Prenatal, Intrapartum and Infant Antibiotic Use and Atopic Diseases in Childhood

产前、产时和婴儿抗生素的使用和儿童期特应性疾病

• 批准号: 9220712
• 负责人: Lyndsey Darrow
• 金额: $ 74.46万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-08 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9220712
• 关键词: 2 year old; 6 year old; Acute; Address; Age; Air Pollution; Allergic rhinitis; Anaerobic Bacteria; Animal Experiments; Antibiotics; Asthma; Atopic Dermatitis; Behavior; Birth; Birth Records; Breast Feeding; California; Cephalosporins; Cesarean section; Characteristics; Child; Childhood; Chronic; Clinical; Complement; Computerized Medical Record; Data; Data Quality; Databases; Detection; Development; Diagnosis; Disease; Disease Outcome; Dose; Eczema; Enrollment; Equilibrium; Etiology; Exposure to; Extrinsic asthma; Future; Hay fever; Health Maintenance Organizations; Healthcare; Hypersensitivity; Immune; Immune system; Industrialization; Infant; Knowledge; Life; Link; Long-Term Effects; Macrolides; Measures; Mediating; Medical History; Methodology; Methods; Metronidazole; Modeling; Mothers; Nitrofurantoin; Observational Study; Outcome; Patients; Penicillins; Pharmaceutical Preparations; Pharmacy facility; Phenotype; Pregnancy; Prevalence; Public Health; Recording of previous events; Records; Registries; Research; Residual state; Resources; Respiratory Tract Infections; Rhinitis; Risk; Role; Sample Size; School-Age Population; Societies; Source; Sulfonamides; System; Systems Development; Testing; Vagina; Vital Statistics; cohort; design; early childhood; epidemiology study; follow-up; hazard; improved outcome; infancy; innovation; intrapartum; microbiota; novel; postnatal; prenatal; prenatal exposure; public health relevance; simulation; tool

 DESCRIPTION (provided by applicant): Antibiotics are among the most commonly used medications in pregnancy and early childhood. Increasing evidence suggests that disruption of the ecological balance of microbiota in prenatal and early life can derail the trajectory of immune system development, with implications for development of immune-mediated diseases in the child including asthma, eczema and hay fever, all chronic and highly prevalent diseases in industrialized societies. The proposed research seeks to elucidate the role of prenatal and early postnatal antibiotic exposure on childhood atopic diseases with explicit consideration of sources of bias that may account for the positive associations observed in previous observational epidemiologic studies. We will test the hypotheses that use of antibiotics during pregnancy, in the intrapartum period, and/or in infancy contributes to the etiology of atopic dermatitis, allergi rhinitis and asthma during childhood using a historical birth cohort of 552,000 mother-child pairs enrolled in Kaiser Permanente Northern California (KPNC), a large health maintenance organization. Longitudinal data on children born between 1997 and 2014 and their mothers will be assembled by linking across databases, including electronic medical records and pharmacy dispensing records at KPNC, birth records at the California Department of Public Health, and the KPNC Asthma Registry, a unique resource of KPNC Division of Research established in 1996. The exceptionally large sample size will allow for refined assessment of the timing and type of antibiotic use as well as examination of key potential effect modifiers such as delivery mode (vaginal versus Cesarean section), breastfeeding history, and maternal history of allergy or asthma. We will employ innovative methodological and statistical approaches to identify and reduce the sources of bias common in this kind of research, including reverse causality, confounding by indication, and confounding by unmeasured or poorly measured maternal and child factors such as healthcare-seeking behaviors. Methods will include novel application of a future exposure approach to strengthen causal interpretation of our results and expand the tools available for detection, and potentially correction, of bias in observational epidemiologic studies more broadly. Using these approaches we will answer the following questions: what is the effect of cumulative antibiotic exposures from the prenatal period through infancy on child atopic outcomes; are relationships modified by factors such as delivery mode, breastfeeding history, or maternal asthma or allergy history; what are the effects of the timing, characteristics (e.g., spectrum, class, anaerobe coverage, Gram-positive/Gram-negative coverage), and indication of the antibiotics taken on child outcomes; and are antibiotic exposures associated with persistent disease at school age. The highly translational results will help guide safe clinical use of the most commonly prescribed medications in early life.

 描述（由申请人提供）：抗生素是妊娠期和幼儿期最常用的药物之一。越来越多的证据表明，产前和生命早期微生物群生态平衡的破坏可能会破坏免疫的轨迹。 系统发育，对儿童免疫介导疾病的发展产生影响，包括哮喘、湿疹和花粉症，以及工业化社会中所有慢性和高度流行的疾病。拟议的研究旨在阐明产前和产后早期抗生素暴露对儿童特应性疾病的作用，并明确考虑可能解释先前观察流行病学研究中观察到的正相关的偏差来源。我们将使用大型健康维护组织 Kaiser Permanente Northern California (KPNC) 登记的 552,000 对母子历史出生队列来检验以下假设：怀孕期间、产时期间和/或婴儿期使用抗生素会导致儿童期特应性皮炎、过敏性鼻炎和哮喘的病因。 1997 年至 2014 年间出生的儿童及其母亲的纵向数据将通过跨数据库链接来汇总，包括 KPNC 的电子病历和药房配药记录、加州公共卫生部的出生记录以及 KPNC 哮喘登记处（KPNC 哮喘登记处是 1996 年建立的 KPNC 研究部的独特资源）。超大的样本量将允许对抗生素使用的时间和类型以及抗生素使用的时间和类型进行精细评估。 检查关键的潜在影响因素，例如分娩方式（阴道分娩与剖腹产）、母乳喂养史以及母亲过敏或哮喘病史。我们将采用创新的方法论和统计方法来识别和减少此类研究中常见的偏差来源，包括反向因果关系、适应症混杂以及未测量或测量不良的母婴因素（例如就医行为）造成的混杂。方法将包括未来暴露方法的新颖应用，以加强对我们结果的因果解释，并扩展可用于检测和潜在纠正观察性流行病学研究中偏差的工具 更广泛地说。使用这些方法，我们将回答以下问题：从产前期到婴儿期累积的抗生素暴露对儿童特应性结局有什么影响？关系是否因分娩方式、母乳喂养史、母亲哮喘或过敏史等因素而改变；服用抗生素的时间、特征（例如谱、类别、厌氧菌覆盖率、革兰氏阳性/革兰氏阴性覆盖率）和适应症对儿童结局有何影响；以及与学龄期持续性疾病相关的抗生素暴露。高度转化的结果将有助于指导生命早期最常用处方药物的安全临床使用。