Corticosteroid Use and Risk for Orofacial Clefts EDITORIAL COMMENT

Orofacial clefts are one of the most common birth defects, with a worldwide prevalence of 1.7 per 1000 live births. Epidemiologic studies have reported inconsistent results regarding an association between corticosteroid use in early pregnancy and delivering an infant with an orofacial cleft. Although corticosteroids are used in women of reproductive age for many common conditions, the safety of these medications during pregnancy is uncertain. The authors previously reported that maternal corticosteroid use was associated with an increased risk for cleft lip with or without palate (CLP) but not cleft palate only (CPO) in deliveries in 1997 to 2002. Since that report, the pertinent population has more than doubled, allowing the largest study of corticosteroids and clefts to date. The aim of the present study was to assess the association using larger and more recent data from the National Birth Defects Prevention Study (NBDPS). Information on deliveries in 1997 to 2009 was collected from 10 centers. Infants or fetuses with CLP or CPO were considered cases and analyzed separately. Cases were considered isolated if there were no accompanying major unrelated birth defects or as nonisolated if more than 1 additional major unrelated defect was present. Live-born control infants without birth defects were randomly selected from birth records. Mothers were interviewed by telephone 6 weeks to 24 months after delivery. The mothers were asked whether they had specific medical conditions before or during pregnancy and what medications were used to treat them. The focus was on periconceptional corticosteroid use by any administration route and component that occurred between 4 weeks before and 12 weeks after conception. Outcomes were an association with specific timing of exposure, mode of administration, or corticosteroid component. Logistic regression models were used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Adjustments were made for covariates, including maternal race/ethnicity, education, intake of folic acid, smoking, and study center. Results were presented for deliveries from January 2003 through December 2009 and for pooled data for deliveries from October 1997 through December 2009. From 2003 to 2009, the NBDPS enrolled mothers of 1577 children with CLP, 795 children with CPO, and 5922 control children. A total of 1402 (89%) of the CLP cases and 631 (79%) of the CPO cases were isolated. Any use of corticosteroids 4 weeks before through 12 weeks after conception was reported by mothers of 35 infants (2.3%) with CLP (OR, 1.0; 95% CI, 0.7-1.4), mothers of 13 infants (1.7%) with CPO (OR, 0.7; 95% CI, 0.4-1.2), and mothers of 137 control infants (2.4%). No association was found with route of administration or components of corticosteroids. When earlier and recent data were combined, the cohort included mothers of 2731 infants with CLP, 1429 infants with CPO, and 10,063 controls, delivered in 1997 to 2009. Mothers of 69 infants (2.6%) with CLP (OR, 1.2; 95% CI, 0.9-1.6), 19 infants (1.3%) with CPO (OR, 0.6; 95% CI, 0.4-1.0), and 214 controls (2.1%) reported using any corticosteroids during the specified period. No association was found for route of administration or component of corticosteroid in the combined data, except for prednisone (OR, 1.9; 95% CI, 1.0-3.7). For CLP, ORs ranged from 2.8 (95% CI, 1.3-5.9) for exposures only during weeks 1 to 4 and 5 to 8 after conception to 0.5 (95% CI, 0.1-1.6) for exposures during weeks 9 to 12. Recent data from the NBDPS did not support an association between maternal corticosteroid use during early pregnancy and delivering an infant with an orofacial cleft. These data may help patients and clinicians in making their risk-benefit decisions for using corticosteroids during the first trimester.