Objective:To determine the effectiveness and safety of moderate whole-body hypothermia in newborns with hypoxic-ischemic encephalopathy born in hospitals with and without newborn intensive care facilities or complicated hypothermia equipment.Design: Multicenter, international, randomized controlled trial.Participants: Newborns of 35 weeks' gestation or more, with indicators of peripartum hypoxia-ischemia and moderate to severe clinical encephalopathy, randomly allocated to hypothermia (n=110) or standard care (n=111).Intervention: Whole-body hypothermia to 33.5°C for 72 hours or standard care (37°C). Infants who received hypothermia were treated at ambient environmental temperature by turning off the radiant warmer and then applying refrigerated gel packs to maintain rectal temperature at 33°C to 34°C.Main Outcome Measures: Death or major sensorineural disability at 2 years of age.Results: Therapeutic hypothermia reduced the risk of death or major sensorineural disability at 2 years of age: 55 of 107 infants (51.4%) in the hypothermia group and 67 of 101 infants (66.3%) in the control group died or had a major sensorineural disability at 2 years (risk ratio, 0.77 [95% confidence interval, 0.62-0.98]; P=.03). The mortality rate decreased, and the survival rate free of any sensorineural disability increased. Adverse effects of hypothermia were minimal.Conclusions: Whole-body hypothermia is effective and appears to be safe when commenced within 6 hours of birth at the hospital of birth in term and near-term newborns with hypoxic-ischemic encephalopathy. This simple method of hypothermia could be used within strict protocols with appropriate training on correct diagnosis and application of hypothermia in nontertiary neonatal settings while awaiting retrieval and transport to the regional neonatal intensive care unit.

Key Points Question Is prenatal opioid exposure associated with differences in childhood cognitive and motor development? Findings In this systematic review and meta-analysis of 26 studies including 1455 children exposed to prenatal opioids compared with unexposed children, prenatal opioid exposure was associated with lower cognitive scores. The largest difference was seen between ages 6 months and 6 years. Meaning The negative consequences of prenatal opioid exposure on neurocognitive and physical development appear to be present from 6 months and persist beyond school age.

In the modern era of neonatal management, male infants still have higher mortality and poorer long-term neurologic outcome. Gender differences for mortality and long-term neurologic outcome appear to lose significance at 27 weeks gestation.