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: 10089462
• 负责人: Akila Subramaniam
• 金额: $ 63.02万
• 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/10089462
• 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.

项目概要/摘要 “围产期接触阿奇霉素辅助预防后的儿童肺部及相关结果 剖宫产”是一项大型多中心非劣效性随访队列研究，旨在评估长期 围产期暴露后足月微生物组介导的儿童肺部和胃肠道 (GI) 影响 切口前辅助阿奇霉素与安慰剂（加标准头孢菌素）相比，可预防 剖宫产手术部位感染的母体 C/SOAP 辅助阿奇霉素随机试验。 (4/2011–11/2014) 表明孕产妇感染（子宫内膜炎和伤口）显着减少 感染）对阿奇霉素组的短期新生儿结局没有任何显着影响。 孕产妇感染（死亡的一个主要原因）的减少是如此显着，以至于阿奇霉素的使用被发现 节省成本——计划外剖腹产每次使用可节省约 360 美元，相当于 2.7 亿美元 然而，鉴于阿奇霉素辅助治疗的热情已经减弱。 阿奇霉素对新生儿肠道微生物群（菌群失调）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（哮喘、喘息、特应性、 2018 年 9 月，ACOG 建议“考虑”辅助治疗。 阿奇霉素，但强调需要研究其对微生物介导的长期结果的影响。 在这项研究中，我们将围产期阿奇霉素辅助暴露与标准暴露进行比较。 单独进行剖宫产预防与儿童肺部或胃肠道发病率增加无关（即非 我们建议对处于最佳目标的 C/SOAP 试验队列的后代进行长期随访研究。 在参与母体 C/SOAP 试验的 14 个站点中，年龄为 7 岁（范围为 6-8 岁），我们预计至少有 1410 人。 2013 名母亲参加 C/SOAP 的儿童（70% 的随访）将接受单次研究访视 我们将实现以下具体目标： 1) 比较儿童呼吸道疾病的发生率，特别是生理性肺疾病的发生率 损害，基于异常肺功能测试的主要复合结果，医生 7 岁时诊断出哮喘，或使用呼吸救援药物（范围 6-8） 围产期暴露于辅助阿奇霉素与安慰剂后（单独标准预防） 2) 根据主要综合指标比较儿童胃肠道 (GI) 发病率 医生诊断胃肠道疾病（嗜酸性食管炎或 IBD）的结果或评分异常 围产期暴露后 7 岁队列后代（范围 6-8）经过验证的 GI 问卷（罗马 IV） 阿奇霉素辅助治疗与安慰剂对比 这项研究是提供来自美国大型试验的长期安全数据的唯一机会，以告知和 加强新​​推荐的剖宫产辅助阿奇霉素的使用。