Intrapartum opioid analgesia and childhood neurodevelopmental outcomes among infants born preterm

Abstract

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

Objective: We aimed to examine the association between parenteral opioids used as labor analgesia and perinatal outcomes and childhood neurodevelopment until 2 years of age among infants born prematurely. We hypothesized that intrapartum exposure to parenteral opioids is associated with impaired neurodevelopment and adverse perinatal outcomes.

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

Results: Of the 1404 women included, 535 (38%) received parenteral opioids as labor analgesia. Women receiving parenteral opioids were more likely to be younger, Hispanic, and present with cervical dilation ≥4 cm. Parenteral opioid recipients had lower rates of illicit nonopioid drug or tobacco use, a lower rate of cesarean delivery, lower educational level and were less likely to be undergoing induction. Women receiving parenteral opioids who underwent cesarean delivery were less likely to do so because of a nonreassuring fetal status. In the unadjusted and adjusted analyses, there were no significant differences in the primary outcomes of psychomotor or mental developmental delay at 2 years of age (adjusted odds ratio, 0.96; confidence interval, 0.76-1.20). The only significant difference in secondary outcomes was a shorter O₂ requirement duration in the parenteral opioid group (2 vs 4 days; P=.002).

Conclusion: Among a population of preterm infants vulnerable to neurologic impairment, intrapartum exposure to parenteral opioids was not associated with an increased risk for neurodevelopmental delay up to 2 years of age, nor did these infants have worse perinatal outcomes.

Keywords: BSID; anesthesia; antenatal; brain; cesarean; child development; impairment; intramuscular; intravenous; labor; learning disability; mental delay; motor delay; narcotic; neurodevelopment; neurologic; neurotoxicity; opiate; parenteral; perinatal; pregnancy; prenatal.