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.)