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: 10249196
• 负责人: Akila Subramaniam
• 金额: $ 64.63万
• 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 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10249196
• 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; 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; follow-up; functional disability; gastrointestinal; gastrointestinal function; global health; gut dysbiosis; hospital readmission; infant gut microbiome; intrapartum; male; microbiome research; neonatal death; neonatal morbidity; neonatal outcome; neurodevelopment; neurodevelopmental effect; obesity in children; obesity risk; offspring; overweight child; 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.

项目总结/文摘