Case definition
Cases were defined as all LB, FD from 20 weeks gestational age, and TOPFA with CA types (corresponding to EUROCAT subgroups) which were signals identified from the literature, excluding those with a genetic syndrome (see Figure 2 and supplementary Table S1). We conducted a literature review of case-control and cohort studies reported in Medline and Reprotox databases from creation up to March 2016, to identify signals of specific CA associated with first trimester use of antibiotics. We defined a signal as a statistically significant result of increased risk, or a risk ratio ≥ 3, with at least two exposed cases in the first trimester.35 As this report focuses on macrolides, the signals identified for the macrolides up to 2016 are shown in Table 1.