Maternal–infant vitamin D coupling and neonatal hypocalcemia: a six-year cohort integrating preterm risk, onset timing, and pandemic effects

Neonatal hypocalcemia is among the most common metabolic abnormalities in early life, particularly in preterm and critically ill infants. Maternal and neonatal vitamin D deficiency, sepsis, and perinatal factors play central roles in its pathogenesis. The COVID-19 pandemic may have further influenced vitamin D status and hypocalcemia frequency. This study aimed to determine the incidence, etiological factors, biochemical characteristics, and treatment outcomes of neonatal hypocalcemia over a six-year period and to evaluate the impact of the COVID-19 pandemic on vitamin D status and hypocalcemia burden. This retrospective cohort included all neonates admitted to the NICU between January 2017 and January 2023 (Ethics Approval No: 3987). Hypocalcemia was defined as total calcium < 8 mg/dL in term infants or < 7 mg/dL in preterm infants and/or ionized calcium < 1.1 mmol/L. Maternal and neonatal demographic, clinical, and biochemical parameters were reviewed. Subgroup analyses compared term vs. preterm infants and early- (< 72 h) vs. late-onset (≥ 72 h) hypocalcemia, as well as pre-pandemic and pandemic periods. Among 3,364 NICU admissions, 322 neonates (9.57%) had hypocalcemia, of whom 72.7% were preterm. Maternal vitamin D deficiency or insufficiency was present in 50.0%, and neonatal deficiency in 72.3%. Sepsis occurred in 50.9% of cases and was significantly more frequent in preterm infants. Late-onset hypocalcemia was characterized by lower 25(OH)D levels and higher parathyroid hormone (PTH) concentrations compared with early-onset cases (both p < 0.05). During the COVID-19 period, the incidence of hypocalcemia increased, maternal and neonatal vitamin D deficiency became more prevalent, and the duration of calcium therapy was longer (all p < 0.05). Neonatal hypocalcemia was frequent, particularly among preterm infants, and was strongly associated with maternal–infant vitamin D deficiency. The distinct biochemical profile of late-onset hypocalcemia and the pandemic-related worsening of vitamin D status underscore the importance of adequate maternal supplementation and vigilant neonatal monitoring.