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: 10322099
• 负责人: Akila Subramaniam
• 金额: $ 62.42万
• 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 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10322099
• 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; 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; 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; nasal swab; 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.

项目摘要/摘要 “围产期暴露于辅助阿奇霉素预防后，儿童肺和相关结果 对于剖宫产”是一项大型的多中心非劣效率随访研究研究，旨在评估长期 围产期暴露后，术语微生物组介导的儿童肺和胃肠道（GI）作用 与安慰剂（加上标准的头孢菌素）相比，辅助阿奇霉素在切口之前 剖宫产的手术部位感染。辅助阿奇罗霉素的母体C/SOAP随机试验 （4/2011–11/2014）表现出孕产妇感染的显着降低（子宫内膜炎和伤口 感染）对阿奇霉素组的短期新生儿结局没有任何显着影响。这 孕产妇感染的降低（主要的死亡原因）是如此明显，以至于发现了阿奇霉素的使用 省略成本 - 在未完成的剖宫产中为每种用途节省约360美元，相当于2.7亿美元 美国的每个医疗保健费用。但是，对辅助阿奇霉素的热情已得到缓和 阿奇霉素在新生儿肠道微生物组（营养不良）上引起的变化的报告可能是 与影响呼吸和胃肠道功能的免疫/炎症性疾病有关（哮喘，喘息，特应， 炎症性肠病[IBD]）。 2018年9月，ACOG建议对辅助手段进行“考虑” 阿奇霉素，但强调需要研究其对微生物组介导的长期结局的影响。 在这项研究中，我们假设与标准相比，围产期暴露于辅助阿奇霉素 仅剖宫产的预防与儿童肺部或胃肠道发病率无关（即非 - 下）。我们建议对最佳目标C/SOAP试验队列的后代进行长期随访研究 参加父母C/SOAP试验的14个地点的7岁（6-8岁）。我们期望至少1410 在2013年的儿童（70％的随访）中，母亲被录取了C/肥皂将进行一次研究访问 纳入肺和胃肠道健康的评估。我们将解决以下具体目标： 1）比较儿童期呼吸道发病的事件，特别是生理肺 损害，基于异常肺功能测试的主要综合结果，物理学 诊断哮喘或上一年7岁（6-8岁）的呼吸救援药物的使用 围产期暴露于辅助阿奇霉素与安慰剂（仅标准预防）之后 2）比较基于主要复合材料的儿童胃肠道（GI）发病率的事件 GI疾病（嗜酸性食管炎或IBD）的身体诊断结果或在A 围产期暴露后7岁（6-8）的同胞后代之间经过验证的GI问卷（罗马IV） 辅助阿奇霉素与安慰剂 这项研究是从美国大型试验中提供长期安全数据的唯一机会，以告知和 加强新​​建议使用辅助阿奇霉素进行剖宫产。