The share of unscheduled cesarean deliveries in which patients received the antibiotic azithromycin rose from 2.2% to 39.6% over roughly a decade, and postpartum infections after those surgeries declined, according to an analysis of more than 1.6 million U.S. births published in JAMA. Researchers estimated that the change corresponded to roughly 6,000 fewer postpartum infections each year.
The study cannot prove the antibiotic caused the drop, but it suggests that results from a landmark 2016 clinical trial are showing up in everyday hospital care. The analysis tracked patients who received prenatal care and gave birth in health systems across all 50 states and Washington, D.C.
For expectant parents, especially those planning to labor, the finding points to a specific question worth raising before delivery. Cesarean deliveries performed after labor begins carry a higher infection risk than planned ones.
Uptake Rose from 2% to Nearly 40% After a 2016 Trial
The 2016 C/SOAP trial, published in the New England Journal of Medicine, tested a single dose of azithromycin added to standard pre-surgery antibiotics in 2,013 women having nonelective cesareans at 14 U.S. hospitals. Infections occurred in 6.1% of women who received azithromycin and 12.0% of those who received a placebo, a reduction of about half. The American College of Obstetricians and Gynecologists endorsed the practice in 2018, saying azithromycin should be considered for unscheduled cesarean deliveries.
The new analysis, led by researchers at Beth Israel Deaconess Medical Center in Boston, used Epic Cosmos, a large database of electronic health records. It compared births from January 2013 to September 2016 with births from January 2017 through December 2024, CIDRAP reported. Because the researchers could not reliably identify scheduled cesareans, they compared cesarean births with vaginal births.
Among cesarean births, azithromycin use rose from 2.2% to 39.6%. Use among vaginal births barely moved, going from 0.01% to 0.04%. After adjustment, the researchers attributed a 37.6-percentage-point increase to the period after the trial.
Infection Trends Moved in the Right Direction, with Caveats
Postpartum infections within six weeks of delivery fell from 9.2% to 8.0% after cesarean births, while they rose from 2.0% to 2.7% after vaginal births. Comparing those two trends produced an absolute reduction of 2.0 percentage points, or a 20% relative reduction.
Declines appeared across several infection types, including sepsis, surgical site infections, and endometritis, an infection of the uterine lining. Sepsis after cesarean delivery dropped from 1.8% to 0.9%, Medscape reported.
"The current study suggests that perioperative azithromycin use at the time of unscheduled cesarean delivery is associated with decreased infection in a large, real-world cohort outside the clinical trial setting that is representative of the US population," the authors wrote.
The design has clear limits. This was a difference-in-differences analysis of observational records, not a randomized trial, and other changes in obstetric care over 12 years may have contributed.
Fewer than half of the cesarean patients received azithromycin. The authors say that helps explain why the population-wide benefit was smaller than the 50% reduction seen in the trial.
Labor-Room Surgery Carries Higher Infection Stakes
Cesarean delivery is common. The CDC's National Center for Health Statistics reports 1,173,391 cesarean births in 2024, or 32.4% of all deliveries. Postpartum infection rates after cesareans range from 10% to 20% and are nearly twice as high for unscheduled procedures, according to the researchers.
Estimates of how many cesareans are unscheduled vary. The study team put the figure at about 30% of roughly 1 million cesarean births in 2024. The lead investigators of the 2016 trial, writing in an accompanying editorial, said up to 60% of U.S. cesarean deliveries are unscheduled and occur after labor begins.
"The current evidence indicates that failure to implement this strategy represents a missed opportunity to reduce preventable maternal morbidity and potentially mortality," the editorial authors wrote. They noted that even the modest relative reduction translates into thousands of infections prevented each year, along with fewer hospital readmissions and lower health care costs.
Antibiotic stewardship is also part of the picture. The CDC notes that any antibiotic use can cause side effects and contribute to antimicrobial resistance, although the benefits outweigh those risks when antibiotics are needed.
Questions Expectant Parents Can Raise Before Delivery
Parents do not need to request a specific drug, since the decision belongs with the delivery team. Still, it is reasonable to ask at a prenatal visit which antibiotics the hospital uses if an unplanned cesarean becomes necessary and whether azithromycin is part of that plan. People with a known allergy to azithromycin or related antibiotics should mention it early. Because hospitals set these protocols in advance, asking before labor gives the most useful answer.
After delivery, watch for fever, worsening pain, unusual discharge, or redness, swelling, or drainage at the incision. Those symptoms warrant a prompt call to the care team. Confusion, a racing heart, clammy skin, or shortness of breath can signal sepsis and require emergency care.
Practice still varies. The published summaries did not break down azithromycin use by state or health system, so families cannot tell from these reports how their local hospital compares. The editorial authors say the findings strengthen the case for more consistent use.
Current guidance has not changed. Adjunctive azithromycin for unscheduled cesareans has been an endorsed option since 2018, and this analysis adds real-world support without settling cause and effect.
Key Questions Answered
What did the study find?
Azithromycin use during unscheduled cesareans rose from 2.2% to 39.6%, while postpartum infections after cesarean births fell from 9.2% to 8.0%. The researchers estimated about 6,000 fewer infections a year.
Does this prove azithromycin caused the decline?
No, because the study used observational records rather than random assignment. Other changes in obstetric care may also have contributed.
Why are unscheduled C-sections riskier?
Postpartum infection rates are nearly twice as high after unscheduled cesareans as after planned ones, according to the researchers. That higher risk is why the 2016 trial focused on nonelective procedures.
Should I ask for azithromycin?
The choice belongs to the delivery team, but it is reasonable to ask what antibiotics the hospital uses for unplanned cesareans. Share any antibiotic allergies in advance.
What signs of infection should new parents watch for?
Fever, worsening pain, unusual discharge, or redness and drainage at the incision warrant a call to the care team. Confusion, a racing heart, or trouble breathing needs emergency care.
How common are C-sections in the U.S.?
The CDC reports 1,173,391 cesarean births in 2024, or 32.4% of deliveries. Estimates of the unscheduled share range from about 30% to as high as 60%.
