Systematic review of gabapentinoid use during pregnancy and its impact on pregnancy and childhood outcomes: A ConcePTION study.

Objective: In the general population, there has been a noticeable rise in the dispensing of gabapentinoids in recent years. The aim of this study was to provide an overview of all available data on the use and safety of gabapentinoids during pregnancy.

Methods: A systematic review was performed in PubMed and Reprotox using the search terms: "gabapentin", "pregabalin", "antiepileptic drugs" and terms associated with pregnancy. We included all studies in English that reported on the use and safety of gabapentin and pregabalin during pregnancy. We excluded abstracts, literature reviews, case reports and studies involving fewer than 5 exposures. Descriptive analyses and narrative syntheses were performed.

Results: A total of 27 high-quality studies were described. The prevalence of gabapentinoid use during pregnancy remained very low, at less than 1%. Five studies reported significant findings with increased risks of overall congenital anomalies, specific anomalies (nervous system, eyes, oro-facial clefs, urinary and genital system), miscarriage, stillbirth and specific neurodevelopmental outcomes after exposure to pregabalin during pregnancy. Concerning exposure to gabapentin, increased risks of preterm birth, preeclampsia, small-for-gestational-age and NICU admission were reported in two studies.

Conclusions: Prenatal exposure to pregabalin is associated with an increased risk of congenital anomalies and long-term neurodevelopmental outcomes while gabapentin exposure was associated with an increased risk of preeclampsia, preterm birth and small-for-gestational age. Larger studies are needed to confirm these data and explore additional outcomes. The combined evidence from this systematic review and animal studies raises concerns about the safety of using gabapentinoids during pregnancy. Careful evaluation of the benefit-risk balance for both mother and fetus/infant is essential when these medications cannot be avoided during pregnancy.