A review of evidence for a role of magnesium and possibly copper deficiency in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a neonatal disorder of unknown cause characterized by rapid necrosis of the bowel, primarily the ileum and colon. It is a worldwide problem. NEC is the most common gastrointestinal emergency in the neonatal intensive care unit, and ranks second as a cause of neonatal death. The incidence of NEC is inversely proportional to the birth weight and the degree of maturity. Infants born at or before 28 weeks gestational age have not received 80 per cent of the magnesium and 67 per cent of the copper found at term. Congenital deficiencies of these essential minerals may be compounded by high renal or gastrointestinal losses and high metabolic demand during the preterm infant's accelerated growth. Platelet thrombi appear early in the intestinal microvasculature in NEC. Platelet thrombosis and release of vasoconstrictor, platelet aggregating thromboxane A2 (TXA2) in human NEC appears to potentiate the intestinal ischaemia and necrosis in neonates who develop NEC. Magnesium and copper deficiency each enhance the synthesis of TXA2. Plasma levels of the inflammatory cytokines tumour necrosis factor (TNF) and interleukin-6 (IL-6) are increased in NEC and in magnesium deficiency; these experimentally produce shock and tissue injury, especially of the intestine. The synthesis of the potent vasoconstrictor endothelin is increased in magnesium deficiency. NEC has been regarded as a luminal insult that causes local generation of destructive oxygen free radicals. Tissues from animals deficient in magnesium are more susceptible to oxidative injury and lipid peroxidation than tissues from normal animals. Magnesium and copper deficiency impair antioxidant defence through decreased synthesis of glutathione and reduced activity of Cu/Zn superoxide dismutase, respectively. Although the aetiology of NEC is unknown, there appears to be sufficient data to implicate magnesium and possibly copper deficiencies in the pathogenesis. Consequences of deficiency of one or both minerals may include increased synthesis or activity of injurious mediators: IL-1, IL-6, TNF, TXA2, endothelin, and oxygen free radicals. A prospective trial of magnesium supplementation, but not copper supplementation, in very premature neonates can be recommended, with NEC as one of the outcome measures.