When used in early pregnancy, many classes of common antibiotics are associated with an increased risk of miscarriage, according to a study published Monday in the Canadian Medical Association Journal.
Macrolides, quinolones, tetracyclines, sulfonamides and metronidazole were related to higher rates of pregnancy loss, the researchers say. However, a greater chance of pregnancy loss was not seen with the most frequently used antibiotics, including penicillin.
"It is reassuring to see that first-line treatments and antibiotics that are the most used in the population (penicillin, cephalosporin) were not associated with an increased risk of miscarriage," Dr. Anick Bérard, lead researcher and a member of the Faculty of Pharmacy at the Université de Montréal, wrote in an email.
Nitrofurantoin -- often used to treat urinary tract infections -- and erythromycin -- prescribed for respiratory and skin infections as well as chlamydia, pelvic inflammatory disease and syphilis -- also were not linked to a higher risk of pregnancy loss. Erythromycin is also given to pregnant women to prevent Group B streptococcal infection in newborns.
Doctors do not prescribe tetracyclines during pregnancy because of concerns over birth defects, and quinolones are commonly avoided as well. Macrolides are often prescribed when penicillin cannot be used to fight streptococcal and pneumococcal infections. Suflonamides treat urinary tract infections, ear infections, bronchitis and eye infections. Metronidazole is used on infections of the vagina, stomach, skin, joints and respiratory tract.
Risk is 'small'
In 2013, Danish researchers reported a connection between the antibiotic clarithromycin and miscarriage.
"Repetition of findings are essential in order to assess causality," Bérard said, explaining that antibiotic prescribing patterns differ from country to country, so it is important to look at this research question from the perspective of various patient populations.
Bérard and her team looked at data from the medical records of women in the Quebec Pregnancy Cohort between 1998 and 2009. Covered under Quebec's drug insurance plan, participants ranged in age from 15 to 45 years old.
Bérard's research team compared pregnancy outcomes when different types of antibiotics were prescribed in early pregnancy.
Bérard and her team found 8,702 cases of diagnosed spontaneous abortions, occurring on average at 14 weeks of pregnancy. The team compared these with 87,020 pregnancies in which a miscarriage did not occur.
Of the women who miscarried, 16.4% (1,428 women) had taken antibiotics during early pregnancy, compared with 12.6% (11,018) of the women who had not taken them. Antibiotic use was defined by filled prescriptions.
"Our study looked at antibiotics exposure during early pregnancy only," Bérard noted.
Generally, when a woman does not take antibiotics during pregnancy, her risk of a miscarriage is approximately 6% to 7%. In the study, women who took certain antibiotics in early pregnancy had an increased risk of 9% to 10%.
"The risk remains small," Bérard said.
Decreased risk of miscarriage
The women who miscarried were more likely to be older, to be living alone and to have multiple health issues and infections, all of which were taken into account when calculating the increased risk for women taking antibiotics. Despite the care taken with the calculations, Bérard noted that the infections themselves could contribute to pregnancy loss and therefore explain some of the increased risk.
"With the exception of nitrofurantoin, our findings confirm results from previous studies," Bérard said.
"We also found that nitrofurantoin, mostly used to treat urinary tract infections, are actually decreasing the risk of miscarriage," she said. This result needs to be replicated by other studies and research, she said, given that hers is the first research team to show this.
The result showing that quinolone and tetracycline are associated with an increased risk of miscarriage is "concordant with guidelines that say that they should not be used during pregnancy," Bérard noted.
"The take-home message is that infections need to be treated during pregnancy," she said, adding that women should discuss the best treatment option for an infection with their health care providers.
Dr. Sharmila Makhija, professor and university chairwoman in the Department of Obstetrics & Gynecology and Women's Health at Albert Einstein College of Medicine and Montefiore Health System, described the new study as "a comprehensive analysis of additional classes of commonly used antibiotics in pregnancy."
Although overall, the design of the study was strong, Makhija and the authors themselves acknowledge a weakness in that there were low numbers in some of the comparison groups of patients.
According Dr. R. Phillips Heine, member of the American College of Obstetricians and Gynecologists' Committee on Obstetric Practice, it's "unfortunate" that the study was published in its current form. In an email, Heine wrote that the study's finding were overstated and that the authors did not provide a good discussion of the limitations of the research.
"One major concern is that many of these antibiotics -- tetracycline, (doxycycline, a type of tetracycline) and the quinolones -- are not used in known pregnancies. This implies that the pregnancies were early and were missed by the prescribing clinician," Heine said.
"Many of the antibiotics that were associated with abortion are not used in obstetrics," he noted.
The safety of any particular antibiotic depends on a patient's individual diagnosis, according to the American College of Obstetricians and Gynecologists, which does not provide a list of antibiotics that are safe during pregnancy but instead offers guidance for health care providers.