PH Linked to Bronchopulmonary Dysplasia Resolves Over Time in Many Preemies, Study Reports

Pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) resolves over time in nearly two-thirds of premature babies, a study shows.

However, the findings also revealed that being male, steroid use, and greater PH severity were associated with increased mortality in these patients.

The study, “Death or resolution: the “natural history” of pulmonary hypertension in bronchopulmonary dysplasia,” was published in the Journal of Perinatology.

PH is a common consequence of BPD in premature newborns. BPD is a form of chronic lung disease, characterized by damage to the airway passages, or bronchi. Extreme prematurity, intrauterine growth restriction, prolonged mechanical ventilation, or use of oxygen supplementation, and maternal preeclampsia/hypertension are risk factors for PH in BPD.

Although PH in preemies has been associated with a poor prognosis, the natural history of PH and outcomes in BPD patients remain unclear.

This study was intended to address this issue, and to identify factors associated with poor outcomes in preemies at 36 weeks, post-menstrual age (PMA) — calculated by adding the gestational age to the newborn’s chronological age.

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Researchers reviewed data from patients who were followed at the Stanford University School of Medicine — Lucile Packard Children’s Hospital from 2000 to 2017. The 61 infants in the study had evidence of PH by echocardiography at 36 weeks PMA, and were born at 32 weeks or less (mean age 26.5 weeks). All babies had BPD, with 89% classified as severe.

In total, 17 premature PH patients (28%) died, 13 during the first hospitalization. Median PMA at death was 58 weeks.

Researchers found that factors associated with mortality in these babies included being male, use of postnatal steroids — hydrocortisone or dexamethasone — for managing respiratory symptoms, and higher systolic pulmonary artery pressure (sPAP). At the time of death, 15 infants were on pulmonary vasodilator therapy.

When assessing PAP data in 84% of the included patients, the team found that sPAP and the sPAP/systolic blood pressure ratio were markedly higher in the preemies who did not survive.

Median age at follow-up was 190 weeks PMA. At this point, 44 out of 61 babies were alive (72.1%), and most of them (66%) showed PH resolution on their most recent echocardiography. Nine of these infants were still on pharmacologic or oxygen therapy. Diuretics, bronchodilators, and inhaled corticosteroids were also frequently used.

The fact that most of the patients were off therapy at follow-up contrasts with other forms of PH, the researchers said.

When other coexisting conditions were examined, retinopathy (disease of the eye’s retina), abnormalities in the ears, nose and throat, and requiring a gastrostomy tube for feeding were all present. Most patients (75%) had to be readmitted to the hospital after discharge, while 16 patients (26%) had pulmonary vein stenosis — narrowing or blockage in the pulmonary veins — 69% of whom were alive at follow-up. This condition was found to have no association with increased mortality.

The researchers concluded that “PH resolved in most survivors in this study population,” and that “mortality in those with BPD-PH was associated with male sex, post-natal steroid use, and increased severity of PH, but not with [pulmonary vein stenosis].”

Thy emphasized that the findings need to be backed up by a multi-institutional study with a larger sample size, and that evaluating whether “earlier multi-modal therapy would decrease morbidity and mortality in the BPD-PH population” should be a key goal.