This analysis used data from the Quebec pregnancy cohort and included 139,938 liveborn singletons. As the analysis aimed to compare pregnancies exposed to only one class of antibiotics, those exposed to multiple antibiotics or to other anti-infective drugs were excluded. Exposure was defined as having filled a prescription for any type of antibiotic within the first trimester of pregnancy (total 15,469 pregnancies; 11%). Eight specific organ system major congenital malformations (MCMs) diagnosed during the first year of life were investigated (13,852 diagnosed; 9.9%).
The most common antibiotic classes (penicillins, macrolides, cephalosporins, quinolones and urinary anti-infectives) were not associated with an increased risk of MCMs overall; only the “other antibacterials” group were (OR 1.34; 95% CI 1.01-1.76). However some classes were associated with organ-specific malformations. For example macrolide exposure was associated with an increased risk of digestive system malformations (1.46; 1.04-2.06; 35 exposed cases) and quinolone exposure increased the risk of urinary system malformations (1.89; 1.09-3.28; 14 exposed cases).
The following were the main findings associated with individual antibiotics:
· Clindamycin exposure was associated with an increased risk of MCMs (adjusted OR 1.34; 95% CI 1.02-1.77; 60 exposed cases), musculoskeletal system malformation (1.67; 1.12-2.48; 29 exposed cases) and ventricular/atrial septal defect (1.81; 1.04-3.16; 13 exposed cases)
· Ofloxacin exposure was associated with an increased risk of MCMs (8.3; 1.6-43; 3 exposed cases)
· Phenoxymethylpenicillin exposure was associated with an increased risk of nervous system malformations (1.85; 1.01-3.39; 11 exposed cases)
· Erythromycin exposure was associated with an increased risk of urinary system malformations (2.12; 1.08-4.17; 9 exposed cases)
· Moxifloxacin was associated with an increased risk of respiratory system malformations (5.48; 1.32-22.76; 2 exposed cases)
· Doxycycline was associated with an increased risk of circulatory system malformation (2.38; 1.21-4.67; 9 exposed cases), cardiac malformations (2.46; 1.21-4.99; 8 exposed cases) and ventricular/atrial septal defect (3.19; 1.57-6.48; 8 exposed cases)
Amoxicillin, cephalosporins and nitrofurantoin were not associated with an increase in the risk of MCMs overall or any organ-specific malformation.
As the authors highlight, the results of many of these analyses should be interpreted with caution due to the small number of exposed cases. In addition there was missing information on potentially important confounders such as smoking, folic acid and alcohol intake, and despite adjustment for many potential confounders, the possibility of residual confounding cannot be ruled out.
The authors comment that although the absolute risks remain small (e.g. a 67% increase in risk of musculoskeletal system malformations if exposed to clindamycin would translate to an increase in the absolute risk from 1.3% to 2.1%), physicians should consider prescribing safer antibiotics for maternal infections, where possible, until more data are available.