Clinical impact of treprostinil in neonates with persistent pulmonary hypertension refractory to inhaled nitric oxide - A retrospective cohort study

Sep 30, 2026

Persistent pulmonary hypertension of the newborn (PPHN) has limited options when unresponsive to inhaled nitric oxide (iNO). A retrospective cohort study evaluated intravenous treprostinil use and whether early response classification could guide management. Among 114 neonates receiving iNO therapy from 2014 to June 2025, infants were grouped as fast, slow, or non-responders based on oxygenation index change within 24 hours. Treprostinil was selectively used in severe non-responders, with outcomes compared to unexposed infants.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Background and rationale

Methods

Study design and patient classification

Results

Baseline differences and outcomes

Effect on oxygenation and iNO weaning

Discussion

Clinical implications of early response classification

® Observational Study Clinical impact of treprostinil in neonates with persistent pulmonary hypertension refractory to inhaled nitric oxide A retrospective cohort study Tae Hyeong Kim, MD, PhDa , Song Ee Youn, MD, PhDa , Sung-Hoon Chung, MD, PhDa ,* | Abstract
Persistent pulmonary hypertension of the newborn (PPHN) has limited options when unresponsive to inhaled nitric oxide (iNO) . We evaluated the role of intravenous treprostinil and whether early response classification could inform management. We retrospectively analyzed 114 neonates who had received iNO therapy during the period from 2014 to June 2025. Based on oxygenation index change during the 1st 24 hours after iNO initiation, infants were classified as fast, slow, or non-responders. Treprostinil was used selectively in severe cases; among 32 non-responders, 16 received adjunctive intravenous treprostinil starting at 6 ng/kg/min and titrated to a maximum of 20 ng/kg/min by clinical response. Baseline characteristics and outcomes were compared between treprostinil-exposed and unexposed infants in the overall cohort. In the non-responder subgroup, time to taper iNO to 10 ppm was compared and a multivariable Cox model was fitted. Compared with unexposed infants, the treprostinilexposed group had lower gestational age, higher initial oxygenation index, and more frequent inotropic support, indicating greater illness severity, yet mortality and extracorporeal membrane oxygenation use were not significantly different between the 2 groups. Among non-responders, oxygenation improved more quickly in treprostinil-exposed infants, who achieved iNO tapering to 10 ppm earlier (P = .005) . Treprostinil exposure was independently associated with earlier clinical stabilization in the Cox model (hazard ratio = 4.99, 95% confidence interval: 1.47–16.98, P = .010) . No major adverse effects were observed. In neonates with PPHN unresponsive to iNO, intravenous treprostinil was associated with faster improvement in oxygenation and earlier iNO tapering among non-responders, despite greater baseline severity. Classifying early treatment responses could assist in selecting infants who are more likely to benefit from additional therapies. | | --- | | Abbreviations: ECMO = extracorporeal membrane oxygenation, FiO₂ = fraction of inspired oxygen, iNO = inhaled nitric oxide, MAP = mean airway pressure, OI = oxygenation index, PPHN = persistent pulmonary hypertension of the newborn. | | Keywords: nitric oxide, oxygenation, persistent pulmonary hypertension of the newborn, premature infant, treprostinil | 1. Introduction Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition that can be life-threatening, as it reflects a failure of the normal transition of the circulatory system afterbirth. When pulmonary vascular resistance remains elevated, blood continues to shunt from right to left through fetal pathways, resulting in marked hypoxemia that requires intensive treatment and monitoring. [1] The incidence of PPHN has been estimated at approximately 1.9 cases per 1000 live births. Even with modern advances in neonatal intensive care, many infants still face serious complications, and mortality remains a concern. This burden is especially evident in preterm infants and in those presenting with profound hypoxemic respiratory failure. [2] At the physiological level, PPHN reflects a combination of impaired vasodilation, structural changes within the pulmonary vasculature, and continued vasoconstriction. Together, these factors prevent the normal postnatal decline in pulmonary arterial pressure. [3] First-line management typically includes mechanical ventilation, optimization of fluid and hemodynamic status, and administration of inhaled nitric oxide (iNO), a selective pulmonary vasodilator that targets cyclic guanosine monophosphate pathways to relax the pulmonary vasculature. [4] However, a significant proportion of affected neonates show either incomplete

FAQs

How were neonates classified for treatment response in the study?

Infants were classified as fast, slow, or non-responders based on the change in oxygenation index during the first 24 hours after iNO initiation.

What outcomes differed between treprostinil-exposed and unexposed infants?

In the non-responder subgroup, oxygenation improved more quickly with treprostinil exposure, and iNO tapering to 10 ppm occurred earlier. Mortality and extracorporeal membrane oxygenation use were not significantly different overall.

What did the multivariable analysis show about treprostinil exposure?

Treprostinil exposure was independently associated with earlier clinical stabilization, with a hazard ratio of 4.99 (95% confidence interval 1.47–16.98, P = .010).

Were major adverse effects observed with intravenous treprostinil?

No major adverse effects were observed in the study.

Sep 30, 2026

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