Cord blood glutathione depletion in preterm infants: correlation with maternal cysteine depletion.

BACKGROUND: Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants. OBJECTIVE: Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH. METHODOLOGY: Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry. PRINCIPAL FINDINGS: Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants. CONCLUSION: The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.

Symptomatic acquired zinc deficiency in at-risk premature infants: high dose preventive supplementation is necessary.

Zinc is a cofactor for several enzymes involved in many metabolisms. Zinc deficiency induces various disorders such as acrodermatitis enteropathica, either inherited or acquired. We report three cases of premature infants (24-31 wks gestational age) with low birthweight (650 to 940 g) and enteropathy, two of whom presented with necrotizing enterocolitis. All infants were fed by total parenteral nutrition. At a chronological age ranging from 73 to 80 days, all infants developed a periorificial dermatitis. Before the onset of the first signs, they had received zinc supplementation ranging from 146% to 195% of the recommended dose (400 microg/kg/day). Increased zinc supplementation over a course of 6-18 days induced a complete resolution of symptoms in all cases. No abnormality in the neurologic examination and no recurrence were observed at the end of the zinc treatment. Low birthweight premature infants with enteropathy on total parenteral nutrition are at risk of developing zinc deficiency. The usual recommended zinc supplementation is probably insufficient for those infants. A delay in the diagnosis of zinc deficiency may lead to severe complications.

Fatal effects of a neonatal high-protein diet in low-birth-weight piglets used as a model of intrauterine growth restriction.

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 micromol/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 micromol/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.