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

基本信息

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
项目类别：
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

项目摘要

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、湿疹和花粉热，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的影响。特应性疾病，并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差来源，我们将检验妊娠期间、产时和/或婴儿期使用抗生素有助于这一假设。使用北加州 Kaiser Permanente (KPNC) 的 552,000 对母子历史出生队列，了解儿童时期特应性皮炎、过敏性鼻炎和哮喘的病因，KPNC 是一家大型健康维护组织，对 1997 年至 2014 年出生的儿童进行了纵向数据分析。他们的母亲将通过跨数据库链接来收集，包括 KPNC 的电子病历和药房配药记录、加州部门的出生记录公共卫生部和 KPNC 哮喘登记处，这是 1996 年成立的 KPNC 研究部的独特资源。异常大的样本量将允许对抗生素使用的时间和类型进行精细评估，并检查关键的潜在效果调节剂，例如如分娩方式（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，包括反向研究。因果关系、适应症的混杂以及未测量或测量不良的母婴因素（例如寻求医疗行为）的混杂。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，以及观察流行病学研究中偏差的潜在纠正更广泛地使用这些方法，我们将回答以下问题：从产前到婴儿期累积的抗生素暴露对儿童特应性结局的影响是什么？病史；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的影响是什么；以及抗生素暴露与持续性疾病相关吗？学校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。