Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children

Abstract

Objective Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. Methods A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. Results Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. Conclusion The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.

Prevalence of Metabolic Bone Disease in Tube-Fed Children Receiving Elemental Formula

“…Our findings are similar to those of previous cases of metabolic bone disease associated with NC use [15, 16]. The low urinary phosphorus concentration implicates phosphorus malabsorption rather than inappropriate renal phosphate loss.…”

“…Although none of our children had severe complications with hypocalcemia during the transition period, other reports describe patients with more severe complications, including tetany and possible hypocalcemia-associated cardiac arrest [15]. …”

“…A recent international case series described 51 young children and infants (from 17 centers) who developed hypophosphatemia and severe metabolic bone disease while receiving nutritional support primarily from NC [15]. Abulebda et al [16] detailed a young child receiving NC who developed extensive metabolic bone disease leading providers to initially suspect child abuse because of multiple low-trauma fractures.…”

Unexplained case of hypophosphataemic rickets

“…Clinical features of low phosphate include generalised weakness, neurological abnormalities and the development of rickets. The causes of hypophosphataemia can be broadly classified into the following: (i) acute extracellular to intracellular shift, (ii) decreased intake, (iii) decreased intestinal absorption and (iv) increased renal excretion …”

“…It may be seen in premature infants who are purely breastfed with no added fortification. Reduced intestinal absorption may occur in the setting of generalised malabsorptive states, vitamin D deficiency or due to the use of phosphate‐binding agents such as antacids . Increased renal excretion may be due to primary hyperparathyroidism, secondary hyperparathyroidism due to vitamin D deficiency or resistance or primary renal phosphate‐wasting disorders.…”