(29) Childhood Obesity and Other Outcomes in Offspring Exposed to Adjunctive Azithromycin from the C/SOAP Trial

Objective:
In the Cesarean Section Optimal Prophylaxis (C/SOAP) trial, azithromycin (AZI) reduced puerperal infections by 50% compared to placebo (patients in both groups received standard cesarean antibiotic prophylaxis). However, concerns about AZI’s effect on the neonatal microbiome and thus, long-term childhood health persist. As such, we compared childhood health outcomes in offspring from the C/SOAP trial after perinatal exposure to AZI versus placebo.

Study Design:
We performed a non-inferiority (NI) prospective follow-up study (from Jan 2021-July 2025) assessing health in children aged 7-14 of women enrolled in the original C/SOAP trial (2011-14).  Children were compared by exposure to AZI or placebo. Our primary outcome was childhood obesity (BMI ≥95th percentile for age/sex). Secondary outcomes included select adverse respiratory and gastrointestinal (GI) outcomes. Risk differences (RD), with 95% confidence intervals [CI] were calculated and evaluated using a NI margin (NIM) of 10%. Multivariable analyses were planned a priori to adjust for known potential confounders.

Results:
Of the 2,013 participants from C/SOAP, 1,990 were eligible for follow-up, and 1,024 were successfully contacted. Of those contacted, 505 children of these participants (49.3%) enrolled: 255 (50.5%) exposed to AZI and 250 (49.5%) placebo. Characteristics were similar between groups (Table 1). The rate of childhood obesity in the AZI group was non-inferior (adjusted RD -10.4% [-20% to -0.8%]; [-0.8% < NIM 10%]) and potentially lower than placebo (26.7% AZI vs 34.4% placebo). Non-inferiority was also observed for almost all secondary outcomes (upper CI bounds < 10% NIM, Table 2). Of note, microbiome-mediated GI disorders were significantly lower in the AZI group.

Conclusion:
In this C/SOAP follow-up study, adjunctive AZI for cesarean prophylaxis was non-inferior to placebo in terms of rate of childhood obesity and other microbiome-mediated disorders. Despite the low follow-up and pending respiratory (spirometry) and neurodevelopment data; these findings are reassuring regarding child health outcomes after perinatal exposure to AZI.