Neurodevelopmental impact of hydrocortisone exposure in extremely low birth weight infants: outcomes at 1 and 2 years

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Abstract

OBJECTIVE:

Postnatal steroids are used in neonatal intensive care units despite known side effects. Hydrocortisone (HC) use persists as it is believed to have less deleterious effects on neurodevelopmental (ND) outcome compared to other steroids. The literature is sparse with respect to the ND impact of HC use in recent years. Hence, we sought to examine the effect of HC use on ND outcome in a contemporary cohort of extremely low birth weight (ELBW) infants.

STUDY DESIGN:

A total of 175 ELBW infants (86 HC exposed, 89 steroid naive) born in 2008 to 2010 were compared for mortality, morbidity and ND outcome at 8 and 20 months corrected age. Outcome measures included neurologic exam and results of the Bayley Scales of Infant and Toddler Development-III (BSITD-III). Multiple regression analyses adjusted for the effect of other risk factors on outcome.

RESULT:

Overall, 65 (75%) of the HC and 74 (83%) of the no-HC groups survived to discharge. HC infants were smaller (mean birth weight (BW) 719 ± 127 g vs 837 ± 99 g) and of lower gestational age (GA) (mean GA 26.0 ± 1.7 weeks vs 27.5 ± 1.8 weeks) compared to the no-HC group. Patients in the HC group were more likely to be a multiple, have a severely abnormal head ultrasound, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis and receive treatment for patent ductus arteriosus and hypotension than those in the no-HC group. Of the HC group, the mean age at treatment was 20 ± 19 days, mean duration of treatment 49 ± 37 days. At 8 months, the HC group had lower mean motor (87 ± 18 vs 95 ± 15, P = 0.028) and fine motor (9 ± 2.9 vs 10.5 ± 2.6, P = 0.005) and higher rate of subnormal motor (44 vs 15%, P = 0.002) and fine motor scores (24 vs 6.5%, P = 0.017). In regression analyses, HC exposure >7 days was significantly related to worse outcome on fine motor scores at 8 months while cumulative days of HC exposure was a predictor of worse outcome on language at 8 months and motor outcome at 20 months. Each additional day of HC exposure increased the odds of subnormal receptive and expressive language in the first year of life by 4 and 2%, respectively, and increased odds of subnormal motor function by 2% in the 2nd year of life.

CONCLUSION:

HC exposure for >7 days is associated with worse performance in fine motor skills in the first year of life, while cumulative HC exposure negatively impacts receptive and expressive language skills in the first year and motor skills in the second year of life after adjusting for neonatal and social risk factors.

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