Gabapentin Use During the 3rd Trimester of Pregnancy
Gabapentin should be used with significant caution during the third trimester, and only when the potential maternal benefit clearly justifies the substantial fetal and neonatal risks, including preterm birth, small-for-gestational-age infants, and NICU admission.
FDA Classification and Official Guidance
Gabapentin is classified as Pregnancy Category C by the FDA, indicating that animal studies have demonstrated developmental toxicity at clinically relevant doses, and there are no adequate well-controlled studies in pregnant women 1.
The FDA label explicitly states that gabapentin is "developmentally toxic" based on preclinical data, with embryo-fetal toxicity observed in mice, rats, and rabbits at doses similar to or lower than those used clinically 1.
Animal studies showed increased skeletal variations in mice, hydroureter/hydronephrosis in rat offspring at all doses tested, and increased embryo-fetal mortality in rabbits at all doses 1.
Neonatal animal studies demonstrated that gabapentin caused marked decreases in neuronal synapse formation during periods corresponding to the human third trimester, raising concerns about neurodevelopmental impacts 1.
Third Trimester-Specific Risks
Maternal and Obstetric Complications
Preterm birth risk is significantly elevated when gabapentin is used late in pregnancy (RR 1.28,95% CI 1.08-1.52) or throughout pregnancy including the third trimester (RR 1.22,95% CI 1.09-1.36) 2.
Small-for-gestational-age (SGA) risk is increased with late pregnancy exposure (RR 1.39,95% CI 1.01-1.91) and with exposure throughout pregnancy (RR 1.32,95% CI 1.08-1.60) 2.
NICU admission rates are substantially higher when gabapentin exposure occurs both early and late in pregnancy (RR 1.35,95% CI 1.20-1.52) 2.
Preeclampsia risk was reported as increased in one study, though this finding did not persist after full adjustment for confounders 2.
Neonatal Withdrawal and Adaptation
Atypical and difficult-to-control withdrawal signs and symptoms have been reported in neonates exposed to gabapentin in utero, particularly concerning when there is dual exposure with opioids 3.
The FDA label warns that the effects on nursing infants are unknown, and gabapentin is secreted into breast milk, with potential infant exposure up to 1 mg/kg/day 1.
Congenital Malformation Risk (First Trimester Context)
While your question focuses on third trimester use, understanding first trimester risks is relevant for ongoing exposure:
Overall major congenital malformations do not appear significantly increased with gabapentin monotherapy (adjusted RR 1.07,95% CI 0.94-1.21) 2.
However, cardiac defects show concerning signals, particularly with sustained use requiring ≥2 dispensings (RR 1.40,95% CI 1.03-1.90) 2.
A 2024 systematic review reported that pregabalin (a related gabapentinoid) is associated with increased risks of congenital anomalies, while gabapentin specifically showed associations with preeclampsia, preterm birth, and SGA 4.
Clinical Decision-Making Algorithm
When Gabapentin Cannot Be Avoided
Conduct thorough risk-benefit analysis weighing maternal seizure control or pain management against documented fetal risks 1.
Use the lowest effective dose and consider whether therapy can be temporarily discontinued or reduced during the third trimester 1.
Implement enhanced fetal surveillance including serial growth ultrasounds to monitor for SGA 2.
Plan for potential preterm delivery and ensure NICU availability given the 28-35% increased risk 2.
Prepare for neonatal withdrawal monitoring, particularly if there is concurrent opioid exposure 3.
Alternative Considerations
For epilepsy management, discuss with neurology whether alternative antiepileptic drugs with more favorable pregnancy safety profiles can be substituted 1.
For neuropathic pain, consider non-pharmacologic interventions or medications with better-established safety data in late pregnancy 3.
Breastfeeding Considerations
Gabapentin is secreted into breast milk, and the FDA states it should only be used during nursing "if the benefits clearly outweigh the risks" 1.
The maximum infant dose through breast milk is approximately 1 mg/kg/day, but effects on the nursing infant remain unknown 1.
Registry Enrollment
- Strongly encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 to contribute to safety data collection 1.
Critical Caveats
The 2024 systematic review concluded that "the combined evidence from this systematic review and animal studies raises concerns about the safety of using gabapentinoids during pregnancy" and emphasized that "careful evaluation of the benefit-risk balance for both mother and fetus/infant is essential" 4.
A 2023 review specifically stated that "gabapentin use should be considered with caution during pregnancy and during the post-partum period" and called for well-controlled prospective studies 3.
Most available safety data comes from epilepsy populations; extrapolation to other indications (neuropathic pain, anxiety) may not be appropriate given different risk-benefit calculations 3.