Maternal use of antibiotics and the risk of orofacial clefts: a nationwide cohort study

Purpose To study the association between antibiotic use in early pregnancy and the risk of isolated orofacial clefts. Methods We conducted a cohort study of 806 011 live births in Denmark from 1996 through September 2008. Individual-level information on prescribed antibiotics during pregnancy, orofacial cleft diagnosis, and possible confounders were ascertained from nationwide health registries. The main outcome measure was prevalence odds ratios (PORs) of orofacial clefts by exposure to antibiotics. Results Maternal use of any antibiotics in early pregnancy was not associated with an increased risk of cleft lip with or without cleft palate (CL/P) (POR, 1.08; 95% CI, 0.89-1.30) or cleft palate alone (CP) (POR, 1.14; 95% CI, 0.86-1.51). Further analyses of specific classes showed an increased risk of CL/P associated with 2nd month use of doxycycline/tetracycline (2 exposed cases; POR, 7.30; 95% CI, 1.81-29.46) and sulfamethizole (18 exposed cases; POR, 1.76; 95% CI, 1.10-2.81). An increased risk of CP was seen for first trimester use of trimethoprim (2 exposed cases; POR, 14.29; 95% CI, 3.46-59.05) and 3rd month use of pivmecillinam (9 exposed cases; POR, 2.34; 95% CI, 1.20-4.54). Conclusion Antibiotic use in early pregnancy was not a major risk factor for isolated orofacial clefts in our study. Some classes of antibiotics used in the critical period for development of CL/P and CP may increase the risk; however, other factors such as indications for use and chance may explain these findings. Copyright (C) 2011 John Wiley & Sons, Ltd.