A Case-Control Study of Hypoxic-Ischemic Encephalopathy in Newborn Infants at 36 Weeks Gestation

Research www.AJOG .
org
OBSTETRICS
A case-control study of hypoxic-ischemic encephalopathy
in newborn infants at >36 weeks gestation
Breda C. Hayes, MD; Cliona McGarvey, PhD; Siobhan Mulvany, MSc; John Kennedy, MD; Michael P. Geary, MD;
Tom G. Matthews, MD; Mary D. King, FRCPCH
OBJECTIVE: The purpose of this study was to determine risk factors and 489 control infants were included. Variables that were associated
that are associated with hypoxic ischemic encephalopathy (HIE). independently with HIE included higher grade meconium, growth
restriction, large head circumference, oligohydramnios, male sex, fetal
STUDY DESIGN: This was a case-control study that included newborn
bradycardia, maternal pyrexia and increased uterine contractility.
infants with HIE who were admitted to the hospital between January
CART analysis ranked high-grade meconium, oligohydramnios, and
2001 and December 2008. Two control newborn infants were chosen
the presence of obstetric complications as the most discriminating
for each case. Logistic regression and classification and regression
variables and defined distinct risk groups with HIE rates that ranged
tree (CART) analysis that compared control infants and cases with
from 0e86%.
grade 1 HIE and control infants and cases with grades 2 and 3 HIE was
performed. CONCLUSION: CART analysis provides information to help identify the
time at which intervention in labor may be of benefit.
RESULTS: Two hundred thirty-seven cases (newborn infants with
grade 1 encephalopathy, 155; newborn infants with grade 2 en- Key words: CART, hypoxic ischemic encephalopathy, meconium,
cephalopathy, 61; newborn infants with grade 3 encephalopathy, 21) oligohydramnios, uterine contraction
Cite this article as: Hayes BC, McGarvey C, Mulvany S, et al. A case-control study of hypoxic-ischemic encephalopathy in newborn infants at >36 weeks gestation. Am J
Obstet Gynecol 2013;209:29.e1-19.
I ntrapartum asphyxia in mature new-

born infants causes 10-15% of cases of
cerebral palsy, and its prevention is a neonatal encephalopathy rate in newborn
M ATERIALS
Patient selection
AND M ETHODS
Inclusion criteria were newborn infants

major justification for the hospitalization infants with a birthweight of >2.5 kg who were born at the Rotunda Maternity
of low-risk mothers who give birth in (which is often a marker of acute intra- Hospital in Dublin from January 2001
developed countries.1-4 Despite advances partum neonatal brain injury) show no to December 2008 at 36 weeks 0 days’
in obstetric and neonatal care over the last decline.6 gestation and who required admission to
4 decades, the rate of cerebral palsy in The objective of this study was to the neonatal intensive care unit at 24
normally formed newborn infants with a determine risk factors that are associated hours after delivery with evidence of
birthweight of >2.5 kg has not declined.5 with the development of hypoxic ische- encephalopathy. Newborn infants who
In addition, the seizure rate and the mic encephalopathy (HIE). were born between January 2001 and
July 2005 were identified retrospectively.
Newborn infants who were born between
From Rotunda Hospital (Drs Hayes, Kennedy, Geary, Matthews, and King and Ms Mulvany), July 2005 and December 2008 were
Children’s University Hospital (Drs McGarvey, Matthews, and King), and UCD School of Medicine identified prospectively.
and Medical Science (Dr King), Dublin, Ireland. Grade of encephalopathy was assigned
Received Jan. 8, 2013; revised Feb. 27, 2013; accepted March 16, 2013. as the highest stage of encephalopathy
Funding for this study was provided by Friends of the Rotunda, an official fundraising arm and (Sarnat and Sarnat7 grading) that had
registered Charity (CHY240) of the Rotunda Hospital. been documented in the clinical notes
The authors report no conflict of interest. and/or as noted on serial examination by
Presented orally at the annual meeting of the Pediatric Academic Societies and Asian Society for a member of the research team (B.C.H.,
Pediatric Research, Denver, CO, April 30-May 3, 2011, and the First Irish Congress of Obstetrics, M.D.K., or S.M.). Two control newborn
Gynaecology, and Perinatal Medicine, Wicklow, Ireland, April 24, 2010.
infants (the infants who were born
Reprints: Breda C. Hayes, MD, Rotunda Hospital, Parnell Square, Dublin, D1, Ireland. bhayes@ before and after each case) were chosen
rotunda.ie.
for each case. Exclusion criteria for
0002-9378/free ª 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.03.023
cases were out-born infants, <36 weeks’
gestation, the presence of a major
For Editors’ Commentary, see Contents congenital anomaly, or any primary
cause for encephalopathy other than
JULY 2013 American Journal of Obstetrics & Gynecology 29.e1

Research Obstetrics www.AJOG.org
TABLE 1
Obstetrics definitions used in data acquisition
Variable Definition
Antenatal trauma Significant fall, accident, or abdominal injury in the antenatal period
Late booking Initiation of antenatal care at >24 weeks’ gestation
Pregnancy-induced hypertension Maternal blood pressure 140/90 mm Hg on 2 separate occasions >4 hours apart
Preeclampsia New onset hypertension and proteinuria at >20 weeks’ gestation
Proteinuria >0.3 g protein/d in a 24-hour urine collection or, in the absence of a 24-hour urine collection, the
presence of 2þ protein on dipstick
Gestational diabetes mellitus Glucose intolerance with onset or first recognition during pregnancy and a normal glucose tolerance
test by 6 weeks after delivery
Substantial antepartum hemorrhage Vaginal blood loss equal to or greater than a menstrual period
Nonsubstantial antepartum hemorrhage Vaginal blood loss less than a menstrual period
Fetal bradycardia Decrease in the baseline fetal heart rate <100 beats/min
Late decelerations Transient decrease in fetal heart rate that occurs at or after the peak of a uterine contraction
Fetal tachycardia Increase in baseline fetal heart rate to 160 beats/min
Early decelerations Transient decrease in fetal heart rate that coincides with the onset of a uterine contraction
Fetal heart rate variability The beat-to-beat changes in fetal heart rate
Unsatisfactory cardiotocogram The presence of a fetal bradycardia and/or late decelerations and/or fetal tachycardia and/or early
decelerations (transient decrease in fetal heart rate that coincides with the onset of a uterine
contraction) and/or fetal heart rate variability <5 beats/min
Satisfactory cardiotocogram Baseline rate: 110-160 beats/min; moderate variability; absence of any late or variable decelerations;
accelerations that may or may not be present
High-grade meconium Grade 3 (thick or pea soup consistency) meconium or meconium that requires tracheal suction
Maternal pyrexia Temperature 38 C measured with a tympanic thermometer
Duration of first stage of labor The time from when the cervix was fully effaced and at least 1-cm dilated (in the presence of regular
contractions) up to the time of full dilation
Shoulder dystocia Difficult delivery of the shoulders that required additional obstetric maneuvers to release the shoulders
after gentle downward traction failed
Uterine rupture A defect that involves the entire uterine wall that was symptomatic and required surgical intervention
Placental abruption Presence of retroplacental hematoma and clinical symptoms (as assessed by the clinical team at the
time of delivery)
Hayes. HIE in newborn infants >36 weeks gestation. Am J Obstet Gynecol 2013.
hypoxia-ischemia. Exclusion criteria for that were associated independently with cases with grades 2 and 3 HIE. Criteria for
control infants were out-born infants, HIE and with a classification and regres- inclusion included reaching statistical
<36 weeks’ gestation, the presence of a sion trees (CART) analysis to help define significance (P < .25) in the univariate
major congenital anomaly, or any signs of the distinct clinical groups at higher analysis (Tables 2-4) and clinical impor-
encephalopathy in the neonatal period. risk of HIE. CART analysis examines a tance. Factors of clinical importance were
If an infant was excluded as a control, dataset to find the best variables and defined as factors that have been associ-
then the infant who was delivered either associated cutoff points to group the data ated with asphyxia and/or neonatal en-
before or after this infant was chosen. into those with and without the outcome cephalopathy from previous published
The obstetrics definitions that were in question. Splitting stops when the studies or deemed important from clinical
used in data acquisition are outlined in statistical process determines no further practice. Logistic regression analysis was
Table 1. discriminating advantage with any of the used to produce estimates of the odds
Further details on data acquisition are remaining factors.8 Two analyses were ratios.
available in the Appendix. carried out: 1 analysis compared control Ethical approval was obtained from
The data were analyzed by logistic re- infants and cases with grade 1 HIE; 1 the research ethics committee at The
gression analysis to identify the variables analysis compared control infants and Rotunda Hospital.
29.e2 American Journal of Obstetrics & Gynecology JULY 2013

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TABLE 2
Univariate analysis of preconception, antenatal, peripartum, and neonatal factors
Control infants Grade 1 Grade 2 Grade 3 Unadjusted
Variable n % n % n % n % P valuea odds ratio 95% CI
Maternal age, yb
20 35 7.2 19 12.2 5 8.2 3 14.3 .24 Reference
21-25 93 19.0 39 25.0 12 19.6 4 19.05 0.75 0.407e1.36
26-30 137 28.1 35 22.4 17 27.9 2 9.5 0.51 0.28e0.92
31-37 189 28.7 49 31.4 21 34.4 10 47.6 0.55 0.31e0.96
38 34 6.9 14 8.9 6 9.8 2 9.5 0.84 0.40e1.74
b
Maternal age, y
<25 108 22.1 51 32.7 14 22.95 7 33.3 .084 0.67 0.47e0.95
25 380 77.9 105 67.3 47 77.05 14 66.7
Nationality
Irish/English 355 72.8 118 75.2 36 59.0 12 57.1 < .05 0.84 0.60e1.18
Other 133 27.3 39 24.8 25 41.0 9 42.9
Maternal smoking
0 380 80.5 115 76.2 38 66.7 17 89.5 .17 Reference
1-10/D 58 12.3 25 16.6 12 21.05 2 10.5 1.51 0.97e2.36
JULY 2013 American Journal of Obstetrics & Gynecology
11-20/D 31 6.6 10 6.6 6 10.5 0 0 1.16 0.61e2.18

>20/D 3 0.6 1 0.7 1 1.8 0 0 1.5 0.25e9.08
Maternal smoking
No 380 80.5 115 76.2 38 66.7 17 89.5 .19 Reference
c
Yes 92 19.5 36 23.8 19 33.3 2 10.5 .05 1.39 0.95e2.03
Obstetrics
Mother consumed alcohol
during pregnancy
No 7 1.5 4 2.56 1 1.67 1 4.76 NA NA NA
Yes 72 14.9 31 19.87 10 16.67 5 23.8 NA NA NA
Research
Missing 404 83.6 212 77.5 49 81.67 15 71.4 NA NA NA
Hayes. HIE in newborn infants >36 weeks gestation. Am J Obstet Gynecol 2013. (continued)
29.e3
Research
TABLE 2
Univariate analysis of preconception, antenatal, peripartum, and neonatal factors (continued)
Weekly units of alcohol consumed by mother
during pregnancy
Obstetrics
1-2 42 59.2
3-4 14 19.7 21 67.7 2 50.0 3 60.0 .83
5-7 11 15.5 6 19.4 3 30.0 2 40.0
8 4 5.6 2 6.5 0 0 0 0
Regular weekly intake of alcohol (any amount) 92 19.5 2 6.5 2 20.0 0 0
Family history of seizures
No 466 96.9 148 94.9 59 98.3 19 95.0 .33 Reference
Yes 15 3.1 8 5.1 1 1.7 1 5.0 1.38 0.61e3.12
Obstetric history
No 308 64.0 111 71.0 30 51.0 14 67.0 .64 Reference
Yes 173 36.0 45 29.0 29 49.0 7 33.0 < .05 c
0.93 0.67e1.30
Medical/surgical history
No 218 45.7 66 42.3 30 49.2 5 25.0 .33 Reference
Yes 259 54.3 90 57.7 31 50.8 15 75.0 1.14 1.57
Maternal history of respiratory problems
No 442 92.7 145 92.95 59 96.7 17 85.0 Reference
Yes 35 7.3 11 7.05 2 3.3 3 15.0 .98 0.92 0.49e1.70
Maternal history of cardiovascular problems
No 456 95.6 147 94.2 60 98.4 19 95.0 .79 Reference
Yes 21 4.4 9 5.8 1 1.6 1 5.0 1.06 0.50e2.44
Maternal history of gastrointestinal problems
No 445 93.3 142 91.0 56 91.8 17 85.0 .17 Reference
Yes 32 6.7 14 8.97 5 8.2 3 15.0 1.43 0.81e2.52
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Maternal history of neurologic problems
No 445 93.3 143 91.7 57 93.4 17 85.0 .31 Reference
Yes 32 6.7 13 8.3 4 6.6 3 15.0 1.29 0.72e2.30
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TABLE 2
Maternal history of hematologic problems
No 427 89.5 141 90.4 55 90.2 15 75.0 .34 Reference
Yes 50 10.5 15 9.6 6 9.8 5 25.0 1.06 0.64e1.75
Maternal history of muscular problems
No 437 91.6 137 87.8 56 91.8 17 85.0 .29 Reference
Yes 40 8.4 19 12.2 5 8.2 3 15 1.41 0.84e2.36
Maternal history of depression
No 443 92.9 147 94.2 58 95.1 15 75.0 .27 Reference
Yes 34 7.1 9 5.8 3 4.9 5 25.0 < .05 c
1.01 0.55e1.85
Maternal history of infertility
No 464 97.3 147 94.2 60 98.4 17 85.0 .05 Reference
Yes 13 2.7 9 5.8 1 1.6 3 15.0 < .05c 2.08 0.95e4.57
Maternal history of hypothyroidism
No 469 98.3 154 98.7 61 100.0 20 100.0 .26 Reference
Yes 8 1.7 2 1.3 0 0 0 0 0.50 0.105e2.38
Maternal history of problems (other)

No 369 77.4 118 75.6 46 75.4 12 60.0 .17 Reference
Yes 108 22.6 38 24.4 15 24.6 8 40.0 1.19 0.93e1.71
Primiparity
No 261 54.2 51 32.7 26 43.3 8 38.1 < .001 Reference
Obstetrics
Yes 221 45.9 105 67.3 34 56.7 13 61.9 2.08 1.51e2.87
Parity
0 350 72.6 119 76.3 40 66.7 15 71.4 .485 Reference
1 94 19.5 27 17.3 11 18.3 2 9.5 0.86 0.57e1.30
Research
2 32 6.6 8 5.1 8 13.3 0 0 1.01 0.54e1.89
3 6 1.2 2 1.3 1 1.7 4 19.1 2.36 0.78e7.15
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TABLE 2
Obstetrics
Gestational age at time of booking
<12 wk 72 14.9 21 13.5 8 13.3 3 14.3 .06
13-15 wk 223 46.2 73 47.1 23 38.3 6 28.6
16-18 wk 82 16.9 30 19.4 11 18.3 3 14.3
19-23 wk 46 9.5 16 10.3 5 8.3 4 19.0
24-30 wk 26 5.4 8 5.2 5 8.3 3 14.3
31-37 wk 21 4.4 4 2.6 3 5.0 0 0
38-42 wk 10 2.1 1 0.7 4 6.7 1 4.8
Not booked 3 0.62 2 1.3 1 1.7 1 4.8
Gestation age at time of booking 24 wk
No 423 87.6 140 90.3 47 78.3 16 76.2 .08 Reference
Yes 60 12.4 15 9.7 13 21.7 5 23.8 1.06 0.66e1.72
Serology
Negative 463 96.9 152 98.1 57 95.0 20 95.2 .66 Reference
Positive 15 3.1 3 1.9 3 5.0 1 4.8 0.95 0.38e2.36
Trauma in pregnancy
No 471 97.7 148 96.1 54 93.1 18 90.0 .01 Reference
Yes 11 2.3 6 3.9 4 6.9 2 10.0 2.35 1.02e5.41
Medications (any) during pregnancy
No 425 90.4 140 91.5 45 81.8 15 83.3 .11 Reference
Yes 45 9.6 13 8.5 10 18.2 3 16.7 1.23 0.74e2.06
Substantial antepartum hemorrhage
No 436 90.6 131 86.2 46 77.97 12 60.0 < .001 Reference
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Yes 45 9.4 21 13.8 13 22.03 8 40.0 2.16 1.37e3.41
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TABLE 2
Growth scans
No 129 26.7 24 15.5 10 16.95 1 5.0 < .001 Reference
Intrauterine growth restriction 8 1.7 6 3.9 0 0 0 0 2.76 0.89e8.49
Normal 345 71.4 125 80.7 48 81.4 19 95.0 2.03 1.34e3.07
Large for dates 1 0.2 0 0 1 1.7 0 0 3.68 0.22e60.42
Abnormal growth
No 345 94.5 125 95.4 48 98.0 19 100.0 .93 Reference
Yes 9 2.5 6 4.6 1 2.0 0 0 1.4 0.52e3.84
Biophysical profile
8/8 313 93.7 118 91.5 45 95.7 19 100.0 .51 Reference
6/8 18 5.4 8 6.2 2 4.3 0 0 0.96 0.43e2.13
Other 3 0.9 3 2.3 0 0 0 0 1.73 0.34e8.68
ARM
No 157 32.5 62 39.5 15 25.9 12 57.1 .18 Reference
Yes 326 67.5 95 60.5 43 74.1 9 42.9 < .05 c

0.78 0.56e1.09
Amniotic fluid volume
Normal 447 92.6 132 84.6 49 84.5 19 90.5 < .05
Oligohydramnios 28 5.8 21 13.5 8 13.8 2 9.5
Polyhydramninos 8 1.7 3 1.9 1 1.7 0 0
Obstetrics
Oligohydramnios
No 455 94.2 135 86.5 50 86.2 19 90.5 .01 Reference
Yes 28 5.8 21 13.5 8 13.8 2 9.5 2.48 1.45e4.25
Induction of labor
Research
No 363 75.3 114 73.1 47 79.7 18 85.7 .39 Reference
Yes 119 24.7 42 26.9 12 20.3 3 14.3 0.98 0.68e1.40
29.e7
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TABLE 2
Method of induction of labor
Obstetrics
No induction 362 76.0 116 74.0 47 79.7 18 85.7 .38 Reference
Prostin, ARM, or syntocinon 32 6.7 13 8.3 3 5.11 1 4.8 1.07 0.57e1.98
Combination of 2 methods 45 9.5 16 10.3 5 8.5 2 9.5 1.03 0.60e1.75
Combination of 3 methods 37 7.8 11 7.1 4 6.8 0 0 0.81 0.44e1.52
Stage 1: duration in hours
0 92 20.5 22 15.6 13 25.0 8 44.4 .08
1-2 106 23.7 26 18.4 8 15.4 1 5.6
3-4 8 1.8 5 3.6 6 11.5 0 0
5-6 95 21.2 17 12.1 4 7.7 1 5.6
7-8 68 15.2 22 15.6 8 15.4 1 5.6
9-12 42 9.4 18 12.7 3 5.8 2 11.1
>12 20 4.5 20 14.2 6 11.5 2 11.1
Not fully dilated 17 3.8 11 7.8 4 7.7 3 16.7
Syntocinon
Stage 1
No 310 66.0 72 48.3 30 54.6 14 73.7 < .05 Reference
Yes 160 34.0 77 51.7 25 45.5 5 26.3 1.75 1.27e2.43
Stage 2
None 307 66.0 65 46.8 25 49.0 15 75.0 .01 Reference
In progress 124 26.7 59 42.5 16 31.4 4 20.0 1.82 1.27e2.61
Stopped 34 7.3 15 10.8 10 19.6 1 5.0 2.23 1.28e3.90
Stage 2
No 307 66.0 65 46.8 25 49.0 15 75.0 < .05 Reference
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Yes 158 34.0 74 53.3 26 51.0 5 25.0 1.91 1.37e2.66
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TABLE 2
Maximum no. of pains per 15 minutes
On partogram
0 44 10.1 8 5.7 10 19.6 3 20.0 < .05
2-4 36 8.2 9 6.4 2 3.9 1 6.7
5-6 172 39.4 35 24.8 15 29.4 4 26.7
7-8 145 33.2 57 40.4 13 25.5 4 26.7
>9 40 9.2 32 22.7 11 21.6 3 20.0
>9
No 397 90.8 109 77.3 40 78.4 12 80.0 < .001 Reference
Yes 40 9.2 32 22.7 11 21.6 3 20.0 2.86 1.80e4.53
>7
No 337 77.1 75 53.2 34 66.7 11 73.3 < .01 Reference
Yes 100 22.9 66 46.8 17 33.3 4 26.7 2.39 1.67e3.41
Analgesia (any)
No 75 15.7 11 7.1 5 8.8 2 9.5 .02 Reference
Yes 404 84.3 143 92.9 52 91.2 19 90.5 2.19 1.27e3.76
Entonox
No 345 72.0 108 70.1 45 78.9 16 76.2 .46 Reference
Yes 134 28.0 46 29.9 12 21.1 5 23.8 0.96 0.68e1.37
Pethidine
No 429 89.6 127 82.5 52 91.2 18 85.7 .33 Reference
Obstetrics
Yes 50 10.4 27 17.5 5 8.8 3 14.3 1.53 0.96e2.44
Epidural
No 208 43.4 58 37.7 29 50.9 12 57.1 .37 Reference
Yes 271 56.6 96 62.3 28 49.1 9 42.9 1.01 0.74e1.39
Research
General anesthesia
No 485 99.4 135 86.0 51 83.6 14 66.7 < .001 Reference
Yes 3 0.6 22 14.0 10 16.4 7 33.3 31.74 9.69e103.92
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TABLE 2
Spinal anesthesia
No 441 92.2 139 93.3 49 86.0 20 95.2 .57 Reference
Obstetrics
Yes 37 7.7 10 6.7 8 14 1 4.8 1.09 0.61e1.95
Other analgesia (paracetamol, TENS, fentanyl,
remifentanil, solpadeine)
No 470 98.1 144 97.3 55 100.0 21 100.0 .48
Yes 9 1.9 4 2.7 0 0 0 0
Dilation
Fully dilated 431 96.2 130 92.2 48 92.3 15 83.3 .01 Reference
Never fully dilated 17 3.8 11 7.8 4 7.7 3 16.7 2.38 1.20e4.72
Analgesia given
None 75 15.7 11 7.14 5 8.8 2 9.5 < .001 Reference
Epidural only 198 41.3 51 33.1 20 35.1 6 28.6 1.59 0.89e2.84
Epidural plus other analgesia 73 15.2 45 29.2 8 14 3 14.3 3.19 1.71e5.98
Other analgesia, excluding epidural 133 27.8 47 30.5 24 42.1 10 47.6 2.53 1.41e4.54
Mode of delivery
Spontaneous vaginal 291 60.0 45 28.7 15 25.4 7 33.3 < .001 Reference
Ventouse 84 17.4 45 28.7 10 16.95 1 4.7 2.94 1.91e4.53
Forceps 7 1.5 3 1.9 4 6.8 3 14.3 6.32 2.32e17.21
Elective cesarean 41 8.5 1 0.6 1 1.7 0 0 0.215 0.05e0.91
Emergency cesarean 48 9.9 52 33.1 25 42.4 9 42.9 7.92 5.09e12.34
Ventouse and forceps 11 2.3 7 4.5 0 0 0 0 2.81 1.05e7.53
Instrument delivery/emergency cesarean 2 0.4 4 2.6 4 6.8 1 4.8 19.9 4.20e94.29
Other 193 39.8 112 71.3 44 74.6 14 66.7 3.89 2.78e5.46
Spontaneous vaginal/elective cesarean 332 638.6 46 29.3 16 27.1 7 33.3 < .001 Reference
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Intervention (any) 152 31.4 111 70.7 46 72.9 14 66.7 5.42 3.84e7.61
Emergency cesarean delivery
No 434 89.7 101 64.3 30 50.9 11 52.4 < .001 Reference
Yes 50 10.3 56 35.7 29 49.2 10 47.6 5.86 3.96e8.67
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TABLE 2
Maternal pyrexia
No 464 96.3 129 82.3 52 88.1 17 81.0 < .001 Reference
Yes 18 3.7 26 16.8 7 11.9 4 19.0 4.85 2.69e8.73
Maternal antibiotics
No 457 94.6 136 88.9 51 91.1 17 85.0 .01 Reference
Yes 26 5.4 17 11.1 5 8.9 3 15.0 2.16 1.22e3.84
d
Presentation
Cephalic 466 96.9 151 96.2 55 94.8 21 100.0 .83 Reference
Breech 10 2.08 1 0.64 2 3.5 0 0 0.619 0.16e2.27
Other 5 1.04 5 3.2 1 1.7 0 0 2.47 0.74e8.21
d
Presentation
Cephalic 466 96.9 151 96.2 55 94.8 21 100.0 .84 Reference
Breech/other 15 3.12 6 3.8 3 5.2 0 0 1.23 0.53e2.87
e
Complications
None 468 97.1 122 78.7 48 81.4 15 71.4 < .001 Reference
Shoulder dystocia 11 2.3 20 12.9 7 11.9 2 9.5 6.72 3.28e13.73

Other 3 0.6 13 8.4 4 6.8 4 19.05 17.84 5.25e60.53
e
Complications
No 468 97.1 122 78.7 48 81.4 15 71.4 < .001 Reference
Yes 14 2.9 33 21.3 11 18.6 6 28.6 9.1 4.91e16.86
Obstetrics
Fetal heart rate tracing
Deemed satisfactory 133 31.1 18 11.8 6 10.7 0 0 < .001 Reference
Unsatisfactory 295 68.9 135 88.2 50 89.3 17 100.0 3.76 2.35e6.02
Meconium
Research
Low grade 443 91.9 110 70.06 35 59.3 16 76.2 < .001 Reference
High grade 39 8.1 47 29.9 24 30.7 5 23.8 5.40 3.53e8.28
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TABLE 2
Resuscitation
No 345 92.7 6 3.9 4 6.6 0 0 < .001 Reference
Obstetrics
Yes 27 7.3 147 96.1 57 93.4 21 100.0 287.5 136e605.4
Birthweight percentile for gestational age
3rd 31 6.4 17 10.8 10 16.4 0 0 .53 Reference
3rd-97th 422 87.6 132 84.1 45 74.0 19 90.5 < .05c 0.53 0.307e0.911
97th 29 6.0 8 5.1 6 9.8 2 9.5 0.63 0.28e1.40
Occipitofrontal head circumference percentile
for gestational age
3rd 22 4.7 5 3.3 7 11.9 0 0 .26 Reference
3rd-97th 424 90.6 140 93.3 42 71.2 17 94.4 < .001 c
0.85 0.41e1.76
97th 22 4.7 5 3.3 10 16.9 1 5.6 1.33 0.51e3.46
Occipitofrontal head circumference percentile
for gestational age 97th percentile
No 446 95.3 145 96.7 49 83.1 17 94.4 < .05 Reference
Yes 22 4.7 5 3.3 10 16.95 1 5.6 1.55 0.79e3.00
Birth order
Singleton 486 99.6 153 97.5 60 98.4 21 100.0 .18 Reference
Twin 2 0.4 4 2.6 1 1.6 0 0 5.22 1.00e27.13
Sex
Female 241 49.4 75 47.8 22 36.1 9 42.9 .10 Reference
Male 247 50.6 82 52.2 39 63.9 12 57.1 1.24 0.90e1.69
36-37 wks’ gestation
No 452 94.0 143 91.7 55 91.7 13 65.0 .001 Reference
Yes 29 6.0 13 8.3 5 8.3 7 35.0 1.86 1.06e3.25
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ARM, artificial rupture of membranes; CI, confidence interval; NA, not available because of missing numbers; TENS, transcutaneous electrical nerve stimulation.
a
l2 test for trend; b The first analysis looks at age 20 years and then in 5-year groupings up to 38 years. The second analysis simply looks at <25 years or >25 years; c c2 test; d The first category of presentation looks at cephalic, breech and “other” (grouping
all other types of presentation) as 3 separate groups. The second analysis groups breech with all other types of presentation; e The first analysis studies shoulder dystocia as a separate group, the second combines it with all other complications.
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R ESULTS
484 (100.00)
720 (100.00)
155 (100.00)
61 (100.00)
20 (100.00)
7 ¼ unemployed; 10 ¼ unclassified; b Pearson c2 (21) ¼ 31.1671; P ¼ .071; c The combined classifications: 0 ¼ SEG 1-5; 1 ¼ SEG 6,7; 10 ¼ SEG 10; d Pearson c2 (3) ¼ 2.2547 reflects no significant difference using Pearson c2 between socioeconomic
Socioeconomic grouping (SEG) classification: 1 ¼ higher managerial, professional; 2 ¼ intermediate managerial, administrative, professional; 3 ¼ skilled manual workers; 4 ¼ semiskilled manual workers; 5 ¼ unskilled manual workers; 6 ¼ casual laborers;
Two hundred forty-five cases and 490
control infants were included. Maternal
Total
records of 8 case newborn infants and
1 control newborn infant could not be
located within the timeframe of data
25 (5.17)
41 (5.69)
10 (6.45)
6 (9.84)
collection. Thus, results for 237 case
Socioeconomic grouping, n (%)c,d

newborn infants (155 newborn infants
10
0
with grade 1 encephalopathy, 61 newborn
206 (42.56)
293 (40.69)
52 (33.55)
26 (42.62)
9 (45.00)
infants with grade 2 encephalopathy, and
21 newborn infants with grade 3 en-
cephalopathy) and 489 control newborn
1
infants are described. An Apgar score of
5 at 10 minutes, a continued need for
253 (52.27)
386 (53.61)
93 (60.00)
29 (47.54)
11 (55.00)
resuscitation (including endotracheal or
mask ventilation) at 10 minutes after
0
birth, and/or acidosis within 60 minutes
of birth (defined as any occurrence
484 (100.00)
720 (100.00)
155 (100.00)
61 (100.00)
20 (100.00)
of umbilical cord, arterial, or capillary
pH 7.10) was present in 93 of 155 of
Total
newborn infants (60%) with grade 1 HIE;
47 of 61 newborn infants (77%) with
25 (5.17)
41 (5.69)
10 (6.45)
6 (9.84)
grade 2 HIE, and 21 of 21 newborn
infants (100%) with grade 3 HIE. De-
10
0
mographic characteristics of case new-
186 (38.43)
269 (37.36)
48 (30.97)
26 (42.62)
9 (45.00)
born infants and control newborn infants
are presented in Table 5.
Among the cases, 7 women (3%) did
7
not have electronic fetal heart rate

monitoring (2 women who underwent
20 (4.13)
24 (3.33)
4 (2.58)
Socioeconomic grouping as per maternal occupation at booking, n (%)b
elective cesarean delivery and 5 women

who proceeded to emergency cesarean
0
0
6
delivery or spontaneous vaginal delivery

37 (7.64)
57 (7.92)
15 (9.68)
4 (6.56)
1 (5.00)
without time for electronic fetal heart rate

monitoring); intermittent electronic fetal
5
heart rate monitoring was applied in a

8 (13.11)
2 (10.00)
further 19 women (8%). All remaining

25 (5.17)
43 (5.97)
8 (5.16)
cases had continuous fetal heart rate

monitoring.
4
Among control infants, 50 women

87 (17.98)
28 (18.06)
8 (13.11)
2 (10.00)
125 (17.36)
(10.2%) did not have electronic fetal

heart rate monitoring (37 women who
Maternal socioeconomic groupinga
underwent elective cesarean delivery and

3
13 women who proceeded to emergency

72 (14.88)
38 (24.52)
7 (11.48)
4 (20.00)
121 (16.81)
cesarean delivery or spontaneous vaginal

delivery without time for electronic
HIE, hypoxic ischemic encephalopathy.
fetal heart rate monitoring); intermittent

groups for grade of HIE; P ¼ .521.
2
electronic fetal heart rate monitoring was

applied in a further 84 women (17.2%).
2 (10.00)
32 (6.61)
4 (2.58)
2 (3.28)
40 (5.56)
All remaining control infants had con-

tinuous fetal heart rate monitoring.
1
Results of univariate analysis are

TABLE 3
of HIE
available (Table 2). The following factors

Grade
Total
reached statistical significance (P < .25)

0
1
2
3
and were included in the multivariate

large head circumference, oligohy-

TABLE 4 dramnios, male sex, fetal bradycardia,
Payment status and grade of encephalopathy and maternal pyrexia. A novel factor
Health that was identified is increased uterine
Grade of insurance, Medical Cash, Public, Total, contractility. Defining terminal nodes
encephalopathy n (%) card, n (%) n (%) n (%) n (%)
and their associated complication rates
0 165 (33.88) 115 (23.61) 7 (1.44) 200 (41.07) 487 (100.00) demonstrates how CART analysis can
1 50 (32.05) 34 (21.79) 2 (1.28) 70 (44.87) 156 (100.00) provide useful information to help guide
2 19 (31.15) 14 (22.95) 2 (3.28) 26 (42.62) 61 (100.00)
the time that intervention in labor may
be of benefit.
3 8 (38.10) 5 (23.81) 0 8 (38.10) 21 (100.00) The significant preconception/ante-
TOTAL 242 (33.38) 168 (23.17) 11 (1.52) 304 (41.93) 725 (100.00) natal factors that were associated with
Pearson c2 test (9) ¼ 2.6561 reflects no significant difference found between grades of HIE using Pearson c2 when looking at encephalopathy that were found in this
payment method; P ¼ .976. study differ from those in the Western
HIE, hypoxic ischemic encephalopathy. Australian study.9,10 This study did not
Hayes. HIE in newborn infants >36 weeks gestation. Am J Obstet Gynecol 2013. find an association with a family history
of seizures, maternal hypothyroidism,
analysis: maternal age, nationality, ma- oligohydramnios and the presence of or neurologic problems. The broad
ternal smoking, history of infertility, pri- increased uterine contractility represent definition of encephalopathy that was
miparity, gestational age at booking, late variables that may be recognized in early used in the study by Badawi et al10 may
booking, antenatal trauma, medication labor. Figure 1 shows the results from the have included newborn infants with
use in pregnancy, substantial antepartum CART analysis. encephalopathy of genetic or metabolic
hemorrhage, abnormal growth scans, origin.
artificial rupture of membranes, oligohy- Comparison of control infants to The lack of any association with so-
dramnios, duration of first stage of labor, grades 2 and 3 cases cioeconomic status (ie, public/private
oxytocin use, maximum number of pains Seven variables (significant antepartum booking, medical card status, and ma-
per 15 minutes, use of analgesia, general hemorrhage, maternal pyrexia, fetal bra- ternal employment) was surprising. This
anesthesia, failure to reach full dilation, dycardia, high-grade meconium, birth- is in contrast to the findings of other
mode of delivery, maternal pyrexia, weight <3rd percentile for gestational studies.1,10-12
maternal antibiotics, obstetric complica- age, head circumference >97th percen- To date, there are few studies on the
tions (defined as the presence of shoulder tile for gestational age, and emergency role of induction/augmentation of labor
dystocia, placental abruption, or uterine cesarean/instrument delivery) reached in the causation of HIE.13 Most studies,
rupture), fetal heart rate abnormalities, statistical significance for independent even if combined in metaanalysis, have
high-grade meconium, birthweight, head association with grade 2 and 3 HIE on limited statistical power for the assess-
circumference >97th percentile for ges- logistic regression analysis. Recognition ment of a difference in perinatal mor-
tational age, male sex, and gestation at of possible growth restriction and/or tality rate.14 In this study, the induction
delivery. Given that the decision to large fetal head size represents possible of labor by any method did not increase
deliver by emergency cesarean delivery modifiable variables. Figure 2 shows the the odds of encephalopathy.
represents a number of factors, mode of results from CART analysis. Some vari- Frequency of contractions was a
delivery was not included in the CART ables (maternal pyrexia, large head highly significant risk factor when there
analysis. Mode of delivery was included in circumference) that have been found to were >7 contractions during any
logistic regression analysis. be significant on logistic regression were 15-minute period. There are few studies
not identified to form nodes with the tree on the influence of uterine activity on
Multivariate analysis approach. In CART analysis, the role of fetal status, despite awareness that
Comparison of control infants with these factors may be buried within others increased uterine activity is associated
cases of grade 1 HIE because there is no attempt to identify with higher incidence of an umbilical
Table 6 provides a summary of the lo- independence, rather the goal is to define artery pH of 7.11.15,16 This study
gistic regression analysis. Seven factors and rank the most predictive clinical identified increased uterine contrac-
(artificial rupture of membranes, oligo- groupings. tions as an independent risk factor for
hydramnios, >7 pains documented in asphyxia. In addition to frequency, the
any 15 minutes, maternal pyrexia, ob- C OMMENT duration and amplitude of contractions
stetric complications, high-grade meco- This study identifies a number of are important17 but were not available
nium, and emergency cesarean and/or important factors that place newborn retrospectively. Uterine contraction rate
instrumental delivery) reached statistical infants at a significantly increased risk of over a 15-minute period was chosen
significance for independent associa- not tolerating labor. These include higher because this information was easily
tion with grade 1 HIE. Recognition of grade meconium, growth restriction, a available on the maternal partogram.

There is huge reliance on the car-
diotocogram, despite poor specificity.18 TABLE 5
This study confirms the high false-posi- Demographic characteristics of cases and control infants
tive rate with some abnormality noted Control Grade
on cardiotocogram in 68.9% of control infants, Cases, Grade 1, 2/3, P
Variable n (%) n (%) n (%) n (%) valuea
newborn infants. In this study, fetal
bradycardia was the only fetal heart rate Preconception characteristics
abnormality that reached statistical sig- Nationality < .05
nificance for independent association Irish/English 355 (72.8) 166 (69.5) 118 (75.2) 48 (58.5)
with HIE. Although fetal heart rate trace
is relied on heavily in the management of Other 133 (27.2) 73 (30.5) 39 (24.8) 34 (41.5)
b
labor, uterine contractions (particularly Socioeconomic grouping .07
if not associated with fetal heart rate 1-5 253 (52.3) 133 (51.6) 93 (60.0) 40 (49.4)
changes) are often ignored. This study
6-7 206 (42.6) 87 (33.7) 52 (33.6) 35 (43.2)
highlighted the limitations and useful-
ness of cardiotocogram and found that 10 25 (5.7) 16 (6.2) 10 (6.5) 6 (7.4)
here is over reliance on fetal heart rate Maternal age, y .24
but less recognition of the importance of 20 35 (7.2) 27 (11.3) 19 (12.2) 8 (9.8)
increased uterine activity.
In keeping with previous studies, 21-25 93 (19) 55 (23.1) 39 (25) 16 (19.5)
maternal pyrexia in labor17,19 and higher 26-30 137 (28.1) 54 (22.7) 35 (22.4) 19 (27.9)
grade meconium20,21 were independent 31-37 189 (28.7) 80 (33.6) 49 (31.4) 31 (23.2)
risk factors for the development of
38 34 (6.9) 22 (9.2) 14 (8.9) 8 (9.8)
encephalopathy. It is suggested that
hypoxia-ischemia and infection/inflam- Maternal hypothyroidism 8 (1.6) 2 (0.8) 2 (1.3) 0 .26
mation share common inflammatory Significant obstetric historyc 173 (35.3) 81 (33.1) 45 (29.0) 36 (43.9) < .05
and molecular pathways and therefore Infertility 13 (2.7) 13 (5.3) 9 (5.8) 4 (4.9) .05
have synergistic effects. Cerebral con-
centrations of proinflammatory cyto- Family history of seizures 15 (3.1) 10 (4.1) 8 (5.1) 2 (2.4) .33
kines have been shown to be elevated Infant characteristics
after exposure to either hypoxia-ischemia Male sex 247 (50.6) 133 (54.2) 82 (52.2) 51 (62.2) .10
or infection/inflammation.19 In this
36-37 wks’ gestation 7 (2) 12 (4.9) 6 (3.9) 6 (7.3) < .001
study, 57 of 724 women (7.9%) had
pyrexia in labor, but positive cultures Singleton 486 (99.6) 234 (95.5) 153 (97.5) 81 (98.8) .18
were identified in only 2 cases. Twenty of Birthweight percentile for
57 women (35%) received antibiotics, gestational age
which may have led to false-negative 3rd 31 (6.4) 27 (11.0) 17 (10.8) 10 (12.2) < .05
cultures, although these figures suggest
3-97th 422 (87.6) 196 (80) 132 (84.1) 64 (78.0)
that maternal pyrexia may be inflam-
matory rather than infective. 97th 29 (5.9) 16 (6.5) 8 (5.1) 8 (9.8)
The association between fetal growth Occipitofrontal head 22 (4.7) 16 (6.5) 5 (3.3) 11 (13.4) < .05
restriction and neonatal encephalopathy circumference >97th
is well recognized.22,23 In CART analy- percentile for gestational age
sis, birthweight appeared in multiple a
c2 analysis of trend; b Socioeconomic classification 1 ¼ higher managerial, professional; 2 ¼ intermediate managerial,
administrative, professional; 3 ¼ skilled manual workers; 4 ¼ semiskilled manual workers; 5 ¼ unskilled manual workers;
branches, but with different thresholds. 6 ¼ casual laborers; 7 ¼ unemployed; 10 ¼ unclassified; c Defined as infertility and/or preterm labor and/or recurrent
There are many different causes of fetal miscarriage and/or previous cesarean delivery.
growth restriction, and each may differ Hayes. HIE in newborn infants >36 weeks gestation. Am J Obstet Gynecol 2013.
in its potential to contribute to the
development of encephalopathy.10
A head circumference >97th percen-
tile was associated independently with previous study in rural Nepal found findings of this study. A recent study
grade 2 and 3 HIE and remained so after larger newborn infant head circumfer- examined the accuracy of sonographic
adjustment for birthweight and gesta- ence carried a higher risk of neonatal estimation of fetal head circumference
tion, which suggests that head size asphyxia.24 There was no independent up to 3 days before delivery and noted
rather than overall size of the newborn association with higher newborn birth- that sonographic measurements consis-
infant may be the important factor. A weight, which was similar to the tently underestimated postnatal head

Research
TABLE 6
Logistic regression analysis of case control data
Cases vs control Grade 1 HIE vs control Grades 2 and 3 HIE
infants (all grades) infants vs control infants
Unadjusted Adjusted Adjusted Adjusted
Variable odds ratio 95% CI P value odds ratio 95% CI P value odds ratio 95% CI P value odds ratio 95% CI P value
Maternal age (<25 y) 0.67 0.47e0.95 .025 0.92 0.61e1.60 .982 0.91 0.44e1.30 .316 0.92 0.33e2.65 .886
Obstetrics
Maternal smoking (yes) 1.39 0.95e2.03 .082 1.75 0.97e3.15 .065 1.62 0.80e3.29 .176 2.46 0.94e6.41 .065
Primigravid 2.08 1.51e2.87 .000 1.01 0.55e1.82 .967 1.11 0.37e3.25 .851 4.38 0.86e22.36 .075
Trauma in pregnancy 2.35 1.02e5.41 .044 0.74 0.20e2.64 .644 0.52 0.11e2.43 .410 2.13 0.33e13.45 .419
Significant antepartum 2.16 1.37e3.41 .001 1.75 0.89e4.40 .101 1.12 0.49e2.56 .280 8.24 2.58e26.33 .000
hemorrhage
Artificial rupture of membranes 0.78 0.56e1.09 .150 0.62 0.37e1.01 .054 0.48 0.27e0.85 .011 1.15 0.44e2.99 .772
Oligohydramnios 2.48 1.45e4.25 .001 1.94 0.82e4.55 .128 3.40 2.12e8.23 .000 0.94 0.15e5.82 .951
Stage 2 oxytocin 1.91 1.37e2.66 .000 0.99 0.57e1.72 .990 1.21 0.41e3.57 .724 1.29 0.40e4.17 .668
Maximum no. of pains per 2.39 1.67e3.41 .000 2.07 1.13e3.81 .018 2.26 1.14e4.49 .019 1.23 0.41e3.68 .701
15 min >7
Analgesia (any) 2.19 1.27e3.76 .004 1.02 0.38e2.72 .965 1.07 0.28e4.08 .911 0.62 0.14e2.63 .520
Emergency section/instrument 5.42 3.84e7.61 .000 3.03 1.75e5.24 .000 6.14 1.94e19.45 .002 5.87 1.42e24.12 .014
delivery
Maternal pyrexia 4.85 2.69e8.73 .000 4.45 2.02e9.78 .000 6.07 1.13e32.45 .035 15.93 1.91e132.45 .010
Maternal antibiotics 2.16 1.22e3.84 .008 0.67 0.24e1.81 .433 3.25 0.37e28.51 .286 1.22 0.25e5.99 .802
Complications 9.1 4.91e16.86 .000 13.61 2.67e69.26 .002 10.44 1.51e72.1 .017 8.91 0.59e133.24 .113
Bradycardia 3.27 2.18e4.92 .000 2.63 1.44e4.79 .002 1.43 0.41e4.93 .565 11.04 2.23e54.75 .003
High-grade meconium 5.40 3.53e8.28 .000 5.13 2.86e9.19 .000 4.19 2.12e8.27 .000 13.82 4.59e41.64 .000
Birthweight 3rd percentile 1.86 1.08e3.20 .024 1.85 0.75e4.54 .177 1.27 0.41e3.92 .671 5.31 1.39e20.18 .014
Head circumference 97th 1.55 0.79e3.00 .197 2.65 1.01e6.93 .043 1.29 0.32e5.19 .711 9.32 2.57e33.90 .001
percentile
Sex (male) 1.24 0.90e1.69 .174 0.99 0.62e1.60 .982 0.75 0.44e1.30 .316 1.93 0.78e4.77 .151
Weeks gestationecontinuous 1.05 0.93e1.17 .449 0.98 0.82e1.18 .387 1.04 0.83e1.30 .702 0.82 0.603e1.10 .194
variablea
www.AJOG.org
The following interactions were included in the multivariate analysis: primigravid intervention at delivery; primigravid bradycardia; stage 2 oxytocin intervention at delivery; maternal pyrexia intervention at delivery; maternal antibiotics intervention at
delivery; complications intervention at delivery; complications max number of pains per 15 minutes >7.
CI, confidence interval; HIE, hypoxic ischemic encephalopathy.
a
Included in the multivariate analysis to control for birthweight.
recordings were reviewed independently

FIGURE 1 by a blinded obstetrician (J.K.). Unfor-
CART analysis: comparison of control infants with cases with grade 1 tunately, because a large proportion of
disease fetal heart rate tracings were not located
or had faded with time, only 102 fetal
heart tracings were available. Because of
the relatively small number of fetal heart
rate recordings that were available, in-
formation on fetal heart rate tracings as
documented in the medical chart at the
time of delivery were used in the analyses.
This may have limited the data that were
available on fetal heart rate patterns.
All newborn infants with HIE were
included regardless of demographic
characteristics. Therefore, our results are
applicable to any health care setting with
similar demographics and health care
systems.
The findings of this study may serve to
identify infants who are at risk of not
tolerating the labor process and assist in
the decision-making process regarding
the need for cesarean delivery. -
ACKNOWLEDGMENTS
We thank Myra O’Regan, Associate Professor
of Statistics, Trinity College Dublin, for the
statistical support and the children and their
Analysis shows the hierarchy of factors, the percentage of HIE, and the number of records at each families who participated in this project.
node. A, All subjects with grade 1 HIE and controls. B shows that the presence of an obstetric
complication was the single most discriminating factor. The presence of C, high-grade meconium, D,
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FIGURE 2
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Data acquisition natally were recorded. of labor (as recorded on maternal par-
Preconception variables togram) and whether a full 10 cm of
Maternal age, nationality, family his- Intrapartum and delivery variables dilation was reached was determined
tory, medical history (including thyroid The intrapartum cardiotocogram fea- from maternal notes that included the
and seizure history), obstetric history, tures (if labor had been established) or maternal partogram. Patients with no
parity, tobacco, alcohol, or medication the characteristics of the cardiotocogram labor were coded as length of first stage
exposure as recorded in the maternal that had been performed before delivery labor equal to zero. In addition, the mode
chart was noted. Documented histories (if labor did not occur), as noted in the of delivery for nonlaboring patients who
of infertility, in vitro fertilization, or maternal chart by either the attending had an elective cesarean delivery was
clomiphene citrate use were used as physician or midwife at the time of labor coded with spontaneous vaginal delivery
markers of infertility. Parental occupa- and/or delivery, were recorded. The (0 ¼ spontaneous vaginal delivery or
tions registered on booking and whether amniotic fluid volume during the intra- elective section); those patients with an
the mother held private health insur- partum period either on rupture of the emergency cesarean delivery were coded
ance, paid cash, or was publically funded membranes or by ultrasound assessment with instrument deliveries (1 ¼ forceps,
were recorded as markers of socioeco- was recorded. The grade of meconium ventouse, or emergency cesarean de-
nomic status. With publically funded that had been noted at delivery was livery). Details of any intervention dur-
subjects, those who qualified for a recorded; when this was not stated ing labor and delivery, the presentation
medical card (awarded on the basis clearly, the level that had been noted of the infant in labor, details of compli-
of income below a certain threshold before delivery was documented. The cations that were encountered (shoulder
or ongoing medical costs that would presence of maternal pyrexia and the use dystocia, placental abruption, uterine
lead to undue hardship) were identified of maternal antibiotics in labor were rupture), and the mode of delivery were
separately. noted. All analgesia that had been also recorded.
administered in the intrapartum period
Antenatal variables was documented. Use of spinal, epidural, Infant factors
Apart from late bookers, all women had and/or general anesthesia was recorded. Infant gestation, birthweight, head cir-
a dating ultrasound scan. When the The method of membrane rupture cumference, Apgar score, cord pH, re-
menstrual cycle was regular and the last (spontaneous or artificial) and duration suscitation details, and time to regular
menstrual period was certain and of rupture of membranes before delivery respirations were documented from the
crown-rump length was equivalent to were noted. infant medical record. Neurologic signs
the gestational age 7 days, the expected The type of labor (spontaneous/ on day 1 and 2 of life were recorded from
date of delivery was calculated from induced/augmented) and the method the medical chart.

A Case-Control Study of Hypoxic-Ischemic Encephalopathy in Newborn Infants at 36 Weeks Gestation

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A Case-Control Study of Hypoxic-Ischemic Encephalopathy in Newborn Infants at 36 Weeks Gestation

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Research www.AJOG .

I ntrapartum asphyxia in mature new-

Inclusion criteria were newborn infants

JULY 2013 American Journal of Obstetrics & Gynecology 29.e1

29.e2 American Journal of Obstetrics & Gynecology JULY 2013

11-20/D 31 6.6 10 6.6 6 10.5 0 0 1.16 0.61e2.18

Maternal history of problems (other)

Yes 326 67.5 95 60.5 43 74.1 9 42.9 < .05 c

Shoulder dystocia 11 2.3 20 12.9 7 11.9 2 9.5 6.72 3.28e13.73

Socioeconomic grouping, n (%)c,d

not have electronic fetal heart rate

elective cesarean delivery and 5 women

delivery or spontaneous vaginal delivery

without time for electronic fetal heart rate

heart rate monitoring was applied in a

further 19 women (8%). All remaining

cases had continuous fetal heart rate

Among control infants, 50 women

(10.2%) did not have electronic fetal

underwent elective cesarean delivery and

13 women who proceeded to emergency

cesarean delivery or spontaneous vaginal

fetal heart rate monitoring); intermittent

electronic fetal heart rate monitoring was

All remaining control infants had con-

Results of univariate analysis are

available (Table 2). The following factors

reached statistical signiﬁcance (P < .25)

and were included in the multivariate

JULY 2013 American Journal of Obstetrics & Gynecology 29.e13

large head circumference, oligohy-

29.e14 American Journal of Obstetrics & Gynecology JULY 2013

JULY 2013 American Journal of Obstetrics & Gynecology 29.e15

recordings were reviewed independently

JULY 2013 American Journal of Obstetrics & Gynecology 29.e17

29.e18 American Journal of Obstetrics & Gynecology JULY 2013

JULY 2013 American Journal of Obstetrics & Gynecology 29.e19

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