# Physiology-Based Diagnosis and Management of Bronchopulmonary Dysplasia Associated Pulmonary Hypertension (BPD-PH)

**Authors:** Yogen Singh, Sfurti Nath, Sheen Gahlaut, Belinda Chan

PMC · DOI: 10.3390/children13020272 · 2026-02-15

## TL;DR

This review discusses the evolving understanding of BPD-PH in preterm infants and proposes a physiology-based approach for diagnosis and management.

## Contribution

The paper introduces a pragmatic algorithm for screening and managing BPD-PH based on physiological markers.

## Key findings

- BPD-PH is linked to higher mortality and worse outcomes in preterm infants.
- Impaired pulmonary vascular development is central to BPD-PH pathophysiology.
- Echocardiographic markers help classify BPD-PH for targeted management.

## Abstract

Bronchopulmonary dysplasia (BPD) remains a major long-term morbidity among preterm infants. As lung-protective strategies advance and survival of extremely premature neonates improves, BPD has evolved from a ventilator-induced inflammatory and fibrotic process to a disease marked by arrested pulmonary vascular and alveolar development—pulmonary vascular disease. Within this evolving phenotype, pulmonary hypertension (PH) has emerged as a critical yet underrecognized complication. BPD-associated pulmonary hypertension (BPD-PH) is increasingly linked to higher mortality and worse clinical outcomes, but its pathophysiology, screening strategies to detect early changes, and optimal management remain incompletely understood. This review delineates the pathophysiology of BPD-PH, linking impaired pulmonary vascular development with subsequent maladaptation influenced by genetic, prenatal, and postnatal factors. The phenotypic and hemodynamic spectrum of BPD-PH is further subclassified using echocardiographic markers to support a physiology-based approach to diagnosis and management. We also propose a pragmatic algorithm for screening, evaluation, and longitudinal follow-up. Collectively, this review highlights the need for physiology-driven strategies and clinical studies to improve outcomes in these neonates.

## Linked entities

- **Diseases:** Bronchopulmonary dysplasia (MONDO:0019091), pulmonary hypertension (MONDO:0005149)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, PVR (PVR cell adhesion molecule) [NCBI Gene 5817] {aka CD155, HVED, NECL5, Necl-5, PVS, TAGE4}, SGCB (sarcoglycan beta) [NCBI Gene 6443] {aka A3b, LGMD2E, LGMDR4, SGC}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ANGPT1 (angiopoietin 1) [NCBI Gene 284] {aka AGP1, AGPT, AGPT-1, ANG1, HAE5}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, TEK (TEK receptor tyrosine kinase) [NCBI Gene 7010] {aka CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1}, EDNRB (endothelin receptor type B) [NCBI Gene 1910] {aka ABCDS, ET-B, ET-BR, ETB, ETB1, ETBR}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, PDE5A (phosphodiesterase 5A) [NCBI Gene 8654] {aka CGB-PDE, CN5A, PDE5}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, F2R (coagulation factor II thrombin receptor) [NCBI Gene 2149] {aka CF2R, HTR, PAR-1, PAR1, TR}, S1PR1 (sphingosine-1-phosphate receptor 1) [NCBI Gene 1901] {aka CD363, CHEDG1, D1S3362, ECGF1, EDG-1, EDG1}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}
- **Diseases:** venous obstruction (MESH:D006502), growth faltering (MESH:D006130), left ventricular outflow tract or arch obstruction (MESH:D000092242), hyperoxia (MESH:D018496), fetal growth restriction (MESH:D005317), fibrosis (MESH:D005355), overload (MESH:D019190), inflammation (MESH:D007249), oligohydramnios (MESH:D016104), LV dilation (MESH:C565277), gastro-esophageal reflux (MESH:D005764), ASD (MESH:D006344), respiratory infections (MESH:D012141), Comorbidity (MESH:D004194), injury to (MESH:D014947), lung-vascular (MESH:D055370), lung edema (MESH:D004487), pulmonary edema (MESH:D011654), lung disease (MESH:D008171), Pulmonary Vascular Disease (MESH:D014652), pulmonary venous congestion (MESH:D006940), subglottic stenosis (MESH:D007829), pulmonary inflammation (MESH:D011014), CDH (MESH:D065630), chronic lung disease (MESH:D029424), mitral stenosis or regurgitation (MESH:D008946), hypoxic (MESH:D002534), right heart dilatation (MESH:C566255), LV dysfunction (MESH:D018487), Hypoxemia (MESH:D000860), pulmonary vascular hypoplasia (MESH:C562992), MR (MESH:D008944), VSD (MESH:D006345), cardiac shunts (MESH:C562451), Pulmonary regurgitation (MESH:D011665), stenosis (MESH:D003251), airway (MESH:D000402), vocal cord paralysis (MESH:D014826), hypotension (MESH:D007022), pulmonary arterial hypertension (MESH:D000081029), placental insufficiency (MESH:D010927), atelectasis (MESH:D001261), RV (MESH:C535682), tachypnea (MESH:D059246), 1 BPD (MESH:D001997), tracheobronchial malacia (MESH:C566362), pulmonary artery obstructions (MESH:D000071079), adenoidal hypertrophy (MESH:D006984), PDA (MESH:D004374), infection (MESH:D007239), chamber dilation (MESH:D002311), agitation (MESH:D011595), preterm birth (MESH:D047928), cardiac disorder (MESH:D006331), RV hypertrophy (MESH:D017380), prematurity (MESH:C536271), respiratory, cardiovascular, and neurodevelopmental impairments (MESH:D015619), PVS (MESH:D000071078), TR (MESH:D014262), PR (MESH:D008151)
- **Chemicals:** Oxygen (MESH:D010100), cGMP (MESH:D006152), IP (MESH:C041508), prostaglandins (MESH:D011453), arachidonic acid (MESH:D016718), ceramide (MESH:D002518), cAMP (MESH:D000242), nitric oxide (MESH:D009569), PGI2 (MESH:D011464), Sildenafil (MESH:D000068677), NO (MESH:D009614), treprostinil (MESH:C427248), Bosentan (MESH:D000077300), NT-proBNP (-), Iloprost (MESH:D016285), lipid (MESH:D008055), Milrinone (MESH:D020105), sphingolipid (MESH:D013107)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** A4C

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940002/full.md

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Source: https://tomesphere.com/paper/PMC12940002