Gabapentin and Opioid Coexposure During Pregnancy and Adverse Perinatal Outcomes: A Population-Based Study, 2020-2024

This study aimed to examine the association between prenatal gabapentin exposure, with and without opioid coexposure, and adverse perinatal outcomes.

We conducted a retrospective, population-based cohort study of all live singleton births in West Virginia from January 2020 to July 2024 (n = 77,059). Exposure was categorized as no exposure to gabapentin or opioids, gabapentin alone, opioids alone, or both. Outcomes included birth weight, gestational age, 5-minute APGAR, low birth weight (LBW, <2,500 g), preterm birth, small for gestational age (SGA), neonatal abstinence syndrome (NAS), NICU admission, and congenital anomalies. Logistic and linear regression models were adjusted for maternal age, race, nicotine, and other substance use.

Of 77,059 births, 177 infants (0.23%) were exposed to gabapentin and 2,868 (3.72%) to opioids. Notably, 105 gabapentin-exposed infants (59.3%) were also exposed to opioids. Compared with the group with no exposure to gabapentin or opioid, exposure to gabapentin alone was associated with lower mean birth weight (AMD = -372.6 g, 95% CI: -500.0, -245.2), lower gestational age (AMD = -0.67 weeks, 95% CI: -1.10, -0.23), and higher odds of LBW (AOR = 3.77, 95% CI: 2.23, 6.34), SGA (AOR = 2.93, 95% CI: 1.74, 4.94), and NICU admission (AOR = 5.59, 95% CI: 3.47, 9.01). Coexposure with opioids was associated with a higher risk of preterm birth (AOR = 3.97, 95% CI: 2.64, 5.97), lower 5-minute APGAR (AMD = -0.23, 95% CI: -0.38, -0.07), and higher NAS incidence (89 vs. 43% with gabapentin alone and 77% with opioids alone). Gabapentin use alone was not significantly associated with preterm birth, 5-minute APGAR scores, or congenital abnormalities.

These findings highlight the pattern of gabapentin use during pregnancy, including frequent co-use with opioids. Due to data limitations, causal inferences cannot be drawn. Further research with detailed exposure information and maternal comorbidities is needed to clarify risks and inform clinical care and long-term outcomes.

· Prenatal gabapentin exposure occurred in 2.3 per 1,000 live births (2020-2024).. · Two-thirds of the gabapentin-exposed infants were also exposed to opioids.. · Co-exposed infants had higher rates of adverse outcomes than those with single-substance exposure..