This study investigated the risk of congenital heart defects (CHD) and other congenital anomalies (CA) associated with first trimester use of macrolide antibiotics (mainly erythromycin, spiramycin, clarithromycin and azithromycin) and lincosamides (clindamycin) using a case-malformed control design.

Data included 145,936 babies with a CA diagnosis (livebirths, stillbirths and terminations of pregnancy for CA) from 15 population-based EUROCAT registries in 13 European countries, covering 9 million births 1995–2012. Cases were babies with CHD, anencephaly, orofacial clefts, genital and limb reduction anomalies associated with antibiotic exposure in the literature. Controls were babies with other CA or genetic conditions. Main outcomes were odds ratios adjusted (AOR) for maternal age and registry, with 95 % Confidence Intervals (95 %CI).

Macrolide and lincosamide exposure was recorded for 307 and 28 cases, 72 and 4 non-genetic controls, 57 and 7 genetic controls, respectively. AOR for CHD was not significantly raised (AOR 0.94, 95 %CI: 0.70–1.26 vs non-genetic controls; AOR 1.01, 95 %CI: 0.73–1.41 vs genetic controls), nor significantly raised for any specific macrolide. The risk of atrioventricular septal defect was significantly raised with exposure to any macrolide (AOR 2.98; 95 %CI: 1.48–6.01), erythromycin (AOR 3.68, 95 %CI: 1.28–10.61), and azithromycin (AOR 4.50, 95 %CI: 1.30–15.58). Erythromycin, clarithromycin, azithromycin, and clindamycin were associated with an increased risk of at least one other CA.

Further research is needed on the risk of specific CA associated with macrolide and lincosamide use in the first trimester, particularly relevant for the potential use of azithromycin in the treatment of COVID-19.

这项研究使用了个案设计不正确的对照设计，调查了与妊娠早期使用大环内酯类抗生素（主要是红霉素，螺旋霉素，克拉霉素和阿奇霉素）和林可酰胺类药物（克林霉素）有关的先天性心脏缺陷（CHD）和其他先天性异常（CA）的风险。

数据包括来自欧洲13个国家的15个以人口为基础的EUROCAT注册管理机构进行的145,936例诊断为CA的婴儿（CA的死产，死产和终止妊娠），涵盖1995-2012年的900万例婴儿。文献报道婴儿为冠心病，无脑，口面部裂痕，生殖器官和肢体减少异常以及与抗生素接触有关的婴儿。对照是患有其他CA或遗传病的婴儿。主要结局是针对孕产妇年龄和登记的优势比调整（AOR），置信区间为95％（95％CI）。

分别记录了307例和28例大环内酯和林可酰胺暴露，72例和4例非遗传对照，57例和7例遗传对照。冠心病的AOR没有显着升高（与非遗传对照相比，AOR 0.94，95％CI：0.70-1.26；与遗传对照相比，AOR 1.01，95％CI：0.73-1.41），对于任何特定的大环内酯类药物也没有显着升高。暴露于任何大环内酯类药物（AOR 2.98; 95％CI：1.48–6.01），红霉素（AOR 3.68，95％CI：1.28–10.61）和阿奇霉素（AOR 4.50，95％CI）显着增加房室间隔缺损的风险：1.30–15.58）。红霉素，克拉霉素，阿奇霉素和克林霉素与至少一种其他CA的风险增加相关。

还需要进一步研究与妊娠初期使用大环内酯和林可酰胺相关的特定CA的风险，特别是与阿奇霉素在治疗COVID-19中的潜在用途有关。