While gabapentin (Neurontin) is now used in a wide variety of clinical settings — for epilepsy, pain management, restless leg syndrome, anxiety, and sleep disturbance – there is relatively little information regarding its reproductive safety.  Most recently, a prospective study from researchers at the Motherisk program reports on the outcomes of 223 pregnancies exposed to gabapentin and 223 unexposed pregnancies. In this study, the rates of major malformations were similar in the two groups. There was a higher rate of preterm births and low birth weight (less than 2,500 g) in the gabapentin group.

The data are reassuring; however, it should be noted that we still need greater numbers of exposed cases in order to quantify the risk.  It is estimated that at least 400 to 600 exposures would be required to detect a 2-fold increase in more common malformations.  A recent report (Guttuso et al, 2014) reviews the accumulated data we have regarding the reproductive safety data on gabapentin.  This table (adapted from this report) includes first trimester exposure to gabapentin monotherapy.

Study N MCM Type of Malformations
Montouris et al.Gabapentin Pregnancy Registry 11 0
Morrow et al.UK and Ireland Epilepsy and Pregnancy Register 31 1 Ventricular septal defect (0.3%)
Molgaard-Nielsen et al. (2011)Population-based cohort study of liveborn Infants in Denmark [1996–2008] 59 1 Congenital heart disease (0.3%) – correct
Hernandez-Diaz et al. (2012)North American AED Pregnancy Registry 145 1 Endocardial fibroelastosis (0.3%) – correct
Guttuso et al. 10 2 Tethered spinal cord (0.3%), hydronephrosis (0.3%)
Fujii et al. 36 0
Veiby et al. (2014) 39 0
Additional cases 2 0
Summary 333 5 (1.5%)

Pooling all of the available data we can calculate a crude estimate of risk for malformation in gabapentin-exposed infants.  Out of a total of 333 exposures, there were only 5 malformations.  The overall risk of malformations is 1.5%, which is less than the 3%-4% risk of congenital malformations observed in the general population.

While we do not quite have the 400-600 exposures we would like to have, we are getting closer.  So far, the reproductive safety of gabapentin is looking good.

Ruta Nonacs, MD PhD

Fujii H, et al.  Pregnancy outcomes following gabapentin use: Results of a prospective comparative cohort study. Neurology. 2013 April 3.

Guttuso T, Shaman M, Thornburg LL.  Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy.  Eur J Obstet Gynecol Reprod Biol. 2014; 181:280-3.

Hernandez-Diaz S., Smith C.R., Shen A., et al: Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012; 78: 1692-1699.

Holmes L.B., and Hernandez-Diaz S.: Newer anticonvulsants: lamotrigine, topiramate and gabapentin. Birth Defects Res: A Clin Mol Teratol 2012; 94: 599-606.

Molgaard-Nielsen D., and Hviid A.: Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 2011; 305: 1996-2002.

Morrow J., Russell A., Guthrie E., et al: Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 2006; 77: 193-198.

Veiby G, Daltveit AK, Engelsen BA, Gilhus NE.  Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy.  J Neurol. 2014 Mar;261(3): 579-88.




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