Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case‑Malformed Control Study

Anna-Belle Beau; Erika Cifuentes Castro; Justine Benevent; Marie Beslay; Laia Barrachina-Bonet; Jorieke E H Bergman; Clara Cavero-Carbonell; Alessio Coi; Helen Dolk; Ester Garne; Miriam Gatt; Jonathan Hoareau; Elly Den Hond; Anna Latos-Bielenska; Nathalie Lelong; Mary O'Mahony; Xavier Moisset; Joan Morris; Amanda J Neville; Joanna Sichitiu; Maria Loane; Christine Damase-Michel

doi:10.1007/s40264-026-01672-8

Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case‑Malformed Control Study

Anna-Belle Beau
, Erika Cifuentes Castro
, Justine Benevent
, Marie Beslay
, Laia Barrachina-Bonet
, Jorieke E H Bergman
, Clara Cavero-Carbonell
, Alessio Coi
, Helen Dolk
, Ester Garne
, Miriam Gatt
, Jonathan Hoareau
, Elly Den Hond
, Anna Latos-Bielenska
, Nathalie Lelong
, Mary O'Mahony
, Xavier Moisset
, Joan Morris
, Amanda J Neville
, Joanna Sichitiu

Maria Loane, Christine Damase-Michel

Research output: Contribution to journal › Article › peer-review

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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 regis-trants 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.

Original language	English
Pages (from-to)	1-13
Journal	Drug Safety
Early online date	2 Jun 2026
DOIs	https://doi.org/10.1007/s40264-026-01672-8
Publication status	Published (in print/issue) - 2 Jun 2026

Bibliographical note

Publisher Copyright:
© The Author(s) 2026.

Rights Retention Statement

This Author Accepted Manuscript has been made open access under a Creative Commons Attribution 4.0 International licence (CC BY 4.0) under the terms of Ulster University Rights Retention Policy for Scholarly Works. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Data Availability Statement

EUROmediCAT encourages the use of its data and networks for pharmacovigilance and medication safety research. Individual data are only available to consortium members; however, EUROmediCAT can be commissioned to do a study, or engage in a collaborative study. Requests can be made at https:// euromedicat.eu/ research/ howtoproposeorcommissionspecificstudies.

Funding

Open access funding provided by Université de Toulouse. The ConcePTION project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 821520. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. The research leading to these results was conducted as part of the ConcePTION consortium. This paper only reflects the personal views of the stated authors. Open access funding enabled by Toulouse University Hospital.

Funder number
821520

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Gabapentinoids_and_CAs_-_accepted_versionAuthor Accepted Manuscript, 340 KBLicence: CC BY

Cite this

Beau, A.-B., Castro, E. C., Benevent, J., Beslay, M., Barrachina-Bonet, L., Bergman, J. E. H., Cavero-Carbonell, C., Coi, A., Dolk, H., Garne, E., Gatt, M., Hoareau, J., Hond, E. D., Latos-Bielenska, A., Lelong, N., O'Mahony, M., Moisset, X., Morris, J., Neville, A. J., ... Damase-Michel, C. (2026). Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case‑Malformed Control Study. Drug Safety, 1-13. https://doi.org/10.1007/s40264-026-01672-8

@article{fe1bfca80b0c49dd8f2a56b95aecf087,

title = "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 regis-trants 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. ",

author = "Anna-Belle Beau and Castro, \{Erika Cifuentes\} and Justine Benevent and Marie Beslay and Laia Barrachina-Bonet and Bergman, \{Jorieke E H\} and Clara Cavero-Carbonell and Alessio Coi and Helen Dolk and Ester Garne and Miriam Gatt and Jonathan Hoareau and Hond, \{Elly Den\} and Anna Latos-Bielenska and Nathalie Lelong and Mary O'Mahony and Xavier Moisset and Joan Morris and Neville, \{Amanda J\} and Joanna Sichitiu and Maria Loane and Christine Damase-Michel",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026.",

year = "2026",

month = jun,

day = "2",

doi = "10.1007/s40264-026-01672-8",

language = "English",

pages = "1--13",

journal = "Drug Safety",

issn = "0114-5916",

publisher = "Adis",

}

Beau, A-B, Castro, EC, Benevent, J, Beslay, M, Barrachina-Bonet, L, Bergman, JEH, Cavero-Carbonell, C, Coi, A, Dolk, H, Garne, E, Gatt, M, Hoareau, J, Hond, ED, Latos-Bielenska, A, Lelong, N, O'Mahony, M, Moisset, X, Morris, J, Neville, AJ, Sichitiu, J, Loane, M & Damase-Michel, C 2026, 'Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case‑Malformed Control Study', Drug Safety, pp. 1-13. https://doi.org/10.1007/s40264-026-01672-8

TY - JOUR

T1 - Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case‑Malformed Control Study

AU - Beau, Anna-Belle

AU - Castro, Erika Cifuentes

AU - Benevent, Justine

AU - Beslay, Marie

AU - Barrachina-Bonet, Laia

AU - Bergman, Jorieke E H

AU - Cavero-Carbonell, Clara

AU - Coi, Alessio

AU - Dolk, Helen

AU - Garne, Ester

AU - Gatt, Miriam

AU - Hoareau, Jonathan

AU - Hond, Elly Den

AU - Latos-Bielenska, Anna

AU - Lelong, Nathalie

AU - O'Mahony, Mary

AU - Moisset, Xavier

AU - Morris, Joan

AU - Neville, Amanda J

AU - Sichitiu, Joanna

AU - Loane, Maria

AU - Damase-Michel, Christine

PY - 2026/6/2

Y1 - 2026/6/2

N2 - 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 regis-trants 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.

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 regis-trants 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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UR - https://pure.ulster.ac.uk/en/publications/fe1bfca8-0b0c-49dd-8f2a-56b95aecf087

U2 - 10.1007/s40264-026-01672-8

DO - 10.1007/s40264-026-01672-8

M3 - Article

C2 - 42230530

SN - 0114-5916

SP - 1

EP - 13

JO - Drug Safety

JF - Drug Safety

ER -

Gabapentin and Pregabalin Use in First Trimester of Pregnancy and Risk of Specific Congenital Anomalies: An IMI ConcePTION European Case‑Malformed Control Study

Abstract

Bibliographical note

Rights Retention Statement

Data Availability Statement

Funding

UN SDGs

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