Postnatal betamethasone treatment in extremely preterm infants and risk of neurodevelopmental impairment: a cohort study

Objective To evaluate if postnatal treatment with betamethasone in extremely preterm infants was associated with neurodevelopmental impairment (NDI) at 6.5 years of age. Design Prospective cohort study. Setting Extremely Preterm Infants in Sweden Study (gestational age <27 weeks, born 2004-2007). Patients 428 children born extremely preterm were assessed at 6.5 years of age, 115 treated with betamethasone and 313 not treated. Main outcome measures NDI at 6.5 years of age. Evaluation at 6.5 years included cognitive testing with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), neurological examination and a medical record review. Exposure Treatment with postnatal betamethasone. Main outcome Moderate to severe NDI at 6.5 years of age, defined as a composite including cerebral palsy, and/or impairment in cognition, hearing and vision. Results Moderate to severe NDI was more prevalent in children treated with postnatal betamethasone (49% treated vs 26% not treated, p<0.001). Betamethasone-treated children had worse cognitive development with mean WISC-IV score of 75 (SD 13.7) vs 87 (SD 14.0, p<0.001). The effect was dose dependent: 1.35 mg/kg vs 1.0 mg/kg (p=0.01) in betamethasone-treated children with moderate to severe versus no or mild NDI, respectively. The differences remained after adjustment for potential confounders with logistic regression (adjusted OR (aOR) 1.80, 95% CI 1.14 to 3.21). The difference in NDI also remained after propensity score matching, with crude OR 2.82 (95% CI 1.42 to 5.61, p=0.003) and aOR 2.17 (95% CI 1.07 to 4.69, p=0.04). Conclusion Postnatal treatment with betamethasone is associated with increased risk of NDI at 6.5 years.