Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy

Autor: Dick Lindhout, V K Hiilesmaa, S Koch, H. Meinardi, C M van Duijn, A. Hofman, A H Bardy, E. B. Samren, H. Klepel, Eija Gaily, G B Mannagetta, D. Janz, D. E. Grobbee, Marja-Liisa Granström, A W Deichl
Přispěvatelé: Epidemiology, Clinical Genetics
Jazyk: angličtina
Rok vydání: 1997
Předmět:
Male
Pediatrics
Pathophysiology of Brain and Behaviour
Cohort Studies
0302 clinical medicine
Mental Retardation
Pregnancy
Risk Factors
Multicenter Studies as Topic
Prospective Studies
030212 general & internal medicine
Prospective cohort study
Maternal-Fetal Exchange
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Neurons
education.field_of_study
Abnormalities
Drug-Induced
Brain
Middle Aged
3. Good health
Neurology
Anesthesia
Gestation
Anticonvulsants
Drug Therapy
Combination
Female
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Offspring
Population
Pathofysiologie van Hersenen en Gedrag
03 medical and health sciences
medicine
Humans
education
Nervous System Abnormalities (Non MeSH)
Epilepsy
Dose-Response Relationship
Drug
business.industry
Infant
Newborn
Carbamazepine
medicine.disease
Teratology
Pregnancy Complications
Relative risk
Neurology (clinical)
Nerve Net
business
030217 neurology & neurosurgery
Zdroj: Epilepsia, 38, 981-990
Epilepsia, 38(9), 981-990. Wiley-Blackwell Publishing Ltd
Epilepsia, 38, 9, pp. 981-990
Epilepsia, 38, pp. 981-990
ISSN: 0013-9580
Popis: Summary: Purpose: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and poly-therapy. Methods: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. Results: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2–4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6–15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3–18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4–67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1–57.6). Offspring of mothers using > 1,000 mg VPNday were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed ≥600 mg VPNday (RR 6.8; 95% CI: 1.4–32.7). No difference in risk of MCA was found between the offspring exposed to 601–1,000 mg/day and ≥600 mg/day. Conclusions: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.
Databáze: OpenAIRE
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