Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case-Malformed Control Study
Abstract
INTRODUCTION AND OBJECTIVE: Given the increasing use of gabapentinoids and ongoing safety concerns, we assessed the association between first-trimester exposure to gabapentin and pregabalin and the risk of specific congenital anomalies (CAs) in the offspring. METHODS: Using EUROmediCAT data, we conducted a case-malformed control study based on 170,126 registrants with major CAs from livebirths, fetal deaths (≥20 weeks), and terminations of pregnancy for fetal anomaly in nine European countries (2000-2020), covering 10.6 million births. We compared gabapentinoid use in registrants with a specific CA with those among other registrants with non-genetic CA (main control group) and among registrants with a genetic condition (secondary control group). We estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for registry, birth year, and maternal age. Analyses included specific subgroups of CA with ≥3 exposed registrants. RESULTS: First-trimester gabapentinoid exposure was identified in 37 registrants, with most registered in the Valencian region (Spain) (37.8%), EFEMERIS (France) (13.5%) and three other registries (8.1% each). Over 60% of the exposures were observed during 2015-2020. Seven out of 91 EUROCAT subgroups had ≥3 exposed registrants: congenital heart defects, ventricular septal defects, severe congenital heart defects, limb anomalies, urinary anomalies, genital anomalies, and hypospadias. A significantly higher proportion of exposure (0.4‰, 12 exposed cases) was observed among cases with ventricular septal defect compared with registrants in the non-genetic control group (0.2‰, 17 exposed cases), with an adjusted OR of 2.5 (95% CI 1.1-5.3); and the adjusted OR was elevated but non-significant compared with the registrants in the genetic group (2.3; 95% CI 0.8-6.9). CONCLUSIONS: We observed an association between first trimester exposure to gabapentinoids and ventricular septal defect, the most common cardiac anomaly, although this finding is based on only 37 exposed registrants. While our findings align with some previous studies suggesting teratogenic risks associated with gabapentinoids, they also reveal the challenges of studying rare exposures and rare outcomes.
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BibTeX
@article{beau2026gabapentin,
title = {{Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case-Malformed Control Study}},
author = {Anna-Belle Beau and Erika Cifuentes Castro and Justine Benevent and Marie Beslay and Laia Barrachina-Bonet and Jorieke Bergman and Clara Cavero-Carbonell and Alessio Coi and Helen Dolk and Ester Garne and Miriam Gatt and Jonathan Hoareau and Elly Den Hond and Anna Latos-Bielenska and Nathalie Lelong and Mary O’mahony and Xavier Moisset and Joan Morris and Amanda Neville and Joanna Sichitiu and Maria Loane and Christine Damase-Michel},
journal = {Drug Safety},
year = {2026},
month = jun,
doi = {10.1007/s40264-026-01672-8},
url = {https://hal.science/hal-05794365v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case-Malformed Control Study
AU - Anna-Belle Beau
AU - Erika Cifuentes Castro
AU - Justine Benevent
AU - Marie Beslay
AU - Laia Barrachina-Bonet
AU - Jorieke Bergman
AU - Clara Cavero-Carbonell
AU - Alessio Coi
AU - Helen Dolk
AU - Ester Garne
AU - Miriam Gatt
AU - Jonathan Hoareau
AU - Elly Den Hond
AU - Anna Latos-Bielenska
AU - Nathalie Lelong
AU - Mary O’mahony
AU - Xavier Moisset
AU - Joan Morris
AU - Amanda Neville
AU - Joanna Sichitiu
AU - Maria Loane
AU - Christine Damase-Michel
PY - 2026
DA - 2026/06/02
JO - Drug Safety
DO - 10.1007/s40264-026-01672-8
UR - https://hal.science/hal-05794365v1
AB - INTRODUCTION AND OBJECTIVE: Given the increasing use of gabapentinoids and ongoing safety concerns, we assessed the association between first-trimester exposure to gabapentin and pregabalin and the risk of specific congenital anomalies (CAs) in the offspring. METHODS: Using EUROmediCAT data, we conducted a case-malformed control study based on 170,126 registrants with major CAs from livebirths, fetal deaths (≥20 weeks), and terminations of pregnancy for fetal anomaly in nine European countries (2000-2020), covering 10.6 million births. We compared gabapentinoid use in registrants with a specific CA with those among other registrants with non-genetic CA (main control group) and among registrants with a genetic condition (secondary control group). We estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for registry, birth year, and maternal age. Analyses included specific subgroups of CA with ≥3 exposed registrants. RESULTS: First-trimester gabapentinoid exposure was identified in 37 registrants, with most registered in the Valencian region (Spain) (37.8%), EFEMERIS (France) (13.5%) and three other registries (8.1% each). Over 60% of the exposures were observed during 2015-2020. Seven out of 91 EUROCAT subgroups had ≥3 exposed registrants: congenital heart defects, ventricular septal defects, severe congenital heart defects, limb anomalies, urinary anomalies, genital anomalies, and hypospadias. A significantly higher proportion of exposure (0.4‰, 12 exposed cases) was observed among cases with ventricular septal defect compared with registrants in the non-genetic control group (0.2‰, 17 exposed cases), with an adjusted OR of 2.5 (95% CI 1.1-5.3); and the adjusted OR was elevated but non-significant compared with the registrants in the genetic group (2.3; 95% CI 0.8-6.9). CONCLUSIONS: We observed an association between first trimester exposure to gabapentinoids and ventricular septal defect, the most common cardiac anomaly, although this finding is based on only 37 exposed registrants. While our findings align with some previous studies suggesting teratogenic risks associated with gabapentinoids, they also reveal the challenges of studying rare exposures and rare outcomes.
SN - 0114-5916
ER -