Neonatal Hypocalcemia

What is Neonatal Hypocalcemia?

Hypocalcemia is a condition in which there is low calcium in the blood. In children, hypocalcemia occurs due to malnutrition, premature birth, genetic disorders, and endocrine disorders. 

Total Body Calcium:

99 percent (Skeletal system bone) 

1 percent (ECF)

Complex calcium is the one that is bound to another anion of the body, like it can be bound to lactate, citrate, or phosphorus.

Serum Calcium

Serum albumin levels are physiologically low in preterm children or in cases of sepsis (within 1st week). A common reason for the falsely low-ionized calcium in a child is heparin contamination. Low ionized calcium level is mainly seen in a patient having alkalosis. For every rise in arterial pH by 0.1, there is a fall in ionized calcium level by the value of 0.16 mg/dL. Serum calcium is depicted in two forms:

Total Serum Calcium (tSCa)

This is not very accurate, particularly in the first week of newborns. It is mainly affected by low serum albumin levels. In patients with hypoalbuminemia, the total serum calcium is reduced even if the ionized calcium is normal. For every 1 g/dL fall in the serum albumin, the total serum calcium level falls by 0.8 mg/dL.

Ionized Cerum Calcium (iSCa)

Accurate, especially in the first week of the life of a newborn.

Also read: Fetal Assessment: Key Evaluations & Prenatal Diagnosis

Events in fetal life

Active calcium transmission occurs from mother to fetus in the third trimester (maximally). Up to 80% of the transmission occurs in the third trimester. However, 20% of transmission

occurs in the first and second trimesters. The ratio of mother to fetal calcium level is in the range of 1:1.14. The most important factor controlling mother-to-fetus calcium transfer is PTHrP

(Parathyroid hormone-related peptide): 

• Parathyroid hormone-related peptide is produced from the parathyroid gland.
• PTHrP is known to cause hypercalcemia in malignant disorders.
• PTHrP is involved in the mother-to-child active transfer of calcium.

Vitamin D plays the least important role in the transfer of calcium from the mother to the fetus.

What is PTHrP?

It is coded by a gene on the short arm of chromosome 12p. It is homologous to the parathyroid hormone in the first thirteen amino acids present on the amino terminal (-NH2) in the child. It is produced by the fetal parathyroid gland.

Also read: WHO Recommendations For Care Of The Preterm Or Low Birth Rate

Types of Neonatal Hypocalcemia

Early-onset Neonatal Hypocalcemia (ENH):

Highly common. It is usually asymptomatic and can be symptomatic if it is very severe. The onset of signs and symptoms will be in the first 96 hours of birth.

Late-onset Neonatal Hypocalcemia (LNH):

Relatively rare. It is usually symptomatic. The onset of signs and symptoms will be beyond 96 hours of birth.

Etiology of Early-onset Neonatal Hypocalcemia (ENH)

Prematurity

Due to the premature stoppage of the transplacental calcium transfer to the fetus. Due to an increase in calcitonin level. Due to a decrease in responsiveness of the tissue to the PTH action.

Perinatal Asphyxia

Perinatal asphyxia occurs due to delayed feeds. Increase in phosphate level due to the tissue catabolism. Due to deranged renal function. Due to a decrease in the PTH activity or due to the secretion of asphyxia.

Infant of Diabetic Mother

Macrosomia increases the requirement of calcium level. The decreased magnesium level leads to functional hypoparathyroidism in the first week of life and causes hypocalcemia.

Maternal Hyperparathyroidism

Maternal hyperparathyroidism causes pseudo-hypoparathyroidism in the baby. A maternal increase in PTH level leads to a maternal increase in calcium level. Further, it suppresses the PTH activity in the baby.

Maternal Anticonvulsants

It occurs due to drugs like phenytoin and phenobarbitone. It interferes with the maternal vitamin D metabolism and indirectly also interferes with calcium transfer to the baby.

Iatrogenic

When giving bicarbonate therapy to the baby in the first week of life, it can cause alkalosis, which causes a decrease in the ionized calcium. Phototherapy causes a decrease in melatonin and an increase in the calcium level in bones, which further decreases the calcium and causes ENH. By giving DVET (double volume exchange transfusion) therapy, citrate chelates the ionized calcium.

Also read: Fungal Infections In Neonates

Clinical Representation (Early-onset Neonatal Hypocalcemia)

• Asymptomatic: common

Symptoms

• Non-specific
  • Poor feeding
  • Vomiting
  • Lethargy
  • Apnea
  • Tachypnea
  • Laryngospasm
• Neuromuscular irritability
  • Jitteriness
  • Seizures
  • Myoclonic jerks
  • Exaggerated startle response
• Cardiac features
  • Tachycardia
  • CCF
  • Arrhythmias
  • Prolonged QTc interval
  • Decreased cardiac contractility

Also read: Approach To A Floppy Infant

Investigations in Early-onset Neonatal Hypocalcemia

Investigation of choice includes ionized serum calcium level or serum calcium level

ECG: It is the supportive evidence. The likelihood of a child having hypocalcemia and the QTc interval is not very accurate in the first week of life. Prolonged QTc intervals: If the QTc level is more than 0.45 seconds, then it indicates or supports the evidence of ENH. QTc interval: beginning of Q wave to end to T wave: > 0.45 sec. QoTc interval (beginning of the Q wave to the beginning of the T wave) > 0.22 seconds.

Treatment of ENH (Early-onset Neonatal Hypocalcemia)

It is divided into two parts:

In case of asymptomatic ENH: 

10% calcium gluconate: 8 ml/kg/day (80 mg/kg/day of elemental calcium) either in the form of oral or IV for about 48 hours.  The preferred route is oral. Further, the above dose is given for 24 hours and then stopped.

In case of symptomatic ENH: 

10% of calcium gluconate IV bolus: 2 ml/kg in a diluted ratio of 1:1 in 5% dextrose is given over 10-15 minutes and under ECG monitoring. Further followed by the continuous IV infusion of 80 mg/kg/d for around 48 hours and then half the dose for 24 hours and then stopped.

Also read: Temperature Control In Neonates

Prolonged or Resistant Hypocalcemia

Symptomatic hypocalcemia is unresponsive to adequate doses of calcium therapy. Infants needing calcium supplements for more than 72 hours of age. Hypocalcaemia presenting at the end of the first week.

Late-onset of Hypocalcaemia

Late-onset hypocalcemia, which is usually symptomatic, occurs after the first 72 h and generally by the end of the first week of birth.

Investigations in LNH

For the first-line investigation:

• Serum calcium: either total serum calcium level or ionized serum calcium levels.
• Serum phosphate level
• RFT
• LFT
• Serum alkaline phosphatase
• ABG particularly the arterial pH.
• Chest x-ray with or without wrist x-ray.

Second-line investigation:

• Serum magnesium level
• Serum PTH levels
• Serums 25-hydroxy vitamin D level
• Urine Ca:Cr
• Maternal calcium profile

Also read: Skull Fractures And Traumatic Intracranial Hemorrhage

Treatment of LNH

Hypomagnesemia: Injection of 0.2 ml/kg of 50% MgSO4 deep intramuscular of two doses 12 hours apart. Further followed by the maintenance dose of 0.2 ml/kg/day orally for three days

High phosphate load: Encourage EBF, Avoid animal milk, No role of phosphate binders in neonates

VDDR: Give some form of activated vitamin D: calcitriol (30–60 ng/kg/day).

Hypoparathyroidism: Target calcium-to-phosphate product, which should be less than 55. Initially, Start calcium in a Dose of 50 mg/kg/day in 3 divided doses along with activated vitamin D (Calcitriol) to be

added.

Prognosis

Most ENH resolve in 48-72 hours. LNH secondary to excess phosphate load or hypomagnesemia responds well to the therapy. LNH secondary to the maternal hyperparathyroidism resolved in 6 weeks. LNH due to the baby's hypoparathyroidism needs long-term therapy.

Important Points to Remember 

• Cloherty Says
• Calcium monitoring in asymptomatic infants
• In whom to do:
  • VLBW (Very low birth weight)
  • Infant of a diabetic mother
  • Perinatal asphyxia
• What to check: Serum-ionized calcium
• Timing: 12,24,48 hours of life
• If found Hypocalcemic: Check serum phosphate and serum magnesium additionally
• No role of routine vitamin D estimation in asymptomatic infants
• No role of routine ECG in asymptomatic infants.
• IV calcium is always given under ECG monitoring due to the risk of bradycardia and arrhythmias. Continuous IV infusion is better than frequent boluses. Every 2 hours, check for the IV catheter sites, as the extravasation of the calcium can cause skin necrosis. Never give calcium gluconate via umbilical artery catheter, as it can cause arterial spasms and intestinal necrosis. If given via the umbilical vein, ensure the tip of the catheter is in IVC. If the tip is in the portal vein or its branch, it can cause hepatic necrosis.
• The most important hormone for prenatal use is PTHrP. The most important hormone for postnatal life, especially the first week of Life is PTH and later it will be PTH along with vitamin D and calcitonin. GIT absorption and renal handling of calcium matures at 2 - 4 weeks of postnatal age.

Also read: High-Yield Image Based Questions On Neonatology

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