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

BMJ Open. 2017 Jan 5;7(1):e012836. doi: 10.1136/bmjopen-2016-012836.


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.

Keywords: Antiepileptic drugs; General Practitioner; Prenatal drug exposure; Primary Healthcare.

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / analogs & derivatives
  • Carbamazepine / therapeutic use
  • Child
  • Child, Preschool
  • Denmark / epidemiology
  • Epilepsy / drug therapy
  • Female
  • Follow-Up Studies
  • General Practice / statistics & numerical data*
  • Humans
  • Infant
  • Male
  • Oxcarbazepine
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Primary Health Care / statistics & numerical data*
  • Registries
  • Valproic Acid / therapeutic use
  • Young Adult


  • Anticonvulsants
  • Carbamazepine
  • Valproic Acid
  • Oxcarbazepine