Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Antimicrob Agents Chemother. 2013 Jul;57(7):3307-11. doi: 10.1128/AAC.01691-12. Epub 2013 May 6.
Macrolide antibiotics are largely used in pregnancy for different bacterial infections. Their fetal safety has been studied by several groups, yielding opposing results. In particular, there have been studies claiming an association between macrolides and cardiovascular malformations. Exposure in early infancy has been associated with pyloric stenosis and intussusception. This has led to an avoidance in prescribing macrolides to pregnant women in several Scandinavian countries. The Objectives of the present study was to investigate the fetal safety of this class of drug by linking a large administrative database of drug dispensing and pregnancy outcome in Southern Israel. A computerized database of medications dispensed from 1999 to 2009 to all women registered in the Clalit health maintenance organization in southern Israel was linked with two computerized databases containing maternal and infant hospitalization records. Also, medical pregnancy termination data were analyzed. The following confounders were controlled for: maternal age, ethnicity, maternal pregestational diabetes, parity, and the year the mother gave birth or went through medical pregnancy termination. First- and third-trimester exposures to macrolide antibiotics as a group and to individual drugs were analyzed. During the study period there were 105,492 pregnancies among Clalit women that met the inclusion criteria. Of these, 104,380 ended in live births or dead fetuses and 1,112 in abortion due to medical reasons. In the first trimester of pregnancy, 1,033 women were exposed to macrolides. There was no association between macrolides and either major malformations [odds ratio (OR), 1.08; 95% confidence interval (CI), 0.84 to 1.38)] or specific malformations, after accounting for maternal age, parity, ethnicity, prepregnancy diabetes, and year of exposure. During the third trimester of pregnancy, 959 women were exposed to macrolides. There was no association between such exposure and perinatal mortality, low birth weight, low Apgar score, or preterm delivery. Similarly, no associations were demonstrated with pyloric stenosis or intussusception. Use of macrolides in the first trimester of pregnancy is not associated with an increased risk of major malformations. Exposure in the third trimester is not likely to increase neonatal risks for pyloric stenosis or intussusception in a clinically meaningful manner.
大环内酯类抗生素在妊娠期间被广泛用于治疗各种细菌感染。其胎儿安全性已被多个研究小组研究，结果却相互矛盾。特别是，有研究声称大环内酯类药物与心血管畸形之间存在关联。在婴儿早期暴露于大环内酯类药物与幽门狭窄和肠套叠有关。这导致在几个斯堪的纳维亚国家避免给孕妇开大环内酯类药物。本研究的目的是通过链接以色列南部一个大型药物配药和妊娠结局的行政数据库来调查此类药物的胎儿安全性。从 1999 年至 2009 年，为以色列南部克利利特健康维护组织的所有女性分发药物的计算机数据库与包含母婴住院记录的两个计算机数据库相关联。此外，还分析了医疗性妊娠终止数据。控制了以下混杂因素：母亲年龄、种族、母亲孕前糖尿病、产次和母亲分娩或接受医疗性妊娠终止的年份。分析了大环内酯类抗生素的第一和第三孕期暴露情况，以及个别药物的暴露情况。在研究期间，克利利特妇女中有 105492 例妊娠符合纳入标准。其中，104380 例以活产或死胎结束，1112 例因医疗原因流产。在妊娠的第一个三个月，有 1033 名妇女接触了大环内酯类药物。在考虑了母亲年龄、产次、种族、孕前糖尿病和暴露年份后，大环内酯类药物与主要畸形（比值比[OR]，1.08；95%置信区间[CI]，0.84 至 1.38）或特定畸形之间均无关联。在妊娠的第三个三个月，有 959 名妇女接触了大环内酯类药物。这种接触与围产期死亡率、低出生体重、低阿普加评分或早产均无关。同样，也未发现与幽门狭窄或肠套叠有关。在妊娠的第一个三个月使用大环内酯类药物不会增加主要畸形的风险。在第三个三个月暴露于大环内酯类药物不太可能以临床有意义的方式增加新生儿患幽门狭窄或肠套叠的风险。
