Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity

Objective This study was undertaken to evaluate the effect of exposure to multiple antenatal steroid courses on short-term neonatal morbidity and 2-year infant neurodevelopmental outcome. Study design This was a prospective observational study of 201 preterm singleton infants who received 1 or more courses of corticosteroids to prevent complications of prematurity and were delivered between 24 and 34 weeksʹ gestation at a single institution. Neurodevelopmental outcome of the infants was evaluated at 2 years corrected age. Logistic regression analysis was used to perform multivariate analyses of associations and trends. Results One hundred thirty-eight subjects (68.7%) received at least 1 complete course of betamethasone, whereas 63 (31.3%) patients were treated with dexamethasone. The prevalence of multiple steroid doses exposure was 26.8% (37/138) in betamethasone and 52.4% (33/63) in dexamethasone group. The prevalence of infant leukomalacia, including both prolonged echogenicity and cystic leukomalacia, was 25.9% (34/131) after a complete corticosteroid course, 40% (6/15) after 1, 42.3% (12/28) after 2, and 44.4% (12/27) after more than 2 additional courses, respectively (adjusted P for trend = .011). In the same categories of steroid exposure, the corresponding prevalences of 2-year infant neurodevelopmental abnormalities were 18% (20/111), 21.4% (3/14), 29.2% (7/24), and 34.8% (8/23), respectively (adjusted P for trend = .038). Multivariate study of first grade interaction suggested that the risk of leukomalacia and 2-year infant neurodevelopmental abnormalities associated with multiple doses exposure was confined to dexamethasone. In fact, compared with betamethasone, exposure to multiple doses of dexamethasone was associated with an increased risk of leukomalacia (19/33 compared with 11/37; odds ratio [OR] = 3.21, 95% CI = 1.07-9.77) and overall 2-year infant neurodevelopmental abnormalities (12/28 compared with 6/35; OR = 3.63, 95% CI = 1.03-13.58). Conclusion In this study, multiple antenatal courses of dexamethasone but not betamethasone were associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities.