Original ArticlesAntenatal and Intrapartum Risk Factors for Hypoxic-Ischemic Encephalopathy in a US Birth Cohort
Section snippets
Methods
In this retrospective cohort study, we identified all live, singleton births at 2 Kaiser Permanente Northern California (KPNC) hospitals in Oakland and Santa Clara who were ≥36 weeks of gestational age and born between January 1, 2008, and June 30, 2015. Multiple gestation births and newborns who received a physician diagnosis of congenital viral infection or congenital anomalies were excluded owing to unique predisposing factors in these populations. Study procedures were approved by the
Results
Among 44 960 singleton infants ≥36 weeks of gestational age in the birth cohort, we excluded 384 with congenital anomalies and 4 with congenital viral infection. Of the remaining 44 572 infants, 197 had neonatal acidemia (incidence 4.4 per 1000), 45 had HIE (1.0 per 1000), and 13 had HIE leading to hypoxic-ischemic brain injury or death (0.3 per 1000).
Of 197 infants with neonatal acidemia, 37 (19%) also met study criteria for HIE. Eight infants with HIE did not meet study criteria for neonatal
Discussion
HIE is a heterogeneous condition. In a recent US birth cohort of term and near-term infants, we found that an intrapartum sentinel event and a clinical diagnosis of chorioamnionitis were the strongest risk factors for both HIE and neonatal acidemia. When infants exposed to a sentinel event were excluded from analyses, additional antenatal risk factors for HIE included maternal age ≥35 years, pre-eclampsia, and maternal UTI during pregnancy.
Sentinel events such as uterine rupture or placental
References (65)
- et al.
Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy
Early Hum Dev
(2010) - et al.
A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy
Am J Obstet Gynecol
(2008) - et al.
Global, regional, and national causes of child mortality in 2008: a systematic analysis
Lancet
(2010) - et al.
Threshold of metabolic acidosis associated with newborn complications
Am J Obstet Gynecol
(1997) - et al.
Chorioamnionitis and neonatal encephalopathy in term infants with fetal acidemia: histopathologic correlations
Pediatr Neurol
(2005) - et al.
A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy
Eur J Paediatr Neurol
(2009) - et al.
Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome
J Pediatr
(1981) - et al.
Intrapartum asphyxia: a rare cause of cerebral palsy [published erratum appears in J Pediatr 1988 Aug;113(2):420] [see comments]
J Pediatr
(1988) - et al.
Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial
Lancet
(2005) - et al.
Hyperthermia, inflammation, and perinatal brain injury
Pediatr Neurol
(2013)
Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis
Exp Neurol
Pathophysiology of placental-derived fetal growth restriction
Am J Obstet Gynecol
Placental fetal thrombotic vasculopathy is associated with neonatal encephalopathy
Hum Pathol
Severe fetal placental vascular lesions in term infants with neurologic impairment
Am J Obstet Gynecol
Maternal infections during pregnancy and cerebral palsy in the child
Pediatr Neurol
Childhood outcomes after hypothermia for neonatal encephalopathy
N Engl J Med
Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study [see comments]
BMJ
Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study
BMJ
Antenatal antecedents of moderate or severe neonatal encephalopathy in term infants—a regional review
Aust N Z J Obstet Gynaecol
Antecedents of neonatal encephalopathy in the Vermont Oxford Network Encephalopathy Registry
Pediatrics
A case-control study of hypoxic-ischemic encephalopathy in newborn infants at >36 weeks gestation
Am J Obstet Gynecol
Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy
Pediatrics
Obstetric antecedents to body-cooling treatment of the newborn infant
Am J Obstet Gynecol
Antepartum and intrapartum risk factors for neonatal encephalopathy at term
Am J Perinatol
JCAHO issues warning on kernicterus danger
Hosp Peer Rev
Patterns of brain injury in neonates exposed to perinatal sentinel events
Pediatrics
Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment?
Dev Med Child Neurol
Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group
J Perinatol
Association and prediction of neonatal acidemia
Am J Obstet Gynecol
The limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia
Am J Obstet Gynecol
Fetal acidemia and electronic fetal heart rate patterns: is there evidence of an association?
J Matern Fetal Neonatal Med
Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis
BMJ
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Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy
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2022, Early Human DevelopmentCitation Excerpt :Hayes et al. have reported a higher incidence of sentinel events in mild HIE compared to moderate-severe HIE, similar to our cohort [35]. Parker et al. reported sentinel events to be more common in infants with moderate-severe HIE undergoing hypothermia compared to infants with only acidemia [41]. Two studies have reported a lower incidence of placental inflammation and funisitis in the presence of sentinel events in infants with HIE, similar to our result [20,21].
Trends of neonatal hypoxic-ischemic encephalopathy prevalence and associated risk factors in the United States, 2010 to 2018
2022, American Journal of Obstetrics and GynecologyCitation Excerpt :Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of neonatal morbidity and mortality.1,2 The incidence of HIE is 1 to 3 in 1000 live births in developed countries3–6; the incidence of HIE is approximately 10 times higher in resource-limited countries.7,8 The overall mortality rate of HIE is 15% to 25% with 40% to 50% of survivors developing long-term neurologic disabilities.4–6,8
Acute kidney injury in infants with hypoxic-ischemic encephalopathy
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Funded by the University of California San Francisco (UCSF) National Center of Excellence in Women's Health, through the UCSF Resource Allocation Program. Y.W. provided expert witness testimony in medicolegal cases involving hypoxic-ischemic encephalopathy. E.H. is an obstetrician and senior scientist at Perigen, a company that creates perinatal software. The other authors declare no conflicts of interest.
Portions of this study were presented at the Pediatric Academic Societies annual meeting, April 30-May 3, 2016, Baltimore, Maryland.