Oral melatonin adjunct therapy improves echocardiographic parameters and clinical outcomes in neonates with persistent pulmonary hypertension of the newborn.

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European journal of pediatrics Published April 13, 2026 Medically reviewed April 25, 2026 Study authors: Nofal Sarah M, El-Mashad Abdel-Rahman M, Elmesiry Asmaa M, Abouelenain Amany M, Awny Mostafa M PubMed ↗ NCT07090720 ↗ DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Consider oral melatonin as a potential adjunctive therapy for PPHN, but await larger trials with full statistical reporting and safety data.

This randomized controlled trial investigated the effects of oral melatonin combined with standard therapy compared to standard therapy alone in a cohort of 80 neonates (gestational age ≥36 weeks) with persistent pulmonary hypertension of the newborn confirmed by echocardiography. The study assessed left ventricular function via echocardiographic parameters, serum biomarkers of oxidative stress and inflammation, time to weaning from mechanical ventilation, length of hospital stay, and levels of serum HMGB1 and NT-proBNP protein.

The neonates receiving melatonin adjunct therapy exhibited significantly better left ventricular function compared to the control group, as measured by both conventional and advanced echocardiographic parameters. Additionally, the melatonin group experienced earlier weaning from mechanical ventilation and respiratory support, a shorter length of hospital stay, and lower levels of serum HMGB1 and NT-proBNP. The abstract suggests these improvements may be linked to cardioprotective and antioxidative mechanisms, though this remains an interpretation rather than a proven mechanism.

No adverse events, serious adverse events, discontinuations, or specific tolerability data were reported in the study. The authors note that while the findings support melatonin as a promising adjunctive therapy for neonatal pulmonary hypertension, the modest sample size and lack of reported statistical measures limit definitive conclusions. Further investigation in larger clinical trials is warranted to confirm efficacy and establish safety profiles before widespread clinical adoption.

Study Details

Study typeRct

EvidenceLevel 2

PublishedApr 2026

PMID41954764

TrialNCT07090720

View Original Abstract ↓

UNLABELLED: The aim of this study is to investigate the effects of melatonin on the left ventricular (LV) function in persistent pulmonary hypertension of the newborn (PPHN) and to assess its potential role in enhancing cardiac performance and reducing oxidative stress. This randomized controlled trial was conducted on 80 neonates (≥ 36 weeks' gestational age) with PPHN confirmed by echocardiography (Echo). Participants were assigned to receive standard therapy alone or in combination with oral melatonin. LV function was evaluated using echocardiographic parameters, and levels of serum biomarkers of oxidative stress and inflammation were also measured. Unlike the placebo group, the melatonin group exhibited significantly better LV function, regarding the conventional and advanced echocardiographic parameters. Additionally, melatonin administration was associated with earlier weaning from mechanical ventilation (MV) and respiratory support, shorter hospital stays, lower levels of serum high-mobility group box-1 (HMGB1) protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). CONCLUSION: Melatonin can enhance LV function in PPHN, likely through its cardioprotective and antioxidative mechanisms. These findings support melatonin as a promising adjunctive therapy in neonatal pulmonary hypertension, warranting further investigation in larger clinical trials. TRIAL REGISTRATION: registered on ClinicalTrials.gov (ID: NCT07090720), URL: https://clinicaltrials.gov/study/NCT07090720?cond=NCT07090720&rank=1 , Date: (29/7/2025). WHAT IS KNOWN: • PPHN induces hypoxic respiratory failure, jeopardizing multiorgan function, including LV performance. • Oxidative stress is crucial in pulmonary arterial hypertension development. WHAT IS NEW: • Melatonin's antioxidant and vasodilatory properties may serve as an adjunctive therapy in PPHN and enhance myocardial protection from the hypoxic effect of PPHN.

Oral melatonin adjunct therapy improves echocardiographic parameters and clinical outcomes in neonates with persistent pulmonary hypertension of the newborn.

Study Details

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Oral melatonin adjunct therapy improves echocardiographic parameters and clinical outcomes in neonates with persistent pulmonary hypertension of the newborn.

More on Persistent Pulmonary Hypertension of the Newborn

Study Details

Standardized formal resuscitation training likely reduces neonatal mortality in low- and middle-income countries compared to no training or basic training.

A Simple Training Program Is Saving Newborn Lives in Poor Countries

Clinical research that matters. Delivered to your inbox.

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