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Abstract
Objective Prenatal 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.
Design Population-based cohort study.
Setting Nationwide national registers in Denmark.
Participants All 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 measures The 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.
Results Children 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.
Conclusions We found only minor differences between prenatally AED-exposed and unexposed children in the number of GP contacts.
- Antiepileptic drugs
- Prenatal drug exposure
- Primary Healthcare
- General Practitioner
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Footnotes
Contributors MV and BHB initiated the study and obtained the funding. All authors participated in the design of the study. CHV performed the statistical analyses under the guidance of BHB and AMLW. AMLW wrote the manuscript. All authors were involved in the interpretation of data and critical revision of the manuscript. AMLW had the primary responsibility for the final content. All authors read and approved the final manuscript.
Funding This work was supported by the Programme for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation and administered by the Danish Regions.
Competing interests JC has received honoraria for serving on the Scientific Advisory Board of UCB Nordic and Eisai AB. JC has also received honoraria for giving lectures from UCB Nordic and Eisai AB and funding for a trip from UCB Nordic. JC is involved in clinical trials involving the following companies: Pfizer, Novartis, Eisai AB and Sage Therapeutics.
Ethics approval The study was approved by the Danish Data Protection Agency. Ethical approval was not required according to Danish regulations due to the register-based nature of the study.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.