Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study
07/2023
Journal Article
Authors:
Meador, K. J.;
Cohen, M. J.;
Loring, D. W.;
Matthews, A. G.;
Brown, C.;
Robalino, C. P.;
Birnbaum, A. K.;
Voinescu, P. E.;
Kalayjian, L. A.;
Gerard, E. E.;
Gedzelman, E. R.;
Hanna, J.;
Cavitt, J.;
Sam, M.;
French, J. A.;
Hwang, S.;
Pack, A. M.;
Pennell, P. B.;
Monead Investigator Group
Volume:
22
Pagination:
712-722
Issue:
8
Journal:
Lancet Neurol
PMID:
37479375
URL:
https://www.ncbi.nlm.nih.gov/pubmed/37479375
DOI:
10.1016/S1474-4422(23)00199-0
Keywords:
Child, Preschool Child Humans Female Pregnancy Anticonvulsants/adverse effects Cohort Studies Prospective Studies *Epilepsy/drug therapy Cognition *Prenatal Exposure Delayed Effects/chemically induced/drug therapy
Abstract:
BACKGROUND: The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years. METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (</=20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing. FINDINGS: Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n=284; adjusted least-square mean 102.7, 95% CI 101.4 to 103.9) versus those without epilepsy (n=87; 102.3, 99.8 to 104.7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n=258; adjusted parameter estimate -2.9, 95% CI -6.7 to 1.0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication. INTERPRETATION: We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasise the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute of Child Health and Development.
