Incidence of atopy and childhood infections in uninfected term newborns with perinatal antibiotic exposure

项目总结/摘要 多项临床研究发现婴儿期抗生素暴露与特应性过敏之间存在关联 紊乱研究还表明，使用抗生素后， 培养阴性感染的治疗。过去的研究主要集中在产前给予抗生素， 母亲在怀孕期间，或儿童抗生素，很少调查围产期抗生素暴露 在分娩时给予母亲和出生后立即给予新生儿。抗生素对儿童的影响 疾病很可能是由宿主微生物群落多样性的改变介导的， 免疫反应。出生后的第一个时期是免疫系统与关键免疫系统相互作用的关键时期。 微生物区系分类群和改变最有可能具有持久的影响。围产期抗生素已被证明 导致新生儿肠道微生物组发生显著变化，并在出生后持续数周。日益 使用产时和新生儿抗生素预防早发性新生儿细菌感染意味着约30% 的新生儿在出生时接触抗生素。这种广泛使用围产期 抗生素可能对特应性和感染性疾病的儿童结局有显著影响， 还没有被调查我们假设围产期抗生素暴露与较高的 特应性疾病的发病率和因医生诊断的感染而就诊的儿科门诊。我们的第一个具体 目的是解决围产期抗生素与临床诊断特应性疾病的关系， 五年的生活。我们的第二个具体目标是测量围产期抗生素对非预防性 由于最常见的医生诊断的儿童感染，保健办公室访问。为了实现我们的目标，我们将 形成2007-2012年在两个主要分娩中心分娩的足月婴儿的出生队列， 费城儿童医院（CHOP）儿科护理网络。我们将利用CHOP的大型 来自超过31个中心的综合电子健康记录，从婴儿出生到5岁， 建立一个详细的纵向数据库，涵盖产科、新生儿和儿童健康 护理数据。使用该数据库，我们将确定任何特应性诊断的发生率差异， 接触和不接触以下物质的婴儿因感染而进行的非预防性健康检查 围产期抗生素向母亲及其新生儿提供围产期抗生素暴露， 假设它们是预防新生儿感染的安全方法，发病率低，但 高发病率疾病。我们的研究结果可能会对早期的安全性产生深远的影响。 抗生素暴露，并可能导致新生儿临床实践的重大修订。

PROJECT SUMMARY/ABSTRACT Multiple clinical studies have found an association between antibiotic exposures in infancy and atopic disorders. Studies have also demonstrated a reduced resistance to subsequent infections after antibiotic therapy for culture-negative infection. Past studies have focused on either prenatal antibiotics given to the mother during pregnancy, or on childhood antibiotics, with little investigation of perinatal antibiotic exposure given to mothers at the time of labor and to neonates immediately after birth. Antibiotic effect on childhood diseases is likely mediated by alteration of host microflora diversity, adversely impacting the development of immune responses. The immediate period after birth is a critical time for immune system interaction with key microflora taxa and alterations are most likely to have enduring effects. Perinatal antibiotics have been shown to cause significant changes in the neonatal gut microbiome that persist for weeks after birth. The increasing use of intrapartum and neonatal antibiotics to prevent early-onset neonatal bacterial infection means that ~30% of newborns are now exposed to antibiotics around the time of birth. This widespread use of perinatal antibiotics may have a significant effect of childhood outcomes of atopic and infectious diseases that has not yet been investigated. We hypothesize that perinatal antibiotic exposures will be associated with a higher incidence of atopic diseases and pediatric office visits due to physician-diagnosed infection. Our first specific aim will address the relationship of perinatal antibiotics to the clinical diagnosis of atopic disorders in the first five years of life. Our second specific aim is to measure the impact of perinatal antibiotics on non-preventative care office visits due to the commonest physician-diagnosed childhood infections. To achieve our aims, we will form a birth cohort of term infants delivered from 2007-2012 at the 2 main birthing centers referring newborns to The Children’s Hospital of Philadelphia (CHOP) pediatric care network. We will leverage CHOP’s large integrated electronic health records from over 31 centers to follow infants from their birthing admissions until 5 years of age and form a detailed longitudinal database spanning obstetrical, neonatal and childhood health care data. Using this database we will determine the difference in incidence of any atopic diagnosis and episodes of non-preventative health visits due to infections among infants with and without exposure to perinatal antibiotics. Perinatal antibiotic exposures are provided to mothers and their newborns with the assumption that they constitute safe approaches to the prevention of a neonatal infection, a low incidence but high morbidity disease. The results of our study may have a profound impact the perceived safety of early antibiotic exposures, and could result in a major revision of newborn clinical practice.