Methods
This retrospective case series evaluated all neonates ≥35 weeks of
gestation born with HIE over a ten-year study period from January
1st 2007 to December 31st 2016 at
three tertiary referral academic medical centers. Institutional Review
Board Approval was obtained at all three participating institutions
(Columbia University Medical Centre, Yale New Haven Hospital and
University of Rochester) prior to the commencement of any data
collection. This study received funding in the form of an Award for the
Advancement of Clinical Initiatives from MCIC Vermont, Broad St., New
York, NY. MCIC Vermont did not have a role in conducting this study.
A diagnosis of HIE was based on the presence of fetal acidemia (defined
as arterial cord gas pH <7.0, a base deficit of ≥12 mmol/L, or
both) along with clinical findings such as an Apgar score of
<5 at 5 or 10 minutes, evidence of acute brain injury on
neonatal neuroimaging, or abnormal neurologic findings on neonatal
clinical examination. A structured review of each case was carried out
using a modified version of the template recommended by the American
Academy of Pediatrics for the review of cases of neonatal
encephalopathy.9 Maternal demographic information was
ascertained and risk factors such as pre-gestational and gestational
diabetes, chronic hypertension, preeclampsia, and use of tobacco and
recreational drugs were identified. Obstetric information obtained
included gestational age at delivery, the presence of obstetric
complications such as spontaneous preterm labor, preterm premature
rupture of membranes, term premature rupture of membranes, placenta
previa, vasa previa, trial of labor after cesarean, chorioamnionitis,
antenatal bleeding, and other complications. Information about the fetus
was obtained including diagnoses of fetal growth restriction based on
the presence of ultrasound estimated fetal weight
<10th percentile within 4 weeks of delivery,
suspected macrosomia based on the presence of ultrasound estimated fetal
weight >90th percentile within 4 weeks of
delivery, major congenital anomalies, and prenatally diagnosed genetic
abnormalities.
The labor course and management were abstracted and included total time
in labor, duration of the second stage, time of rupture of membranes and
whether they were ruptured artificially or spontaneously, whether
amniotic fluid was clear, meconium-stained, or blood-stained, use of
oxytocin for induction and augmentation, labor anesthesia, fetal
presentation, time of day of delivery, and mode of delivery including
whether operative delivery was performed. The presence of sentinel
events including uterine rupture, umbilical cord prolapse, amniotic
fluid embolus, or maternal cardiac arrest was ascertained.
Fetal heart rate (FHR) tracings were reviewed and the characteristics in
the first 30 minutes of monitoring and the final 30 minutes prior to
delivery were recorded. FHR characteristics evaluated included fetal
heart rate baseline, the presence of accelerations, the presence of late
decelerations, and whether late decelerations, if present, were
recurrent (present with ≥50% of contractions). FHR tracings were
categorized as category I, II or III according to the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
consensus panel and this was also the source for our definitions for FHR
characteristics.10 Presence or absence of uterine
tachysystole, as defined by the above consensus panel, was additionally
evaluated. Labor course and management and fetal heart tracing findings
were analyzed based upon whether patients were delivered ≤120 minutes or
>120 after presentation.
Neonatal data was obtained including (i) Apgar scores at 5 and 10
minutes, (ii) venous and arterial cord blood sample pH, base deficit,
pO2, and pC02, (iii) neonatal blood sample pH, base deficit, pO2, pC02,
and lactate, (iv) neonatal resuscitation including whether bag/mask,
cardiopulmonary resuscitation, and intubation were required, (v)
neonatal imaging including ultrasound, CT, and MRI findings, (vi) EEG
results, (vii) witnessed seizure-like activity, (viii) use of head or
body cooling, and (ix) presence of multi-system organ involvement. When
available, placental pathology was reviewed.
Study data were collected and managed using Research Electronic Data
Capture (REDCap) electronic data capture tools.11,12REDCap is a secure, web-based software platform designed to support data
capture for research studies, providing an intuitive interface for
validated data capture, audit trails for tracking data manipulation and
export procedures, and automated export procedures for seamless data
downloads to common statistical packages. SAS version 9.4 was used for
statistical analyses (SAS Institute, Cary, NC.)