Corticosteroid use during pregnancy and risk of orofacial clefts

Background

The association between the risk of orofacial clefts in infants and the use of corticosteroids during pregnancy is unclear from the available evidence. We conducted a nationwide cohort study of all live births in Denmark over a 12-year period.

Methods

We collected data on all live births in Denmark from Jan. 1, 1996, to Sept. 30, 2008. We included live births for which information was available from nationwide health registries on the use of corticosteroids during pregnancy, the diagnosis of an orofacial cleft and possible confounders.

Results

There were 832 636 live births during the study period. Exposure to corticosteroids during the first trimester occurred in 51 973 of the pregnancies. A total of 1232 isolated orofacial clefts (i.e., cleft lip, cleft palate, or cleft lip and cleft palate) were diagnosed within the first year of life, including 84 instances in which the infant had been exposed to corticosteroids during the first trimester of pregnancy. We did not identify any statistically significant increased risk of orofacial clefts associated with the use of corticosteroids: cleft lip with or without cleft palate, prevalence odds ratio (OR) 1.05 (95% confidence interval CI] 0.80–1.38]; cleft palate alone, prevalence OR 1.23 (95% CI 0.83–1.82). Odds ratios for risk of orofacial clefts by method of delivery (i.e., oral, inhalant, nasal spray, or dermatologic and other topicals) were consistent with the overall results of the study and did not display significant heterogeneity, although the OR for cleft lip with or without cleft palate associated with the use of dermatologic corticosteroids was 1.45 (95% CI 1.03–2.05).

Interpretation

Our results add to the safety information on a class of drugs commonly used during pregnancy. Our study did not show an increased risk of orofacial clefts with the use of corticosteroids during pregnancy. Indepth investigation of the pattern of association between orofacial clefts and the use of dermatologic corticosteroids during pregnancy indicated that this result did not signify a causal connection and likely arose from multiple statistical comparisons.The anti-inflammatory and immuno-suppressive properties of corticosteroids in pharmacotherapeutic doses has a wide range of clinical uses, such as for the treatment of asthma, atopic dermatitis and other allergic conditions, autoimmune diseases and cancer. However, caution is warranted for the use of corticosteroid medications during pregnancy. Corticosteroid use during pregnancy has been associated with orofacial clefts in animals, and similar risks in humans are suspected.^1,2 The available epidemiologic evidence favours an association, but many of the studies that have been done have been limited by recall bias and a lack of statistical power. The association between risk of orofacial clefts and the use of corticosteroids during pregnancy remains unclear.^3–10We conducted a nationwide cohort study in Denmark with independent and prospective determination of corticosteroid use during pregnancy and the diagnosis of orofacial clefts. Our study comprised all live births from January 1996 to September 2008.