Prenatal exposure to antiepileptic drugs and use of primary healthcare during childhood: a population-based cohort study in Denmark

Abstract

ObjectivePrenatal exposure to antiepileptic drugs (AEDs) has been associated with adverse outcomes in the offspring such as congenital malformations and neuropsychiatric disorders. The objective of this study was to investigate whether prenatal exposure to AEDs is also associated with more frequent use of primary healthcare during childhood.DesignPopulation-based cohort study.SettingNationwide national registers in Denmark.ParticipantsAll live-born singletons in Denmark during 1997–2012 identified in the Danish National Patient Register and followed until 31 December 2013 (n=963 010). Information on prenatal exposure to AEDs for maternal indication of epilepsy and other neurological conditions was obtained from the Danish Register of Medicinal Product Statistics.Main outcome measuresThe primary outcome measure was the number and type of contacts with the general practitioner (GP), excluding routine well-child visits and vaccinations. The secondary outcome measure was specific services provided at the GP contact. The association between prenatal exposure to AEDs and contacts with the GP was estimated by using negative binomial regression adjusting for sex and date of birth of the child, maternal age, cohabitation status, income, education, substance abuse, depression, severe psychiatric disorders and use of antipsychotics, antidepressants and insulin.ResultsChildren exposed prenatally to AEDs (n=4478) had 3% (95% CI 0 to 5%) more GP contacts during the study period than unexposed children. This was primarily accounted for by the number of phone contacts. Within each year of follow-up, exposed children tended to have more contacts than unexposed children, but the differences were small. We found no difference between exposed and unexposed children with regard to specific services provided at the GP contact. For the individual AEDs, we found that exposure to valproate or oxcarbazepine was associated with more GP contacts.ConclusionsWe found only minor differences between prenatally AED-exposed and unexposed children in the number of GP contacts.

Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability

“…It should be noted that although a number of medical problems have been reported in VPA exposed children [27], for the most part their management is no different to that of other children with the same complaints. In a large population based study, the rates of GP contact were increased for valproate exposed children but the increase was small [110]. Consistently, in the Liverpool/Manchester cohort [52], 20/57 (35%) of the VPA monotherapy patients, and 12/26 (46%) exposed to VPA as polytherapy, had needed to consult a doctor for a medical problem compared to 65/283 (23%) controls (unpublished data).…”

Retrospective Analysis of Oxcarbazepine in Pregnant Women With Substance Use Disorders: Focus on Safety

“…Interestingly, prenatal exposure children with low estimated daily doses of OXC were associated with a statistically higher risk of general practitioner contact. 21 The findings from these trials confirm the presence of long-term consequences of prenatal AED exposure. Prospective trials focusing on further identification of these risks and comparison of various AED should be conducted.…”

Too much? Mortality and health service utilisation among Danish children 1999-2016: A register-based study

“…A descriptive cross-sectional study of health service utilisation and medication use indicated a homogeneity across the five Danish administrative regions [26]. Another study illustrated how the incidence of contacts with general practitioner depends on age the pattern being a sharp increase in the first 1–2 years of living followed by an even sharper decrease [27].…”