Moise K J, Huhta J C, Sharif D S, Ou C N, Kirshon B, Wasserstrum N, Cano L
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030.
N Engl J Med. 1988 Aug 11;319(6):327-31. doi: 10.1056/NEJM198808113190602.
Indomethacin is a potent agent in the treatment of premature labor, but its use has been limited because of concern about its constrictive effects on the fetal ductus arteriosus. To study these effects we used serial fetal echocardiography in 13 pregnant women in premature labor who received indomethacin according to three different dose schedules, ranging from 100 to 175 mg per day, for a maximum of 72 hours. The gestational ages of the fetuses ranged from 26.5 to 31.0 weeks. The detection of ductal constriction in 7 of the 14 fetuses by echocardiography led to the discontinuation of indomethacin. Three fetuses also had tricuspid regurgitation. There was no statistically significant difference between the mean (+/- SEM) gestational age of the fetuses with ductal constriction and that of those without constriction (29.3 +/- 0.59 and 28.4 +/- 0.52, respectively). There was no relation between serum indomethacin levels in the mothers and ductal constriction. In all seven fetuses affected, ductal constriction had resolved by the time they were restudied 24 hours after the discontinuation of indomethacin. Persistent fetal circulation was not detected in any of the 11 neonates studied after delivery. Indomethacin used to treat premature labor appears to cause transient constriction of the ductus arteriosus in some fetuses, even after short-term use.
吲哚美辛是治疗早产的一种有效药物,但其应用因担心其对胎儿动脉导管的收缩作用而受到限制。为研究这些影响,我们对13例早产孕妇进行了系列胎儿超声心动图检查,这些孕妇按照三种不同剂量方案接受吲哚美辛治疗,剂量范围为每天100至175毫克,最长使用72小时。胎儿的孕周为26.5至31.0周。超声心动图检查发现14例胎儿中有7例出现导管收缩,导致吲哚美辛停用。另外3例胎儿还出现三尖瓣反流。出现导管收缩的胎儿与未出现收缩的胎儿的平均(±标准误)孕周之间无统计学显著差异(分别为29.3±0.59和28.4±0.52)。母亲血清吲哚美辛水平与导管收缩之间无关联。在所有7例受影响的胎儿中,吲哚美辛停用24小时后再次检查时,导管收缩已消退。在分娩后研究的11例新生儿中,未检测到持续性胎儿循环。用于治疗早产的吲哚美辛似乎会在一些胎儿中引起动脉导管的短暂收缩,即使是短期使用后也是如此。