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Early Mineral Metabolism in Very-Low-Birth-Weight Infants

Pieltain, C.; Rigo, Jacques

Journal of Pediatric Gastroenterology & Nutrition: April 2014 - Volume 58 - Issue 4 - p 393
doi: 10.1097/MPG.0000000000000250
Invited Commentaries

University of Liège, Department of Neonatology, CHU Liège, CHR Citadelle, Liège, Belgium.

Address correspondence and reprint requests to Jacques Rigo, Department of Neonatology, CHR Citadelle, Blvd du XII de Ligne 1, 4000 Liège, Belgium (e-mail:

Received 12 November, 2013

Accepted 12 November, 2013

The authors report no conflicts of interest.

See “Early Postnatal Calcium and Phosphorus Metabolism in Preterm Infants” by Christmann et al on page 398.

Avoiding the development of hypophosphatemia during the first week of life could be a major issue for very-low-birth-weight (VLBW) infants (1,2). Phosphate content is abundant in the cells because it represents the main anion in the intracellular space. It enters into the composition of the nucleic acids, the adenosine triphosphate, and the cell membrane (3,4). In addition to its role in bone mineralization, phosphorus (P) plays a major role in energy metabolism, acid-base status, and cellular growth, and P depletion could be associated with potential deleterious outcomes, such as nephrocalcinosis, insulin resistance (5), and nosocomial infection (6).

Christmann et al (7) provide an illustration of the physiology of the mineral metabolism in preterm infants during parenteral and enteral nutrition (1,2). Calcium (Ca) and P supplies in parenteral and enteral routes are not metabolically equivalent. In parenteral nutrition, Ca and P are directly available for bone deposition as hydroxyapatite with a Ca/P molar ratio of 1.66. In addition, P is necessary for lean body mass accretion accounting for ± 0.33 mmol (10 mg) of P per gram of protein retention. In cases of relative P deficiency, available P is primarily oriented to the cellular metabolism, reducing bone mineralization or inducing bone resorption. Biochemical signs of P deficiency are the development of hypophosphatemia, hypophosphaturia, hypercalcemia, hypercalciuria, and an increase in the renal tubular reabsorption of P (TrP) > 95%.

During the first week of life, Christmann et al (7) provided parenteral nutrition with a Ca/P molar ratio of 1.6 combined with human milk enriched from a starting intake of 50 mL/day onward. The combined use of a parenteral solution (PS) with a Ca/P molar ratio in the range of the bone deposition and unfortified human milk with a relative P deficiency could explain the development of the mineral metabolic disorder. Similar data were reported with the use of a PS with a Ca/P molar ratio of 2.0 and 1.2, respectively (3,6). Optimal P content in PS could be estimated on the basis of the Ca and the amino acid contents (1,3). An adequate Ca/P molar ratio would be close to 1.0 or below 1.0 in the case of high amino acid intake > 2.5/kg/day from the first day of life (1,4). Early P requirement is also increased in VLBW infants with intrauterine growth restriction (8).

After the second week of life, infants were adequately fed enterally, with a minimal contribution of parenteral nutrition (7). P supplementation was still provided to more than 50% of the preterm infants during the third and fourth weeks. Mean total Ca and P intakes were approximately 3.5 mmol of Ca and 3.2 mmol · g−1 · day−1 of P with a Ca/P molar ratio of 1.1. This value below the recommended values for enteral nutrition (9) was associated with an increased urinary P excretion and a large reduction in the TrP below 80%, suggesting a relative P overload. During enteral nutrition, the optimal Ca/P molar ratio depends both on the Ca absorption rate and the protein retention, and is inversely related to the protein retention (1,2). The study by Christmann et al clearly demonstrates that urinary excretion of P and TrP are both sensitive markers in the evaluation of the relative P overload.

The potential role of serum alkaline phosphatase (sAP) as a marker of bone disorder related to P deficiency was not fully addressed by Christmann et al (7). The mean sAP was within the normal range at birth. It increased rapidly, to reach a maximum value by day 7. This maximum level was significantly higher in the group receiving P supplementation. Unfortunately, the unsupplemented group was heterogeneous, with only 32 of 54 infants without any P supplementation during the first week of life. The sharp decrease in sAP from day 7 to week 3 could provide additional evidence of the value of sAP as a sensitive marker of P depletion and bone disorder in VLBW infants. Additional analysis of the relation between the minimum level of serum P concentration during the first week of life and the sAP at day 7 could provide additional evidence and should be developed in a future article.

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