Prenatal valproate exposure increases risk of adverse neurodevelopmental outcome

In a very large nationwide study in 5 Nordic countries, prenatal exposure to the anti-seizure medications (ASM) valproate and topiramate was associated with an increased risk of autism spectrum disorder (ASD) and intellectual disability. Valproate was also associated with early-onset psychiatric disorders compared with non-exposed children.

SCAN-AED is a population-based cohort study (www.scanaed.org) of singleton births using linked health and social register data from Denmark, Finland, Iceland, Norway, and Sweden. The association between prenatal exposure to ASM and adverse neurodevelopmental outcomes was established in 2 prospective population-based studies. One assessed the risk of ASD and intellectual disability [1], the other assessed the risk of psychiatric disorders [2].

In the first study, the total study population was 4,493,373 singletons, of whom 31,019 (0.7%) had prenatal ASM exposure [1]. ASM exposure was associated with an increased risk of ASD and intellectual disability, especially when exposed to valproate or topiramate. For valproate (n=3,042) the adjusted HR (aHR) was 2.9 for ASD, and 4.3 for intellectual disability. For topiramate (n=879) the aHR was 2.5 and 2.8, respectively. For oxcarbazepine and carbamazepine, the risk of ASD and intellectual disability was also significantly increased. Prenatal exposure to valproate and topiramate was also associated with neurodevelopmental disorders when accounting for maternal epilepsy. For valproate and topiramate, association strength for neurodevelopmental disorders compared with unexposed children was dose dependent.

The second analysis included 25,306 singletons of mothers with epilepsy, 15,914 (63%) of whom had had prenatal ASM exposure [2]. An increased risk of early-onset psychiatric disorders was found for prenatal exposure to valproate (aHR 1.85). This risk seemed to be mainly driven by intellectual disorders (HR 3.15), ASD (HR 2.74) and attachment disorders (HR 2.31). For lamotrigine, carbamazepine, and oxcarbazepine there was no increased risk across the spectrum of psychiatric disorders. For other therapies such as topiramate and levetiracetam, there was some evidence indicating an increased risk of psychiatric morbidity in the child, but statistical power was limited.

1. Bjork M, et al. Prenatal antiseizure medication exposure and risk of autism and intellectual disability. SCAN-AED: a Nordic cohort study. OPR-154, EAN 2021 Virtual Congress, 19–22 June.
2. Dreier J, et al. Prenatal exposure to antiseizure medication and the full spectrum of diagnosed psychiatric disorders: A SCAN-AED study. OPR-185, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August 202117 May 2024