Hypothesis: The Role of Magnesium and Possibly Copper in the Pathogenesis of Chronic Lung Disease of the Premature Infant

Abstract

This hypothesis states that magnesium (Mg) and copper (Cu) deficiencies are major contributors to the pathogenesis of chronic lung disease or bronchopulmonary dysplasia (BDP) in premature infants. Infants born before the third trimester of pregnancy have not yet received two thirds of the Mg and Cu found at term. Over 50% of such very premature infants develop respiratory distress syndrome (RDS), which is characterized by increasing respiratory distress with pulmonary edema and atelectasis. Spontaneous recovery often begins on the third day. However, the sickest infants, those who experience recurrent apnea and bradycardia (A/B), may develop BPD, defined as respiratory sequelae that require oxygen for more than 28 days after birth. The BPD lung shows fibrosis, smooth muscle hypertrophy, and alternating atelectatic and emphysematous alveoli. A/B episodes of the premature infant resemble those in audiogenic A/B shock in Mg-deficient weanling rats, with similar pulmonary pathology that resolves spontaneously in survivors. In the rat, electron microscopy reveals aggregated platelets in the pulmonary microvasculature. Specific pharmacologic blockade of the platelet aggregator, vasoconstrictor, and bronchoconstrictor, thromboxane A² (TXA₂) aborts or attenuates the A/B shock in the rat, implicating TXA² in that model. In the infant with BPD, TXA₂ is greatly exaggerated over its biological opponent prostacyclin (PGI₂). The TXA₂:PGI₂ ratio is also greatly increased in both Mg deficiency and Cu deficiency. Since supplementary Mg attenuates apnea in premature neonates, Mg would presumably reduce A/B shock and the shock lung. This would decrease the requirement for high concentrations of oxygen and high insufflation ventilation pressures. The pathogenesis of BPD has been largely attributed to these life-saving measures.