Azithromycin is generally considered one of the safer antibiotics to use during pregnancy, and the CDC recommends it as the preferred treatment for chlamydia in pregnant women. That said, the evidence isn’t perfectly clean. Multiple large studies show no clear increase in birth defects when azithromycin is used during the first trimester, but a few have flagged small, borderline signals that keep researchers from calling it completely risk-free.
If your doctor prescribed azithromycin while you’re pregnant, here’s what the research actually shows and what’s worth knowing.
What the Birth Defect Data Shows
The biggest concern with any medication in pregnancy is whether it increases the chance of birth defects, especially when taken during the first trimester, when organs are forming. Several large studies have looked at this specifically for azithromycin, and the results are reassuring overall, though not unanimous.
Two prospective studies following pregnant women who took azithromycin found a major malformation rate of about 3.4%, which is within the normal background rate for any pregnancy (typically 2% to 4%). Neither study found a statistically significant difference compared to women who didn’t take the drug. A large 2021 register-based study covering over 1.1 million pregnancies in Scandinavia found no increased risk at all, with macrolide-exposed pregnancies actually showing a slightly lower rate of birth defects than unexposed ones.
On the other hand, a 2019 population-wide study of over 900,000 deliveries did find a small, statistically significant increase in malformations among women exposed to macrolide antibiotics (a category that includes azithromycin, erythromycin, and others). And a large meta-analysis pooling data from over 228,000 participants found a borderline 13% increase in risk that just barely missed statistical significance. When researchers have isolated azithromycin specifically from the broader macrolide group, no significant association with birth defects has been found compared to penicillin-type antibiotics.
The bottom line: the data leans toward azithromycin not causing birth defects, but the picture isn’t completely settled because some of the larger studies lump it together with other macrolides that may carry different risk profiles.
Stillbirth and Miscarriage Risk
A meta-analysis pooling seven studies found a 39% higher rate of stillbirth among pregnancies exposed to azithromycin. That sounds alarming, but the finding was not statistically significant, meaning it could easily be due to chance. The number of stillbirth cases in the analysis was small, and some fetal deaths may have been misclassified between miscarriage and stillbirth categories, muddying the data further.
One prospective study tracking 123 women who took azithromycin found a spontaneous miscarriage rate of 4.9%, which was not significantly different from the comparison group. A separate systematic review found that macrolides as a class were associated with a higher risk of miscarriage compared to other antibiotics, but did not find an increased risk of stillbirth or neonatal death. These mixed signals mean the stillbirth question remains open but is not strongly supported by current evidence.
Why Doctors Still Prescribe It
The CDC’s 2021 STI treatment guidelines list azithromycin as the recommended treatment for chlamydia during pregnancy: a single 1-gram oral dose. This is notable because chlamydia left untreated in pregnancy can cause preterm birth, low birth weight, and serious eye and lung infections in the newborn. The alternative, amoxicillin, requires taking pills three times daily for seven days, which makes it harder to complete.
Azithromycin also becomes the go-to option when a pregnant woman needs treatment for certain other infections where the usual first-line drugs (like doxycycline) are unsafe in pregnancy. For a condition called lymphogranuloma venereum, for instance, the standard treatment is doxycycline for 21 days, but since doxycycline can harm fetal bone and tooth development, azithromycin is the practical substitute.
In these situations, the risk of the untreated infection typically outweighs the small, uncertain risks associated with the antibiotic itself.
How It Compares to Other Macrolides
Azithromycin belongs to a family of antibiotics called macrolides, which also includes erythromycin and clarithromycin. Among these, azithromycin appears to have the most favorable safety profile in pregnancy. When studies have broken out results by individual drug rather than lumping the whole class together, azithromycin consistently shows no significant link to birth defects compared to penicillins.
Clarithromycin, by contrast, has raised more concern. Some studies have found higher rates of miscarriage with clarithromycin, and it is generally avoided during pregnancy when alternatives exist. Erythromycin has a longer track record of use in pregnancy and is considered relatively safe, but it causes more gastrointestinal side effects than azithromycin and requires multiple daily doses.
A Possible Link to Pyloric Stenosis
One specific concern that has been studied is whether macrolide exposure before birth increases the risk of infantile hypertrophic pyloric stenosis, a condition where the muscle controlling the stomach’s outlet thickens and blocks food from passing into the small intestine. It typically shows up in the first few weeks of life and requires surgery to correct.
A systematic review and meta-analysis found that prenatal macrolide exposure was associated with a 47% higher risk of pyloric stenosis in cohort studies, though the overall pooled result across all study types was not statistically significant. The evidence is not conclusive, and the absolute risk of pyloric stenosis is low to begin with (roughly 2 to 3 per 1,000 births in the general population), so even a modest increase in relative risk translates to a very small increase in absolute terms.
What This Means for You
Azithromycin is not a medication to take casually during pregnancy, but it is one that major health agencies actively recommend for specific infections when the benefit is clear. The weight of evidence from studies covering hundreds of thousands of pregnancies suggests it does not meaningfully increase the risk of birth defects when taken in the first trimester. The signals around stillbirth and pyloric stenosis are weak and inconsistent.
If you’ve already taken azithromycin during pregnancy, the data should be reassuring. If you’ve been prescribed it and are hesitant, the key question is what infection is being treated and whether a safer alternative exists for your specific situation. For chlamydia, azithromycin remains the standard of care in pregnancy precisely because the risks of skipping treatment are well-documented and serious, while the risks of the drug itself remain small and uncertain.