Background: Nitrates in drinking water are generally considered the sole source of nitrite poisoning with methemoglobinemia in infantile methomoglobinemia (IM). However, IM, which occurs during the first 4 months of life, is actually a constellation of cyanosis and hypoxia associated with methemoglobinemia that can result from several other causes.
Methods: This review reexamines the role of nitrate levels in drinking water as a cause of IM and identifies other sources of nitrates that can affect public health and cause chronic diseases.
Results: Causes of IM include nitrites in foods, environmental chemical exposures, commonly prescribed pharmaceuticals, and the endogenous generation of oxides of nitrogen. Infants with congenital enzyme deficiencies in glucose-6-phosphate dehydrogenase and methemoglobin reductase are at greater risk of nitrite-induced methemoglobinemia from nitrates in water and food and from exposures to hemoglobin oxidizers.
Conclusion: Early epidemiological studies demonstrated significant associations between high groundwater nitrate levels and elevated methemoglobin levels in infants fed drinking water-diluted formulas. However, more recent epidemiological investigations suggest other sources of nitrogenous substance exposures in infants, including protein-based formulas and foods and the production of nitrate precursors (nitric acid) by bacterial action in the infant gut in response to inflammation and infection.
Keywords: Congenital methemoglobinemia; drinking water; glucose-6-phosphate dehydrogenase deficiency; nitrates; nitrites.