Is it safe to take gabapentin (Neurontin) during pregnancy?

Gabapentin Use During Pregnancy

Gabapentin should be used with caution during pregnancy, as it carries FDA Pregnancy Category C classification and emerging evidence suggests potential risks for cardiac malformations, preterm birth, small-for-gestational-age infants, and NICU admissions, though the absolute risks appear modest. 1, 2

FDA Classification and General Safety Profile

• Gabapentin is classified as FDA Pregnancy Category C, meaning there are no adequate and well-controlled studies in pregnant women, and the drug should only be used if potential benefits justify potential risks to the fetus 1

• Animal studies demonstrated developmental toxicity at doses similar to or lower than clinical doses, including skeletal variations in mice, hydroureter/hydronephrosis in rats, and increased embryo-fetal mortality in rabbits 1

• Neonatal mice exposed to gabapentin during synaptogenesis (equivalent to human third trimester) showed marked decreases in neuronal synapse formation, though the clinical significance remains unknown 1

Risk of Major Congenital Malformations

The evidence on overall major malformations is reassuring, but cardiac defects warrant attention:

• A large US Medicaid study of 4,642 first-trimester exposures found no increased risk of major 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 (RR 1.40,95% CI 1.03-1.90) 2

• A 2024 meta-analysis showed pooled unadjusted results with 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) 3

• Among 294 first-trimester gabapentin-monotherapy exposures across multiple registries, only 5 major congenital malformations were reported (1.7%), comparable to the general population rate of 1.6-2.2% 4

Obstetrical and Neonatal Outcomes

Late pregnancy exposure carries the most consistent risks:

• Preterm birth: Increased risk with late pregnancy exposure (RR 1.28,95% CI 1.08-1.52) or exposure throughout pregnancy (RR 1.22,95% CI 1.09-1.36) 2

• Small-for-gestational-age: Elevated risk with early exposure (RR 1.17,95% CI 1.02-1.33), late exposure (RR 1.39,95% CI 1.01-1.91), or exposure throughout pregnancy (RR 1.32,95% CI 1.08-1.60) 2

• NICU admissions: Significantly increased with exposure throughout pregnancy (RR 1.35,95% CI 1.20-1.52 in adjusted analysis; RR 1.99,95% CI 1.70-2.32 in another cohort) 2, 3

• One prospective study found 38% of infants exposed to gabapentin until delivery required NICU or special care nursery admission versus 2.9% in the comparison group (p < 0.001) 5

• Preeclampsia: No increased risk after adjustment for confounders 2

Comparison with Pregabalin

• A 2024 systematic review found pregabalin exposure associated with increased risks of overall congenital anomalies, specific anomalies (nervous system, eyes, oro-facial clefts, urinary and genital system), miscarriage, stillbirth, and neurodevelopmental outcomes 6

• Gabapentin appears to have a more favorable safety profile than pregabalin, though both gabapentinoids raise concerns 6

Clinical Decision-Making Algorithm

When gabapentin is being considered during pregnancy:

1. First trimester exposure: Weigh the 1.7% baseline malformation risk against potential cardiac defect risk (particularly with consistent use). Consider alternative medications with better-established safety profiles first 1, 2

2. Late pregnancy exposure: Recognize the consistent evidence for preterm birth, SGA, and NICU admission risks. If continuation is necessary, use the lowest effective dose and arrange for enhanced fetal monitoring and neonatal care planning 2, 3

3. Throughout pregnancy: This carries cumulative risks across all adverse outcomes. Strongly consider discontinuation or dose reduction, particularly in the third trimester 2

4. Existing exposure: If a patient presents already taking gabapentin, do not abruptly discontinue due to seizure risk in epilepsy patients. Taper gradually while transitioning to safer alternatives when possible 1

Important Caveats

• Most studies have potential for residual confounding by indication, as gabapentin users often have pain conditions, epilepsy, or psychiatric disorders that independently affect pregnancy outcomes 2, 5

• The absolute risks remain relatively small, and untreated maternal conditions (particularly seizures) may pose greater risks than medication exposure 1

• Gabapentin is secreted into breast milk, and effects on nursing infants are unknown; use only if benefits clearly outweigh risks 1

• Pregnant patients taking gabapentin should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334) to contribute to safety data 1