Hum Reprod. 2021 May 17;36(6):1674-1681. doi: 10.1093/humrep/deab023.

Maternal use of hormonal contraception and epilepsy in offspring.

Human reproduction (Oxford, England)

H I M Halane, M Hargreave, S K Kjaer, J Christensen, L S Mørch

PMID: 33580954 DOI: 10.1093/humrep/deab023

Abstract

STUDY QUESTION: Is maternal use of hormonal contraception associated with the development of epilepsy in the offspring?

SUMMARY ANSWER: We found that maternal use of hormonal contraception was associated with a slightly increased risk of epilepsy in the offspring.

WHAT IS KNOWN ALREADY: Foetal exposure to exogenous hormones has been associated with changes in brain development. However, little is known about maternal hormonal contraception use and development of epilepsy in the offspring.

STUDY DESIGN, SIZE, DURATION: A nationwide cohort of all live born children born in Denmark between 1 January 1998 and 31 December 2014, was followed from day 29 after birth for epilepsy (first diagnosis of epilepsy or first redeemed prescription for anti-epileptic medication) to censoring (emigration, death) or 31 December 2015, whichever occurred first.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Diagnoses of epilepsy were obtained from the National Patient Registry. The Danish National Prescription Registry supplied information on redeemed prescriptions for hormonal contraception and anti-epileptic medication. Maternal hormonal contraception use was categorized as never use (reference group), previous use (prescriptions redeemed >3 months before pregnancy start) and recent use (prescriptions redeemed ≤3 months before or during pregnancy).

MAIN RESULTS AND THE ROLE OF CHANCE: The data show that 17 585 children developed epilepsy during a median follow-up of 9.2 years (9 732 635 person-years). The hazard ratio (HR) for epilepsy was 1.07 (95% CI 1.02-1.13) in children of mothers who had used any type of hormonal contraception recently, compared with children of mothers who had not used hormonal contraception. The HR was similar for recent use of oral combined products, while the HRs for recent or previous use of non-oral combined products were 1.32 (95% CI 0.98-1.77) and 1.16 (95% CI 1.02-1.32), respectively. For non-oral progestin-only products, the HRs were 1.19 (95% CI 1.04-1.38) and 1.53 (95% CI 1.31-1.80), respectively, for recent and previous use.

LIMITATIONS, REASONS FOR CAUTION: There may be some misclassification of maternal hormonal contraception use, as some women may not have used the redeemed prescriptions or used them at a different point in time; potentially leading to an attenuation of the estimates. In addition, although we were able to account for known risk factors for epilepsy, unknown or residual confounding cannot be ruled out.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings are based on nationwide population-based data and can therefore be applied to other similar populations. However, as this is the first study in this field, further studies are needed to confirm our findings.

STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study, which was supported by internal funding at the Unit of Virus, Lifestyle and Genes. All authors report no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.

© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: [email protected].

Keywords: Denmark; clinical neurology; drug in pregnancy; epilepsy in children; maternal hormonal contraception use; nation-wide population-based cohort studies; risk factors

MeSH terms

• Child
• Cohort Studies
• Denmark / epidemiology
• Epilepsy* / drug therapy
• Epilepsy* / epidemiology
• Female
• Hormonal Contraception*
• Humans
• Mothers
• Pregnancy
• Risk Factors

Publication Types

• Journal Article
• Research Support, Non-U.S. Gov't