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: 9438474
• 负责人: Lyndsey Darrow
• 金额: $ 72.7万
• 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 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9438474
• 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系统的轨迹。 系统发育，对儿童免疫介导疾病的发展有影响，包括哮喘、湿疹和花粉热，这些都是工业化社会中流行率很高的慢性疾病。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，明确考虑可能解释先前观察性流行病学研究中观察到的正相关的偏倚来源。我们将使用在大型健康维护组织Kaiser Permanente北方加州（KPNC）登记的552，000对母婴对的历史出生队列，检验妊娠期、分娩期和/或婴儿期使用抗生素与儿童期特应性皮炎、过敏性鼻炎和哮喘病因有关的假设。1997年至2014年出生的儿童及其母亲的纵向数据将通过跨数据库的链接进行收集，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，这是KPNC研究部门于1996年建立的独特资源。特别大的样本量将允许精确评估抗生素使用的时间和类型，以及检查关键的潜在影响因素，如分娩方式（阴道与剖宫产），母乳喂养史和母体过敏或哮喘史。我们将采用创新的方法和统计方法来识别和减少此类研究中常见的偏倚来源，包括反向因果关系、适应症混淆以及未测量或测量不良的母婴因素（如寻求医疗保健行为）混淆。方法将包括未来暴露方法的新应用，以加强对我们结果的因果解释，并扩展可用于检测的工具，并可能纠正观察性流行病学研究中的偏倚 更广泛地说。使用这些方法，我们将回答以下问题：从产前到婴儿期的累积抗生素暴露对儿童特应性结局的影响;分娩方式、母乳喂养史或母亲哮喘或过敏史等因素是否改变了这种关系;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），以及所用抗生素对儿童结局的适应症;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早期生命中最常用处方药的安全临床使用。