Elevated hypoxia-inducible factor-1α in pediatric patients with patent ductus arteriosus: a pilot study

Children with complex cyanotic congenital heart disease (CHD) and with pulmonary hypertension (PH) commonly experience hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of cellular responses to low oxygen, and its levels are elevated in these conditions. However, HIF-1α concentrations in non-cyanotic CHD, such as patent ductus arteriosus (PDA), remain largely unknown. This study aimed to evaluate circulating serum HIF-1α levels in patients with PDA and compare them with those in healthy children and in patients with complex CHD after Fontan palliation. Eighty children were assigned to three groups: PDA group ( n = 34), Fontan group ( n = 23), and healthy controls ( n = 23). Complete blood counts, serum HIF-1α levels, and baseline clinical characteristics were collected. Multiple regression analysis was performed to identify predictors of HIF-1α variability. Receiver operating characteristic (ROC) curves were analyzed to evaluate the ability of selected variables to predict increased HIF-1α levels. Patients with PDA exhibited the highest median [IQR] HIF-1α levels (0.62 [0.41–1.18] ng/mL), compared to patients in the Fontan group (0.52 [0.34–0.73] ng/mL), and healthy controls (0.48 [0.33–0.63] ng/mL) ( p = 0.03). In the combined CHD cohort, hemoglobin, age, and red blood cell count formed the best predictive model, explaining 53.9% of HIF-1α variance ( p < 0.01). Hematocrit < 36.6% and hemoglobin < 12.9 g/dL showed the best diagnostic accuracy for identifying HIF-1α > 1.1 ng/mL. Children with PDA, even without PH, exhibit elevated circulating HIF-1α. Further research is needed to clarify the clinical relevance of HIF-1α in non-cyanotic CHD.