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

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.