Magnesium Deficiency in the Cause of the Sudden Infant Death Syndrome: An Updated Hypothesis

Abstract

This is a hypothesis that the sudden infant death syndrome (SIDS, crib death) results from a relative magnesium (Mg) deficiency in respect to calcium in a stressed, young infant. Multiparity in the very young, poor mother living under stressful urban conditions favors the development of maternal and fetal magnesium deficiency. The prematurely born infant has reduced magnesium stores and may have respiratory distress at birth, requiring diuretics and respiratory stimulants that provoke increased urinary loss of magnesium. The relative calcium excess in a stressed infant results in platelet aggregation chiefly in the pulmonary microvasculature with massive release of thromboxane A₂ (TXA₂), catecholamines and other mediators of shock. TXA₂ causes apnea and sudden death by promoting constriction of pulmonary and coronary vessels, bronchoconstriction, and further platelet aggregation. These effects normally are counterbalanced by prostacyclin, PGI₂, which is synthesized in the vascular endothelium. PGI₂ production is curtailed by shock and by endothelial injury imposed by tobacco and cocaine smoke and polluted urban air. TXA₂ is essentially unopposed. Death may be instantaneous or may follow a period of hyperventilation, resulting in well-expanded lungs. The infant's increased physical activity, increased permeability of blood vessels, relative thrombocytopenia, and a brief spike of hypertension from TXA₂ and catecholamines released from platelets contribute to the development of intrathoracic petechiae. A coagulopathy develops, and blood remains fluid. Anaerobic metabolism and magnesium deficiency reduce ATP production. The exhausted infant dies. Death occurs between 2 and 4 months of age, when protection from magnesium, glucocorticoids, and PGI₂ are reduced and when testosterone, which favors platelet aggregation, is increased in males. Biochemically proving magnesium deficiency is difficult in the infant postmortem. A prospective therapeutic trial of magnesium can be recommended.