Long-term neurodevelopmental outcome in preterm-born children treated with hydrocortisone

Despite improved treatment strategies, bronchopulmonary dysplasia (BPD) remains a problem in neonatal intensive care. Therapy of BPD is often based on corticosteroids, which improve short-term respiratory function, leading to a reduction in supplemental oxygen requirements and earlier extubation. Among these, dexamethasone (DXM) is the primary drug used to treat BPD. The use of DXM was quite widespread in the late 1990s, when more than 25% of very low birth weight infants were exposed to this drug. However, many short- and long-term side effects of DXM therapy have been reported. Although short-term adverse effects are generally mild in intensity, an early DXM therapy is supposed to be associated with long-term neurodevelopmental consequences, such as cerebral palsy (CP). These reports of long-term adverse outcomes led to a joint statement by the American Academy of Pediatrics and the Canadian Paediatric Society discouraging routine use of postnatal DXM to treat or prevent BPD. However, dexamethasone is not the only glucocorticoid available, and the rationale for choosing it as drug of choice is unclear. For instance, hydrocortisone (HYC) has been proposed as an alternative to DXM in BPD treatment.
On these basis, a Dutch group experienced in HYC therapy investigated the impact of HYC administration on long-term neurodevelopment in preterm infants, measured at school age.
In particular, preterm infants with a gestational age < 32 weeks and/or body weight < 1500 g were considered in this analysis. Sixty-two children receiving HYC for BPD (starting dose, 5 mg/kg/day; median duration, 27.5 days) were compared with 164 nontreated neonates. At the age of 7 or 8 years (occasionally 9 and 10 years), the children underwent
intelligence, memory, visual-motor integration and motor function tests. Conventional MRI of the brain was obtained.
Results show that HYC-treated infants were younger, lighter, and sicker than non–steroid-treated ones. Despite this discrepancy, after adjustments for gestational age, body weight, sex, mechanical ventilation, and small for gestational age, it has been observed that mean intelligence, memory, and visual-motor integration tests results were perfectly comparable in the two groups. Motor function and incidence of CP in both groups was not different (11% vs 7%). Occurrence of brain lesions on MRI was similar for the two groups.
Overall, these results are consistent with earlier reports from the same authors, which showed improved outcomes for HYC-treated infants, if compared with DMX treated ones. Moreover, these findings are in line with information provided by a multicenter randomized trial, in which infants treated with HYC (1 mg/kg/day) showed no evidence of neurodevelopmental compromise at 18 to 22 months adjusted age, when compared with infants treated with placebo.
However, it should be emphasized that data on HYC pharmacokinetics are at present very limited and therefore any conclusion might be premature. Even if results of this analysis are quite promising, larger study are expected to provide a complete evaluation of long-term effects of HYC.

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