Van Driel D, Wesseling J, Rosendaal F R, Odink R J, Van der Veer E, Gerver W J, Geven-Boere L M, Sauer P J
Department of Pediatrics, Beatrix Children's Hospital, University Hospital Groningen, Groningen, The Netherlands.
Am J Med Genet. 2000 Dec 18;95(5):438-43. doi: 10.1002/1096-8628(20001218)95:5<438::aid-ajmg6>3.3.co;2-q.
Anticoagulation with coumarins is an effective therapy during pregnancy. Fetal exposure to coumarin derivatives during the first trimester, however, is associated with skeletal anomalies (warfarin or coumarin embryopathy). Information about long-term effects of prenatal coumarin exposure on the skeletal development is not available. We investigated growth and body proportions at school age of children exposed to coumarins in utero. A blind population-based cohort study was conducted on 307 exposed children and 267 non-exposed controls ages 8-15 years. The exposed cohort was based on a prospective registry of coumarin-treated pregnant women. Anthropometric data included height, weight, head circumference, and measurements to evaluate body proportions. The mean height of exposed children did not differ from that of the non-exposed children (mean difference 0.01 SD). In addition, no differences were found for the proportional measures. As a group, children exposed in the first trimester showed no evidence of growth impairment. Two children in this group, however, were born with signs of coumarin embryopathy and one of these displayed a deficit in height at school age. Long-term growth was not affected by a high cumulative dosage or exposure after the first trimester. We conclude that, when exposure during the first trimester is avoided, coumarin therapy during pregnancy has no demonstrable risk for the child's skeletal development.
香豆素类抗凝剂在孕期是一种有效的治疗方法。然而，胎儿在孕早期接触香豆素衍生物与骨骼异常（华法林或香豆素胚胎病）有关。关于产前接触香豆素对骨骼发育的长期影响尚无相关信息。我们调查了子宫内接触香豆素的儿童在学龄期的生长情况和身体比例。对307名8至15岁的接触组儿童和267名未接触组对照儿童进行了一项基于人群的盲法队列研究。接触组基于接受香豆素治疗的孕妇的前瞻性登记。人体测量数据包括身高、体重、头围以及评估身体比例的测量值。接触组儿童的平均身高与未接触组儿童无差异（平均差异0.01标准差）。此外，在比例测量方面未发现差异。作为一个群体，孕早期接触香豆素的儿童没有生长发育受损的迹象。然而，该组中有两名儿童出生时患有香豆素胚胎病的体征，其中一名在学龄期身高存在缺陷。长期生长不受高累积剂量或孕早期后接触的影响。我们得出结论，若避免孕早期接触，孕期使用香豆素治疗对儿童骨骼发育无明显风险。
