Adjunctive azithromycin for caesarean delivery reduces obesity in offspring

Children born to mothers who received adjunctive azithromycin prophylaxis for caesarean delivery are less likely to become obese later in life than their counterparts who received a placebo, according to the follow-up study of the C/SOAP* trial presented at SMFM 2026.

In the parent C/SOAP trial, women who underwent a caesarean delivery and received azithromycin had a 50-percent reduction in the risk of composite maternal infection within 6 weeks postpartum compared with those on placebo. [N Engl J Med 2016;375:1231-1241]

However, concerns regarding the impact of azithromycin on long-term neonatal outcomes remain, said lead author Dr Akila Subramaniam from the Center for Research in Women’s Health, University of Alabama at Birmingham, Alabama, US.

Hence, the researchers conducted a prospective follow-up study involving 506 children (mean age 10 years) whose mothers had participated in the original C/SOAP trial from 2011 to 2014. Children were categorized by exposure to azithromycin 500 mg IV (n=256) or placebo (n=250).

Despite the high obesity rates observed at follow-up, infants born to mothers exposed to azithromycin had a lower rate of childhood obesity, defined as BMI >95th percentile for age/sex, compared with those exposed to placebo (27 percent vs 35.2 percent), corresponding to an adjusted risk difference of -9.7 percent (confidence interval [CI], -19.1 to -0.2). [SMFM 2026, abstract 29]

In addition, the rate of childhood overweight (BMI >85th percentile) was slightly lower in the azithromycin group than the placebo group (40.6 percent vs 41.6 percent), with an adjusted risk difference of -1.4 percent (CI, -10.9 to 8.2).

These findings indicated that azithromycin was noninferior to placebo regarding childhood obesity and overweight status, said Subramaniam.

With regard to secondary outcomes, respiratory morbidity—including clinical diagnosis of asthma (17.6 percent vs 16.8 percent), any prescription for asthma medication (22.3 percent vs 23.2 percent), positive asthma screening (14.5 percent vs 15.2 percent), and a history of respiratory illness (3.5 percent vs 4 percent)—was comparable between the azithromycin and placebo groups.

On the other hand, a higher rate of respiratory symptoms, such as coughing, wheezing, or shortness of breath, was observed with azithromycin than with placebo (23.4 percent vs 15.6 percent; adjusted risk difference, 7.6 percent, CI, -0.2 to 15.3), which Subramaniam said was the only outcome not demonstrating noninferiority for azithromycin.

The prevalence of other outcomes, including atopic disease (6.3 percent vs 7.2 percent; adjusted risk difference, -2.6 percent) and gastrointestinal disorder (3.5 percent vs 8 percent; adjusted risk difference, -5.5 percent), was lower among infants exposed to azithromycin compared with those exposed to placebo.

In this C/SOAP follow-up study, “adjunctive azithromycin for caesarean prophylaxis was noninferior to placebo in terms of childhood obesity and other microbiome-mediated disorders,” said Subramaniam.

“Despite the low follow-up and pending respiratory (spirometry) and neurodevelopmental data, these findings are reassuring for safety regarding child health after perinatal exposure to azithromycin for preoperative caesarean prophylaxis in labouring women,” she emphasized.