Doxycycline in first trimester pregnancy increases miscarriage risk

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Taking doxycycline, a commonly prescribed antibiotic, during the first trimester of pregnancy may increase the risk of pregnancy loss, a new study suggests.

The antibiotic is broad-spectrum, meaning it targets a wide range of bacteria. It's often used to treat acne, respiratory infections and sexually transmitted infections, such as chlamydia and syphilis. Doctors generally avoid prescribing the drug during the second and third trimesters because it belongs to a class of antibiotics that can bind to calcium in developing bones. Animal studies suggest that this may disrupt fetal bone development.

However, evidence on doxycycline's safety during early pregnancy has been mixed and limited. The new study, published Tuesday (Nov. 10) in the journal Annals of Internal Medicine , provides clearer evidence of a link between doxycycline use in the first trimester and pregnancy loss.

"I would advise physicians to carefully consider the benefit-risk balance when prescribing doxycycline to women who are pregnant or planning a pregnancy," study first author Almut Winterstein , a pharmacist and drug-safety researcher at the University of Florida, told Live Science in an email.

A higher risk than other antibiotics

Using information from two U.S. insurance databases, the researchers analyzed 224,870 pregnancies in people ages 12 to 55. More than 218,230 of these patients were treated for respiratory tract infections, and over 6,630 were treated for acne, between conception and the end of the first trimester. About 4,385 of the women filled a prescription for doxycycline during that time frame, while the others received an alternative antibiotic.

Among women with respiratory infections, those prescribed doxycycline had a 40% to 54% higher risk of pregnancy loss, compared with those prescribed amoxicillin, another broad-spectrum antibiotic in a different class. The exact level of risk varied between the two databases.

The researchers also compared the doxycycline users against women prescribed macrolides, the class of antibiotics that includes azithromycin (or "Z-Pak"). Again, the doxycycline users saw a higher risk — 39% and 36% higher, respectively.

Among the patients treated for acne, doxycycline users had a 49% higher risk of pregnancy loss in one database than those given the antibiotic clindamycin. In the second database, though, the difference wasn't statistically significant. Winterstein said that may be because there were fewer patients included in that analysis.

Overall, doxycycline was associated with seven to 11 additional pregnancy losses per 100 pregnancies, compared with the other antibiotic options assessed, the researchers reported.

The researchers examined the risk associated with taking various antibiotics in the first 12 weeks of pregnancy. (Image credit: MementoJpeg via Getty Images) What drives the risk?

It is not yet clear how the drug might contribute to pregnancy loss. Because the study was observational, it cannot prove that the antibiotic itself caused those losses, which included miscarriages and stillbirths. (Miscarriage is pregnancy loss before 20 weeks of pregnancy, whereas stillbirth refers to pregnancy loss after the 20th week.)

Animal studies hint that doxycycline could interfere with early placental development, potentially making it harder for the placenta to support a growing pregnancy, Luke Grzeskowiak , an associate professor and clinical pharmacist at Flinders University in Australia who was not involved in the study, said in an email.

The study authors also noted in their report that the drug may have direct effects on the developing embryo. But these explanations remain hypothetical; the researchers have not established that either mechanism occurs in humans.

"Pregnancy loss affects around one in four pregnancies and can happen for many reasons," Grzeskowiak noted. Although doxycycline exposure may add to that risk, taking the antibiotic does not necessarily mean pregnancy loss will occur. The available data suggests that it is just one risk factor among many.

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Because doxycycline may be prescribed before a pregnancy is recognized, doctors should consider the possibility of pregnancy when prescribing this drug to women of reproductive age, particularly those who are sexually active, Grzeskowiak suggested. That does not mean doctors should avoid prescribing the antibiotic to these women, he emphasized; rather, clinicians should consider pregnancy plans and medical history when choosing a treatment.

In some cases, doxycycline may still be the best option for a severe infection, Winterstein told Live Science, and that infection could itself put a pregnancy at risk. But for less-serious infections, safer alternatives may be available, she said.

This article is for informational purposes only and is not meant to offer medical advice.