Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study
Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study
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DOI：
10.1093/ije/dyx272
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发表时间：
2018-04-01
影响因子：
7.7
通讯作者：
Burgner, David P.
中科院分区：
文献类型：
--
作者：
Miller, Jessica Eden;Wu, Chunsen;Burgner, David P.
背景：生命早期的微生物组有助于免疫发育。怀孕期间使用抗生素会改变微生物组，并可能影响后代的疾病风险。我们调查了孕妇在怀孕前和怀孕期间的抗生素暴露与儿童因infection.Methods住院的风险之间的关系：我们使用了1995年至2009年期间基于人口的丹麦国家数据库怀孕。婴儿从出生到第一次感染相关住院、死亡、14岁生日、移民或2009年底进行随访。暴露是孕妇在怀孕前和怀孕期间服用的抗生素。结果：141359（18%）的母亲在怀孕期间至少有一个抗生素处方，230886（29.4%的人有完整的数据）在怀孕前18个月。在776657例活产单胎婴儿中，222524例（28.6%）儿童发生了443546例感染相关住院。妊娠期抗生素暴露与儿童感染相关住院风险增加相关[风险比（HR）1.18，95%置信区间（CI）1.17-1.19]。在母亲仅在怀孕期间使用抗生素，而其孩子未在住院前接受抗生素治疗的情况下，这种关联仅存在于阴道分娩的孩子中。当妊娠期抗生素处方更接近分娩时，以及母亲接受更多妊娠期抗生素时，感染相关住院的风险更高。母亲在妊娠前（而非妊娠期间）暴露于抗生素的儿童也增加了感染相关住院的风险（HR 1.10，95%CI 1.07-1.12）。结论：妊娠前或妊娠期间暴露于抗生素与儿童住院感染的风险增加相关。母体来源的微生物组的改变和共享的遗传和环境决定因素是可能的贡献机制。
Background: The early life microbiome contributes to immune development. Antibiotics during pregnancy alter the microbiome and may influence disease risks in the offspring. We investigated the relationship between maternal antibiotic exposure before and during pregnancy, and risk of childhood hospitalization with infection.Methods: We used population-based Danish national databases for pregnancies between 1995 and 2009. Infants were followed from birth until their first infection-related hospitalization, death, 14th birthday, emigration or end-2009. Exposure was maternal antibiotics prescribed before and during pregnancy. Outcome was infection-related hospitalization.Results: 141 359 (18%) mothers had at least one antibiotic prescription during pregnancy, 230 886 (29.4% of those with complete data) in the 18 months before pregnancy. Of 776 657 live-born singletons, 443 546 infection-related hospitalizations occurred in 222 524 (28.6%) children. Pregnancy antibiotic exposure was associated with increased risk of childhood infection-related hospitalization [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.17-1.19]. In mothers prescribed antibiotics only during pregnancy whose child did not receive pre-hospitalization antibiotics, this association was present only in those born vaginally. Higher risks of infection-related hospitalization occurred when pregnancy antibiotic prescriptions were closer to birth and in mothers receiving more pregnancy antibiotics. Children born to mothers exposed to antibiotics before (but not during) pregnancy also had increased risk of infection-related hospitalization (HR 1.10, 95% CI 1.07-1.12).Conclusions: Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections. Alteration of the maternally derived microbiome and shared heritable and environmental determinants are possible contributory mechanisms.