Am J Perinatol
DOI: 10.1055/a-1827-7518
Original Article

Pilot Study Investigating Brain Natriuretic Peptide, Troponin, Galectin-3, and miRNA-126a-5p as Biomarkers of Persistent Pulmonary Hypertension in Neonates with Hypoxic-Ischemic Injury Receiving Therapeutic Hypothermia

Eni Jano
1   Division of Neonatology, Department of Pediatrics, NYU Grossman School of Medicine, New York, New York
,
Michelle J. Vaz
2   Department of Pediatrics, NYU Grossman School of Medicine, Bellevue Hospital Center Neonatal Intensive Care Unit, New York, New York
,
Pradeep N. Mally
2   Department of Pediatrics, NYU Grossman School of Medicine, Bellevue Hospital Center Neonatal Intensive Care Unit, New York, New York
,
Elena V. Wachtel
2   Department of Pediatrics, NYU Grossman School of Medicine, Bellevue Hospital Center Neonatal Intensive Care Unit, New York, New York
› Author Affiliations

Abstract

Objective The objective was to evaluate the utility of brain natriuretic peptide (BNP), troponin, galectin-3 (Gal-3), and microRNA (miRNA)-126a-5p as screening biomarkers for persistent pulmonary hypertension of the newborn (PPHN) by comparing expression in serum of infants with hypoxic-ischemic injury that develop PPHN to those that do not.

Study Design This was a prospective, observational pilot study including neonates with hypoxic-ischemic injury undergoing therapeutic hypothermia (TH) at two regional perinatal medical centers. PPHN in this population was diagnosed clinically and confirmed by echocardiogram. Serial measurements of biomarkers were performed from 6 to 96 hours post-TH initiation in 40 patients.

Results Of 40 infants in the study, 10 (25%) developed PPHN and 30 (75%) did not. Baseline demographics and hemodynamics were similar between the groups. Patients with PPHN had a significantly higher need for vasopressors compared with patients without PPHN (70 vs. 27%, p = 0.007). Mean serum BNP and troponin levels were significantly higher in the PPHN group peaking at 12 to 24 hours and decreasing following PPHN treatment initiation. miRNA-126a-5p expression was increased in patients with PPHN compared with patients without, with statistical significance detected at 12 hours (p = 0.005) and 96 hours (p = 0.01). Mean circulating Gal-3 levels were not statistically different between the two groups; however, Gal-3 was elevated in all patients with hypoxic-ischemic injury on TH compared with healthy infants from prior studies.

Conclusion BNP and troponin are readily available, low-cost biomarkers that showed significant serial elevations in the PPHN group of the study and, thus, may have value in screening for PPHN in the setting of hypoxic-ischemic encephalopathy (HIE). Gal-3 was elevated in all patients with HIE and may be a useful biomarker of hypoxic injury in infants being evaluated for TH. Elevations in miRNA-126a-5p were not consistently seen in this study. Larger studies are required to establish an association between PPHN and these biomarkers in patients with and without HIE.

Key Points

  • Serum biomarkers of persistent pulmonary hypertension of the newborn

  • Serum biomarkers of hypoxic-ischemic injury



Publication History

Received: 01 November 2021

Accepted: 11 April 2022

Accepted Manuscript online:
18 April 2022

Article published online:
06 June 2022

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