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：
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
项目类别：
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

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（由应用提供）：抗生素是怀孕和幼儿期间最常用的药物之一。越来越多的证据表明，产前和早期生命中微生物群生态平衡的破坏会使免疫的轨迹轨迹系统开发，对儿童免疫介导的疾病的发展具有影响，包括哮喘，湿疹和花粉症，这些疾病都是工业化社会中的慢性和高度普遍疾病。拟议的研究旨在阐明产前和早期产后抗生素暴露在儿童期特应疾病中的作用，并明确考虑偏见的来源，这可能会影响先前观察性的流行病学研究中观察到的积极关联。我们将测试在怀孕期间，在体内期间和/或婴儿期使用抗生素的假设，这有助于在儿童期使用552,000个母亲的历史性出生队列，在儿童时期的童年时期，童年时期的童年时期的病因，北部北部的kaisererente callantia（Kaiserertementia callantia callantia callantia）（Kaiserente）（Kaiserente）（Kaiserente）（Kaiserente）（Kaiserente）（Kaiserente）的较大健康（Kaiserente）（Kaise）。关于1997年至2014年之间出生的儿童及其母亲的纵向数据，将通过跨数据库链接，包括电子病历和药房分配KPNC的记录，加利福尼亚公共卫生部的出生记录，KPNC哮喘注册表以及KPNC哮喘登记册，允许使用量的KPNC的独特范围。检查关键潜在效应修饰符，例如输送模式（阴道与剖宫产部分），母乳喂养史以及过敏或哮喘的产妇病史。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见来源，包括反向热量，通过指示混淆，并因未能测量或测量不佳的母亲和儿童因素（例如寻求医疗保健行为）而混淆。方法将包括对未来暴露方法的新颖应用，以对我们的结果进行强有力的因果解释，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使用这些方法，我们将回答以下问题：从婴儿期到婴儿期累积的抗生素暴露对儿童的累积抗生素暴露有何影响？关系是由诸如分娩模式，母乳喂养史或母乳哮喘或过敏病史等因素所修改的；定时，特征（例如光谱，类别，厌氧覆盖范围，革兰氏阳性/革兰氏阴性覆盖范围）的影响是什么，以及对儿童结局的抗生素的指示；并且是与学龄前疾病有关的抗生素暴露。高度翻译的结果将有助于指导早期最常见的处方药的安全临床使用。