Laura Fuglsang Bech 1 , Christoffer Polcwiartek 2,3,4 , Kristian Kragholm 2,3 , Mikkel Porsborg Andersen 2 , Christopher Rohde 5 , Christian Torp-Pedersen 2,3,4 , Jimmi Nielsen 5 , Søren Hagstrøm 6,4 Show Affiliations »
Abstract
OBJECTIVES: In utero exposure to antiepileptic drugs has previously been associated with adverse outcome among offspring, but evidence on longer term milestone development remains limited. We investigated the association between in utero exposure to antiepileptic drugs and learning disabilities in the first year of compulsory education among offspring and assessed which antiepileptic drugs carried the highest risk. METHODS: This population-based case-cohort study used Danish nationwide register data from 2005 to 2008. Cases were offspring exposed to antiepileptic drugs in utero, and controls were unexposed offspring of mothers previously redeeming antiepileptic drug prescriptions. Offspring were followed from birth until the first year of compulsory education from 2011 to 2015. Learning disabilities were defined as mental retardation, specific developmental disorders, autism spectrum disorders, emotional/behavioural disorders or having special educational needs. Logistic regression was used to compute ORs with 95% CIs adjusted for potential confounding. RESULTS: Of 117 475 incident singleton births, 636 cases and 434 controls were included (median age: 6.1 years, males: 55.7%). Learning disabilities were identified among 7.1% cases compared with 3.7% for controls. During any trimester, the adjusted OR of the association between in utero exposure to antiepileptic drugs and learning disabilities was 2.20 (95% CI 1.16 to 4.17). Among cases not exposed to polytherapy (n=556), in utero exposure to lamotrigine compared with another antiepileptic drug was associated with the lowest adjusted risk (OR 0.42, 95% CI 0.19 to 0.92), and valproate carried a higher risk (OR 4.67, 95% CI 1.73 to 12.59). CONCLUSION: In utero exposure to antiepileptic drugs was significantly associated with learning disabilities among offspring. Lamotrigine should preferentially be considered over, for example, valproate if clinically feasible. © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.
OBJECTIVES: In utero exposure to antiepileptic drugs has previously been associated with adverse outcome among offspring, but evidence on longer term milestone development remains limited. We investigated the association between in utero exposure to antiepileptic drugs and learning disabilities in the first year of compulsory education among offspring and assessed which antiepileptic drugs carried the highest risk. METHODS: This population-based case-cohort study used Danish nationwide register data from 2005 to 2008. Cases were offspring exposed to antiepileptic drugs in utero, and controls were unexposed offspring of mothers previously redeeming antiepileptic drug prescriptions. Offspring were followed from birth until the first year of compulsory education from 2011 to 2015. Learning disabilities were defined as mental retardation , specific developmental disorders , autism spectrum disorders , emotional/behavioural disorders or having special educational needs. Logistic regression was used to compute ORs with 95% CIs adjusted for potential confounding. RESULTS: Of 117 475 incident singleton births, 636 cases and 434 controls were included (median age: 6.1 years, males: 55.7%). Learning disabilities were identified among 7.1% cases compared with 3.7% for controls. During any trimester, the adjusted OR of the association between in utero exposure to antiepileptic drugs and learning disabilities was 2.20 (95% CI 1.16 to 4.17). Among cases not exposed to polytherapy (n=556), in utero exposure to lamotrigine compared with another antiepileptic drug was associated with the lowest adjusted risk (OR 0.42, 95% CI 0.19 to 0.92), and valproate carried a higher risk (OR 4.67, 95% CI 1.73 to 12.59). CONCLUSION: In utero exposure to antiepileptic drugs was significantly associated with learning disabilities among offspring. Lamotrigine should preferentially be considered over, for example, valproate if clinically feasible. © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.
Entities: Chemical
Disease
Keywords:
Antiepileptic drugs; Cognitive functioning; In utero exposure; Learning disabilities; Neurodevelopment
Mesh： See more »
Substances： See more »
Year: 2018
PMID： 30076271 DOI： 10.1136/jnnp-2018-318386
Source DB: PubMed Journal: J Neurol Neurosurg Psychiatry ISSN： 0022-3050 Impact factor: 10.154