There are concerns regarding neurobehavioral changes in infants exposed to parenteral opioids during labor, yet long-term neurodevelopment remains unstudied.


We aimed to examine the association between parenteral opioids for labor analgesia and perinatal outcomes and childhood neurodevelopment until two years of age among infants born preterm. We hypothesized that intrapartum exposure to parenteral opioids is associated with impaired neurodevelopment and adverse perinatal outcomes.

Study design

Secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm birth. Women delivering a singleton, non-anomalous, live infant prior to 37 weeks gestation were considered for inclusion. Women were excluded if they were missing exposure or primary outcome data, were exposed to general anesthesia, or reported use of heroin or unspecified illicit drugs. Women reporting use of non-opioid illicit drugs such as cocaine and marijuana were not excluded. Groups were compared based on exposure or non-exposure to parenteral opioids (intravenous or intramuscular) for labor analgesia. The primary outcome was any psychomotor or mental developmental delay at 24 months by Bayley Scales of Infant Development II. Secondary outcomes were BSID subdomains and adverse perinatal outcomes. Multivariable logistic regression models were performed and adjusted odds ratios with 95% confidence intervals were estimated.


Of 1,404 women included, 535 (38%) received parenteral opioids for labor analgesia. Women receiving parenteral opioids were more likely to be younger, Hispanic, and present with cervical dilation ≥4cm. Parenteral opioid recipients had lower rates of illicit non-opioid drug or tobacco use, a lower rate of cesarean delivery, lower educational achievement, and were less likely to be undergoing induction. Women receiving parenteral opioids who underwent cesarean delivery were less likely to do so due to non-reassuring fetal status. In unadjusted and adjusted analyses, there were no significant differences in the primary outcome of psychomotor or mental developmental delay at two years of age (aOR 0.96, CI 0.76-1.20). The only significant difference in secondary outcomes was a shorter oxygen requirement duration in the parenteral opioid group (2 vs. 4 days, p=0.002).


Among a population of preterm infants vulnerable to neurologic impairment, intrapartum exposure to parenteral opioids was not associated with an increased risk of neurodevelopmental delay up to two years of age, nor did these infants have worse perinatal outcomes.

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