Despite current targeted therapies, premature babies with bronchopulmonary dysplasia or BPD — a disease in which the lungs become irritated and fail to develop properly, causing breathing difficulties — associated with pulmonary hypertension (PH) continue to have high mortality rates, a study found.
Nevertheless, infants who live past their hospital discharge are likely to have a positive clinical outcome and to stop using these therapies within their first years of life, the researchers said.
The findings were reported in the study, “Targeted Therapy for Pulmonary Hypertension in Premature Infants,” published in the journal Children.
Babies who are born prematurely have a higher risk of developing both BPD and PH, two severe lung disorders, since their lungs are underdeveloped and more likely to sustain injuries.
The two conditions also seem to be associated to some extent, with PH estimated to be present in 14-28% of premature babies with BPD. Statistics also indicate that, among these infants, PH is associated with a relatively high risk of mortality (14-47%).
“Several drugs approved for adults with pulmonary arterial hypertension (PAH) are used off-label in these patients, including targeted therapies such as phosphodiesterase (PDE) type 5 inhibitors, endothelin receptor antagonists, and prostanoids,” the investigators wrote.
Of note, PDE-5 inhibitors cause blood vessels to relax, thus increasing blood flow and reducing blood pressure. Endothelin receptor antagonists (ERAs) reduce the amount of endothelin in blood vessels — endothelin causes blood vessels to constrict (become narrower), resulting in an increase in blood pressure. Prostanoids are powerful vasodilators that can open up narrowed blood vessels to allow more blood flow into the lungs.
Expert consensus guidelines recommend these therapies be started in infants whose PH symptoms remain after their underlying respiratory and heart conditions have been addressed by other means.
However, “although these medications are widely used in this population, there is little data on safety, tolerability, and outcomes for infants treated with these medications for PH,” the researchers wrote.
Therefore, investigators at the Columbia University Irving Medical Center, in New York, and their colleagues analyzed the clinical outcomes of premature babies with BPD associated with PH (BPD-PH), who were treated with different types of targeted therapies at their care center.
A total of 101 premature infants — 61 boys and 40 girls — born at a median gestational age of 25 weeks (approximately six months) between 2005 and 2016 were included in the study. All of the children were followed up until January 2020.
More than half (57.4%) of the babies were treated with only one therapy, while the remaining 42.6% received between two and four different medications.
Among the babies included in the study, nearly all (98.0%) were treated with sildenafil — sold as Revatio by Pfizer — a PDE-5 inhibitor. Approximately one-third (34.7%) were given inhaled iloprost, which is sold as Ventavis by Actelion Pharmaceuticals in the U.S. and Bayer in Europe.
A smaller percentage of infants (12.9%) received bosentan, an ERA sold as Tracleer by Actelion, while 11.9% were given intravenous (into-the-vein) epoprostenol, which is sold as Flolan by GlaxoSmithKline and Veletri by Actelion. Under-the-skin (subcutaneous) treprostinil — sold as Remodulin by United Therapeutics — was given to 8.9% of the newborns.
A total of 33 babies (32.7%) died over the course of the study, including 10 (9.9%) whose cause of death was associated with severe PH.
In the group of 57 babies (83.8%) who lived and had available follow-up data, 44 (77.2%) were able to discontinue treatment with the targeted therapies within a median period of two years.
Overall, “targeted PH therapy was well tolerated among infants with BPD-PH,” the researchers wrote.
But mortality “remains high mostly due to co-morbid conditions,” they added.
“However, for those patients that survive to discharge, their subsequent survival is good and PH therapies can often be weaned off in the first few years of life,” the team concluded.
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