Childhood follow-up study of obesity and neurodevelopment after perinatal exposure to adjunctive azithromycin prophylaxis for cesarean delivery

剖宫产围产期暴露于阿奇霉素辅助预防后肥胖和神经发育的儿童期随访研究

• 批准号: 10028725
• 负责人: Akila Subramaniam
• 金额: $ 74.43万
• 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: 2020-07-20 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10028725
• 关键词: 7 year old; Accounting; Address; Adoption; Adverse effects; Age; American College of Obstetricians and Gynecologists; Antibiotic Prophylaxis; Antibiotics; Asthma; Award; Azithromycin; Biometry; Birth; Breast Feeding; Budgets; Cause of Death; Cefazolin; Cephalosporins; Cerebral Palsy; Cesarean section; Cessation of life; Child; Childbirth; Childhood; Cohort Studies; Companions; Complement; Cost Savings; Data; Diet; Dose; Endometritis; Enrollment; Exposure to; Follow-Up Studies; Functional disorder; Funding; Future; Grant; Growth; Half-Life; Health; Health Care Costs; Health Policy; Human Milk; Immune; Incidence; Infection; Infection prevention; Inflammatory; Intervention; Life; Longitudinal Studies; Longterm Follow-up; Lung; Macrolides; Maternal Mortality; Measures; Mediating; Metabolic; Methods; Mothers; Motor; National Institute of Child Health and Human Development; Neurodevelopmental Impairment; Newborn Infant; Obesity; Operative Surgical Procedures; Outcome; Overweight; Parents; Perinatal; Perinatal Exposure; Placebos; Population; Postoperative Period; Prophylactic treatment; Puerperal Infection; Recommendation; Reporting; Research Design; Risk; Risk Factors; Safety; Savings; Site; Surgical Wound Infection; Surgical incisions; United States National Institutes of Health; Visit; Weight Gain; Woman; Wound Infection; aged; antimicrobial; authority; base; behavioral impairment; biobank; biophysical properties; cognitive ability; cohort; dysbiosis; follow-up; functional disability; gastrointestinal; gastrointestinal function; global health; hospital readmission; infant gut microbiome; intrapartum; male; microbiome research; neonatal death; neonatal morbidity; neonatal outcome; neurodevelopment; neurodevelopmental effect; obesity in children; obesity risk; offspring; placental transfer; prenatal; prenatal exposure; prevent; primary outcome; pulmonary function; randomized trial; respiratory; response; social factors; trial design

PROJECT SUMMARY/ABSTRACT We propose a large multi-center non-inferiority follow-up cohort study designed to evaluate long-term obesity/growth and neurodevelopment after perinatal exposure to adjunctive azithromycin as compared with placebo (plus standard cephalosporin) 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/unscheduled cesarean and $270 million/year in US healthcare costs. However, enthusiasm for adjunctive azithromycin has been tempered given reports of changes induced by azithromycin on the newborn gut microbiome that may be associated with childhood weight gain/obesity and neurodevelopmental impairment. In September 2018, ACOG suggested “consideration” of adjunctive azithromycin, but emphasized the need for studies of its effect on long-term childhood outcomes. In response to these concerns, we proposed an R01 study evaluating pulmonary and gastrointestinal (GI) health after perinatal azithromycin exposure (6th percentile score). Reviewers emphasized the need to evaluate obesity/growth and neurodevelopment (NIH officers advised a separate application due to cap limitations). Thus, in this proposal, we hypothesize that perinatal exposure to adjunctive azithromycin compared to standard cesarean prophylaxis alone is not associated with increased risk of obesity/weight gain or neurodevelopmental impairment (i.e. is non-inferior). We propose a follow-up study of the offspring of the C/SOAP trial cohort at target age of 7 years (range 6-9) at the 14 sites in the parent 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 growth/biometry and neurodevelopment assessments to address the following specific aims: 1) To compare the incidence of obese/overweight children (primary outcome), and other biophysical measurements, between cohort offspring aged 7 (range 6-9 years) after perinatal exposure to adjunctive azithromycin versus placebo (standard prophylaxis alone) 2) To compare neurodevelopmental outcomes including cognitive ability (primary outcome), functional and behavioral impairment, and motor proficiency, between cohorts at age 7 (range 6-9 years) after perinatal exposure to adjunctive azithromycin versus placebo This study, along with the companion study evaluating pulmonary and GI outcomes (award notice pending), is the only opportunity to efficiently provide comprehensive 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 我们提出了一项大型多中心非劣效性随访队列研究，旨在评估长期 与围产期暴露于辅助阿奇霉素后的肥胖/生长和神经发育相比 安慰剂（加上标准头孢菌素）以预防剖腹产时手术部位感染。 C/SOAP 辅助阿奇霉素的随机试验 (4/2011–11/2014) 表明， 母体感染（子宫内膜炎和伤口感染）对短期新生儿没有任何显着影响 阿奇霉素组的产妇感染（死亡的主要原因）的减少非常明显。 值得注意的是，使用阿奇霉素可以节省成本 – 节省约 360 美元/计划外剖腹产和 270 美元 然而，人们对阿奇霉素辅助治疗的热情已经减弱。 给出了阿奇霉素对新生儿肠道微生物群引起的变化的报告，这些变化可能与 2018 年 9 月，ACOG 提出儿童体重增加/肥胖和神经发育障碍。 “考虑”辅助阿奇霉素，但强调需要研究其对长期的影响 为了回应这些担忧，我们提出了一项评估肺部和儿童结局的 R01 研究。 围产期阿奇霉素暴露后胃肠道 (GI) 健康（第 6 个百分位数评分）。 需要评估肥胖/生长和神经发育（NIH 官员建议单独申请，因为 因此，在本提案中，我们追求围产期阿奇霉素的辅助暴露。 与标准剖宫产预防相比，单独预防与肥胖/体重增加风险增加无关 或神经发育障碍（即非劣等）。 我们预计母试验的 14 个地点的 C/SOAP 试验队列的目标年龄为 7 岁（范围 6-9 岁）。 2013 名母亲参加 C/SOAP 的儿童中的 1410 名（70% 随访）将接受一项研究 访问结合生长/生物测量和神经发育评估来实现以下具体目标： 1) 比较肥胖/超重儿童的发生率（主要结果）和其他生物物理指标 围产期暴露于 7 岁队列后代（范围 6-9 岁）之间的测量 阿奇霉素辅助治疗与安慰剂对比（单独标准预防） 2) 比较神经发育结果，包括认知能力（主要结果）、功能和 7 岁组（范围 6-9 岁）之间的行为障碍和运动能力 围产期阿奇霉素辅助暴露与安慰剂对比 这项研究以及评估肺部和胃肠道结果的配套研究（奖励通知待定）是 这是有效提供来自美国大型试验的全面长期安全数据的唯一机会 并加强新推荐的剖宫产辅助阿奇霉素的使用。