Fatal Effects of a Neonatal High-Protein Diet in Low-Birth-Weight Piglets Used as a Model of Intrauterine Growth Restriction

Abstract

Background: Although full-term infants suffering intrauterine growth restriction (IUGR) are routinely fed high-protein (HP) formulas to ensure catch-up growth, the effects of HP intake are poorly understood. An IUGR piglet model provides an opportunity to investigate these effects. Methods and Results: Twelve IUGR piglets were artificially fed HP formulas (50% more protein in comparison to sow milk) from the 2nd day of life (d2) until d28. Unexpectedly, all HP piglets developed poor growth, severe hypotonia and polypnea between d10 and d16. One third died spontaneously. This syndrome was investigated to understand its pathophysiology and to adopt a strategy to restore health. Blood and urine biochemistry and amino acid concentrations were investigated in 10 HP piglets and 8 piglets that were fed a normal-protein (NP) formula. In comparison to NP piglets, HP piglets showed significant hypokalemia (2.7 ± 0.6 vs. 3.6 ± 0.6 mmol/l; p < 0.01), hypophosphatemia (1.5 ± 0.2 vs. 3.0 ± 0.3 mmol/l; p > 0.01), hypercalcemia (3.0 ± 0.3 vs. 2.5 ± 0.2 mmol/l; p < 0.01), hyperammonemia (365 ± 4 vs. 242 ± 15 µmol/l; p < 0.05), elevated blood urea (6.5 ± 0.4 vs. 1.3 ± 0.4 mmol/l; p < 0.01) and elevated taurine concentrations (50.2 ± 8.5 vs. 17.7 ± 2.7 µmol/l; p < 0.01). Conclusions: These altered parameters indicated inadequate potassium and phosphorus dietary supplies in HP piglets. When the HP formula was supplemented with monocalcium phosphate and monopotassium phosphate (HP-sup), serum biochemistry was normalized in piglets fed this formula (n = 8). This experimental strategy restored growth in IUGR piglets fed HP-sup, without a toxic effect. The current findings suggest that use of an HP formula without a proportional increase in its phosphorus and potassium content induces pathology similar to the refeeding syndrome in IUGR piglets.