Gaml-Sørensen Anne, Brix Nis, Ernst Andreas, Lunddorf Lea L H, Sand Sofie A, Ramlau-Hansen Cecilia H
Department of Public Health, Research Unit for Epidemiology, Aarhus University, Bartholins Allé 2, 8000, Aarhus C., Denmark.
Department of Public Health, Research Unit for Epidemiology, Aarhus University, Bartholins Allé 2, 8000, Aarhus C., Denmark.
Eur J Obstet Gynecol Reprod Biol. 2020 Jul;250:1-8. doi: 10.1016/j.ejogrb.2020.04.031. Epub 2020 Apr 20.
To investigate if prenatal exposure to antibiotics is associated with earlier timing of pubertal development in sons and daughters.
This population-based cohort study is based upon the Puberty Cohort and includes a sample of 15,638 children born 2000-2003 in Denmark. Information on maternal use of antibiotics was collected around gestational week 30 and 6 months postpartum. The children were followed-up half-yearly from 11 years of age and throughout sexual maturation providing information on Tanner stages, acne and axillary hair, in addition to voice break and first ejaculation in sons and menarche in daughters. Due to the half-yearly collection of data on pubertal timing, the data was censored and therefore analysed using a multivariable censored time-to-event regression model. We examined both prenatal exposure to antibiotics at any time in pregnancy and trimester-specific prenatal exposure to antibiotics and pubertal timing, adjusting for maternal baseline socioeconomic and lifestyle characteristics. Mean age differences for the pubertal milestones between exposure groups were estimated. A combined estimate for overall pubertal timing was calculated based on combining all pubertal milestones into one model for sons and daughters, using Huber-White robust variance estimation which handles the risk of type 1 errors due to multiple testing of correlated outcomes. An active comparator approach with restriction to women reporting to have a urinary tract infection (cystitis) treated with either penicillin or sulfonamides was employed in a sub-analysis.
The prevalence of any maternal use of antibiotics in pregnancy was 21.1 %. There was no association between prenatal exposure to antibiotics and timing of pubertal development for the individual milestones. The adjusted combined estimate for pubertal timing in sons prenatally exposed to antibiotics at any point in pregnancy was -0.4 (95 % confidence interval (CI): -1.2; 0.4) months compared to unexposed sons. The adjusted combined estimate for pubertal timing in daughters prenatally exposed to antibiotics at any point in pregnancy was -0.1 (95 % CI: -0.9; 0.7) months compared to unexposed daughters. Both the trimester-specific analyses and the active comparator analysis revealed similar results.
Prenatal exposure to antibiotics was not associated with pubertal timing.
研究孕期暴露于抗生素是否与子女青春期发育时间提前有关。
这项基于人群的队列研究以青春期队列研究为基础，纳入了2000年至2003年在丹麦出生的15638名儿童样本。在妊娠第30周左右和产后6个月收集母亲使用抗生素的信息。从11岁起对这些儿童进行半年一次的随访，直至性成熟，除了记录男孩的变声和首次射精以及女孩的月经初潮外，还提供关于坦纳分期、痤疮和腋毛的信息。由于青春期发育时间的数据是半年收集一次，因此数据进行了截尾处理，并使用多变量截尾事件时间回归模型进行分析。我们研究了孕期任何时间的抗生素产前暴露以及孕期特定阶段的抗生素产前暴露与青春期发育时间的关系，并对母亲的基线社会经济和生活方式特征进行了调整。估计了暴露组之间青春期发育里程碑的平均年龄差异。基于将所有青春期发育里程碑合并到一个针对男孩和女孩的模型中，计算了青春期发育总体时间的综合估计值，使用了处理因相关结局多次检验导致的一类错误风险的稳健方差估计。在一项亚分析中采用了主动对照方法，限制在报告患有尿路感染（膀胱炎）并接受青霉素或磺胺类药物治疗的女性中进行。
孕期母亲使用抗生素的总体患病率为21.1%。抗生素产前暴露与各个青春期发育里程碑的时间之间没有关联。与未暴露的儿子相比，孕期任何时间产前暴露于抗生素的儿子青春期发育时间的调整后综合估计值为-0.4（95%置信区间（CI）：-1.2；0.4）个月。与未暴露的女儿相比，孕期任何时间产前暴露于抗生素的女儿青春期发育时间的调整后综合估计值为-0.1（95%CI：-0.9；0.7）个月。孕期特定阶段分析和主动对照分析均得出了类似的结果。
产前暴露于抗生素与青春期发育时间无关。
