Merlob Paul, Levitt Orly, Stahl Bracha
Beilinson Teratology Information Service and Drug Information Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Paediatr Drugs. 2002;4(11):755-60. doi: 10.2165/00128072-200204110-00007.
The treatment approach of diabetes mellitus during pregnancy requires a combination of diet, exercise, multiple home glucose determinations and intensive insulin regimens. During the last decade there was an increased interest in the use of oral antihyperglycemic agents (OAHAs) as an alternative to insulin in achieving good glycemic control. OAHAs are divided into four groups: derivatives of sulfonylurea, biguanides, glucosidase inhibitors and thiazolidinediones. This review describes the possible teratogenic effects of the use of OAHAs during pregnancy and the effects of these drugs during lactation. Animal and human studies assessing the teratogenic effects of OAHAs have yielded conflicting data because the risk of major malformations in infants of mothers with diabetes appears to be related to maternal glycemic control rather than the antidiabetic therapy. A major concern with the use of OAHAs during pregnancy is neonatal hypoglycemia, which may be severe and persist for days. Therefore, insulin is still the drug of choice because it has not been implicated as a teratogen in human pregnancies. In addition, because of the lack of data regarding the use of OAHAs in pregnancy, we cannot draw firm conclusions about all of the available drugs. However, OAHAs, especially glibenclamide (glyburide), may be beneficial in a situation where the proper use of insulin is problematic. Because there are very limited clinical data on the exposure of OAHAs to the infant via breast milk, and the potentially serious effect of neonatal hypoglycemia, the safest recommendation is not to breast feed while taking OAHAs. Well-conducted, prospective, controlled studies regarding the feasibility of OAHAs in pregnant women with diabetes and during lactation are needed.
妊娠期糖尿病的治疗方法需要饮食、运动、多次家庭血糖测定和强化胰岛素治疗方案相结合。在过去十年中,人们越来越关注使用口服降糖药(OAHAs)作为胰岛素的替代药物来实现良好的血糖控制。OAHAs分为四类:磺脲类衍生物、双胍类、糖苷酶抑制剂和噻唑烷二酮类。本综述描述了妊娠期使用OAHAs可能产生的致畸作用以及这些药物在哺乳期的影响。评估OAHAs致畸作用的动物和人体研究得出了相互矛盾的数据,因为糖尿病母亲婴儿出现重大畸形的风险似乎与母亲的血糖控制有关,而非抗糖尿病治疗。妊娠期使用OAHAs的一个主要担忧是新生儿低血糖,这可能很严重且会持续数天。因此,胰岛素仍然是首选药物,因为它在人类妊娠中未被认为是致畸剂。此外,由于缺乏关于妊娠期使用OAHAs的数据,我们无法对所有可用药物得出确凿结论。然而,在胰岛素使用存在问题的情况下,OAHAs,尤其是格列本脲(优降糖)可能有益。由于关于OAHAs通过母乳暴露于婴儿的临床数据非常有限,以及新生儿低血糖的潜在严重影响,最安全的建议是在服用OAHAs期间不要母乳喂养。需要针对OAHAs在糖尿病孕妇和哺乳期的可行性进行精心设计的前瞻性对照研究。