Childhood Pulmonary and Related Outcomes after Perinatal Exposure to Adjunctive Azithromycin Prophylaxis for Cesarean Delivery (C/SOAP Follow-Up Study)

围产期暴露于剖宫产辅助预防阿奇霉素后的儿童肺部及相关结果（C/SOAP 随访研究）

• 批准号: 9885315
• 负责人: Akila Subramaniam
• 金额: $ 74.15万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-20 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9885315
• 关键词: 7 year old; Accounting; Address; Adoption; Adverse effects; Affect; Age; American College of Obstetricians and Gynecologists; Amniotic Fluid; Antibiotic Prophylaxis; Antibiotics; Asthma; Azithromycin; Birth; Cause of Death; Cefazolin; Cephalosporins; Cesarean section; Child; Childbirth; Childhood; Cohort Studies; Cost Savings; Data; Development; Diagnosis; Disease; Dose; Endometritis; Enrollment; Eosinophilic Esophagitis; Exposure to; Follow-Up Studies; Food; Functional disorder; Funding; Future; Gastrointestinal Diseases; Half-Life; Health; Health Care Costs; Health Policy; Human Milk; Immune; Impairment; Incidence; Infection; Infection prevention; Inferior; Inflammatory; Inflammatory Bowel Diseases; Intervention; Intestines; Longitudinal Studies; Longterm Follow-up; Lung; Maternal Mortality; Measures; Mediating; Methods; Morbidity - disease rate; Mothers; Newborn Infant; Nose; Operative Surgical Procedures; Oral; Outcome; Parents; Pathway interactions; Perinatal Exposure; Pharmaceutical Preparations; Physicians; Physiological; Placebos; Placenta; Population; Prophylactic treatment; Pulmonary function tests; Questionnaires; Recommendation; Reporting; Research Design; Respiratory physiology; Risk; Risk Factors; Rome; Safety; Savings; Site; Surgical Wound Infection; Surgical incisions; Swab; Time; Umbilical Cord Blood; Visit; Wheezing; Woman; Wound Infection; aged; antimicrobial; atopy; authority; base; biobank; cohort; dysbiosis; environmental allergy; follow-up; gastrointestinal; gastrointestinal function; global health; hospital readmission; infant gut microbiome; intrapartum; microbiome; neonatal outcome; offspring; placental transfer; prenatal; prevent; pulmonary function; randomized trial; rectal; respiratory; respiratory morbidity; trial design

PROJECT SUMMARY/ABSTRACT “Childhood Pulmonary and Related Outcomes after Perinatal Exposure to Adjunctive Azithromycin Prophylaxis for Cesarean Delivery” is a large multi-center non-inferiority follow-up cohort study designed to evaluate long- term microbiome-mediated childhood pulmonary and gastrointestinal (GI) effects after perinatal exposure to adjunctive azithromycin as compared with placebo (plus standard cephalosporin) prior to incision to prevent surgical site infections at cesarean delivery. The parent C/SOAP randomized trial of adjunctive azithromycin (4/2011–11/2014) demonstrated a significant reduction in maternal infections (endometritis and wound infection) without any significant effect on short-term neonatal outcomes in the azithromycin group. This reduction in maternal infection (a major cause of death) was so significant that azithromycin use was found to be cost-saving – saving ~$360 for each use in unscheduled cesareans, corresponding to $270 million dollars annually in US healthcare costs. However, enthusiasm for adjunctive azithromycin has been tempered given reports of changes induced by azithromycin on the newborn gut microbiome (dysbiosis) that may be associated with immune/inflammatory diseases affecting respiratory and GI function (asthma, wheezing, atopy, inflammatory bowel disease [IBD]). In September 2018, ACOG suggested “consideration” of adjunctive azithromycin, but emphasized the need for studies of its effect on microbiome-mediated long-term outcomes. In this study, we hypothesize that perinatal exposure to adjunctive azithromycin compared to standard cesarean prophylaxis alone is not associated with increased childhood pulmonary or GI morbidity (i.e. is non- inferior). We propose a long-term follow-up study of the offspring of the C/SOAP trial cohort at optimal target age of 7 years (range 6-8) at the 14 sites that participated in the parent C/SOAP trial. We expect at least 1410 of 2013 children (70% follow-up) whose mothers were enrolled in C/SOAP will undergo a single study visit incorporating assessment of pulmonary and GI health. We will address the following specific aims: 1) To compare the incidence of childhood respiratory morbidity, specifically physiologic pulmonary impairment, based on a primary composite outcome of abnormal pulmonary function testing, physician diagnosis of asthma, or use of respiratory rescue medications in the previous year at age 7 (range 6-8) after perinatal exposure to adjunctive azithromycin versus placebo (standard prophylaxis alone) 2) To compare the incidence of childhood gastrointestinal (GI) morbidity based on a primary composite outcome of physician diagnosis of GI disease (eosinophilic esophagitis or IBD) OR an abnormal score on a validated GI questionnaire (Rome IV) between cohort offspring aged 7 (range 6-8) after perinatal exposure to adjunctive azithromycin versus placebo This study is the only opportunity to provide long-term safety data from a large US trial to inform and strengthen the newly recommended use of adjunctive azithromycin for cesarean delivery.

项目总结/文摘