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.
