Describe mechanisms, causes, and effects of neonatal hypocalcemia, and its management.
In the normal transition to extrauterine life, circulating calcium levels reach a nadir at 24–48 hours post-birth. By 48 hours, parathyroid hormone (PTH) responds to this dip with a gradual increase in serum calcium levels. This occurs via a vitamin D–independent mechanism. This normal mechanism can be in disarray if hypomagnesemia leading to poor parathyroid function or, in a subset of infants, PTH does not respond to the calcium nadir in a timely manner, or if end-organ unresponsiveness to PTH occurs for a short time period. Infants who are most at risk for symptomatic early hypocalcemia include preterm infants (<32 weeks), infants of diabetic mothers, and asphyxiated infants. Other infants with risk factors for hypocalcemia include small for gestational age (SGA) infants with other morbidity, infants of pre-eclamptic mothers, and infants of hyperparathyroid mothers. Late hypocalcemia occurs at 7–8 days and historically was due to high phosphate loads with bovine milk and early formulas. Other causes of late hypocalcemia include hypoparathyroidism, vitamin D deficiency, maternal hyperparathyroidism, and renal insufficiency. It is difficult to provide adequate calcium through a peripheral intravenous route, and central venous access is required to avoid tissue necrosis from extravasation. Solubility of calcium and phosphorus limits the amounts that can be provided in parenteral infusions, and such intake is also limited by amino acid intake, volume, cysteine, pH, time, temperature, and lipids. Phosphate salts that improve solubility are available in Europe but not in the United States. Historically, studies to identify the calcium-to-phosphorus molar ratio optimal for retention of both minerals point to a ratio of 1.3:1. However, this research is limited, and a range of molar ratios from 0.8:1 to 1.5:1 may result in similar retention. In fact, studies with high parenteral protein infusion demonstrate optimal calcium and phosphorus retention at a molar ratio of 1:1 for at least the first postnatal days.
Calcium infusion should be provided by 24 hours of life for preterm infants and “sick” infants of diabetic mothers, and asphyxiated infants. Calcium 60–80 mg/kg/day should be provided parenterally. Central access is required to provide this concentration of calcium infusion. Phosphorus 48–60 mg/kg/day should be provided. This amount of phosphorus is difficult to provide intravenously. Absolute minimum parenteral intake amounts to avoid bone demineralization and fracture risk are 52 mg/kg/day of calcium and 31 mg/kg/day of phosphorus. Symptoms of hypocalcemia which include neurological, cardiovascular, neuromuscular irritability (jittery, exaggerated startle), seizures, heart failure, and prolonged QT interval are clear indications for treatment with intravenous calcium.
In early days, normal serum ionized is 1.1–1.3 mmol/L and hypocalcemia <1 mmol/L and <0.9 for preterm infants in early days. Normal serum total is 8.8–12 mg/dL, and hypocalcemia is defined as <7 mg/dL with normal albumin.
The World Health Organization recommends at least 40 mg/kg/day elemental calcium. To match in utero accretion, 90–120 mg/kg/day is required. With the limitations in current parenteral nutrition products, 60–80 mg/kg/day is a realistic goal and should provide adequate intravenous calcium intake. This amount of calcium requires central access for delivery.
Provide 1.3 mmol/kg/day (perhaps 1 mmol/kg/day) phosphorus to avoid bone mineralization deficit and fracture.
Preterm infant receiving early parenteral protein delivery.
Recognize mineral metabolism associated with sustaining preterm infant nutrition from placental to parenteral nutrition.
Current nutritional practices for very preterm infants include protein delivery to at least match intrauterine support. Very low birth weight infant in-hospital growth is improved with parenteral protein delivery of 3–3.5 g/kg/day. Historically, preterm infants did not receive mineral delivery in the first postnatal days, and most received dextrose water after birth, perhaps supplemented with calcium. When protein was not delivered in the early days, cellular metabolism was in a dormant state and intracellular ions, ...