Targeted Therapy for Pulmonary Hypertension in Premature Infants

Abstract

Pulmonary hypertension (PH) is common in premature infants with bronchopulmonary dysplasia (BPD) and is associated with significant mortality. Despite expert consensus suggesting the use of targeted therapies such as phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids, there is little data on safety and outcomes in infants with BPD-associated PH (BPD-PH) treated with these medications. We sought to describe the pharmacologic management of BPD-PH and to report outcomes at our institution. Premature infants with BPD-PH born between 2005 and 2016 were included. Follow-up data were obtained through January 2020. A total of 101 patients (61 male, 40 female) were included. Of these, 99 (98.0%) patients were treated with sildenafil, 13 (12.9%) with bosentan, 35 (34.7%) with inhaled iloprost, 12 (11.9%) with intravenous epoprostenol, and nine (8.9%) with subcutaneous treprostinil. A total of 33 (32.7%) patients died during the study period and 10 (9.9%) were secondary to severe to pulmonary hypertension. Of the surviving patients, 57 (83.8%) had follow-up data at a median of 5.1 (range 0.38–12.65) years and 44 (77.2%) were weaned off PH medications at a median 2.0 (range 0–8) years. Mortality for BPD-PH remains high mostly due to co-morbid conditions. However, for those patients that survive to discharge, PH therapies can frequently be discontinued in the first few years of life.

Life-threatening bronchopulmonary dysplasia: a British Paediatric Surveillance Unit Study

“… 33 Retrospective studies have associated sildenafil use with haemodynamic improvement and reduced mortality, although efficacy data are limited, and prospective studies to establish optimal PHT screening and treatment regimens required. 33 34 …”

“…Recognised PHT was significantly associated with death, major NDI and/or longterm ventilation, highlighting this as an important prognostic factor potentially amenable to treatment. 33 Retrospective studies have associated sildenafil use with haemodynamic improvement and reduced mortality, although efficacy data are limited, and prospective studies to establish optimal PHT screening and treatment regimens required. 33 34 By 1 year of age, 16% infants died, however this cohort did not include BPD-related deaths before 38 weeks, so overall mortality is higher.…”

Neonatal and Postneonatal Pulmonary Hypertension

“…In this issue of Children, Nees et al present data on targeted therapy in 101 preterm infants with BPD and PH (Figure 1). Although the mortality rate was high (32.7%), few deaths occurred after hospital discharge and 77.2% of patients at follow-up were weaned off PH medications by a median of 2 years (range 0-8 y) [17]. [17] showing the course of preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH).…”

“…Although the mortality rate was high (32.7%), few deaths occurred after hospital discharge and 77.2% of patients at follow-up were weaned off PH medications by a median of 2 years (range 0-8 y) [17]. [17] showing the course of preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). The chest X-rays A and B show reduction in pulmonary vascularity after occlusion of the patent ductus arteriosus (PDA) by the transcatheter method.…”

“… Graphic summary of Nees et al [ 17 ] showing the course of preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). The chest X-rays A and B show reduction in pulmonary vascularity after occlusion of the patent ductus arteriosus (PDA) by the transcatheter method.…”