Population, Policy and Practice Programme, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Administrative Data Research Centre for England, University College London, London, United Kingdom.
PLoS One. 2019 Feb 19;14(2):e0212212. doi: 10.1371/journal.pone.0212212. eCollection 2019.
Evidence on adverse effects of maternal macrolide use during pregnancy is inconsistent. We conducted a systematic review and meta-analysis to investigate the association between macrolide use during pregnancy and adverse fetal and child outcomes.
We included observational studies and randomised controlled trials (RCTs) that recorded macrolide use during pregnancy and child outcomes. We prioritized comparisons of macrolides with alternative antibiotics (mainly penicillins or cephalosporins) for comparability of indication and effect. Random effects meta-analysis was used to derive pooled odds ratios (OR) for each outcome. Subgroup analyses were performed according to specific types (generic forms) of macrolide. Of 11,186 citations identified, 19 (10 observational, 9 RCTs) studies were included (21 articles including 228,556 participants). Macrolide prescribing during pregnancy was associated with an increased risk of miscarriage (pooled ORobs 1·82, 95% CI 1·57-2·11, three studies, I2 = 0%), cerebral palsy and/or epilepsy (ORobs 1·78, 1·18-2·69; one study), epilepsy alone (ORobs 2·02, 1·30-3·14, one study; ORRCT 1.03, 0.79-1.35, two studies), and gastrointestinal malformations (ORobs 1·56, 1·05-2·32, two studies) compared with alternative antibiotics. We found no evidence of an adverse effect on 12 other malformations, stillbirth, or neonatal death. Results were robust to excluding studies with high risk of bias.
Consistent evidence of an increased risk of miscarriage in observational studies and uncertain risks of cerebral palsy and epilepsy warrant cautious use of macrolide in pregnancy with warnings in drug safety leaflets and use of alternative antibiotics where appropriate. As macrolides are the third most commonly used class of antibiotics, it is important to confirm these results with high quality studies.
关于孕妇使用大环内酯类药物的不良影响的证据并不一致。我们进行了一项系统评价和荟萃分析，以调查怀孕期间使用大环内酯类药物与不良胎儿和儿童结局之间的关系。
我们纳入了记录怀孕期间使用大环内酯类药物和儿童结局的观察性研究和随机对照试验（RCT）。我们优先比较了大环内酯类药物与替代抗生素（主要是青霉素或头孢菌素）的比较，以确保适应症和效果的可比性。使用随机效应荟萃分析得出每个结局的汇总优势比（OR）。根据大环内酯类药物的特定类型（通用形式）进行亚组分析。在确定的 11186 篇参考文献中，有 19 项（10 项观察性研究，9 项 RCT）研究入选（21 篇文章包括 228556 名参与者）。怀孕期间使用大环内酯类药物与流产风险增加相关（汇总观察性 OR 1.82，95%CI 1.57-2.11，三项研究，I2=0%）、脑瘫和/或癫痫（OR 1.78，1.18-2.69；一项研究）、单纯癫痫（OR 2.02，1.30-3.14，一项研究；ORRCT 1.03，0.79-1.35，两项研究）和胃肠道畸形（OR 1.56，1.05-2.32，两项研究）相比，替代抗生素。我们没有发现对其他 12 种畸形、死产或新生儿死亡有不良影响的证据。结果在排除高偏倚风险的研究后仍然稳健。
观察性研究中一致存在流产风险增加的证据，脑瘫和癫痫的风险不确定，这使得在怀孕期间谨慎使用大环内酯类药物，并在适当情况下使用替代抗生素，药物安全说明书中应警告相关风险。由于大环内酯类药物是第三大常用抗生素类别，因此用高质量的研究来证实这些结果非常重要。
