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

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