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Hydrocortisone use unrelated to neurodevelopmental impairment in preterm infants
Using early low-dose hydrocortisone in extremely preterm infants did not contribute to any statistically significant neurodevelopmental concerns, including an increased risk of cerebral palsy, at 2 years of age, according to a study published recently in JAMA.
“Preterm birth is frequently associated with perinatal inflammation, a major risk factor for bronchopulmonary dysplasia, brain damage and subsequent neurodevelopmental impairments,” Olivier Baud, MD, from the neonatal intensive care unit at Assistance Publique-Hôpitaux de Paris in Paris, and colleagues wrote. “Because glucocorticoids alleviate systemic inflammation, they have been proposed as a therapeutic option in very preterm infants. Postnatal dexamethasone therapy led to short-term benefits … but was associated with cerebral palsy and other adverse neurodevelopmental events.”
The researchers also noted that clinical trials using low-dose hydrocortisone to maintain respiratory benefits while avoiding possible adverse effects on the infant brain have been inconclusive.
To assess the neurodevelopmental outcomes at 2 years after using low-dose hydrocortisone therapy in preterm infants (n = 523), the researchers conducted an exploratory secondary analysis of the Early Low-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants (PREMILOC) trial.
Patients were randomly assigned into two groups, with one receiving a placebo (n = 267) and the other receiving hydrocortisone (n = 256). Neonates were administered 0.5 mg/kg twice daily for 1 week. They were then treated with the same dosage once daily for the following 3 days.
Out of the total participants, 406 survived to 2 years of age, and 379 were evaluated at 22 months (adjusted age). Most children evaluated did not have neurodevelopmental impairment in either group, with 73% in the hydrocortisone groups and 70% in the placebo group. Mild neurodevelopmental impairment was seen in 20% of patients who received hydrocortisone and 18% of patients who did not. Additionally, moderate to severe impairment was seen in 7% of those who were administered the drug and 11% of those in the placebo group.
No scores between the two groups were statistically different, including the prevalence of cerebral palsy or other major neurological impairments.
“Other than hydrocortisone, caffeine citrate is the only therapy that has been shown to exert a beneficial effect on both bronchopulmonary dysplasia and neurodevelopmental impairment at 18 months of age in very low-birth-weight infants, but not at 5 years of age,” Baud and colleagues wrote. “Until other potential interventions, such as those targeting lung angiogenesis or using mesenchymal stem cells, can be tested, caffeine and hydrocortisone appear to be the most reasonable options for preventing bronchopulmonary dysplasia and improving long-term outcomes.” — by Katherine Bortz
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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The effects of early low dose hydrocortisone on school age performance are not known. At present, early low dose hydrocortisone is unlikely to be adopted as standard clinical practice in neonatal intensive care units in the United States as this study involves different clinical practices and a distinct patient population. However, it is reassuring that preliminary data suggest that low dose hydrocortisone given in the first week of life does not worsen early neurodevelopmental outcomes.
Susan LaTuga, MD, MSPH
Attending neonatologist
Children’s Hospital at Montefiore
Deborah Campbell, MD, FAAP
Chief, Division of Neonatology
Children's Hospital at Montefiore
