2023-05-25 04:24:23
Why is this important?
The risks of congenital and neurodevelopmental anomalies associated with exposure to antiepileptics in utero have been widely described, in particular for valproate. On the other hand, the link with possible psychiatric disorders has still been little explored. It therefore seemed important to compare the different antiepileptics with regard to this risk. This Nordic cohort study of more than 38,000 children of epileptic mothers questioned the existence of an association between exposure to different antiepileptics during pregnancy and the occurrence of psychiatric disorders during childhood and adolescence. .
Methodology
This prospective study conducted from population registers followed 38,661 children born alive from a singleton pregnancy to mothers with epilepsy in Denmark, Finland, Iceland, Norway and Sweden, between January 1996 and December 2017. The primary endpoint of he assessment was the existence of a diagnosis of psychiatric disorders (all disorders combined) or neurodevelopmental disorders during childhood or adolescence according to the international classification of diseases (ICD-10F).
Principle results
Of the 38,661 children identified by the registers (51.3% boys) with a follow-up of up to 22 years, 16,458 had been exposed to antiepileptics in utero.
Prenatal exposure to valproate monotherapy was associated with an almost 2-fold increased risk of psychiatric disorders (Hazard ratio (HR): 1.8 [1,60-2,03]), compared to an absence of exposure to this molecule, in particular developmental delay (language, learning, motor functions), ADHD, autism spectrum disorders and intellectual retardation. And at 18, the children concerned had a risk of psychiatric disorders greater than 40%.
Apart from valproate, none of the other antiepileptics used as monotherapy was associated with an increased risk of psychiatric disorders. However, polytherapies showed an increased risk, greater when they included valproate (HR 1.85 [1,56-2,18]) than when they did not contain any (HR 1.32 [1,15-1,51]).
Children who had been exposed to valproate in utero had a higher risk of developing early disorders: intellectual retardation, autism spectrum disorders, developmental and attachment disorders and ADHD. But there was no association with the onset of later disorders such as anxiety, mood disorders, substance abuse, or even schizophrenia spectrum disorders.
While prenatal exposure to lamotrigine, carbamazepine, and oxycarbazepine was not associated with an increased risk of any psychiatric disorders, exposure to levetiracetam was associated with higher levels of anxiety (HR 2.17 [1,26-3,72]) and ADHD (HR 1.78 [1,03-3,07]). Topiramate exposure was also associated with an increased risk of ADHD (HR 2.38 [1,40-4,06]), intellectual retardation (HR 2.23 [0,90-5,50]) and autism spectrum disorders (HR 1.93 [1,95-3,94]).
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