Is gabapentin (Neurontin) safe to use during pregnancy?

Gabapentin Use During Pregnancy

Gabapentin should be used during pregnancy only when the potential benefit clearly justifies the potential risk to the fetus, as it is FDA Pregnancy Category C with concerning evidence of developmental toxicity in animal studies and emerging human data showing increased risks of adverse neonatal outcomes. 1

FDA Classification and Animal Data

• Gabapentin is classified as FDA Pregnancy Category C, meaning there are no adequate and well-controlled studies in pregnant women 1
• In animal studies, gabapentin was developmentally toxic at doses similar to or lower than those used clinically, including skeletal variations in mice, hydroureter/hydronephrosis in rats at all doses tested, and increased embryo-fetal mortality in rabbits at all doses 1
• Neonatal mice exposed to gabapentin during synaptogenesis (equivalent to the third trimester in humans) showed marked decreases in neuronal synapse formation, though the clinical significance remains unknown 1

Human Pregnancy Outcomes: Major Malformations

• A large US Medicaid study of 4,642 first-trimester exposures found no increased risk of major congenital malformations overall (adjusted RR 1.07,95% CI 0.94-1.21) 2
• However, when requiring ≥2 gabapentin dispensings (suggesting more consistent use), the risk of cardiac defects increased significantly (RR 1.40,95% CI 1.03-1.90) 2
• Earlier registry data from 294 first-trimester monotherapy exposures reported 5 major congenital malformations (1.7%), comparable to the general population rate of 1.6-2.2% 3
• A 2024 systematic review found that pregabalin (a related gabapentinoid) was associated with increased risks of overall congenital anomalies and specific anomalies affecting the nervous system, eyes, oro-facial clefts, and urinary/genital systems, raising broader concerns about this drug class 4

Adverse Maternal and Neonatal Outcomes

• Gabapentin exposure late in pregnancy was associated with increased risk of preterm birth (RR 1.28,95% CI 1.08-1.52) 2
• Small for gestational age (SGA) risk was elevated with early exposure (RR 1.17,95% CI 1.02-1.33), late exposure (RR 1.39,95% CI 1.01-1.91), or both (RR 1.32,95% CI 1.08-1.60) 2
• NICU admission risk increased with exposure throughout pregnancy (RR 1.35,95% CI 1.20-1.52) 2
• The systematic review confirmed these findings, reporting increased risks of preeclampsia, preterm birth, SGA, and NICU admission with gabapentin exposure 4
• No increased risk of preeclampsia was found after adjustment for confounders in the Medicaid study 2

Neonatal Withdrawal Syndrome

• Neonatal gabapentin withdrawal syndrome has been documented, presenting with signs requiring clinical recognition 5
• Withdrawal symptoms can be atypical and difficult to control, particularly in neonates with dual exposure to opioids and gabapentin 6
• Clinicians should anticipate possible withdrawal symptoms and consider gradual tapering over weeks to months, similar to adult protocols 5

Clinical Decision-Making Algorithm

When gabapentin cannot be avoided:

• Use the lowest effective dose necessary 1
• Avoid use during the first trimester if possible, given the signal for cardiac defects with consistent use 2
• If treatment extends into late pregnancy, counsel patients about increased risks of preterm birth, SGA, and NICU admission 2
• Arrange for close neonatal monitoring after delivery for withdrawal symptoms 5
• Consider enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 1

Critical Caveats

• The combined evidence from human studies and animal data raises substantial concerns about gabapentin safety during pregnancy, particularly with the 2024 systematic review concluding that "careful evaluation of the benefit-risk balance for both mother and fetus/infant is essential" 4
• Opioid use disorder is the greatest risk factor for gabapentin misuse, and dual exposure creates additional neonatal risks 6
• The FDA label explicitly states gabapentin is "potentially developmentally toxic" based on preclinical data 6
• Given the emerging evidence of harm, gabapentin should only be continued during pregnancy when no safer alternative exists and the maternal condition poses greater risk than the medication 1, 4