title: Neurological outcome in school-age children after in utero exposure to coumarins.
abstract: The effect of prenatal exposure to coumarins (acenocoumarol, phenprocoumon) on neurological outcome was assessed in a cohort of 306 children aged 7-15 years. Findings were compared with those in a non-exposed cohort of 267 children, matched for sex, age, and demographic region. We used a neurological examination technique which pays special attention to minor neurological dysfunction (MND). None of the children was found to be neurologically abnormal. However, exposure to coumarins during gestation increases the risk for MND in children of school age, odds ratio (OR) 1.9 (CI(95) 1.1-3.4), predominantly after exposure in the second or third trimester, odds ratio 2.1 (CI(95) 1.2-3.8). We found a dose-response relationship with an odds ratio of 1.2 (CI(95) 1.0-1.5) per mg coumarin derivative prescribed per day. The results suggest that coumarins have an influence on the development of the brain which can lead to mild neurological dysfunctions in children of school age.
authors.affiliation: Department of Paediatrics, Beatrix Children's Hospital, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Wesseling
authors.forename: D
authors.initials: D
authors.lastname: Van Driel
authors.forename: M
authors.initials: M
authors.lastname: Smrkovsky
authors.forename: E
authors.initials: E
authors.lastname: Van der Veer
authors.forename: L M
authors.initials: LM
authors.lastname: Geven-Boere
authors.forename: P J
authors.initials: PJ
authors.lastname: Sauer
authors.forename: B C
authors.initials: BC
authors.lastname: Touwen
mesh_terms: D000074:Acenocoumarol / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects*; D001927:Brain Diseases / Q000139:chemically induced* / Q000453:epidemiology; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010644:Phenprocoumon / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies
chemical_list: D000925:Anticoagulants; D000074:Acenocoumarol; D010644:Phenprocoumon