Largest cohort study to examine risk by antibiotic class and type
by Molly Walker, Staff Writer, MedPage Today July 19, 2017
• Several common types of antibiotics were linked both to major congenital and to organ specific malformations in infants when taken during the first trimester of pregnancy.
• Note that exposure to clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin, increased the risk of these birth defects, although there was no increased risk of major congenital malformations linked to exposure to amoxicillin, cephalosporins, or nitrofurantoin.
Several common types of antibiotics were linked both to major congenital and to organ specific malformations in infants when taken during the first trimester of pregnancy, a retrospective Canadian cohort study found.
Exposure to antibiotics, such as clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin, increased the risk of these birth defects, reported Flory T. Muanda, MD, of the University of Montreal, and colleagues.
However, there was no increased risk of major congenital malformations linked to exposure to amoxicillin, cephalosporins, or nitrofurantoin, the authors wrote in the British Journal of Clinical Pharmacology.
They added that while animal studies showed a link between exposure to certain antibiotics, those results could not be extrapolated to humans, and characterized the evidence from human studies on the subject as “inconclusive,” with conflicting results about the link between major congenital malformations in the fetus and the safety of certain antibiotics.
But to their knowledge, they said, “this is the largest cohort study investigating the risk of [major congenital] … [and] organ specific malformations associated with the use of antibiotic classes and types during pregnancy.”
Researchers examined data from the Quebec pregnancy cohort, an ongoing population-based cohort with data on all pregnancies covered by Quebec Public Prescription Drug Insurance from 1998 to 2008, comprising about 140,000 infants.
Exposure to antibiotics was defined as having filled at least one prescription for any type of antibiotics within the first trimester or a prescription for antibiotics before pregnancy, which overlapped the early part of pregnancy. Major congenital malformations were defined according to ICD-9 and ICD-10 codes.
Overall, 15,469 pregnancies (11%) were exposed during the first trimester. Almost 60% of antibiotics users were exposed to penicillins only, followed by 15% exposed to macrolides only, and 6.5% to cephalosporins only.
The authors found that users of antibiotics were more likely to be welfare recipients, less educated, living alone, and have more comorbidities and infections than those not exposed to antibiotics.
Ofloxacin had more than an eight-fold increased risk of major congenital malformations (adjusted OR 8.30, 95% CI 1.60-43.00), although this was on the basis of just three cases, hence the wide confidence interval.
Clindamycin was linked with an increased risk in these malformations with 60 cases seen (adjusted OR 1.34, 95% CI 1.02-1.77).
Organ specific malformations varied by antibiotic exposure. Both clindamycin and doxycycline were linked with increased risk of ventricular/atrial septal defects (adjusted OR 1.67, 95% CI 1.12-2.48, 29 exposed cases and adjusted OR 3.19, 95% CI 1.57-6.48, eight exposed cases, respectively).
Doxycycline was linked with an increase in other cardiovascular malformations, such as circulatory system malformations (adjusted OR 2.38, 95% CI 1.21-4.67, nine exposed cases) and cardiac malformations (adjusted OR 2.46, 95% CI 1.21-4.99, eight exposed cases).
The authors noted that the findings for doxycycline were consistent with a previous study suggesting increased risk of heart defects associated with tetracyclines.
Their findings for clindamycin were novel, however, as no previous studies have investigated the risk of malformations with the use of this antibiotic, they said. But prior research found nitrosatable drugs, such as clindamycin, linked to an increased risk of many congenital malformations, including heart malformations.
The authors also found that phenoxymethylpenicillin was linked with an increased risk of nervous system malformations (adjusted OR 1.85, 95% CI 1.01-3.39, 11 exposed cases), while erythromycin exposure was linked to a higher risk of urinary system malformations (adjusted OR 2.12, 95% CI 1.08-4.17), and moxifloxacin was associated with an increased risk of respiratory system malformations (adjusted OR 5.48, 95% CI 1.32-22.76, two exposed cases).
Limitations include potential unmeasured confounders, such as smoking, folic acid and alcohol intake, as well as that the study was underpowered to detect associations between individual antibiotics and specific malformations due to the low number of cases.
They concluded that, despite the small absolute risks associated with these birth defects, “physicians should consider prescribing safer antibiotics for the treatment of maternal infections when possible.”
This study was supported in part by grants from the Canadian government.
Muanda disclosed financial support from the University of Montreal and the Canadian Network for Advanced Interdisciplinary Methods for comparative effectiveness research.
One co-author disclosed being the endowment Research Chair of the Famille Louis Boivin on Medications, Pregnancy and Lactation at the Faculty of Pharmacy at the University of Montreal and being a consultant for plaintiffs in litigations involving antidepressants with birth defects.