NEW YORK (Reuters Health) - Hydrocortisone treatment given to extremely preterm infants 14 to 28 days after birth does not improve the odds of surviving without moderate or severe bronchopulmonary dysplasia (BPD), a study of 800 newborns shows.
The lung damage and scarring due to oxygen and ventilator therapy affects about half of babies born extremely early. Dexamethasone has been used since the 1990s to try to prevent it, a practice now tempered by the drug's neurodevelopmental side effects that include stunted growth and cognitive disability.
There had been hope that hydrocortisone would be as effective and safer. The new, federally funded test, published in the New England Journal of Medicine, was designed to confirm very preliminary evidence suggesting that the drug might be beneficial.
It was not.
The rate of survival without moderate or severe bronchopulmonary dysplasia at 36 weeks was 16.6% among hydrocortisone recipients and 13.2% with saline placebo, a 27% improvement that was not statistically significant, with a 95% confidence interval of 0.93 to 1.74.
The drug had no effect on the odds of survival without moderate or severe neurodevelopmental impairment. The rates were 36.9% with hydrocortisone versus 37.3% with placebo, judged at 22 to 26 months of corrected age.
The rate of hypertension - 1.0% in the placebo group - was 4.3 times higher in the steroid group.
Chief author Dr. Kristi Watterberg speculated that the findings may prompt some clinicians to give dexamethasone - but at a lower dose than what was used in the 1990s - "because it looks like it's probably more efficacious."
But the studies showing that it is useful "were small and done a long time ago, and I think it needs a large randomized trial with our current population of babies, who are as little as 22 weeks when they're born, to see if that treatment will stand up to scrutiny," Dr. Watterberg, professor emerita of pediatrics at the University of New Mexico Health Sciences Center in Albuquerque, told Reuters Health by phone.
Dexamethasone "may be beneficial in babies at high risk for BPD, but if you give it to babies at low risk, the adverse effects probably outweigh the benefits," she said.
Fifty neonatal intensive-care units participated in the study. Infants who had an estimated gestational age at birth of less than 30 weeks were enrolled from 2011 into early 2018. All had received mechanical ventilation via an endotracheal tube for at least seven days.
The treatment, given intravenously when possible and orally if necessary, was tapered over 10 days.
Although the treatment didn't affect the primary outcome, hydrocortisone did increase the odds of successful extubation during treatment. The rate was 44.7% with the steroid and 33.6% without, a significant difference.
The hydrocortisone babies had a median of three fewer days of mechanical ventilation.
"However, similar numbers in each group had been extubated by 36 weeks of postmenstrual age, and total duration of supplemental oxygen therapy and length of hospital stay did not differ substantially between the two groups," the researchers report.
Whether the results drive clinicians to give hydrocortisone just to get the babies off a ventilator faster "will be interesting to see because everybody hates seeing the babies on a ventilator," Dr. Watterberg said. "The babies hate it. It's clearly a stress for them. The steroids will help you extubate babies, but it won't change BPD. That's something people will have to wrestle with."
Aside from the higher risk of hypertension, both groups had similar rates of other adverse events such as culture-proven sepsis or necrotizing enterocolitis.
The children in the study are in the process of being evaluated at the 5- to 6-year mark to look for long-term side effects of the therapy.
With the latest findings and past unsuccessful attempts to find a way to prevent BPD, "we should stop looking for the silver bullet and move toward assessing a combination of interventions," Dr. Anne Greenough of King's College London writes in a linked editorial.
"Despite the many randomized, controlled trials, we are far from determining the appropriate formulation, timing, dosage, and duration of glucocorticoids in this vulnerable group," she notes. "Glucocorticoids should therefore not be given to prevent BPD. We should instead focus further research on their potential role in the amelioration of severe respiratory disease."
SOURCE: https://bit.ly/3L0plVz and https://bit.ly/3qhwzg1 The New England Journal of Medicine, online March 23, 2022.
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