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The Blue Baby Syndromes

Did environment or infection cause a blood disorder in newborns?

Roger P. Smith

Nitrates to Nitrites

Comly realized that he needed to explain the sensitivity of newborns to nitrates in order to complete the picture. He also needed an explanation for how biologically inert nitrate was responsible for oxidizing hemoglobin to methemoglobin. The most plausible candidate for the oxidizing agent was nitrite, which was known to be a potent generator of methemoglobin. To find it, he needed to look no further than the diverse normal microflora of the infant gut. Many common organisms found in the bowel were known to convert nitrate to nitrite; the nitrite could then be readily absorbed into the blood to do its damage.

In adults, however, ingested nitrates—more than 97 percent of which come from vegetables and other foods, not water—never come in contact with intestinal microflora, which are found largely in the colon. Nitrates are absorbed rapidly in the duodenum and excreted promptly in the urine. That led to a consideration of the second-most common finding in affected infants, namely evidence of gastrointestinal upset in the form of vomiting or diarrhea, things so usual as to excite little attention. A few infants who were tested were found to have high gastric pH in relation to adult values. Presumably the acidic milieu of the stomach and duodenum discourages microflora from invading the small intestine of adults. But if the pH were high enough in newborns, perhaps nitrate-reducing organisms could survive in the small intestine and come in contact with unabsorbed nitrate. This problem should be self-solving as infants mature, because acid production in their stomachs increases to adult levels by about six months of age. That coupled with a relative deficiency in the enzyme that reverses methemoglobin production in infant red blood cells could be enough to explain their sensitivity to nitrates. As Comly’s explanation stands, it is both complete and plausible, but a long way from scientifically proven.

Largely because of Comly’s recommendation, 10 parts per million of nitrate nitrogen quickly became the standard for potable water supplies in the U.S., and that maximum was reaffirmed in 1995 in the most recent review by the National Research Council. Unfortunately, nitrate removal from raw drinking water involves considerable expense. Conventional treatment processes are ineffective. A much more expensive process of ion exchange is the only one currently used. But those at risk—infants under three months of age—are one of the most vulnerable and emotionally charged groups in our population, one that all agree we would most like to protect.

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