Darbepoetin reduces death, BPD risks in preterm infants

Infants treated with darbepoetin through 35 weeks’ postmenstrual age (PMA) have a lower risk of death or grade 2‒3 bronchopulmonary dysplasia (BPD) and a reduced duration of exposure to positive airway pressure, reports a study presented at PAS 2024.

However, use of darbepoetin shows no significant impact on the rates of measured postdischarge respiratory outcomes.

“Reduction in red [blood] cell (RBC) transfusions may explain, at least in part, the observed decrease in BPD [risk] with darbepoetin,” said lead author Erik A Jensen, MD, assistant professor of paediatrics at Children’s Hospital of Philadelphia, Haddonfield, New Jersey, US.

Jensen and his team performed a post hoc analysis of the NICHD Neonatal Research Network (NRN) Darbe trial, which found reduced rates of grade 2‒3 BPD at 36 week’s PMA in infants randomized to receive darbepoetin versus placebo. [PAS 2023, abstract 2150.4]

In this secondary analysis, the authors compared rates of in-hospital and postdischarge respiratory morbidities through 22‒26 months’ corrected age among trial participants in the NRN Generic Database and Follow-up Registry. The NRN Darbe Trial randomly assigned 650 infants born at 23‒28 weeks’ gestation to receive weekly darbepoetin (10 ug/kg; n=322) or placebo (n=328) through 35 weeks’ PMA.

Mediation analyses were carried out to determine whether differences in RBC transfusion number through 36 weeks’ PMA or calculated RBC mass at 42 days of age had influence on the observed difference in grade 2‒3 BPD rates.

Four infants were withdrawn from the trial. Among the remaining participants, 552 survived to 36 weeks’ PMA, and 541 made it to follow-up. Of the survivors, 502 had available data (249 in the darbepoetin arm and 253 in the placebo arm). [Jensen, E, et al, PAS 2024]

Infants who received darbepoetin, compared with those given placebo, had lower rates of grade 2‒3 BPD to 36 weeks’ PMA (35 percent vs 46 percent; relative risk [RR], 0.78, 95 percent confidence interval [CI], 0.64‒0.96) and death or grade 2‒3 BPD at 36 weeks’ PMA (45 percent vs 54 percent; RR, 0.85, 95 percent CI, 0.85‒0.99).

Likewise, the darbepoetin group had reduced mean number of days receiving invasive ventilation (20 vs 25 days; adjusted mean difference [aMD], ‒4.3, 95 percent CI, ‒8.1 to ‒0.40) and positive airway pressure (50 vs 57 days; aMD, ‒5.2, 95 percent CI, ‒9.3 to ‒1.04) through 36 weeks’ PMA and 120 days’ postnatal age.

On the other hand, no between-group differences were noted in the use of O2 therapy (37 percent vs 38 percent; adjusted [a]RR, 0.96, 95 percent CI, 0.78‒1.17) and respiratory medications (21 percent vs 23 percent; aRR, 0.92, 95 percent CI, 0.63‒1.34) at discharge. Postdischarge respiratory outcomes assessed at 22‒26 months’ corrected age were also similar between the darbepoetin and placebo groups.

RBC transfusion

Mediation analyses revealed that the “lower mean number of RBC transfusions and higher calculated RBC mass explained 76 percent and 67 percent, respectively, of the effect of darbepoetin on the reduced risk of grade 2‒3 BPD in survivors to 36 weeks/ PMA,” said Jensen.

In the combined regression model, however, only the lower number of RBC transfusions showed a significant association with the reduced risk of BPD. Notably, 90 percent of the darbepoetin effect on the reduced risk of death or grade 2‒3 BPD was driven by fewer RBC transfusions.

“Strategies that safely eliminate the need for RBC transfusions should continue to be investigated as potential means to improve outcomes in extremely preterm infants,” Jensen said.