Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-β) signaling pathways. Defects in the BMP9 gene have been documented in hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, which is occasionally associated with PAH. Selective enhancement of endothelial BMPR2 with BMP9 reverses pulmonary arterial hypertension. We report the case of a 5-year-old Hispanic boy who was diagnosed with severe PAH and right heart failure at 3 years of age. During his stay in the pediatric intensive care unit, treatment was initiated with inhaled nitric oxide and intravenous epoprostenol; he subsequently was transitioned to treprostinil, sildenafil, and prophylactic enoxaparin. Now, two years later, the child is asymptomatic on sildenafil, bosentan, subcutaneous treprostinil, and warfarin. Genetic screening revealed a novel homozygous nonsense mutation in the BMP9 gene (c.76C > T; p.Gln26Ter). The child had no telangiectasias or arteriovenous malformations; family history also was negative. Subsequent parental testing showed both parents were heterozygous for the same mutation, indicating that the child inherited the BMP9 mutant allele from each parent. To our knowledge, this is the first report of a BMP9 mutation in a patient with PAH. The homozygous nonsense mutation may account for the early onset and severity of PAH in this patient and also fit the ‘two-hit’ model we proposed previously. The absence of clinical symptoms for PAH in the parents may be due to incomplete penetrance or various expressivities of the BMP9 mutations. Our study expands the spectrum of phenotypes related to BMP9 mutations.

Early pulmonary vascular disease (PVD) and established pulmonary hypertension (PH) are common associations of bronchopulmonary dysplasia (BPD). Diagnosis of PH is often made by echocardiography because of technical and logistic difficulties with the neonatal population. Optimization of respiratory support is the focus of treatment, however, medical therapies are being used with increased frequency. The prognosis for PH associated with BPD (PH-BPD) is tied to the child's respiratory status. PH is associated with increased risk of death in this population, so active screening and treatment is recommended to minimize morbidity and mortality. In this review, we discuss the pathophysiology of PH in infants with BPD, evaluate the current understanding of screening, diagnosis, and follow-up evaluation; describe comorbid conditions; and provide a framework for targeted physiology-based management strategies.

Pulmonary vein stenosis (PVS) has emerged as a critical problem in premature infants with persistent respiratory diseases, particularly bronchopulmonary dysplasia (BPD). As a parenchymal lung disease, BPD also influences vascular development with associated pulmonary hypertension recognized as an important comorbidity of both BPD and PVS. PVS is commonly detected later in infancy, suggesting additional postnatal factors that contribute to disease development, progression, and severity. The same processes that result in BPD, some of which are inflammatory-mediated, may also contribute to the postnatal development of PVS. Although both PVS and BPD are recognized as diseases of inflammation, the link between them is less well-described. In this review, we explore the relationship between parenchymal lung diseases, BPD, and PVS, with a specific focus on the epidemiology, clinical presentation, risk factors, and plausible biological mechanisms in premature infants. We offer an algorithm for early detection and prevention and provide suggestions for research priorities.

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise clinical features of infants with DEVLD/DEVLD-PH and identify decision-making challenges including genetic evaluations, the role of lung biopsies, the use of imaging modalities and treatment approaches. The importance of working with team members from multiple disciplines, enhancing communication and providing sufficient counselling services for families is emphasised to create an interdisciplinary consensus.

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared using mixed regression modeling with an interaction term. There was a significant difference in pre‐ versus post‐intervention slope with the most score drop the first week post‐intervention (−2.1 + /− 0.8, p = 0.014). The mean score also dropped through weeks 2 (slope −0.8 + /− 0.8, p = 0.013) and 4 (slope −1.0 + /− 0.5, p = 0.001) post‐intervention. There was a significant difference in pre‐ and post‐intervention slopes for diuretics (p = 0.018) and the combined score of respiratory support, FiO₂ need, and respiratory symptoms (p = 0.018). This study demonstrated significant improvement in BPD‐ASD score, diuretic need, and respiratory status after ASD closure in BPD‐ASD patients ≤ 10 kg that was outside of the natural course of BPD. Our study was limited by its small, single‐center, retrospective nature. Future studies should be performed in a larger multicenter population to both validate the scoring system and compare to non‐intervention infants.