Gabapentin Safety in Pregnancy
Gabapentin should be used with caution during pregnancy, as it is classified as FDA Pregnancy Category C with evidence of developmental toxicity in animal studies and emerging human data showing increased risks of preterm birth, small-for-gestational-age infants, and NICU admissions, though the evidence for major congenital malformations remains mixed. 1
FDA Classification and Animal Data
- Gabapentin is FDA Pregnancy Category C, meaning there are no adequate and well-controlled studies in pregnant women 1
- Animal studies demonstrate developmental toxicity at doses similar to or lower than clinical doses, including:
- Skeletal variations in mice at doses ≥1000 mg/kg/day 1
- Hydroureter and/or hydronephrosis in rat offspring at all tested doses (≥500 mg/kg/day) 1
- Increased embryo-fetal mortality in rabbits at all doses tested 1
- Marked decrease in neuronal synapse formation when administered during the rodent equivalent of the third trimester 1
Risk of Congenital Malformations
The evidence regarding major congenital malformations is conflicting:
- A large US Medicaid study (n=4,642 first-trimester exposures) found no increased risk of major malformations overall (adjusted RR 1.07,95% CI 0.94-1.21) or cardiac defects (RR 1.12,95% CI 0.89-1.40) 2
- However, requiring ≥2 gabapentin dispensings increased the risk of cardiac defects (RR 1.40,95% CI 1.03-1.90) 2
- A 2024 meta-analysis showed increased risk of major congenital malformations (RR 1.44,95% CI 1.28-1.61) and cardiac malformations (RR 1.66,95% CI 1.11-2.47) in pooled unadjusted analyses 3
- A 2024 systematic review reported that pregabalin (a related gabapentinoid) showed increased risks of congenital anomalies, while gabapentin data were more focused on obstetric complications 4
Obstetric and Neonatal Complications
The most consistent evidence shows increased risks of adverse pregnancy outcomes:
Preterm Birth
- Gabapentin exposure late in pregnancy: RR 1.28 (95% CI 1.08-1.52) 2
- Exposure both early and late in pregnancy: RR 1.22 (95% CI 1.09-1.36) 2
Small-for-Gestational-Age
- Early pregnancy exposure: RR 1.17 (95% CI 1.02-1.33) 2
- Late pregnancy exposure: RR 1.39 (95% CI 1.01-1.91) 2
- Both early and late exposure: RR 1.32 (95% CI 1.08-1.60) 2
NICU Admission
- Exposure both early and late in pregnancy: RR 1.35 (95% CI 1.20-1.52) 2
- A Manitoba cohort study confirmed increased NICU admission risk (adjusted RR 1.99,95% CI 1.70-2.32) 3
- Meta-analysis showed pooled RR of 3.15 (95% CI 2.90-3.41) for NICU admissions 3
Preeclampsia
- No increased risk after adjustment for confounders 2
Neonatal Withdrawal Concerns
- Atypical and difficult-to-control withdrawal signs and symptoms have been reported in neonates exposed to gabapentin in utero, including those dually exposed to opioids 5
- The FDA label notes that gabapentin is secreted into human milk, and nursed infants could be exposed to approximately 1 mg/kg/day 1
Clinical Recommendations
When gabapentin cannot be avoided during pregnancy:
- Use the lowest effective dose and limit duration of exposure, particularly avoiding late pregnancy exposure when possible 2
- Avoid gabapentin if possible during the first trimester if the indication is not urgent, given conflicting data on cardiac malformations 2, 3
- Monitor closely for preterm labor, fetal growth restriction, and preeclampsia throughout pregnancy 2
- Prepare for potential NICU admission and neonatal withdrawal symptoms 2, 5, 3
- Enroll patients in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 to contribute to safety data 1
Important Caveats
- The risk-benefit calculation changes significantly with concurrent opioid use, as gabapentin misuse is most common in individuals with opioid use disorder 5
- Most safety data come from observational studies with potential for residual confounding by indication (e.g., underlying pain conditions, psychiatric comorbidities) 2, 3
- Abrupt discontinuation can cause serious problems, including status epilepticus in patients with epilepsy 1