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.