Prenatal exposure to antiepileptic drugs and dental agenesis

Pernille E Jacobsen; Tine B Henriksen; Dorte Haubek; John R Østergaard

doi:10.1371/journal.pone.0084420

Prenatal exposure to antiepileptic drugs and dental agenesis

PLoS One. 2014 Jan 8;9(1):e84420. doi: 10.1371/journal.pone.0084420. eCollection 2014.

Authors

Pernille E Jacobsen¹, Tine B Henriksen², Dorte Haubek¹, John R Østergaard³

Affiliations

¹ Section of Pediatric Dentistry, Department of Dentistry, Health, Aarhus University, Aarhus, Denmark.
² Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus Universty Hospital, Aarhus, Denmark.
³ Center for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.

Abstract

Objective: The aim of the study was to investigate the association between prenatal exposure to AEDs and the risk of dental agenesis and to differentiate between the possible effects of the different drugs used.

Methods: Data on 214 exposed and 255 unexposed children, aged 12-18 years, were extracted from the Prescription Database of the Central Denmark Region and North Denmark Region and the Danish Medical Birth Registry. The children's dental charts were examined for the presence of dental agenesis.

Results: Overall, children exposed to AED in utero had an increased risk of developing dental agenesis, but as a group, the difference was not significant (OR = 1.7; [95% CI: 0.8-3.6]). The risk of developing dental agenesis was three-fold increased (OR = 3.1; [95% CI: 1.3-7.4]) in children exposed to valproate in mono- or in poly-therapy with other AEDs than carbamazepine or oxcarbazepine. The risk was further increased (OR = 11.2; [95% CI: 2.4-51.9]) in children exposed to valproate and carbamazepine or oxcarbazepine in combination.

Conclusions: The present study shows that dental agenesis is a potential congenital abnormality that is related to prenatal exposure to valproate, and dental agenesis may be considered a sensitive marker for the teratogenicity of valproate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Anticonvulsants / adverse effects*
Child
Congenital Abnormalities / etiology*
Female
Humans
Male
Pregnancy
Prenatal Exposure Delayed Effects / chemically induced*
Tooth / drug effects*
Tooth / growth & development*

Substances

Anticonvulsants

Grants and funding

The study was financially supported by the Calcin Foundation from the Danish Dental Association, the DOFT Foundation from the Association of Community Dental Service and the Aarhus University Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.