(35) Association Between Antiseizure Medication Prescribing and Its Indications During Pregnancy and Offspring Neuro-Developmental Outcomes Between 1995 and 2020 in the UK

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1080

Presenting Author(s)

Paul Madley-Dowd
– Bristol Medical School, University of Bristol, Bristol, Bristol, United Kingdom

Co-Author(s)

Harriet Forbes
– Bristol, Gloucestershire, United Kingdom
Viktor H. Ahlqvist
– Karolinska Institutet, Karolinska Institutet, Stockholm, Stockholms l�n, Sweden
Jessica Rast
– A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA, United States
Caichen Zhong
– Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA, United States
Brian K. Lee
– Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA, USA, United States
Dheeraj Rai
– Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom, United Kingdom

Background: The teratogenic potential of valproate especially in relation to adverse neurodevelopmental outcomes is well documented. However, the safety of other anti-seizure medications (ASMs) during pregnancy is not well understood.

Objectives: To examine whether ASM prescribing in pregnancy and its indications are associated with adverse neurodevelopmental outcomes in exposed children.

Methods: This is an intergenerational cohort study with prospectively collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD which holds primary care data from around 9% of the UK population and is approximately representative in terms of age and sex. We identified children born between 1995 and 2016 with at least 4 years follow up and linkage to their mother’s GP records during pregnancy. We identified maternal prescriptions for ASMs (Lamotrigine, valproate, carbamazepine, pregabalin, levetiracetam, gabapentin or other) recorded in primary care during the pregnancy period and their likely indications (including epilepsy, bipolar disorder, generalized anxiety disorder and others). Child neurodevelopmental outcomes included autism, attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID) identified using Read codes and ICD-10 codes in GP records and linked hospital episode statistics data. We will examine associations for prescribing in the first trimester, initiation during the first trimester and discontinuation early and late into pregnancy using log-binomial regression adjusted for confounders. We will implement exposure discordant sibling analyses, stratification on indication and other methods to aid with causal interpretation of findings.

Results: We have identified 304,321 children from 300,214 pregnancies among 236,879 women. Of these, ASMs were prescribed in the first trimester in 2030 (0.68%) pregnancies including lamotrigine 603 (0.20%), valproate 331 (0.11%), carbamazepine 482 (0.16%), pregabalin 218 (0.07%), levetiracetam 167 (0.06%), and gabapentin 270 (0.09%). We have identified 9659 (3.17%) children with neurodevelopmental disorders including 6475 (2.13%) cases of autism, 3479 (1.14%) cases of ADHD and 927 (0.30%) cases of ID in the cohort. Analyses are ongoing and results of the study will be available by the time of presentation.

Conclusions: The results will help provide pregnant women and their clinicians with useful information to make informed choices about ASM use in pregnancy.