Title:
IV or IM opioids for labor analgesia and childhood neurodevelopmental and perinatal outcomes among preterm infants

Authors/Institutions:
Lindsay Speros Robbins, MD, MPH^1,2, Christina T Blanchard, MS¹, Alan T Tita, MD, PhD^1,2, Lorie M Harper, MD, MSCI^1,2

¹Center for Women’s Reproductive Health, University of Alabama at Birmingham, ²Department of Obstetrics and Gynecology, University of Alabama at Birmingham

Objective:
A Cochrane Review concluded the effects of parenteral opioids in labor on infants are unclear with no definitive evidence of harm; ACOG cites concern for neonatal respiratory depression and neurobehavioral changes with opioid analgesia. We examine the impact of IV or IM opioids in labor on perinatal outcomes and neurodevelopment until two years among preterm infants.

Study Design: 
Secondary analysis of a multicenter RCT assessing magnesium for prevention of cerebral palsy in preterm infants. Women were included if they delivered a singleton, non-anomalous, living infant < 37wks. Women were excluded if they were missing exposure or primary outcome data, used heroin or unspecified drugs in pregnancy, or received general anesthesia. The exposure was IV/IM opioid in labor compared to no IV/IM opioid. Primary outcome was mild-moderate developmental delay at 24mos by Bayley Scales of Infant Development II (BSID). Secondary outcomes were BSID subdomains, transient tachypnea of the newborn, respiratory distress syndrome, seizure, poor tone, hypotension, ventilator or oxygen use, and NICU days. Chi square, Fisher’s Exact, Student’s t-test, Wilcoxon Rank Sum tests, and multivariable logistic regression models were performed.

Results:
Of 1404 women included, 535 (38%) received IV/IM opioids in labor. IV/IM recipients were more likely to be younger, Hispanic, and present in preterm labor. IV/IM group had lower rates of cocaine, marijuana, or tobacco use, cesarean delivery (CD), and indicated induction. Fetal distress was less commonly the reason for CD in the IV/IM group. Magnesium and betamethasone exposures were similar. There were no deaths. In unadjusted and adjusted analyses, there were no significant differences in primary or secondary outcomes, aside from a shorter oxygen requirement in the IV/IM opioid group (2 vs 4 days, p=0.002), which may be due to the lower CD rate.

Conclusion:Among these preterm infants vulnerable to neurologic impairment, IV/IM opioid use in labor does not appear to be associated with increased risk of neurodevelopmental delay up to two years or poorer perinatal outcomes.

Table 1. Demographic, pregnancy, and delivery characteristics

Table 2. Childhood neurodevelopmental and perinatal outcomes

*adjusted for gestational age at delivery, exposure to magnesium, alcohol, cocaine, marijuana, tobacco.

^†corrected for prematurity