RT Journal Article
SR Electronic
T1 Risk of early neurodevelopmental outcomes associated with prenatal exposure to the antiepileptic drugs most commonly used during pregnancy: a French nationwide population-based cohort study
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e034829
DO 10.1136/bmjopen-2019-034829
VO 10
IS 6
A1 Pierre-Olivier Blotière
A1 Sara Miranda
A1 Alain Weill
A1 Yann Mikaeloff
A1 Hugo Peyre
A1 Franck Ramus
A1 Zureik Mahmoud
A1 Joël Coste
A1 Rosemary Dray-Spira
YR 2020
UL http://bmjopen.bmj.com/content/10/6/e034829.abstract
AB Objectives To assess the association between prenatal exposure to monotherapy with the antiepileptic drugs (AEDs) most commonly used during pregnancy and the risk of various neurodevelopmental outcomes compared with lamotrigine.Design Nationwide population-based cohort study.Setting French national healthcare databases.Participants Children born alive between 2011 and 2014 and prenatally exposed to AED monotherapy.Primary and secondary outcome measures Outcomes included neurodevelopmental disorders (NDD), defined by International Classification of Diseases, 10th Revision codes F70-F98—pervasive developmental disorders (PDD, F84) and mental retardation (MR, F70-F79) were studied separately—and visits to speech therapists. The reference group comprised children prenatally exposed to lamotrigine. Children were followed until outcome, loss to follow-up, death or 31 December 2016. We performed inverse probability of treatment weighting analyses using the propensity score, which included maternal and infant characteristics. Hazard ratios (HRs) were calculated using Cox models.Results The cohort comprised 9034 children, 2916 of which were exposed to lamotrigine, 1627 to pregabalin, 1246 to clonazepam, 991 to valproic acid (VPA), 621 to levetiracetam, 502 to carbamazepine, 477 to topiramate, 378 to gabapentin and 143 to oxcarbazepine. None of these AEDs, except VPA, was associated with an increased risk of any of the four neurodevelopmental outcomes investigated. Exposure to VPA was associated with increased risks of NDDs (HR=2.7, 95% CI (1.8 to 4.0)), PDD (HR=4.4 (2.1 to 9.3)), MR (HR=3.1 (1.5 to 6.2)) and visits to speech therapists (HR=1.5 (1.1 to 1.9)), with a dose-response relationship.Conclusions No increased risk of any of the neurodevelopmental outcomes investigated in this study was observed with prenatal exposure to levetiracetam, pregabalin, oxcarbazepine, topiramate, gabapentin, clonazepam or carbamazepine, compared with lamotrigine. However, this study corroborates the well-known association between maternal use of VPA during pregnancy and the risk of neurodevelopmental disorders in the offspring. Longer follow-up is necessary to confirm these findings.