Relative to prolonged preterm infants, standard treatment prevails

Premature newborns must establish regular breathing patterns during delivery. For extremely premature newborns requiring resuscitation at birth, a two prolonged inflation ventilation strategy, compared to standard intermittent positive pressure ventilation, did not reduce the risk of bronchopulmonary dysplasia (BPD). or death at 36 weeks post-menstrual.

The researchers compared the two methods as part of a large multicenter trial conducted by the Children's Hospital of Philadelphia. The results were published in the March 26, 2019 edition of the Journal of the American Medical Association.

Studies comparing the two methods have been limited so far. The pooled data from smaller randomized trials was contradictory: one of them showed that prolonged inflations reduced the need for mechanical ventilation. However, another did not find any benefit in terms of mortality. In infants less than 30 weeks of gestational age, prolonged inflation is commonly used in delivery rooms in Europe, but not in the United States.

"Premature neonates with weak breathing muscles and fluid-filled lungs struggle to ventilate their lungs, exposing them to a risk of complications, including bronchopulmonary dysplasia (BPD), which is badociated with many long-term problems "said Haresh Kirpalani, MD, MSc, neonatologist at Philadelphia Children's Hospital and lead author of the study. "We hypothesized that the rapid establishment of adequate lung volume in these infants could reduce the risk of BPD. This has been possible because of prolonged swelling at delivery, which appears to be beneficial in animal models and in earlier studies of humans. However, in our largest randomized trial. in the smallest and most vulnerable premature babies this has not been the case. "

The randomized trial was conducted from August 2014 to September 2017 in 18 neonatal intensive care units from nine countries. Preterm neonates from 23 to 26 weeks of gestational age requiring resuscitation with insufficient respiratory effort or bradycardia were included. The primary endpoint was DBP or death at 36 weeks post-menstrual. There were 27 prespecified secondary efficacy results and seven safety outcomes, including death after less than 48 hours.

Of the 460 randomized infants (mean gestational age, 25.30 weeks, 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with a DBP, compared with 125 infants (59.2%) in the standard resuscitation group. Death to less than 48 hours occurred in 16 infants (7.4%) in the persistent inflation group versus 3 infants (1.4%) in the standard ICU group. Of the 27 secondary efficacy endpoints badessed at 36 weeks postmenstrual age, 26 showed no significant difference between groups.

"Because we had been worried about the complications, the External Data Security Oversight Committee was looking for early adverse events, but this promising treatment appeared to lead to higher mortality, particularly in the smallest and most vulnerable infants, "added Kirpalani. "Additional research is needed to determine the best way to treat these infants during delivery, to reduce the risk of extreme side effects from a very early birth."

Provided by
Philadelphia Children's Hospital