ArticleBMC pediatrics2026
Association between serum methemoglobin levels and hemodynamically significant patent ductus arteriosus in preterm infants: a retrospective cohort study.
Article in BMC pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPulmonary overcirculation secondary to a hemodynamically significant patent ductus arteriosus (hsPDA) increases endothelial shear stress, triggering the release of endogenous nitric oxide (NO). Since NO rapidly oxidizes hemoglobin to methemoglobin (MetHb), we hypothesized that preterm infants with hsPDA would exhibit elevated serum MetHb levels. This study aimed to investigate the association between peak MetHb levels and hsPDA requiring treatment.
methodsThis retrospective cohort study included preterm infants (< 34 weeks' gestation) admitted to a tertiary NICU. Infants were stratified into two groups: those requiring pharmacological or surgical treatment for hsPDA (hsPDA group, n = 30) and those not requiring treatment (Control group, n = 96). MetHb levels were obtained from routine daily arterial blood gas analyses performed during the first 7 postnatal days. The primary outcome was the comparison of peak MetHb levels between groups.
resultsInfants in the hsPDA group were significantly more immature (26.8 vs. 30.1 weeks; p < 0.001). While baseline (Day 1) MetHb levels were comparable, the hsPDA group exhibited significantly higher Peak MetHb levels during the first week compared to controls (3.58% ± 0.25 vs. 3.32% ± 0.35; p = 0.004). This elevation was most pronounced on postnatal days 3 and 4. In a refined multivariate logistic regression model adjusted for gestational age, invasive ventilation duration, and early erythrocyte transfusion, elevated Peak MetHb remained independently associated with hsPDA (Adjusted Odds Ratio: 1.76; 95% CI: 1.08-2.88; p = 0.024). A Peak MetHb cutoff of > 3.4% demonstrated significant predictive value (AUC = 0.74). Synchronized analysis at physical ductal closure confirmed a significant drop in MetHb levels (p < 0.001), indicating dynamic reversibility.
conclusionsSevere hsPDA is associated with a significant, transient elevation in serum methemoglobin levels during the first week of life. While this observational data cannot establish causality, the 'oxidative spike' may reflect the systemic spillover of endothelium-derived nitric oxide released in response to pulmonary overcirculation. With further prospective validation, monitoring MetHb trends could serve as an accessible adjunctive marker to aid in evaluating the hemodynamic burden of a patent ductus arteriosus.
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