Objective: The aim of this study was to investigate key antecedents of moderate and severe neonatal hypoxic ischemic encephalopathy (HIE) in a large contemporary Australian birth cohort. Design: A retrospective cohort study of all births meeting the inclusion criteria between 2016-2020. Setting: The Mater Mothers’ Hospital, Brisbane, Australia. This is a quarternary perinatal center and Australia’s largest maternity hospital. Population: All non-anomalous, singleton liveborn infants, >35+0 weeks gestation. Methods: Univariate and multivariate firth logistic regression were used to account for imbalanced frequency classes. Main outcome measure: Neonatal moderate and severe HIE. Results: Overall, 133/46041 (0.29%) infants were diagnosed with HIE, and 56 (0.12%) were diagnosed with moderate/severe HIE. Nulliparity, type 1 diabetes mellitus and maternal intensive care unit admission were associated with increased odds of moderate/severe HIE. Intrapartum risk factors included emergency cesarean birth, emergency cesarean for non-reassuring fetal status or failure to process, intrapartum hemorrhage, and an intrapartum sentinel event (shoulder dystocia, cord prolapse, uterine rupture, placental abruption). Neonatal risk factors included male sex, birth at late preterm gestation (35+0 – 36+6 weeks), Apgar score <4 at 5 minutes, severe respiratory distress requiring ventilatory support and severe acidosis at birth. Conclusions: This cohort study identified a series of potentially modifiable maternal and obstetric risk factors for HIE. Risk factors for HIE do not appear to have changed significantly despite recent advances in obstetric care. Key words: pregnancy, fetus, fetal distress, intrapartum hypoxia, hypoxic ischemic encephalopathy, cerebral palsy Funding source: The authors acknowledge research support by the Mater Foundation.

Background Neonatal hypoxic ischaemic encephalopathy (HIE) is the most common cause of encephalopathy in the neonatal period and carries a high risk of mortality and long‐term morbidity. Aim The aim of this study was to investigate key antecedents of moderate and severe HIE in a large contemporary birth cohort. Methods A retrospective cohort study of births meeting criteria was conducted between 2016 and 2020 at the Mater Mothers' Hospital, Brisbane, Australia. This is a quaternary perinatal centre and Australia's largest maternity hospital. Univariate and multivariate Firth logistic regression were used to account for imbalanced frequency classes between non‐HIE and HIE groups. Maternal variables and intrapartum factors were investigated for associations with neonatal moderate and severe HIE. Results Overall, 133 of 46 041 (0.29%) infants were diagnosed with HIE: 77 (0.17%) with mild HIE and 56 (0.12%) with moderate/severe HIE. Nulliparity, type 1 diabetes mellitus and maternal intensive care unit admission were associated with increased odds of moderate/severe HIE. Intrapartum risk factors included emergency caesarean birth, emergency caesarean for non‐reassuring fetal status or failure to process, intrapartum haemorrhage and an intrapartum sentinel event (shoulder dystocia, cord prolapse, uterine rupture and placental abruption). Neonatal risk factors included male sex, late preterm gestation (35+0–36+6 weeks), Apgar score less than four at 5 min, severe respiratory distress requiring ventilatory support and severe acidosis at birth. Conclusions This cohort study identified a series of potentially modifiable maternal and obstetric risk factors for HIE. Risk factors for HIE do not appear to have changed significantly with evolution in modern obstetric care.