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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.