL zinc protoporphyrin, is elevated when lead levels are greater
(0.24 mmol/L) set by the CDC. (7) Multiple studies have than 20 mg/dL (>0.97 mmol/L). In children with higher
shown that in utero exposure to even low levels of lead BLLs, serial measurement of erythrocyte protoporphyrin
can affect infant and child growth and neurodevelopment levels is a useful indicator of the effects of lead as well as
likely due to altered neuronal connectivity and atypical pat- the efficacy of treatment. (9) A plain abdominal radiograph
terns of brain development. (7)(8) Results of a cohort to assess for radio-opaque lead flecks is reserved for symp-
study by Fruh et al(7) demonstrated that BLLs were related tomatic children with a history of pica or ingestion of lead-
to impaired executive function and behavioral difficulties. containing products and in children with an unexpected
Similarly, Markowitz(9) reported an inverse relationship acute rise in BLL. (12)
between BLL and IQ, with an estimated 0.5-point loss for
every 1-mg/dL (0.05-mmol/L) increase in BLL, as well as a CONCLUSION
direct relationship between lead levels of 20 mg/dL and Despite improvements in environmental policies and signifi-
greater ($0.97 mmol/L) and attention deficits and disrup- cant reduction in US average BLLs, lead exposure remains a
tive and aggressive behaviors in children. Lead poisoning concern for pregnant and lactating women. Elevated mater-
can also present as encephalopathy, seizure, and death nal BLLs are not uncommon with lead exposure during
with significantly elevated levels higher than 100 mg/dL pregnancy. This is a unique case of a newborn demonstrat-
(>4.83 mmol/L). (9) To mitigate these effects, chelation ing significantly high BLLs at birth after in utero exposure.
therapy should always be considered when the BLL reaches
45 mg/dL (2.17 mmol/L). At levels lower than 45 mg/dL Lessons for the Clinician
(<2.17 mmol/L), chelation therapy has not been shown to • Primary prevention is still needed despite our general
decrease the negative effects of lead. (10) education about lead exposure.
Accumulation of lead in other organs may also have • Continuous efforts must be made to bring awareness
subclinical effects. Lead inhibits erythropoiesis by reduc- and eliminate prenatal exposure to lead to prevent detri-
ing erythropoietin production and decreasing red blood mental outcomes in vulnerable infants.
cell survival. Gouty nephropathy with decreased glomeru- • More importantly, due to the potential neurodevelopmental
lar filtration may occur, resulting in renal insufficiency impact of lead, prompt identification and close monitoring
and Fanconi syndrome. Spermatogenesis may likewise be- of infants with elevated lead levels should be emphasized.
come impaired. Other effects include hearing loss, hyper-
tension, and stunted growth. (9)
Routine blood lead testing of pregnant women is not
recommended by the American College of Obstetricians
and Gynecologists. Individuals are evaluated based on cer- Neonatal-Perinatal Content
tain risk factors, including recent emigration from areas Specification
of high ambient lead contamination; living or working • Know the effects on the fetus and/or newborn infant
near a point source of lead; using lead-glazed ceramic pot- of exposure during pregnancy to environmental agents
tery; eating nonfood substances; renovating or remodeling (mercury, pesticides, etc).
older homes without lead protection; using alternative

substances, herbs, or therapies; using imported ceramics;
engaging in high-risk activities, such as pottery making;
having a history of previous lead exposure; or living with References
someone with an elevated lead level. Blood lead testing is 1. Ettinger AS, Guthrie Wengrovitz A, eds. Guidelines for the
then performed if a single risk factor is identified. (11) Identification and Management of Lead Exposure in Pregnant and
In a child with an elevated BLL, screening for iron defi- Lactating Women. Atlanta, GA: US Department of Health and
Human Services; 2010, Available at https://www.cdc.gov/nceh/lead/
ciency anemia, including a complete blood cell count, ferri- publications/leadandpregnancy2010.pdf
tin level, and C-reactive protein level, should be performed. 2. Goldstein GW. Lead poisoning and brain cell function. Environ
Liver and renal function testing is performed for children Health Perspect. 1990;89:91–94

3. Lidsky TI, Schneider JS. Lead neurotoxicity in children: basic 8. Thomason ME, Hect JL, Rauh VA, et al. Prenatal lead exposure
mechanisms and clinical correlates. Brain. 2003;126(Pt 1):5–19 impacts cross-hemispheric and long-range connectivity in the
4. Markowitz M. Lead poisoning. Pediatr Rev. 2000;21(10):327–335 human fetal brain. Neuroimage. 2019;191:186–192
5. Shah-Kulkarni S, Ha M, Kim BM, et al. Neurodevelopment in early 9. Markowitz M. Lead poisoning: an update. Pediatr Rev.
childhood affected by prenatal lead exposure and iron intake. 2021;42(6):302–315
Medicine (Baltimore). 2016;95(4):e2508 10. Hauptman M, Bruccoleri R, Woolf AD. An update on childhood
6. Hu H, Tellez-Rojo MM, Bellinger D, et al. Fetal lead exposure lead poisoning. Clin Pediatr Emerg Med. 2017;18(3):181–192
at each stage of pregnancy as a predictor of infant mental 11. Committee on Obstetric Practice. Committee opinion No. 533: lead
development. Environ Health Perspect. 2006;114(11): screening during pregnancy and lactation. Obstet Gynecol.
1730–1735 2012;120(2)(pt 1):416–420
7. Fruh V, Rifas-Shiman SL, Amarasiriwardena C, et al. Prenatal 12. Harvey B, ed. Managing Elevated Blood Lead Levels Among Young
lead exposure and childhood executive function and behavioral children: Recommendations from the Advisory Committee on Childhood
difficulties in project viva. Neurotoxicology. 2019;75: Lead Poisoning Prevention. Atlanta, GA: Centers for Disease Control
105–115 and Prevention; 2002
e518 NeoReviews

MATERNAL-FETAL CASE STUDIES
Surgical Management of Appendicitis

During Pregnancy
Sania Rahim, MD,* Brett C. Young, MD*†
*Department of Obstetrics-Gynecology, Beth Israel Deaconess Medical Center, Boston, MA
†
Department of Obstetrics-Gynecology, Mount Auburn Hospital, Cambridge, MA
CASE PRESENTATION
A 35-year-old gravida 2, para 1-0-0-1 mother at 33.1 weeks’ gestation presented to
the emergency department with a 2-day history of low-grade fever; nonbloody,
nonbilious emesis; nonbloody diarrhea; and right lower quadrant pain. She noted
sporadic contractions. Physical examination demonstrated right lower quadrant
tenderness with rebound and guarding on examination. No fundal tenderness
was present. Initial vital signs demonstrated a temperature of 100.3 F (37.9 C), a
pulse of 105 beats/min, and a blood pressure of 121/73 mm Hg. Fetal monitoring
revealed a reactive nonstress test, with maternal contractions every 4 minutes.
The patient’s cervix was closed on examination. Laboratory evaluation was
significant for leukocytosis, with a white blood cell count of 23,000/mL
(23 × 109/L). The differential diagnosis included appendicitis, preterm labor, intra-
amniotic infection, and gastroenteritis. General surgery consultation was obtained
given the possible diagnosis of appendicitis.
Further evaluation of the maternal clinical status included imaging with pel-
vic ultrasonography, which was normal, with nonvisualization of the appendix.
The ovaries were normal. The fetus had active movement and normal amniotic
fluid. A pelvic magnetic resonance image (MRI) demonstrated an enlarged ap-
pendix measuring 8 mm in diameter with periappendiceal fat infiltration (Fig 1).
CASE PROGRESSION
An urgent consultation was placed with general surgery, who advised expedited
surgical management to avoid appendiceal rupture. Multidisciplinary care with
maternal-fetal medicine and general surgery occurred with discussion about the
surgical approach for the appendectomy. She received a dose of ceftriaxone and
metronidazole preoperatively. The patient was counseled regarding the benefits
and risks of surgical management compared with medical management with
antibiotics alone. The potential risks of medical management alone, including
progression and appendiceal rupture, development of preterm labor, and mater-
AUTHOR DISCLOSURES Drs Rahim and
nal systemic infection, were discussed. The patient agreed to surgical manage- Young have disclosed no financial
ment with intermittent fetal monitoring. relationships relevant to this article. This
A preoperative huddle occurred with the multidisciplinary care team, including commentary does not contain a
general surgery, maternal-fetal medicine, neonatology, anesthesia, and nursing. investigative use of a commercial
Preparation regarding maternal surgical positioning, intermittent fetal monitoring product/device.

postoperative fetal monitoring was reassuring (Fig 2). On
postoperative day 1, the patient was discharged, still pregnant,
to resume scheduled prenatal care.
Maternal Outcome
The patient presents in spontaneous labor at 39.3 weeks’
gestation. She has an uncomplicated vaginal birth and is
discharged on postpartum day 2.
Neonatal Outcome
The male neonate was delivered at term weighing 3,856 g,
with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively.
The neonate was admitted to the regular nursery without is-
sue and was discharged with his mother.
DISCUSSION
Figure 1. Magnetic resonance image demonstrating acute appendicitis at
33 weeks' gestation. The red circle denotes the appendix measuring 8 mm Appendicitis is the leading cause of nonobstetric surgery in
in greatest diameter in the right lower pelvis. The red arrow points to the
fetus in the uterus.
pregnant individuals. Similar to nonpregnant patients, ap-
pendicitis in pregnant patients is most commonly caused
by ultrasonography, and general anesthesia occurred. The by obstruction of the appendiceal lumen. Diagnosis can of-
patient proceeded to the operating room for laparoscopic ten be delayed or more difficult in pregnancy due to the
appendectomy with possible open appendectomy. Prepara- shifts in anatomy with the gravid uterus, atypical symptoms
tion was made for the rare possibility of a cesarean delivery. or symptoms that are mistaken for other pregnancy-related
symptoms, and physiologic changes in laboratory values in
OUTCOME normal pregnancy, such as leukocytosis. (1)
An uncomplicated laparoscopic appendectomy was per- Overall, the goal of managing acute appendicitis in
formed. There was no evidence of appendiceal perforation. pregnancy centers around the principle of maintaining
Intermittent fetal monitoring was performed by the obstetri- maternal stability with prompt treatment to optimize ma-
cian via ultrasonography using a sterile transducer cover. A ternal and fetal outcomes. Although elective surgery is typ-
cesarean delivery kit was available, and the neonatology team ically deferred until after pregnancy, acute appendicitis
was aware of the ongoing procedure. The fetal heart rate re- warrants expedited pursuit of surgical management before
mained normal. The patient was extubated and tolerated the appendiceal perforation occurs. Ruptured appendicitis in-
procedure well, with no complications. She remained hemo- creases the risk of maternal sepsis, abscess formation, and
dynamically stable postoperatively, and a repeated white blood pregnancy complications such as preterm labor and still-
cell count improved to 16,000/mL (16 × 109/L). Two hours of birth. Prompt recognition with appropriate evaluation and
Figure 2. Postoperative reactive fetal monitoring demonstrating a category 1 fetal tracing.
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Approximately 2% of pregnant individuals require non-
obstetric surgery during pregnancy. Typically, procedures
described as elective should be delayed until the postpar-
tum period as long as the delay does not cause deleterious
• effects to the pregnant person’s health. Due to the chal-
lenges of conducting randomized clinical trials in the
• pregnant population, data to guide specific recommenda-
• tions regarding surgery in pregnancy are lacking. A medi-
cally necessary surgery should not be delayed regardless of
the trimester or denied due to the risk of adversely affect-
• ing not only the pregnant individual but also her fetus. De-
lays in surgical treatment of medically necessary conditions
such as appendicitis, cholecystitis or choledocholithiasis can
Figure 3. Surgical Considerations in Pregnancy.
lead to pregnancy complications and deterioration of both
the maternal and fetal statuses. Although there may be risk
targeted treatment are essential in avoiding these compli-
of surgical complications from any procedure, in a preg-
cations. (1)
nant individual, delays resulting in a more advanced medi-
Imaging is an essential component of the diagnostic
cal condition, such as systemic infection, increase the
evaluation for all pregnant patients with suspected acute
likelihood of pregnancy complications. Given the physio-
appendicitis. The American College of Obstetricians and
logic changes in pregnancy and unique anatomic differ-
Gynecologists’ Committee on Obstetric Practice has rec-
ences in the abdomen and pelvis from the gravid uterus,
ommended that with respect to imaging during preg-
consultation with obstetrics is advised to optimize the surgi-
nancy, ultrasonography and MRI should be the modalities
cal setup and procedure (Fig 3).
of choice given their lack of ionizing radiation, which can
There has not been demonstrated teratogenic risk with the
negatively impact the developing fetus. (2) Ultrasonogra-
use of any anesthetic agents in pregnancy, and, therefore,
phy is a low-risk and readily available imaging modality standard use of anesthetic agents similar to the nonpregnant
that can be used as an initial imaging step to evaluate for population in conjunction with anesthesia personnel is ad-
appendicitis or another pelvic pathology. The appendix vised. (4) Unique anatomic changes with the gravid uterus
may not be imaged due to the gravid uterus or the varied warrant tilting the patient slightly, avoiding the direct supine
location of the appendix in pregnancy. (2) MRI provides position, which may result in hypotension from vena caval
additional benefit compared with ultrasonography given compression. (4) Optimizing mean arterial pressure in a
its ability to provide more detailed visualization of soft tis- pregnant person during surgery lessens the likelihood of hy-
sue structures. MRI has lower rates of nonvisualization poperfusion of the uterus. Similarly, fetal heart rate monitor-
compared with ultrasonography. Furthermore, there is evi- ing may be considered concurrently during a surgery in a
dence that MRI can improve diagnostic accuracy by de- viable fetus and used as an additional assessment of optimiz-
creasing the rate of negative appendectomies in pregnant ing maternal positioning and cardiorespiratory management.
patients. (3) Note that the use of gadolinium in contrasted (4) The likelihood of need for an unexpected cesarean deliv-
MRI studies during pregnancy has been controversial due ery intraoperatively is low, particularly with an intraoperative
to unknown effects on the developing fetus. MRI without hemodynamically stable maternal status. Obstetric personnel
gadolinium can reliably assess the appendix. If MRI is not with the capability to perform an emergency cesarean delivery
available in a timely manner and diagnostic imaging is in- are necessary if fetal monitoring is to occur. (4)
dicated, computed tomography (CT) of the pelvis can be Appendectomy is the definitive surgical treatment for
considered after discussion of the risks and benefits. (2) most cases of appendicitis in both pregnant and nonpreg-
The radiation exposure from CT of the pelvis may be asso- nant patients. (1) There are many important considerations
ciated with a slight increased risk of neonatal malignancy in performing nonobstetric procedures in pregnant pa-
by a factor of 2 above a background risk of 1 in 3,000. A tients, including proper maternal positioning, coordinated
single CT scan of the pelvis using a low-dose radiation multidisciplinary care, and monitoring of both maternal
protocol is expected to deliver a lower radiation exposure and fetal hemodynamics according to gestational age. If
than the stated radiation threshold in pregnancy. (2) managed appropriately, there is relatively low risk for any

need to proceed to urgent delivery. This patient presented in References
the third trimester with acute appendicitis and had an un-
complicated surgery and recovery resulting in a term uncom- 1. Aptilon Duque G, Oladipo AF, Lotfollahzadeh S. Appendicitis in
plicated delivery. pregnancy. In: StatPearls. Treasure Island, FL: StatPearls Publishing;
2024 [Internet], Available at http://www.ncbi.nlm.nih.gov/books/
NBK551642/. Accessed May 5, 2024
2. Committee Opinion No. 723: guidelines for diagnostic imaging
American Board of Pediatrics during pregnancy and lactation. [published correction appears in
Neonatal-Perinatal Content Obstet Gynecol. 2018;132(3):786] Obstet Gynecol. 2017;130(4):
Specification e210–e216
3. Kereshi B, Lee KS, Siewert B, Mortele KJ. Clinical utility of magnetic
• Know the effects on the fetus and/or newborn
resonance imaging in the evaluation of pregnant females with
infant of maternal surgery and anesthesia (eg suspected acute appendicitis. Abdom Radiol (NY). 2018;43(6):
appendectomy). 1446–1455
4. ACOG Committee Opinion No. 775: nonobstetric surgery during
pregnancy. Obstet Gynecol. 2019;133(4):e285–e286
e522 NeoReviews

VISUAL DIAGNOSIS
A Necrotic Ulcer in an Extremely

Premature Infant
Victoria Hayes Aguilar, MD,* Jodi Amador, DNP,† Christina Marie Hulgan, DO,‡ Matthew Saxonhouse, MD,‡
Andrew J. Rand, MD,§ Keerti L. Dantuluri, MD, MPH¶
*Department of Pediatrics, Levine Children’s Hospital at Atrium Health, Charlotte, NC
†
Division of Neonatology, Department of Pediatrics, Levine Children’s Hospital at Atrium Health, Charlotte, NC
‡
Division of Neonatology, Department of Pediatrics, Wake Forest University School of Medicine, Levine Children’s Hospital at Atrium Health, Charlotte, NC
§
Department of Pathology, Atrium Health, Charlotte, NC
¶
Division of Infectious Diseases, Department of Pediatrics, Wake Forest University School of Medicine, Charlotte, NC
THE CASE
A 9-day-old boy born at 24 0/7 weeks’ gestation with a large necrotic area in the
right malar region.
Prenatal and Birth Histories

• Born to a 22-year-old primigravida woman.
• Prenatal course notable for maternal tobacco and marijuana use.
• Estimated gestational age: 24 0/7 weeks.
• Spontaneous vaginal delivery with preterm premature rupture of membranes
due to unstoppable labor.
• Apgar scores: 2, 4, and 8 at 1, 5, and 10 minutes, respectively.
• Infant is intubated in the delivery room due to respiratory distress and brought to
the NICU for further care.
• Birthweight: 629 g (41 percentile).
• Birth length: 13 in (33 cm) (85 percentile).
• Birth head circumference: 8.3 in (21 cm) (28 percentile).
Presentation
AUTHOR DISCLOSURE Dr Saxonhouse is
At 9 days of age, the infant had an unplanned extubation, followed by reintuba-
the co-director of Specialty Review in
tion, that led to a skin laceration, which appears like a small abrasion that was Neonatology and has received payment
scabbed, on the infant’s right malar region. After the endotracheal tube tape was as part of the review course for Neonatal
Insider. Drs Aguilar, Amador, Hulgan,
retaped 3 days later, this area appears necrotic, covering a larger area than the
Rand, and Dantuluri have disclosed no
initial abrasion. The NICU team orders a complete blood cell count and blood financial relationships relevant to this
culture, and the infant is started on vancomycin and cefepime. The white blood article. This commentary does not
cell count is 8,810/mL (8.81 × 109/L), with a differential count of 35% neutro-
investigative use of a commercial
phils, 3% bands, 23% lymphocytes, 23% monocytes, 3% metamyelocytes, 3% product/device. This case is based on a
myelocytes, and 1% varying other cell types. The infant’s hemoglobin level is presentation by Dr Victoria Hayes Aguilar
10.8 g/dL (108 g/L), with a platelet count of 76 × 103/mL (76 × 109/L). The follow- at the North Carolina Pediatric Society,
Wilmington, NC, Poster Session,
ing day, the infant is transferred to our hospital for evaluation by plastic surgery Presentation Date: September 9, 2023,
and pediatric infectious diseases. Poster Number: 22.
Vol. 25 No. 8 AUGUST 2024 523

PROGRESSION with growth of Enterococcus faecalis and Candida albicans,
Vital Signs prompting adjustment of the antimicrobial regimen to
• Heart rate: 158 beats/min. piperacillin-tazobactam and fluconazole. At 22 days of age,
• Respiratory rate: 30 breaths/min. the necrotic ulcer sloughs off, resulting in decreased subcuta-
• Blood pressure: 81/43 mm Hg. neous and deep tissue at the ulcer site (Fig 2), and the tissue
• Oxygen saturation: 100% on high-flow oscillator ventila- is sent for culture and pathologic examination.
tor (fraction of inspired oxygen, 1.0; mean airway pres-
sure, 15 mm Hg; Hertz, 13; amplitude, 28). DIFFERENTIAL DIAGNOSIS
• Facial necrotic ulcer in a preterm infant.
Physical Examination (Day 13) • Ecthyma gangrenosum (EG).
• General: Small-for–gestational age infant, intubated and • Cutaneous mucormycosis.
sedated. • Necrotizing fasciitis.
• Head: Normocephalic; normal, open, flat fontanelles; sym-
metrical facies; patent nares; intact palate; no neck mass or ACTUAL DIAGNOSIS
crepitus. Cutaneous Mucormycosis
• Oral cavity: Pink mucosae, intact palate, no lymphadenopathy. Initially, the patient is diagnosed as having EG due to the
• Lungs: Symmetrical chest rise, bilateral and equal venti- positive wound culture growing E faecalis and C albicans,
lator sounds. which are common organisms of EG. (1) However, the
• Cardiovascular: Normal S1, S2 heart sounds; regular rate
wound culture from the necrotic tissue grows E faecalis, C
and rhythm; grade I/VI murmur, capillary refill time of
albicans, and Rhizopus species. Furthermore, the pathology
4 seconds, femoral pulses equal and strong.
report demonstrates necrotic tissue with numerous fungal
• Abdomen: Normal bowel sounds; no hepatosplenome-
hyphae morphologically suggestive of mucormycosis (Fig 3),
galy; nondistended, nontender.
prompting the definitive diagnosis of cutaneous mucormy-
• Genitourinary: Normal preterm male genitalia; patent anus.
cosis with superimposed E faecalis and C albicans infection.
• Skeletal: Spine appears normal.
Based on these results, piperacillin-tazobactam and flu-
• Skin: 2x2-cm necrotic ulcer on the right malar region
conazole are discontinued and intravenous deoxycholate
with visible base and clear drainage (Fig 1).
• Neurologic: sedated.
A repeated blood culture is sent along with a wound cul-
ture. The plastic surgery team recommends deferring surgery
and pursuing medical management. The pediatric infectious
diseases team recommends the addition of fluconazole for
possible fungal infection. All blood culture results are nega-
tive. The wound culture results are reported at 18 days of age
Figure 2. Necrotic ulcer has sloughed off at 22 days of age, resulting in

Figure 1. Necrotic ulcer at 13 days of age. decreased subcutaneous and deep tissue at the ulcer site.
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Figure 3. Pathology of necrotic ulcer. A and B. Necrotic skin with diffuse fungal organisms morphologically consistent with mucormycosis. C and D. Organisms
are nonpigmented, broad (5–15 mm in diameter), ribbonlike hyphae with right-angle branching and few septations, identified on the hematoxylin-eosin stain.
amphotericin B is initiated. When the infant is 51 days old, Rhizopus, Mucor, Lichtheimia species, and Rhizomucor species.
plastic surgery performs a punch biopsy of the wound mar- Pathogen identification occurs through histopathologic exami-
gin to ensure that the infection is cleared. At 79 days of age, nation of tissue and culture, both of which were performed
the biopsy culture from the wound margins finalizes as neg- in this patient. (2)
ative, and deoxycholate amphotericin B is discontinued. Deoxycholate amphotericin B is used to initially treat cutane-
This patient receives 56 days of treatment with deoxycholate ous mucormycosis, but surgical debridement is typically crucial
amphotericin B for cutaneous mucormycosis and never re- to ensure that appropriate source control is obtained. (3) Al-
quires surgical debridement. though rare, previous cases of neonatal cutaneous mucormycosis
The patient is successfully discharged from the NICU at have been reported, and at least 1 case details successful manage-
104 days of age on home oxygen via low-flow cannula for ment with amphotericin B alone, similar to our patient. (4)
chronic lung disease and ad lib feedings. His physical exam- Similar to cutaneous mucormycosis, EG occurs in immu-
ination at that time shows a well-healed right malar region nocompromised or critically ill patients. EG is associated with
with scar (Fig 4). One month after discharge, he is evaluated
by pediatric plastic surgery. Plastic surgery plans to evaluate
annually for a few years to assess for the development of im-
paired tissue growth due to scar tissue and whether fat
grafting will be indicated. At the time this manuscript was
written, the patient did not required surgical intervention.
What the Experts Say

Cutaneous mucormycosis is a rare mold infection that most
often occurs in immunocompromised patients, frequently
in the respiratory tract and skin. (2) Cutaneous infections can
result from traumatic wounds, similar to this patient. Other
risk factors identified for cutaneous mucormycosis include
prematurity, low birthweight, broad-spectrum antibiotic use,
and corticosteroid therapy. (3) Common pathogens include Figure 4. Well-healed right malar region with scar at 3 months of age.
Vol. 25 No. 8 AUGUST 2024 525

hemorrhagic pustules that evolve into necrotic, gangrenous ul-
cers with black-gray eschar. (1) These ulcers usually are the se- American Board of Pediatrics
quelae of pathogenic perivascular invasion of vessels that leads Neonatal-Perinatal Content
to ischemic necrosis. The most common bacterial cause of EG
Specifications
is Pseudomonas aeruginosa, but multiple other pathogens have
• Know the clinical manifestations and diagnostic fea-
been reported, including Escherichia coli, Staphylococcus aureus, tures of neonatal fungal infections.
Streptococcus pyogenes, Aeromonas species, and Citrobacter spe- • Know the epidemiology, prevention, and pathogenesis
cies. (1)(2)(5) A viral pathogen to consider is herpes simplex vi- of neonatal fungal infections.
rus, whereas fungal pathogens include Candida, Aspergillus, • Know the treatment and complications of neonatal
and Fusarium species. (1) E faecalis is not a bacterial cause that fungal infections.
has commonly been reported as a cause of EG. Common sites
for EG include the axillary and anogenital regions; the arms,
legs, trunk, and face are less-often-reported sites. (6)
Necrotizing fasciitis, in contrast to cutaneous mucor- References
mycosis, can occur in neonates regardless of their im-
1. Sahoo B, Bhasin H, Ganjoo S, Abrol P. Ecthyma gangrenosum in a
mune status and develops secondary to infection (usually neonate. Indian J Paediatr Dermatol. 2020;21(4):313–315
polymicrobial). Necrotizing fasciitis is typically associated 2. American Academy of Pediatrics. In: Kimberlin DW, Barnett ED,
with tissue edema, rapid progression of inflammation, Lynfield R, Sawyer MH, eds. Red Book: 2021-2024 Report of the
and hemodynamic instability. (7) Our patient had a more Committee on Infectious Diseases, 32nd ed. Itasca, IL: American
confined infection and did not have evidence of systemic Academy of Pediatrics; 2021
toxicity, making this type of infection less likely. 3. Oh D, Notrica D. Primary cutaneous mucormycosis in infants and
neonates: case report and review of the literature. J Pediatr Surg.
2002;37(11):1607–1611
4. Vittitow SL, Rusu CA, Abubakar MO, Burnsed J, Gru AA, Zlotoff BJ.
Summary Primary cutaneous mucormycosis in a premature neonate treated
conservatively with amphotericin B. Pediatr Dermatol.
• Necrotic ulcers in premature infants can be caused by 2022;39(1):99–102
a wide range of pathogens, and a broad differential di-
5. Pandit AM, Siddaramappa B, Choudhary SV, Manjunathswamy BS.
agnosis should be considered during evaluation.
Ecthyma gangrenosum in a new born child. Indian J Dermatol
• Mold infections should be considered in premature Venereol Leprol. 2003;69(1):52–53
neonates who experience skin injuries.
6. Shah M, Crane JS. Ecthyma gangrenosum. In: StatPearls. Treasure
• Prompt treatment, including antimicrobial therapy and Island, FL: StatPearls Publishing; 2023 [Internet], Available at https://
sometimes surgical debridement, is required for good
www.ncbi.nlm.nih.gov/books/NBK534777/
outcomes of necrotic ulcers in preterm infants.
7. Hsieh WS, Yang PH, Chao HC, Lai JY. Neonatal necrotizing fasciitis:
a report of three cases and review of the literature. Pediatrics.
1999;103(4):e53
526 NeoReviews

VIDEO CORNER
VIDEO
CORNER
Ultrasonography-Guided Lumbar
Puncture
Eric P. Will, PA-C,* Marıa V. Fraga, MD†
*Children’s Hospital of Philadelphia, Philadelphia, PA
†
Department of Clinical Pediatrics, Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, PA
Editor’s Note: NeoReviews is excited to present the first in a series within Video Corner
with a focus on neonatal point-of-care ultrasonography (POCUS). In this series, we
delve into various practical applications of this clinical tool in the field of neonatology.
Join us as we explore some insightful perspectives on applying POCUS to your day-to-
day practice from experts in this arena. Stay tuned for this exciting new series.
INTRODUCTION
Lumbar puncture (LP) is a procedure commonly performed in neonates and infants, most
often to evaluate for infection. This procedure can be at times challenging, with significant
consequences of unsuccessful attempts, including missed diagnoses of meningitis,
prolonged hospitalizations, unnecessary use of antibiotics, significant patient discom-
fort, and rarely even neurologic injury. Point-of-care ultrasonography has emerged as
a powerful tool to optimize success in a variety of procedures in pediatrics, including LP.
INDICATIONS, CONTRAINDICATIONS, AND RISKS

Indications, contraindications, and risks of this procedure are identical to those
established for traditional LP. However, ultrasonography guidance can be help-
ful to identify patients in whom LP might be challenging or dangerous. Some
patients are found to have miniscule amounts of cerebrospinal fluid by ultraso-
nography. Other patients are found to have spinal cord anomalies, such as a
low-lying conus or a tethered cord. Many of these patients can still have an LP
performed, although instead of using a static approach, dynamic guidance may
be preferred to ensure procedural safety (see the steps later herein).
REQUIRED MATERIALS
The materials required for this procedure are mostly the same as those used for tra-
ditional LP. An ultrasonography machine is additionally necessary, and the probe
AUTHOR DISCLOSURE Mr Will and
used for this procedure is usually a linear probe. There are a multitude of different Dr Fraga have disclosed no financial
linear probe models depending on the manufacturer, but both large footprint and relationships relevant to this article.
small footprint linear probes can be used depending on the patient’s size. These This commentary does not contain a
probes are high frequency (typically $10 mHz, with some probes reaching frequen- investigative use of a commercial
cies as high as 22 mHz), which results in higher-resolution images; this is quite product/device.

(Fig 1). This view is important to determine how much ce-
rebrospinal fluid is present and to confirm normal anat-
omy. Quantification of cerebrospinal fluid volume is not
technically feasible, but if a layer of hypoechoic fluid is
visualized under ultrasonography (and the patient is not
deemed to be “dry,” with no fluid visible), an LP is reason-
able to attempt. In addition, depth to the dura mater can
be determined, which becomes useful when performing
the LP to ensure that the needle is not advanced too
deeply. As demonstrated in Video 1, a midline marking
can be made when a crisp and centered view of the conus
Video 1. Demonstration of Ultrasonography-Guided Lumber Puncture. medullaris (Fig 2A) and spinal canal is obtained. The
probe can then be rotated 90 into the second plane,
useful for delineating the fine structures in the spinal col- which is the transverse/axial plane. Once in this plane, the
umn. If the user plans to designate landmarks for static probe is slid up and down the back centered over the
guidance after sterilizing the patient, or if electing to use dy- spine until the hypoechoic spinal cord is again visualized.
namic ultrasonography guidance, a sterile probe sleeve and Once identified, the probe can be slid inferiorly just until
sterile ultrasonography gel are required. A sterile surgical the point where the cord disappears, which can be marked
marking pen is also necessary for static guidance to desig- off as the termination of the conus medullaris (Fig 2B).
nate landmarks of the spinal anatomy on the skin. This marking is extremely important because it ensures
procedural safety by confirming that the spinal cord is out
STEPS FOR ULTRASONOGRAPHY-GUIDED LP of the path of the needle. From here, the probe can be slid
Ultrasonography-guided LP can be performed using either further inferiorly until the spinal canal narrows, which
static or dynamic guidance. When performing this procedure can be marked as the lower limit of where LP should be
under static guidance (Video 1), the spinal anatomy is first visu- effectively and more successfully attempted. Figure 3 de-
alized by ultrasonography, and landmarks are identified to denotes the landmarks to be placed on the infant’s skin
termine the optimal intervertebral spaces to access the spinal when the infant is lying in the supine position.
canal to obtain cerebrospinal fluid for sampling (Fig 1). Infants The more advanced ultrasonography-guided LP approach
are the ideal patients for this ultrasonography-guided procedure uses dynamic guidance. In this method, the same struc-
given that their bones are incompletely ossified, which allows tures are identified, but the needle is then inserted into an
for the ultrasonography beams to penetrate through the spinous intervertebral space and advanced into the spinal canal un-
processes, preserving the definition of the structures within. Spi- der direct visualization with ultrasonography guidance. This
nal ultrasonography is more challenging in older children with can be technically challenging and typically requires some
ossified bones, where bony structures create posterior acoustic experience with other dynamic ultrasonography procedures,
shadowing over the spine, obscuring its view and allowing only such as vascular access. To perform this procedure, the nee-
for the identification of the intervertebral spaces. dle is inserted just into the skin at the site of an appropriate
With the static guided procedure, the first plane that intervertebral space (typically identified with ultrasonogra-
images are obtained in is the longitudinal/sagittal plane phy just before insertion of the needle). The probe is then
placed just next to the needle in a longitudinal/sagittal ori-
entation along the spine, cephalad to the needle in relation
to the patient’s anatomic position. Once the needle tip is
identified, the probe is held still, and the needle is advanced
until it is seen puncturing the dura mater and entering the
spinal canal. It is important that the patient remains still to
properly visualize the needle as it is being advanced, which
can sometimes require the use of nonpharmacologic anal-
gesia methods or pharmacologic sedation.
Figure 1. Longitudinal/sagittal cross-sectional view of the spine. The infant’s
head is on the left side of the image, and the legs are on the right side. This
still image of the spine shows the conus medullaris (red arrow), cauda CONCLUSION
equina (green arrow), dura mater (white arrow), and cerebrospinal fluid
Point-of-care ultrasonography can be an intimidating venture
(blue circle). Note the numbers on the right side, which represent
distance from the skin in centimeters. to dive into, especially with a patient population consisting of
e528 NeoReviews

Figure 2. Transverse/axial views of the spine. A. Still image of the spine with the conus medullaris (red arrow). Note the numbers on the right side, which
represent the distance from the skin in centimeters. B. As the probe moves caudally toward the infant’s feet, the conus medullaris disappears and the
cauda equina appears (green arrow). Also shown is the cerebrospinal fluid (blue circle) in the anterior space where the tip of the spinal needle should be
placed during the lumbar puncture.
are necessary. Static ultrasonography guidance for LPs has be-

come an adjunct to traditional LP, increasing safety and suc-
cess rates (with the cited study demonstrating an increase in
the first-attempt success rate from 31% without ultrasonogra-
phy to 58% with static guidance). (1) Additional studies have
shown that the use of ultrasonography decreases rates of trau-
matic taps (with both cited studies demonstrating lower red
blood cell counts in the fluid obtained when ultrasonography
Figure 3. Demarcations of an infant’s back when lying in the supine
position. Solid black lines denote markings after appropriate sagittal place- was used for LP guidance). (2)(3) With some practice, dynamic
ment of the probe; solid blue lines, markings at the beginning of the high- guidance can be used to successfully obtain cerebrospinal fluid
est level of the spine where it is safe to place the lumbar needle; solid
purple lines, markings at the lower limit for safe placement of the lumbar from practically any infant, making it extremely useful espe-
needle. The lines can then be joined as shown by the dotted lines. The cially when managing complex patients. Although point-of-
ideal position of entry of the lumbar needle is shown by the green line.
care ultrasonography to guide LP is not the current standard
of care for this procedure, its use by trained and experienced
neonates and small infants. Ultrasonography-guided LP is a neonatal clinicians can be valuable in the NICU population.
great example of one of the first procedures that neonatal
physicians, nurse practitioners, and physician assistants inter- References
ested in ultrasonography can successfully accomplish. The
1. Neal JT, Kaplan SL, Woodford AL, Desai K, Zorc JJ, Chen AE. The
views are simple and easy to obtain, and novices can perform
effect of bedside ultrasonographic skin marking on infant lumbar
these scans without difficulty. Interpretation of these images puncture success: a randomized controlled trial. Ann Emerg Med.
is also simple; most of the images look similar to familiar an- 2017;69(5):610–619.e1
atomic illustrations found in textbooks. Competency in this 2. Olowoyeye A, Fadahunsi O, Okudo J, Opaneye O, Okwundu C.
Ultrasound imaging versus palpation method for diagnostic lumbar
procedure can be obtained with relative ease because the scan-
puncture in neonates and infants: a systematic review and meta-
ning and patient marking can be completed without perform- analysis. BMJ Paediatr Open. 2019;3(1):e000412
ing an LP; only a few supervised spine ultrasonography 3. Stoller JZ, Fraga MV. Real-time ultrasound-guided lumbar puncture
images with confirmation of correct anatomic identification in the neonatal intensive care unit. J Perinatol. 2021;41(10):2495–2498
ANSWER KEY FOR AUGUST 2024 NEOREVIEWS

Nonimmune Hydrops Fetalis:
1. E; 2. B; 3. A; 4. C; 5. D
When Life Is Expected to Be Brief: A Case-Based Guide to Prenatal Collaborative Care:
1. C; 2. E; 3. D; 4. B; 5. A


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FEBRUARY

NeoReviews® and NeoReviewsPlus™ are supported,

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Amelia Q. Schuyler, Frances R. Koch, Christopher G. Goodier Colby Day, Jacksonville, FL

Answer Key appears on page 529.

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Nonimmune Hydrops Fetalis

The primary cause of hydrops fetalis is nonimmune. Although idiopathic

OBJECTIVES After completing this article, readers should be able to:

1. Describe the general pathophysiology and common etiologies of

Vol. 25 No. 8 AUGUST 2024 e475

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Table 1. Causes and Mechanisms of Nonimmune Hydrops Fetalis

Modiﬁed with permission from Khairudin et al. (10)

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Vol. 25 No. 8 AUGUST 2024 e477

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Vol. 25 No. 8 AUGUST 2024 e479

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Modiﬁed with permission from Khairudin et al. (10)

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1. Hydrops fetalis is deﬁned as the pathologic accumulation of ﬂuid in at least

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When Life Is Expected to Be Brief:

A perinatal palliative care program can be created at any institution to

OBJECTIVES After completing this article, readers should be able to:

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INTRODUCTION fetus A with cervical myelomeningocele, and a large ompha-

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Vol. 25 No. 8 AUGUST 2024 e491

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1. On a 20-week anatomic ultrasonographic image, a fetus is diagnosed as

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Understanding Obstetrical Surgical

1. Understanding cesarean delivery indications, preoperative considerations,

OBJECTIVES After completing this article, readers should be able to:

1. Summarize current cesarean delivery epidemiologic data.

AUTHOR DISCLOSURE Drs Schuyler,

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