Methemoglobinemia among infants is a rare and potentially fatal condition caused by genetic enzyme deficiencies, metabolic acidosis, and exposure to certain drugs and chemicals. The most widely recognized environmental cause of this problem is ingestion of nitrate-containing water. Ingestion of copper causes abdominal discomfort, nausea, diarrhea, and in cases of high-level exposure, vomiting. This report summarizes an investigation by the Division of Health, Wisconsin Department of Health and Social Services, of methemoglobinemia associated with ingestion of nitrate- and copper-containing water in an infant during 1992.

A 6-week-old girl (birth weight: 7 lbs 9 oz) was hospitalized June 1 for treatment of dehydration. On admission she weighed 6 lbs 10.5 oz and appeared "dusky." She was afebrile and had no signs of infection. A history obtained from her parents indicated that during her first 3 weeks she had appeared well and had consumed approximately 20 ounces per day of soy-based formula (consisting of a liquid concentrate diluted with 1 part water). During her 5th week, she developed loose stools and began to vomit after eating.

Diagnoses on admission included vomiting with failure to thrive and dehydration secondary to vomiting. She was treated and was discharged on June 2. On June 8, because of an acute weight loss (6 oz) and limited consumption of formula (less than or equal to 3 oz) during the previous 24 hours, she was readmitted to the local hospital. On admission, she weighed 6 lbs 12 oz and appeared cachectic. Her hemoglobin level was 13 g/dL, with 21.4% methemoglobin. She continued to vomit yellow- to blue-tinged liquid following ingestion of fluids. Methemoglobinemia was diagnosed, and supportive treatment, including oral fluids and oxygen, was initiated. Within 24 hours, her methemoglobin level declined to 11.1%. Further evaluation at a referral center did not identify any underlying medical problems. Since discharge, her parents have used bottled water for drinking and for preparation of formula and food.

The family's house was situated on a river between a river bank and approximately 100 acres of corn and alfalfa. Water was supplied by a 28-foot deep vacuum-sandpoint well located in a basement pump room. Water used for drinking and food preparation was filtered by a reverse-osmosis (R/O) unit installed for nitrate removal when the family purchased the house in 1989. Water samples collected from the R/O unit and from the well during the infant's hospitalization contained 9.9 mg/L and 58 mg/L nitrate-N *, respectively. During the investigation in late July, the well water contained 39.6 mg/L nitrate-N and was free of coliform bacteria. An early morning first draw sample collected from the kitchen faucet contained 7.8 mg/L copper **. Results of tests for corrosivity included a pH of 6.3 and an alkalinity of 16 mg/L (as CaCO superscript ((3))). Flushing the kitchen faucet for several minutes reduced the copper level to 0.2 mg/L. A midday water sample from the R/O system contained 0.6 mg/L copper.

Based on these analyses, the Wisconsin Division of Health recommended that the family use bottled water for drinking and for preparation of food.

Reported by: L Knobeloch, PhD, K Krenz, H Anderson, MD, Environmental Epidemiologist, Div of Health, Wisconsin Dept of Health and Social Svcs; C Hovell, Trempealeau County Nursing Svcs, Whitehall, Wisconsin.

Editorial Note

Editorial Note: In 1991 and 1992, a total of 1825 exposures to nitrates/nitrites -- including 542 among children less than 6 years of age -- from environmental and other sources were reported to the Association of Poison Control Centers (1,2). The most common environmental cause of methemoglobinemia in infants in the United States is ingestion of water contaminated with nitrates from agricultural fertilizers, barnyard runoff, or septic-tank effluents. Acute toxicity may result after nitrate is reduced to nitrite in the stomach and saliva (3). Nitrite reacts with the oxygen-carrying protein, hemoglobin, reducing it to methemoglobin (Figure 1), which is unable to transport oxygen to the tissues (4). Methemoglobin levels above 10% may result in clinical anoxia (3), and levels above 60% can cause stupor, coma, and death if the condition is not quickly treated.

The symptoms described in this report appear to have been induced by simultaneous exposure to copper and nitrates at levels close to the federal drinking water standards for these substances; this phenomenon has not previously been implicated as contributing to the development of methemoglobinemia in infants. Copper is an effective emetic and gastrointestinal irritant, and ingestion of water containing copper levels of 2.8-7.8 mg/L has been associated with vomiting and diarrhea among adults and school-aged children (5,6). Although the dose required to cause acute symptoms in infants is unknown, children aged less than 1 year may be more sensitive to copper than older persons (7). Elevated copper levels in water used to prepare the infant's formula may have caused loose stools and vomiting after eating. Repeated vomiting and diarrhea may have resulted in dehydration and weight loss and, in turn, reduced gastric acidity sufficiently to enhance the growth of nitrate-reducing bacteria and facilitate conversion of ingested nitrates to nitrites. In addition, systemic copper poisoning has been reported to increase methemoglobin levels independent of nitrate exposure (8) -- an effect attributed to the ability of copper to inhibit red cell enzymes needed to reduce endogenous methemoglobin (9).

The major source of dissolved copper in drinking water is copper pipes in household plumbing. Water that stands overnight in copper pipes may contain copper levels that exceed the federal drinking water standard. This problem is most often associated with corrosive water supplies or with new copper pipes and can usually be prevented by flushing the household plumbing before using water for drinking or food preparation.

This report underscores that drinking water may be contaminated with nitrates and/or copper in some areas of the United States. Accordingly, health practitioners should routinely advise pregnant women that water from private wells be tested for nitrate. In addition, copper exposure should be considered in the differential diagnosis of unexplained gastrointestinal symptoms.

References

1. Litovitz TL, Holm KC, Bailey KM, Schmitz BF. 1991 Annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1992;10:452-505.

2. Litovitz TL, Holm KC, Bailey KM, Schmitz BF. 1992 Annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med (in press).

3. National Academy of Sciences. The health effects of nitrate, nitrite and N-nitroso compounds. Washington, DC: National Academy Press, 1981.

4. Smith RP. Toxic responses of the blood. In: Klaassen CD, Amdur MO, Doull J, eds. Casarett and Doull's toxicology. New York: MacMillan Publishing, 1986.

5. Spitalny KC, Brondum J, Vogt RL, Sargent HE, Kappel S. Drinking-water induced copper intoxication in a Vermont family. Pediatrics 1984;74:1103-6.

6. Pettersson R, Kjellman B. Vomiting and diarrhea are the most common symptoms in children who drink water with high levels of copper {Swedish}. Lakartidningen 1989;86:2361-2.

7. Syracruse Research Corporation, ed. Toxicological profile for copper. Atlanta: US Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, 1990:46.

8. Chugh KS, Singhal PC, Sharma BK. Methemoglobinemia in acute copper sulphate poisoning {Letter}. Ann Intern Med 1975;82:226-7.

9. Moore GS, Calabrese EJ. G6PD-deficiency: a potential high-risk group to copper and chlorite ingestion. J Environ Pathol Toxicol 1980;4:271-9.

• The U.S. Environmental Protection Agency (EPA) maximum contaminant level (MCL) for nitrate-N in drinking water is 10 mg/L. ** The EPA MCL for copper in drinking water is 1.3 mg/L.

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