Risk of orofacial clefts in offspring following maternal exposure to anti-seizure medications in a UK CPRD GOLD observational study
Abstract
Orofacial clefts (OFC) are complex congenital anomalies characterised by a gap in the upper lip and/or palate, causing speech and feeding difficulties in children. Studies suggest inconsistent findings for an association between anti-seizure medications (ASM) and OFCs. Our study evaluated the association between ASM prescription during pregnancy and OFC in offspring using a United Kingdom primary care-based cohort of 393,281 mothers and 518,050 babies. 3651 and 3199 women were prescribed ASMs during preconception and first trimester respectively, irrespective of indication. Valproate prescription during preconception and first trimester was associated with higher odds of OFCs, with limited evidence after adjustment for potential confounders. Carbamazepine, pregabalin, and levetiracetam showed limited evidence for increased odds of OFCs, and no evidence was found for gabapentin or lamotrigine. No OFC cases were found in children born to mothers exposed to topiramate or phenytoin. Children exposed to ASM polytherapy during first trimester were 6 times as likely to have OFC as compared to ASM monotherapy. While ASMs may contribute to the risk of OFCs, our findings suggest they are unlikely to be a major cause, given that most exposed pregnancies did not result in a cleft and most children with OFCs were not exposed to ASMs.
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BibTeX
@article{jain2026risk,
title = {{Risk of orofacial clefts in offspring following maternal exposure to anti-seizure medications in a UK CPRD GOLD observational study}},
author = {Kritika Jain and Amy J. V. Davies and Sarah J. Lewis and Caichen Zhong and Harriet Forbes and Jessica E. Rast and Florence Z. Martin and Viktor H. Ahlqvist and Neil M. Davies and Torbjörn Tomson and Cecilia Magnusson and Brian K. Lee and Dheeraj Rai and Paul Madley-Dowd},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-74630-0},
url = {https://www.nature.com/articles/s41598-026-74630-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Risk of orofacial clefts in offspring following maternal exposure to anti-seizure medications in a UK CPRD GOLD observational study
AU - Kritika Jain
AU - Amy J. V. Davies
AU - Sarah J. Lewis
AU - Caichen Zhong
AU - Harriet Forbes
AU - Jessica E. Rast
AU - Florence Z. Martin
AU - Viktor H. Ahlqvist
AU - Neil M. Davies
AU - Torbjörn Tomson
AU - Cecilia Magnusson
AU - Brian K. Lee
AU - Dheeraj Rai
AU - Paul Madley-Dowd
PY - 2026
DA - 2026/10/23
JO - Scientific Reports
DO - 10.1038/s41598-026-74630-0
UR - https://www.nature.com/articles/s41598-026-74630-0
AB - Orofacial clefts (OFC) are complex congenital anomalies characterised by a gap in the upper lip and/or palate, causing speech and feeding difficulties in children. Studies suggest inconsistent findings for an association between anti-seizure medications (ASM) and OFCs. Our study evaluated the association between ASM prescription during pregnancy and OFC in offspring using a United Kingdom primary care-based cohort of 393,281 mothers and 518,050 babies. 3651 and 3199 women were prescribed ASMs during preconception and first trimester respectively, irrespective of indication. Valproate prescription during preconception and first trimester was associated with higher odds of OFCs, with limited evidence after adjustment for potential confounders. Carbamazepine, pregabalin, and levetiracetam showed limited evidence for increased odds of OFCs, and no evidence was found for gabapentin or lamotrigine. No OFC cases were found in children born to mothers exposed to topiramate or phenytoin. Children exposed to ASM polytherapy during first trimester were 6 times as likely to have OFC as compared to ASM monotherapy. While ASMs may contribute to the risk of OFCs, our findings suggest they are unlikely to be a major cause, given that most exposed pregnancies did not result in a cleft and most children with OFCs were not exposed to ASMs.
SN - 2045-2322
ER -