Exposures under investigation and exposure comparison groups
Exposure in first trimester of pregnancy to any macrolide (ATC code J01FA), and five specific macrolide subclass erythromycin (ATC code J01FA01), spiramycin (ATC code J01FA02), clarithromycin (ATC code J01FA09), azithromycin (ATC code J01FA10) and clindamycin (ATC code J01FF01)). Two types of exposure comparison groups were used: no antibiotic exposure during pregnancy (primary comparison) and exposure to drugs other than antibiotics, excluding vitamins and minerals (secondary comparison).
Macrolides are used as an alternative for pregnant women who are allergic to penicillins which is considered relatively safer compared to other types of antibiotics.13 Hence we performed sensitivity analyses for selected significant results using penicillins as the exposure comparison in order to account for any residual confounding due to infection. This approach has also been used in other studies.13,19,25