Fatal Outcome of Methemoglobinemia in an Infant
Carl J.Johnson, MD; Pamela A.Bonrud, MS; Terrance L.Dosch; Arthur W.Kilness, MD; Kenneth A.Senger; Darron C.Busch; Michael R.Meyer, MS
CASES of methemoglobinemia in infants and older members of farm families are probably more common than we realize. A 1950 report lists 144 cases of infant methemoglobinemia with 14 deaths in one 30-month period alone in Minnesota.1 In a 1982 survey of 353 physicians in the ten-county Big Sioux region in eastern South Dakota, 29 physicians reported having treated about 80 cases of methemoglobinemia, of which 64 had occurred more than ten years earlier.2 All but one case occurred in infants. This preventable, treatable intoxication continues to contribute to infant mortality today.
Report of a Case
A female infant born on April 30, 1986, was breast-fed at first and later received supplementary feedings with a powdered formula mixed with well water. The mother took her to the family physician for a one-month checkup on May 30. At that time, she looked quite healthy, although the mother reported blueness around the infant’s mouth and of the feet and hands after about 2 weeks of age. This discoloration would come and go. The mother also noted that her daughter had experienced some trouble in breathing and had occasional diarrhea and vomiting. The blueness was attributed by her physician to changes in room temperature.
On June 21, 1986, the mother visited a
pharmacy with the infant. The pharmacist commented that it looked as if the infant was not getting enough oxygen. The infant was given progressively larger amounts of the powdered infant formula prepared with well water. One week later (June 28), the infant began to vomit and had severe diarrhea and severe cyanosis. The parents rushed her to their physician who gave her oxygen for about 15 minutes. However, the infant’s color did not improve. The physician noticed a heart murmur and referred the family to a hospital in another town 33 miles distant for further treatment. The infant stopped breathing during the trip. She was given cardiopulmonary resuscitation after arrival at the hospital but could not be resuscitated. The infant’s blood was noted to be chocolate-brown. The well water at the farm was subsequently found to have a concentration of about 150 mg/L (150 parts per million [ppm]) of nitrate as nitrogen.
Background.—In rural states, such as South Dakota, Minnesota, Nebraska, and Iowa, a large proportion of the population relies on water from individual wells. In 1980, there were 56512 domestic wells in use in South Dakota, providing water to 131700 people. About 66% of these were farm wells.3 There are special problems with the safety of well water for drinking due to poor construction and/or improper location, which may permit infiltration of surface waters contaminated with nitrates as well as other chemicals or microorganisms. (This is especially true of shallow wells, which easily become contaminated during periods of flooding, when runoff may contain chemical fertilizers from nearby cultivated fields. Similar problems can also occur following a heavy rainfall in drought-stricken areas.) A 1981 survey of more than 1000 wells in the Big Sioux river basin found that 27% of the wells had greater concentrations of nitrate in the water than permitted by the Environmental Protection Agency (EPA) (10 ppm or 10 mg/ L of nitrate as nitrogen).4 About 30% of the wells were contaminated with coliform bacteria.
Wells are most often contaminated by nearby feed lots, barnyards, or septic tank systems. In one study, 39% of dug or bored wells were unsafe due to high nitrate content, and 44% were unsafe due to contamination with coliform bacteria. Corresponding data for drilled wells were 22% and 26%; for driven wells, 16% and 8% were unsafe. Properly constructed wells more than 30 m (100 ft) deep are more likely to be safe.5 Average concentrations of nitrates were 25 ppm in the dug or bored wells, 12 ppm in the drilled wells, and 7 ppm in the driven wells. In a recent review by D.Miller of the South Dakota Department of Water and Natural Resources (written communication, Dec 13, 1984) of more than 1000 well water samples sent for testing, 4% of the samples had concentrations greater than 100 ppm, 9% were greater than 50 ppm, 17% were greater than 20 ppm, and 27% exceeded 10 ppm, the EPA maximum contaminant level (samples were probably repeated for some wells). A comprehensive survey of individual well water quality in South Dakota has not been done.
Reprinted with permission from JAMA 257(20):2796–7, Copyright 1987, American Medical Association.
Although persons at any age may be affected by methemoglobinemia, infants are particularly susceptible during the first four months of life.6 Newborn infants normally have a low concentration of methemoglobin reductase (erythrocyte cytochrome 5β-reductase), an enzyme that reduces methemoglobin. This concentration remains low until after 4 months of age.5
Infants who are breast-fed may possibly get some nitrite or nitrate in breast milk, but poisoning usually occurs when infant formula and other infant foods are prepared with contaminated water. Boiling the well water merely concentrates the nitrate. Nitrates do not directly reduce hemoglobin to methemoglobin but can be converted by intestinal microflora to nitrite, which can produce methemoglobinemia.6 Aniline dyes may be absorbed through the skin and also cause methemoglobinemia.6 Other chemical agents that cause methemoglobinemia include naphthalene and menadione (vitamin K3). Chronic effects of subclinical levels of methemoglobinemia on growth, development, and general health apparently have not been studied.
Diagnosis.—When an infant is severely cyanotic with a relative absence of distress, methemoglobinemia should be suspected. These infants have a peculiar lavender color.7 Blood from the heel stick is chocolate-brown and does not become pink when exposed to room air. Diagnosis can be confirmed by excluding other causes of cyanosis and by spectrophotometric analysis of blood for methemoglobin, which has a characteristic absorption peak at 634 µm. When methemoglobinemia levels reach 60% or greater, the patient will collapse and become comatose and may die.6
Treatment.—Patients who are only mildly affected do not require treatment, other than to avoid the contaminated source.6 The methemoglobin levels will be reduced spontaneously over a period of two or three days. A severely affected patient requires therapy with methylene blue.6,7 It may be sufficient to give 1 to 2 mg/kg of body weight of a 1% solution of methylene blue in saline intravenously over a ten-minute period. This converts the methemoglobin to hemoglobin and usually results in prompt relief of distress. If there is not an adequate response within an hour, a second dose can be administered. After the intravenous administration of methylene blue, it can be followed by 3 to 5 mg/kg of methylene blue orally or 200 to 500 mg of ascorbic acid orally.7
Prevention.—Because the consumption of well water with chemical or bacterial contamination may have serious consequences, especially for pregnant women and infants, physicians and community health nurses should be alert to this problem. Such wells should be tested annually to ensure their safety, especially before a new mother returns home with her infant. Further, the quality of well water may deteriorate overnight or change because of drought, a heavy rainstorm, flash flooding, spring thaw, or an application of pesticide or chemical fertilizer in a nearby cultivated field. Special precautions should be taken to ensure the safety of infants or persons in frail health. Public health nurses may make home visits to discuss infant feeding and preparation of formula and the use of well water. Alternative sources of water include water drawn from another well, which has tested safe; bottled water; a new deep well; water passed through a treatment device*; or connecting to a rural water system, if this is available.
Simple in-line filters are not effective for removing nitrates. Deionization, desalination, or reverse osmosis units are available, which do render water safe from nitrate contamination.
1. Rosenfield AB, Huston R: Infant methemoglobinemia in Minnesota, due to nitrates in well water. Bull Univ Minn Med Found 1950;21:315–338.
2. Nelson D, Siegel J, Pieterick C: The Big Sioux Aquifer Water Quality Study: Prevention of Contamination of Rural Domestic Wells by Proper Location and Construction. Brookings, SD, East Dakota Conservancy Subdistrict, 1984, pamphlet 3.
3. 1982 Census of Agriculture, Part 41, South Dakota, publication AC82-A-41. US Dept of Commerce, Bureau of the Census.
4. Meyer M: A Summary of Groundwater Pollution Problems in South Dakota, State/EPA Task 2–3.1–111B. Pierre, South Dakota Dept of Water and Natural Resources, Office of Water Quality, 1986.
5. The Big Sioux Aquifer Water Quality Study. Pierre, South Dakota Dept of Water and Natural Resources, Office of Water Quality, 1984.
6. Cecil R: Textbook of Medicine, ed 16, Wyngaarden JB, Smith LH Jr (eds). Philadelphia, WB Saunders Co, 1982, pp 894–896.
7. Conn HF (ed): Current Therapy. Philadelphia, WB Saunders Co, 1981, p 188.