Gabapentin (Neurontin) is an antiepileptic drug that is now used to treat a wide variety of clinical settings — for the treatment of pain management, restless leg syndrome, anxiety, and sleep disturbance. So far, data regarding the use of gabapentin during pregnancy has been reassuring, and it does not appear that gabapentin
Data from the Medicaid Analytic eXtract
The largest study to date was published in 2020. Using data from the US Medicaid Analytic eXtract (MAX) dataset, Patorno and colleagues conducted a population-based study of 1,753,865 Medicaid-eligible pregnancies, examining the risk of major congenital malformations associated with gabapentin exposure during the first trimester.
- 4,642 pregnancies with first trimester gabapentin exposure were identified (mean age of 28 years; 69% white).
- A reference group consisting of 1,744,447 unexposed pregnancies (mean age of 24 years; 40% white) was also identified.
- The adjusted relative risk (RR) for major malformations in the gabapentin-exposed group was 1.07 (95% CI 0.94-1.21, p = 0.33).
- The relative risk for cardiac defects was 1.12 (0.89-1.40, p = 0.35).
- When they analyzed individuals filling two or more gabapentin prescriptions, the RR for cardiac defects increased to 1.40 (1.03-1.90, p = 0.03).
Dosage: They calculated risk of malformations as a function of gabapentin dosage. They found no association between dosage of medication and risk of malformations, comparing risk in those exposed to less than 900 mg per day versus those exposed to doses of 900 or more per day..
Risk of Complications: They also examined the risk for complications, including preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and neonatal intensive care unit admission associated with gabapentin exposure early, late, or both early and late in pregnancy.
- There was an increased risk of preterm birth among women exposed to gabapentin either late (RR=1.28 [CI 1.08-1.52], p < 0.01) or both early and late in pregnancy (RR=1.22 [1.09-1.36], p < 0.001).
- There was a higher risk of SGA among women exposed to gabapentin early (1.17 [1.02-1.33], p = 0.02), late (1.39 [1.01-1.91], p = 0.05), or both early and late in pregnancy (RR, 1.32 [1.08-1.60], p < 0.01).
- There was also a higher risk of NICU admissions among infants exposed to gabapentin both early and late in pregnancy (RR, 1.35 [1.20-1.52], p < 0.001).
The Bottom Line
The findings of this large population-based study including over 4000 infants with first trimester exposure to gabapentin are consistent with previous studies, indicating no evidence of an association between gabapentin exposure during early pregnancy and overall risk of major malformations. There was a slightly higher risk of cardiac malformations (RR=1.40) when they restricted the analysis to women filling 2 or more prescriptions for gabapentin. While this suggests that gabapentin may be associated with a small increase in risk of cardiac defects, it is also possible, given a relative risk of this magnitude, that there may be confounding by indication. (We have seen this in studies of SSRIs and cardiovascular malformations, where the association between SSRIs and cardiovascular defects disappeared after controlling for confounding factors in larger sample sizes.)
This study also observed that maternal use of gabapentin was associated with a small increase in risk for adverse outcomes, including preterm birth, small for gestational age, and NICU admissions. It should be noted that there is also an increased risk of these outcomes in women with depression and anxiety. In a study of this design, it is impossible to rule out the possibility that anxiety symptoms or other factors in the women treated with gabapentin may also contribute to risk for adverse outcomes.
All in all, the information from this study and others looks reassuring. While we cannot rule out the possibility of a small increase in risk of cardiovascular malformations in gabapentin-exposed infants, it looks as if gabapentin is not a major teratogen.
Ruta Nonacs, MD PhD
References
Patorno E, Hernandez-Diaz S, Huybrechts KF, Desai RJ, Cohen JM, Mogun H, Bateman BT. Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset. PLoS Med. 2020 Sep 1;17(9):e1003322. Free Article.
