2G-04 - Prenatal Opioid Exposure and the Risk of Adverse Neonatal and Neurodevelopmental Outcomes: A Systematic Review and Meta-Analysis

Background: Moderate to severe acute lower back and pelvic pain, often inadequately managed with acetaminophen, are frequently reported during pregnancy. Opioids are a feasible alternative for pain management; however, studies evaluating their safety in pregnancy have yielded conflicting results. Conclusive data regarding the safety of prescription opioid use during pregnancy is needed.

Objectives: To assess the association between prenatal exposure to prescription opioids and the risk of adverse neonatal and neurodevelopmental outcomes through a systematic review, and meta-analysis.

Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta- Analyses Protocols (PRISMA-P) guidelines. A systematic search of PubMed, Google Scholar, Embase and Cochrane databases was conducted by two independent reviewers to identify international observational studies and randomized clinical trials published from January 2000 onward that examined the relationship between prenatal prescription opioid exposure and adverse pregnancy and neurodevelopmental outcomes. Study quality and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) for included studies. A random-effects model was used to estimate pooled odds ratios (ORs) and hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).

Results: A total of 5,222 studies were identified through database searches. Nineteen studies that met the inclusion criteria and demonstrated a low risk of bias were included in the systematic review, while 15 studies (13 cohort studies, 2 case-control studies) were included in the meta-analysis. Prenatal exposure to prescription opioids, as reported in nine studies, was not significantly associated with an increased risk of congenital malformations (OR) = 1.06; CI: 1.00-1.11; I2 = 27%, P = 0.05). However, findings from three studies indicated a slightly higher risk of attention-deficit/hyperactivity disorder (ADHD) among children with prenatal opioid exposure (HR = 1.07; CI: 1.04-1.11, I2 = 2%, P < 0.0001). Additionally, prenatal opioid exposure was associated with a significantly increased risk of preterm birth (OR = 1.32; CI: 1.23-1.43, I2= 89%, P < 0.0001), though substantial heterogeneity was observed among the three studies included in the analysis.

Conclusions: Our findings suggest that opioid use during pregnancy is associated with a significantly increased risk of preterm birth, while the risk for ADHD and congenital malformations remains low. Further research is needed to better understand the long-term effects of prenatal opioid exposure on neonatal and neurodevelopmental outcomes.