Hypocalcemia and Neonates

Neonatal HypocalcemiaUnquestionably, a lot of electrolyte panel laboratory studies get ordered reflexively and have little true clinical utility. The healthy kid (or adult for that matter) with vomiting and diarrhea for two days does not typically benefit from the “Chem 200” {recall, dehydration is a clinical diagnosis}. Labs are useful when they help answer specific questions that they are capable of answering (ex, is the kid hypoglycemic? Not, is the kid dehydrated). That being said, certain populations have varying risks for electrolyte disturbances – one notable one is the neonate (goes along with “never trust a neonate.“). Let us look at one interesting issue – Hypocalcemia in the Neonate.


Hypocalcemia: Basics

  • Calcium forms:
    • Majority of total body calcium is stored in bone.
    • ~40% of serum calcium is protein-bound and not active.
    • ~50% of total serum calcium is ionized (Ca2+) and is biologically active.
    • Total body calcium may remain stable, but the amount of ionized calcium can be altered by chelation and protein binding.
      • Increases in phosphate, citrate, bicarbonate will chelate calcium decreasing ionized calcium.
      • Free fatty acids and an Alkaline pH increases Ca2+ binding to proteins.
      • Acidotic pH decreases Ca2+ binding to proteins.
  • Calcium homeostasis is complex! [Kelly, 2013]
    • Parathyroid Hormone (PTH) directly increased serum calcium levels.
      • Influences bone (release of Ca) and kidneys (absorb Ca)
    • PTH indirectly causes increased GI absorption of Ca via Vitamin D.
    • Calcitonin lowers Ca by targeting bone, renal, and GI tissues.
    • PTH levels are influence by:
      • Elevated Ionized Ca – lowers PTH.
      • Elevated magnesium levels – also inhibit PTH secretion.
        • Interestingly, severely deficient magnesium levels can also inhibit PTH secretion.
      • Severe burns and sepsis can also reduce PTH.
  • Fluctuations in ionized calcium is responsible for symptoms.


Hypocalcemia in the Neonate

  • Neonates are particularly at risk for hypocalcemia.[Thornton, 2013]
    • Fetal skeleton has a high demand for calcium and phosphorus.
    • The mother provides additional calcium to the fetus.
      • The fetus is hypercalcemic relative to the mother.
      • The high serum Ca2+ in the fetus leads to low PTH.
      • Once born, the maternal calcium source is cut off (literally).
      • The parathyroid gland has a blunted response initially, and calcium levels fall.
      • Gestational age is associated with the infant’s parathyroid gland’s ability to respond appropriately (prematurity leads to greater risk).
        • Hypocalcemia is a common consideration in the NICU.
  • Neonatal Hypocalcemia is classified as either Early or Late.
    • Early:
      • Occurs within first 3 days of life.
      • Immature parathyroid gland produce low levels of PTH.
      • Immature kidneys are less responsive to PTH.
      • More commonly seen with:
        • Premature infants
        • Low birth weight infants
        • Infants born to mothers with diabetes
        • Infants born to mothers with hypercalcemia
        • Perinatal asphyxia
    • Late:
      • Occurs after first 3 days of life
      • Classically due to excessive phosphate load (ex, drinking too much cow’s milk, phosphate enemas)
      • Other causes include:
        • Congenital defects in PTH production, secretion, or action
          • DiGeorge sequence – triad of absence of thymus, congenital hypoparathyroidism, and cardiac anomalies.
          • Isolated hypoparathyroidism can be caused by several gene mutations.
          • Pseudohypoparathyroidism – target tissue is resistant to PTH (so PTH level is high, but Calcium is low).
        • Magnesium deficiency
          • Infants who are small for gestation age are at risk.
        • Vitamin D deficiency


Hypocalcemia: Presentation

  • In general, hypocalcemia leads to neuomuscular irritability.
    • Tetany
    • Muscle cramps
    • Fatigue
    • Irritability
    • Distal extremity paresthesias
    • Circumoral numbness (in older patients able to report this)
    • Prolonged QTc
  • Severe hypocalcemia can lead to:
    • Bronchospasm (may mimic asthma)[Kelly, 2013]
    • Focal or Generalized Seizures
      • Neonatal Seizures should not be approached similarly to other seizures.
      • An etiology is found in ~90% of neonatal seizures. [Thornton, 2013]
  • Hypocalcemia can be seen in the critically ill patient as well. [Kelly, 2013]


Hypocalcemia: Treatment

  • Two most common calcium solutions for acute IV administration:
    • 10% Calcium Gluconate
      • 10 mL ampule has 90 mg of elemental calcium.
      • Lower osmolality
      • Can be given peripherally.
    • 10% Calcium Chloride
      • 10 mL ampule has 272 mg of elemental calcium. (that’s 3 times as much!)
      • Hyperosmolar – better to give via Central access (or in a CODE)
    • Bolus of calcium can transiently increase calcium levels, but serum levels will fall again after ~30 min.
  • Magnesium depletion is a common associated finding in the critically ill – consider magnesium administration as well.


Moral of the Morsel



Kelly A1, Levine MA. Hypocalcemia in the critically ill patient. J Intensive Care Med. 2013 May-Jun;28(3):166-77. PMID: 21841146. [PubMed] [Read by QxMD]

Thornton MD1, Chen L, Langhan ML. Neonatal seizures: soothing a burning topic. Pediatr Emerg Care. 2013 Oct;29(10):1107-10. PMID: 24084610. [PubMed] [Read by QxMD]

Walton DM1, Thomas DC, Aly HZ, Short BL. Morbid hypocalcemia associated with phosphate enema in a six-week-old infant. Pediatrics. 2000 Sep;106(3):E37. PMID: 10969121. [PubMed] [Read by QxMD]

Lynch RE1. Ionized calcium: pediatric perspective. Pediatr Clin North Am. 1990 Apr;37(2):373-89. PMID: 2184403. [PubMed] [Read by QxMD]


Sean M. Fox
Sean M. Fox
Articles: 583


  1. We recently cared for a young infant with stridor as her initial presentation of hypocalcemia. Airway anomalies considered but calcium not checked. Later presented with cardiac arrest. Unfortunately, she had a poor neurologic outcome.

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