Background: The teratogenic potential of valproate, especially with respect to adverse neurodevelopmental outcomes, is well documented. However, the safety of other antiseizure medications (ASMs) during pregnancy is not well established.
Objectives: To determine the relationship between the use of ASMs during pregnancy and adverse neurodevelopmental outcomes in offspring.
Methods: This study utilized prospectively collected data from two sources: the UK Clinical Practice Research Datalink (CPRD) GOLD (1995-2018) and the Swedish Developmental Origins of Health and Disease (DOHaD) cohort (1995-2020). The CPRD GOLD database contains primary care data from approximately 9% of the UK population and is representative in terms of age and sex, while the DOHaD cohort contains information on nearly all births in Sweden. The study identified maternal prescriptions for ASMs (carbamazepine, gabapentin, lamotrigine, levetiracetam, valproate, pregabalin, topiramate, or others) recorded during the pre-conceptional and pregnancy periods and their likely indications, such as epilepsy, psychiatric conditions, and somatic conditions. Child neurodevelopmental outcomes, including autism, attention deficit hyperactivity disorder (ADHD), and intellectual disability, were identified using Read codes and ICD-10 codes in the UK, and ICD-9/10 codes in Sweden. Logistic regressions were used to examine the associations between the use of ASMs during pregnancy and neurodevelopmental outcomes, controlling for confounders such as maternal indication and other variables. Results from each cohort were combined using fixed-effects meta-analysis.
Results: We identified 518,050 children in the UK and 2,666,272 children in Sweden. The most common prescription during pregnancy was lamotrigine in both countries (∼0.23%). In our pooled analysis across both cohorts, associations with offspring neurodevelopmental outcomes were found for carbamazepine (OR = 1.25; 95% CI = 1.10-1.41), topiramate (OR = 1.24; 95% CI = 0.90-1.71), and valproate (OR = 1.60; 95% CI = 1.39-1.84), but not for lamotrigine (OR = 0.88; 95% CI = 0.79-0.99). Moreover, we found that there was a pronounced association between topiramate use and offspring intellectual disability (OR = 3.30; 95% CI = 2.04-5.36). Our ongoing analyses use causal inference methods to determine whether the associations are likely to reflect causal effects, and include clinically informative measures to inform risk-benefit assessments.
Conclusions: These results provide valuable information to pregnant women and their healthcare providers in making informed decisions about the use of antiseizure medications during pregnancy.
.jpg "Viktor H. Ahlqvist, MMsc photo")
