Neonatal hypocalcemia caused by maternal hypercalcemia: clinical characteristics, etiology, treatment, and outcome

Maternal hypercalcemia is a rare but potentially serious cause of late-onset neonatal hypocalcemia. Data on the clinical characteristics and outcomes of mother-baby couplets with maternal hypercalcemia and subsequent neonatal hypocalcemia remains scarce.

This retrospective study reviewed medical records of neonates with late-onset hypocalcemia (≥3 days after birth) caused by maternal hypercalcemia at a tertiary medical center in Taiwan from 2014 to 2021. A stepwise diagnostic approach was applied to exclude other secondary causes. The etiologies of maternal hypercalcemia were assessed. Clinical outcomes and treatment responses of the mother-infant dyads were extracted from follow-up records documented during routine clinical care.

A total of seven neonates (6 males, 1 female) were documented. All affected neonates presented with seizure between 5 and 12 days of age. Laboratory findings revealed hypocalcemia (median: 5.3 mg/dL), hyperphosphatemia (median: 10.2 mg/dL), inappropriately intact parathyroid hormone (median: 18.4 pg/mL), and low 25-hydroxyvitamin D₃ levels. Neonates born to mothers with severe hypercalcemia (≥11 mg/dL) had lower serum calcium and higher phosphorus levels compared to those with maternal calcium <11 mg/dL. For all neonates, hypocalcemia and hyperphosphatemia normalized within one month with calcium and 1,25 (OH)₂ Vit. D₃ supplement. During a median 2-year follow-up period, there were no recurrent hypocalcemia cases. One child had delayed speech. Maternal evaluation revealed functional parathyroid adenomas in six of seven (86%) mothers; four underwent parathyroidectomy; two received conservative treatment. One mother with a CASR mutation achieved normocalcemia with calcimimetics. All mothers recovered without serious sequelae.

Late-onset neonatal hypocalcemia should prompt maternal calcium evaluation even in asymptomatic mothers. Maternal total serum calcium levels ≥11 mg/dL may require more intensive neonatal monitoring and prolonged treatment. Genetic testing should be considered in mother with negative result of parathyroid scan.

This study provides the first comprehensive analysis of maternal hypercalcemia-induced neonatal hypocalcemia, identifying functional parathyroid adenomas as the predominant cause (86%). Maternal calcium levels ≥11 mg/dL correlate with more severe neonatal hypocalcemia, establishing evidence-based risk stratification for clinical management. Emphasizes routine maternal calcium screening in late-onset neonatal hypocalcemia and genetic testing when parathyroid imaging is negative. Demonstrates excellent prognosis with complete biochemical normalization in all neonates within three months and minimal long-term neurodevelopmental sequelae.