Association of Hypocalcemia with Persistent Pulmonary Hypertension in Neonates: A Cross Sectional Study in a Tertiary Care Hospital in Lahore, Pakistan

Abstract

Objective: To determine the frequency of hypocalcemia among neonates with persistent pulmonary hypertension of the newborn (PPHN) and to assess its correlation with disease severity and short-term clinical outcomes.

Methodology: This cross sectional study was conducted in the Neonatal Intensive Care Unit (NICU) of Fatima Memorial Hospital, Lahore. A total of 203 neonates with echocardiographically confirmed PPHN were enrolled consecutively. Ionized calcium was measured within 48 hours of echocardiography. Hypocalcemia was defined as ionized calcium <1.10 mmol/L for birth weight ≥1500 g and <0.90 mmol/L for <1500 g. PPHN severity was graded as moderate or severe. Statistical comparisons were performed using Mann-Whitney U, independent t-test, and chi-square tests, with p ≤0.05 considered significant.

Results: Hypocalcemia was present in 59.6% (121/203) of neonates. Severe PPHN occurred in 53.2% of cases. Ionized calcium levels were lower in severe compared to moderate PPHN (0.992 ± 0.148 vs 1.047 ± 0.149 mmol/L; p = 0.017). Severe PPHN was associated with increased need for invasive ventilation (50.0% vs 27.4%, p = 0.002) and high-frequency oscillatory ventilation (25.9% vs 11.6%, p = 0.016). Mortality was higher in severe PPHN (25.9% vs 15.8%), although not statistically significant (p = 0.087). NICU stay and inotrope use were comparable.

Conclusion: Hypocalcemia is common in neonates with PPHN and lower ionized calcium levels are associated with greater disease severity. These findings suggest a potential role of calcium homeostasis in the pathophysiology and clinical course of PPHN, warranting further evaluation as a modifiable risk factor.

Keywords: Echocardiography, Inotropes, Ionized hypocalcemia, Mechanical ventilation, Neonatal hypocalcemia, Neonatal intensive care unit, Persistent pulmonary hypertension of the newborn, PPHN, PPHN severity