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Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

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1. Among extremely preterm infants, low-dose hydrocortisone was not associated with adverse neurodevelopmental outcomes at 2 years of age.

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Evidence Rating Level: 1 (Excellent)

Study Rundown:

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Close to 15 million preterm neonates are born every year and many of these children suffer from significant complications. Glucocorticoids have been utilized as a therapeutic strategy to reduce the inflammation associated with preterm birth. Though they are effective in reducing the severity of bronchopulmonary dysplasia and minimizing the duration of mechanical ventilation, glucocorticoids have been associated with adverse neurodevelopmental events. As such, some guidelines recommend against early postnatal steroids. More recently though, a lower dose of glucocorticoids has been suggested as an optimal therapy. This study is an exploratory analysis of 379 infants enrolled in the PREMILOC (Early Lose-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants) randomized clinical trial that survived to 2 years of age. Infants were assigned to receive hydrocortisone (n = 194) and placebo (n = 185). There was no significant difference in neurodevelopmental impairment among the two groups (mild impairment of 20% in hydrocortisone vs 18% in placebo; moderate-to-severe impairment of 7% in hydrocortisone vs 11% in placebo). There was also no difference in mean global development scores, or the incidence of cerebral palsy and other neurological impairments.

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Overall, the study suggests that early low dose hydrocortisone in extremely preterm infants—beneficial for respiratory status—was not associated with adverse neurodevelopmental outcomes at 2 years of age. Limitations of the study include lack of multiple comparisons for the exploratory outcomes and short end-point at 22 months. Future directions include reassessing neurodevelopment at later ages that may better reflect intellectual ability.

In-Depth [randomized clinical trial]:

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The PREMILOC trial was conducted in France between 2008 and 2014, and enrolled infants born between 24 0/7 weeks and 27 6/7 weeks of gestation before 24 hours of post-natal age. Infants were assigned to receive either placebo or low-dose hydrocortisone. Surviving infants from this multicenter, double-blind, placebo-controlled trial were enrolled in the present study. The primary outcome of the PREMILOC trial was bronchopulmonary dysplasia-free survival at 36 weeks (better with hydrocortisone; 60% vs 51% in placebo). Neurodevelopment at 18 to 24 months was a secondary outcome that was investigated in this study. Follow-up evaluation was completed between 2010 and 2016 and included a standardized neurological examination as well as a quantitative neurodevelopmental assessment using the Brunet-Lézine (RBL) scale. Global developmental quotient scores, RBL sub-scores, and cerebral palsy evaluation were obtained through post-hoc exploratory analysis at 2 years.

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Overall, 523 infants were enrolled in the initial study, and 406 survived to 2 years of age. Of these, 379 (194 in hydrocortisone, and 185 in placebo) were seen at follow-up at a median corrected age of 22 months. Quantitative neurodevelopmental assessment was not different for mild, moderate, or severe neurological impairment amongst the two groups (p = 0.33). No differences in qualitative assessment using the standardized neurological examination (p = 0.87) or mean global developmental quotient score (91.7% in hydrocortisone vs. 91.4% in placebo; between-group difference, 0.3 [95% CI, −2.7 to 3.4]; p = 0.83) were found between the groups.

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