Is gabapentin (Neurontin) safe to use during pregnancy?

Gabapentin Safety in Pregnancy

Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as it is classified as FDA Pregnancy Category C with evidence of developmental toxicity in animal studies and limited human safety data. 1

Safety Profile and Risks

Congenital Malformations

• The FDA label indicates that gabapentin has shown developmental toxicity in animal studies at doses similar to or lower than clinical doses 1
• In human studies, among 294 first-trimester gabapentin monotherapy exposures, the major congenital malformation rate was 1.7%, which is comparable to the general population rate of 1.6-2.2% 2
• However, a more recent study found a possible increased risk of cardiac defects (RR 1.40,95% CI 1.03-1.90) when requiring ≥2 gabapentin dispensings during pregnancy 3

Obstetrical and Neonatal Outcomes

• Increased risks have been identified for:
  • Preterm birth (RR 1.28 for late pregnancy exposure; RR 1.22 for both early and late exposure) 3
  • Small for gestational age (RR 1.17-1.39 depending on timing of exposure) 3
  • NICU admission (RR 1.35 for both early and late pregnancy exposure) 3
  • Potential preeclampsia risk, though this was not significant after adjustment in some studies 3

Neonatal Withdrawal

• There are concerns about atypical and/or difficult-to-control withdrawal symptoms in neonates exposed to gabapentin in utero, particularly when combined with opioid exposure 4

Breastfeeding Considerations

• Gabapentin is secreted into human milk following oral administration 1
• A breastfed infant could be exposed to approximately 1 mg/kg/day of gabapentin 1
• The FDA states that gabapentin should be used in nursing women only if benefits clearly outweigh risks 1

Decision-Making Algorithm

1. Assess necessity of treatment:

   • Determine if the maternal condition requires gabapentin specifically
   • Consider alternative medications with better established safety profiles if appropriate

2. If gabapentin is deemed necessary:

   • Use the lowest effective dose
   • Consider timing of exposure (early vs. late pregnancy has different risk profiles)
   • Monitor for potential complications:
     • Fetal growth (risk of SGA)
     • Signs of preterm labor
     • Maternal blood pressure (potential preeclampsia risk)

3. Delivery planning:

   • Prepare for potential NICU admission
   • Alert pediatric team about in utero gabapentin exposure
   • Monitor neonate for withdrawal symptoms

4. Postpartum considerations:

   • Weigh risks/benefits of breastfeeding if continuing gabapentin
   • Monitor infant for drowsiness, poor feeding, or other adverse effects if breastfeeding

Clinical Pearls and Caveats

• The most recent systematic review (2024) raises concerns about gabapentin exposure during pregnancy being associated with increased risks of preeclampsia, preterm birth, and small-for-gestational age 5
• Careful evaluation of benefit-risk balance is essential when gabapentin cannot be avoided during pregnancy 5
• If possible, consider tapering and discontinuing gabapentin before conception or during early pregnancy if the maternal condition allows
• The safety profile of gabapentin in pregnancy is still being established, with limited human data compared to other more established medications