Impact of Pulmonary Hypertension and Patent Ductus Arteriosus in Preterm Infants with Presumed Pulmonary Hypoplasia

Sol Kim, Yumi Seo, Moon-Yeon Oh, Min Soo Kim, Sook Kyung Yum
Seoul St. Mary’s Hospital and Catholic University of Korea.
Republic of Korea

Biomedicines
Biomedicines 2025; 13:
DOI: 10.3390/biomedicines13071725

Abstract
Objectives: Pulmonary hypertension and hemodynamically significant PDA (hsPDA) involve seemingly opposite physiological features-decreased pulmonary blood flow and pulmonary overcirculation, respectively-but the literature demonstrates variable respiratory consequences in association with each of these morbidities. The aim of this study is to evaluate whether the two factors representing pulmonary circulation provide different contributions to respiratory outcomes in preterm infants with and without pulmonary hypoplasia. 
Methods: The medical records of preterm very low birth weight (VLBW) infants admitted to our unit during the study period from January 2013 to December 2020 were retrospectively reviewed. Preterm VLBW infants were divided into groups according to the presence of presumed pulmonary hypoplasia (PPH). Multivariable logistic regression analysis was performed to assess the association of PPH and pulmonary hypertension or delayed PDA closure with in-hospital outcomes. 
Results: Postnatal age at final treatment for PDA was significantly later [median 33 vs. 19 days, p = 0.025] in the PPH group. Multivariable analysis indicated that early pulmonary hypertension was significantly associated with neonatal death [aOR (95%CI) 11.575 (2.988-44.833) for no-PPH vs. 9.981 (1.334-74.647) for PPH]. Delayed PDA closure was associated with increased odds of adverse respiratory and composite outcomes [aOR (95%CI) 4.929 (1.613-15.055) and 3.320 (1.048-10.515), respectively] but decreased odds of neonatal death in the no-PPH group. However, Cox proportional hazards models did not demonstrate statistically significant associations for PPH, early pulmonary hypertension, or delayed PDA closure with mortality, likely due to time-varying effects and the absence of death events in the subgroup of infants with both PPH and delayed PDA closure. 
Conclusions: PPH is associated with a higher prevalence of air leak syndrome and pulmonary hypertension. Delayed PDA closure exerts different effects on respiratory outcomes in preterm VLBW infants with and without PPH. Although early pulmonary hypertension appears to be a key circulatory factor contributing to neonatal death, its effect may vary over time. These findings underscore the importance of accounting for time-dependent effects when interpreting pulmonary circulatory risk factors in clinical practice.

Category
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Class III. Pulmonary Hypertension Associated with Lung Disease
Class III. Pulmonary Hypertension Associated with Lung Hypoplasia

Age Focus: Pediatric Pulmonary Vascular Disease

Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication

Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes

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