Maternal psychotropic medication use during pregnancy and child health outcomes

Caichen Zhong

doi:10.17918/00001935

Psychotropic medications, particularly antiseizure medications (ASMs), play a crucial role in managing neuro-psychiatric conditions during pregnancy. Extensive studies have examined the teratogenic effects of ASMs, yet evidence is inconsistent for some ASMs. Moreover, there is a lack of a comprehensive understanding of the safety profile of the newer-generation ASMs and their effect on gestational-age-related outcomes. Additionally, few studies have characterized medication use in pregnancies with a higher likelihood of adverse birth outcomes and neurodevelopmental disorders. This thesis aimed to examine the association between ASM use during pregnancy and child health outcomes, including gestational-age-related outcomes and major congenital malformations (MCMs), and to describe the prevalence of medication use in pregnancies at a higher likelihood of adverse child health outcomes. The first two population-based cohort studies included pregnancies from the UK Clinical Practice Research Datalink (1995-2018) (Aim 1 and Aim 2) and Swedish Registries (1995-2020) (Aim 1) to investigate the effects of eight common ASM monotherapies and polytherapy during pregnancy on child health outcomes. Participants in the third study were drawn from the Early Autism Risk Longitudinal Investigation (EARLI) study to estimate the prevalence of medication use during pregnancy across ten drug class coalitions. Various statistical models were used in this thesis, including multinomial logistic regression, logistic regression, log-binomial regression, linear regression, propensity score (PS) weighted analysis, and fixed-effect meta-analysis. Monotherapy use of pregabalin, carbamazepine, gabapentin, valproate, and ASM polytherapy during pregnancy was associated with an increased risk of adverse gestational-age-related outcomes and exposure to valproate, phenytoin, and gabapentin in the first trimester was linked to an approximately 2-fold increase in the risk of overall MCMs. These risks varied among women with different ASM indications. Little evidence was found for the effect of lamotrigine, levetiracetam, and topiramate during pregnancy on child health outcomes. For pregnancies with higher needs, the overall use of over-the-counter and prescription medications was common in the EARLI autism familial cohort. Central nervous system (CNS) agents are the most commonly reported drug coalition, followed by gastrointestinal (GI) drugs and anti-infectives. While most medication use was reported in all three trimesters, the prevalence of medication use varied by maternal pre-pregnancy body mass index (BMI) status and education levels. Findings from this thesis suggest an increased risk of adverse child health outcomes associated with certain ASM monotherapies and polytherapy during pregnancy while providing reassurance regarding the safety of lamotrigine monotherapy. The high prevalence of medication use in pregnancies with a higher likelihood of adverse child health outcomes highlights the need to understand the potential risks and development of tailored clinical guidelines. The study contributes to the growing body of literature to support pregnant individuals and healthcare providers in making informed decisions and optimizing maternal and child health.

Maternal psychotropic medication use during pregnancy and child health outcomes

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Maternal psychotropic medication use during pregnancy and child health outcomes

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