Bergman U, Rosa F W, Baum C, Wiholm B E, Faich G A
Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden.
Lancet. 1992 Sep 19;340(8821):694-6. doi: 10.1016/0140-6736(92)92232-5.
Dysmorphism and mental retardation have been reported in 7 Swedish children born of mothers who had taken high doses of benzodiazepines regularly during pregnancy. To explore this association further, we examined benzodiazepine use during pregnancy in 104,000 women whose deliveries were registered by the US public health insurance system, Medicaid, during 1980-83. Fetal outcomes were assessed from the health claims profiles of their offspring, up to 6-9 years after delivery. 80 pregnant women had received 10 or more benzodiazepine prescriptions during the 4 years. Their records showed heavy general use of health care and frequent alcohol and substance abuse, and other disorders that could confound any effect of the benzodiazepines. For the 80 pregnancies, 3 intrauterine deaths were identified as well as 2 infants with congenital abnormalities whose curtailed records suggested neonatal death. Records of 64 surviving children could be linked to these 80 pregnancies whilst records for 11 apparent survivors could not be located. 6 of the 64 survivors had diagnoses consistent with teratogenic abnormalities. The high rate of teratogenicity after heavy maternal benzodiazepine use occurs with multiple alcohol and substance exposure and thus may not be due to benzodiazepine exposure.
据报道，瑞典有7名儿童出生时存在畸形和智力发育迟缓问题，他们的母亲在孕期曾定期服用高剂量苯二氮卓类药物。为进一步探究这种关联，我们调查了1980年至1983年间由美国公共医疗保险系统医疗补助计划登记分娩的104,000名女性孕期苯二氮卓类药物的使用情况。通过其子女的健康理赔档案评估胎儿出生后6至9年的结局。80名孕妇在这4年期间接受了10次或更多次苯二氮卓类药物处方。她们的记录显示其普遍大量使用医疗保健服务，且频繁酗酒和滥用药物，还存在其他可能混淆苯二氮卓类药物任何影响的疾病。在这80次妊娠中，确认有3例宫内死亡以及2例先天性异常婴儿，其简短记录提示为新生儿死亡。64名存活儿童的记录可与这80次妊娠相关联，而11名明显存活者的记录无法找到。64名存活者中有6例诊断与致畸性异常相符。母亲大量使用苯二氮卓类药物后致畸率很高，同时存在多种酒精和药物接触情况，因此可能并非由苯二氮卓类药物接触所致。
