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

Jhao-Jhuang Ding; Chiao-Fan Chiu; Ya-Ting Su; Shih-Hua Lin; Ming-Chou Chiang; Shih-Ming Chu; Tai-Wei Wu; Reyin Lien; Min-Hua Tseng

doi:10.1038/s41390-025-04577-x

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

Pediatr Res. 2025 Dec 6. doi: 10.1038/s41390-025-04577-x. Online ahead of print.

Authors

Jhao-Jhuang Ding^#^{1

2

3}, Chiao-Fan Chiu^#⁴, Ya-Ting Su⁴, Shih-Hua Lin⁵, Ming-Chou Chiang⁶, Shih-Ming Chu⁶, Tai-Wei Wu^{7

8}, Reyin Lien⁶, Min-Hua Tseng⁹

Affiliations

¹ Department of Pediatrics, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan.
² Department of Pediatrics, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan.
³ Division of Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
⁴ Division of Endocrinology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
⁵ Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan.
⁶ Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
⁷ Fetal and Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁸ Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁹ Division of Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. doc31089@gmail.com.

^# Contributed equally.

PMID: 41353515
DOI: 10.1038/s41390-025-04577-x

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Impact: 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.