Factors associated with early onset hypocalcemia: A retrospective cohort study

Pediatr Int. 2025 Jan-Dec;67(1):e15849. doi: 10.1111/ped.15849.

Abstract

Background: Early onset hypocalcemia, occurring within 3 days of birth, is prevalent among preterm infants. A central line is required to deliver calcium (Ca). The prediction of hypocalcemia is therefore clinically important when the requirement for initial intravascular calcium administration is anticipated.

Methods: This retrospective study included preterm infants born between 2019 and 2023 with a birthweight <1500 g or a gestational age (GA) <32 weeks in a single tertiary center. Hypocalcemia was defined as serum Ca <7 mg/dL or ionized calcium (iCa) <0.8 mmol/L within 72 h after birth. Perinatal factors and laboratory test results associated with hypocalcemia were collected and analyzed.

Results: Of the 348 infants, 20 died within 7 postnatal days, 22 were transferred to other hospitals, and eight were transferred from other hospitals and were thus excluded. Of 298 enrolled infants, 20 were diagnosed with hypocalcemia. In multivariate analysis, male sex, elevated day 1 phosphorus (d1P), magnesium (d1Mg) levels, and maternal premature rupture of membranes (PROM) were significant risk factors for early onset hypocalcemia. These factors, along with birthweight, a widely recognized risk factor, were used to develop predictive models for early onset hypocalcemia. Among the six suggested models, logistic regression exhibited the highest accuracy. Conversely, the random forest model outperformed others in the Youden index and area under the receiver operating characteristic curve.

Conclusions: In our cohort, early onset hypocalcemia was linked to male sex, lower GA, higher d1P and d1Mg, and maternal PROM. Notably, higher d1P has not been previously reported as a risk factor.

Keywords: hyperphosphatemia; hypocalcemia; infant; parathyroid hormone; premature.

MeSH terms

  • Birth Weight
  • Calcium / blood
  • Female
  • Fetal Membranes, Premature Rupture / blood
  • Fetal Membranes, Premature Rupture / epidemiology
  • Gestational Age
  • Humans
  • Hypocalcemia* / blood
  • Hypocalcemia* / diagnosis
  • Hypocalcemia* / epidemiology
  • Infant, Newborn
  • Infant, Premature*
  • Infant, Premature, Diseases / blood
  • Infant, Premature, Diseases / diagnosis
  • Infant, Premature, Diseases / epidemiology
  • Infant, Premature, Diseases / etiology
  • Infant, Very Low Birth Weight
  • Magnesium / blood
  • Male
  • Phosphorus / blood
  • Retrospective Studies
  • Risk Factors
  • Sex Factors

Substances

  • Calcium
  • Phosphorus
  • Magnesium