PEDIATRICS Vol. 107 No. 1 January 2001, pp. 123-129

In Utero Exposure to Coumarins and Cognition at 8 to 14 Years Old

Received Dec 17, 1999; accepted Jul 14, 2000.

Dieneke van Driel^*, Judit Wesseling^*, Pieter J. J. Sauer^*, Eveline van der Veer, Bert C. L. Touwen^§, and Mila Smrkovsky

From the ^* Department of Pediatrics, Beatrix Children's Hospital, University Hospital Groningen,  Pathology and Laboratory Medicine, University Hospital Groningen, ^§ Department of Medical Physiology Section Developmental Neurology, University of Groningen,  Department of Special Education, University of Groningen, Groningen, The Netherlands.

Objective.  To assess the cognitive abilities in school-aged children who have been exposed to coumarins in utero.

Background.  Coumarin derivatives are an effective option for anticoagulant therapy in pregnant women. However, case reports describe anomalies of the fetal central nervous system after in utero exposure to coumarins. It is unclear whether prenatal exposure has an effect on cognitive functioning later in childhood.

Methods.  The exposed cohort consisted of 291 children from mothers who were prospectively registered because of coumarin treatment during pregnancy. The nonexposed cohort included 253 age-matched peers. An IQ was estimated using subtests of the Weschler Intelligence Scale for Children-Revised. Educational achievement was examined with tests for reading, spelling, and arithmetic. In addition, schoolteachers were asked to judge performance on language and arithmetic. The observers were not aware of the exposure status of the child.

Results.  No differences in mean IQ were found between the exposed and nonexposed cohort (mean difference: 1.1; 95% confidence interval [CI]: 3.2-1.1), but an IQ score below 80 was found in 11 children in the exposed compared with 3 children in the nonexposed cohort (odds ratio [OR] = 3.1; CI: 0.8-11.6). Regarding the tests for educational achievement, exposed children as a group performed as well as nonexposed controls. Exposed boys, in comparison with nonexposed boys, showed a higher frequency of poor performance on reading (OR = 2.9; CI: 1.1-7.4) and spelling (OR = 2.5; CI: 1.0-6.0).

Conclusion.  Cognitive functioning in coumarin-exposed children does not differ from nonexposed controls, but a minority of children seem to be prone to the potential negative effects of coumarins during pregnancy.  Key words:  IQ, educational achievement, long-term effect, anticoagulants.

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