We! "”IONS muons owes 0 L I! n E A L T ” onomsmon MONDIALE :fl93NIZATION DELASAN'I'B FEET COWITTEE 0” “ATE-33% women/13 5/ ii.” cHILD HEALTH 12 December 1949 ORIGINAL : ENGLISH CYANOSIS 0? warns PRODUCED BY HIGH NITFATE comammnou IN RLRAL mamas A Bursary of Recent Literature Of particular and timely interest. to paediatricians, and public health and sanitary workers, is the newly mcogjized syndrome in infantS, caused by ‘v-"fv‘ PFGSCF-C‘? of high concentrations of nitrates in rural water supplLC-s. Emacs: it presents an alarming clinical picture, and sometimes coat“. in infams under threo months of age, and because it is an easily preventable illness, and because the true extent and prr'volenm; of this syndrome is still ‘lnlmmm in many coun— tries - this technical summary has been prepared. This problem was first brought. to the attention of the medical 38 A .profession in 1940 when two MICQI‘lCEin workers reported a case of "idiopathic mothemoglobinnmo" in an lull-mt, in a small Montana town. It. was in 1945 that, Cowl";5 reload this clinical picture torthc find- ing of high concentrations of nitrates in the well water which was used to dilute. infanzsi fcrrtul'zs Since 1945 reports have been appear- ing in North America, l,2,4,6,’7,9,10,1o,20,24,26,31,32,39,40,43 Belgianll, Camdian,13’27’34 journals describing almost 260 cases. It is presmed that the con- and English19 paediatric and public-health dition is even more widespread than these reports indicate, since it W occur ammhere in a rural area where well rater is used in infant. feeding. The clinical picture is almost diagnostic. A normal health infant, generally under two months of age, living in a rural area, dEVelops an intense cyoncsis described as an unusual brown—grey skin Colour. This cyanosis comes on within a week after the infant is Placed on an artificial fomula which is diluted with well water. DPWainess and occasional gastro-inbostinal disturbances may follow? but rarely aw 'S’Gpnea. Prysical examination reveals no abnormali- tiEB other than the cyanosis. Chest X—rays and all laboratory tests are DOMAI, with the exception of the blood mthaemoglobin level which 1‘ “Mateo. ‘ " \t‘ n‘ . \. “3r-"cm 2 “ If the use of the contaminated well water is continued, the (3361:1051; . persists, and death from anomcmia may ensue. The mortality has, been estimated at, 10%.32 Adults and older children using the 5511113 water supply are not made sick, and their blood contains normal values of methaomoglobinas In treating these qyanoscd infants, frequently all that. is needed is to rmove the offending well water from the formula. The Clanosis will then disappear within a few hours, and complete News?! Will take place within one or two days. However, in severe cases where immediate measures seen mecessary, the dI‘Ug of choice is methylene blue.3’1'7’18’23’M’d5 This may be administered intra- venously in a dose of l to 2mm per kilogram or body weight, using a 1% solution. Methaemoglobin is normally present. in the bleed to the extent, or 31-33 It is not toxic in itself but it is unable to carry awash. The mcthacmoglobin fonncd in these cases of infant cyanosis is intro-corpusculan8’15’28’35 Various chemicals and drugs heme been found which may produce this type of methacmoglobin, including. acetanilidel, cnalinc dyes, potassium chlorate, the sulfonamides, and. the nitrates.36’42 When nitrates are ingested they are reduced in' the intestinal tract to nitrites and absorbed into the blood .‘31‘.r*eam.‘ua46 I}: has been well established that the nitrite ion is the effective agent in the production of metheemorlobinaemia. One molecule of a nitrite ion reacts with two molecules of haemoglobin to form . methaemoglobin.14 It is believed that the degree and seriousness V of methaemoglobinaemia which an iriant will develop from the ingestion of a nitrate water depends on several factors, e.g. the relative 'amount of nitrate ingested, the presence of nitrite reducing bacteria in the upper gastro-intestinal tract, 6’ 25 the usual low neonatal gastric acidity, the intracorpuecul 1r enzyme activity, and the total haemoglobin content of the blood. These same factors probably help to explain why adults and older children are not affected. Nitrates in well water are generally regarded as an end product. cf'the bacterial decomposition of animal or vegetable matter, and as such the level of nitrate content is a rough guide to the degree 01‘ contamination of a well from those sources. a o WHO/MCH/lB page 3/4 P'ollution by animal 01‘ human excreta is frequent when the wells are old and WORM; dug rather than drilled, provided with inadequate casings or none at all, equipped with faulty coverings, and situated in fmards or grossly insanitary areas. Wells such as these usually have a high bacterial count as well as a high nitrate level. occasionally it has been found, however, that a bacteriologically ' safe well will have a high‘concentration of nitrates,5 and in these instances the bacterial decomposition of the humus of the soil must be suspected as the source of the nitrates. Analyses of water . samples from rural wells in the U.S.A.2’5’2O and Canada 34 show that a high percentage of them contain significant amounts of nitrates, (more than 10 parts per million of the nitrate ion) and small amounts of nitrites. Clinical signs of mothacmoglobinacmia rarely develop in infants unless the nitrate level in the ingested well water is above 10 parts per million. It is recommended therefore that waters containing more than 10 parts per million of nitrate ion be avoided if possible for infant feeding, and those containing more than 20 parts per million of nitrates be definitely avoided.34 For all infants in rural areas, for whom artificial feedings 'are necessary,2 the safest formulas would be those which required the least water in their preparation. In order of‘ safety these would be: (a) , undiluted acidified milk mixtures; (b) cows' milk mixtures; (c) evaporated milk mixtures; (d) dried or powdered milk Indoctiirtesfi’7 In order to lower the nitrate concentration of rural wells to - safe levels, special precautions must be taken. The well site must be carefully chosen with a View especially to good surface drainage, Proper slope of subsurface rock formations, and a safe distance'i‘ran any possible sources of pollution. The construction of the well, ' ‘whethcr dug, drilled, or’ driven, dust be scientifically planned. The equipment of the well, such as pumps, pipes, or tanks, must be carefully selepted and cared for.12’21’29’30’3? ‘ - f 2 ‘ 1. 2. 3. 4. 6. 7. 8. 9. 10. ll. 12. 13. 14. 15. 16. 17' 18. HHC/MCH/l) page 5 BibliogEaEhx Bibliogannhie BIGLER: «It A. El “1830“, 8- 6112133.]. CC-rJErence _ mctnemcrlcb1“emia, (1949) LE._ 35, 116 HURTS: I. H. Water—borne.discases, (1949) Amer. J. ubl. Hith, ' . 39, 974 BROOKS, m. M. methylene blue and hemcrlcbin derivatives in asphyxial pciscninn, (1935) last. J. Physiol. 114, 160 CHAPIN; F. J. fiezhemo:lzbinen1a frcm nitrates in well water, (1947) J. Eich. med. Ste. 46, 938 GOMLY, H. H. Cyanosis in infants caused by nitrates in well water, (1945) J. nmer. med. Ass. 129, 112 COHNBLATH, M. & HARTmANN, n. F. nethsuoglcbinemia in young infants, (1948) J. Pediat..33, 421 DONAHOE, h. E. Cyanesis ju infants with nitrates in drinking water 35 cause, (1949) Pediatrics, 3, 308 EVELYN, K. A. & "£110Y, h. .'. Microdetermination of oxyhemoplobin, methamoalcbi‘ and sulfhemoclobin in sinple sample of blood, (1938) J. bicl. ChL‘m. 126, 655 FEUCETT, R. L. & KILLER, H; C. Methemoclobinemia occurring in infants fei milk diluted with well water of high nitrate content, (1946) J. Pedint. 29, 593 -FEREANT, M. ‘Methenozlobxncmia, (1946) J. Pediat. 29, 535 FERRANT, M. Deux cas de nethémorlc-binénie ches des nourrlssons, Acta Paediatr. belze, 1,17 Georgia Dept of Public Health. hater supglies for suburban and country homes, (1946) Atlanta, Ga 35 p. GOLUBOFF, N, Methaemoplcbinaemia in infants (effect of nitrates of.Water Supply) (1948) Caned. med. Ass. J. 58. 601 GREENBERG, L. A. LESTER, D.-& HAGGAED H. W. The reaction of .hempglobin with nitrite, (1943) J. biol. Chem. 151, 665 HALPERN, B.N. & DUBOST, P,_ chérches sur la méthémoelobine, (1939) Bull. SOC. Chim. biCl. 21, 717 HARPER, E. A. Cyanosis in §nfant5 from polluted well water, (1949) Virsinia'méd.‘Mcn. 76, 1 HAHTMANN, n.F. PERLEY, a. & BARNETT, H. L. A study of some of the physiological effectfi of sulfanilamide: II. Methemoglobin fonnation and its control, (1938) J. clin. Invest. 17, 699 HAUSCHILD, F. Zur ruckbildunv des methampylobins durch methylenblau und thionin, (1939) Klin. fischr. 18,1580 NFC/L5H513 page 6 —' - _ 19. Ila—fan tile metha-:m rlibinaemic. from drinkinv water. .(Ahno'tation) (1943) Lancet, 1, 956 20- JOHNSON, 0. at al Nitrate levels in water from rural Iowa WeIIS, (1046) J. 10‘"? med. SOCI 36,4 21. Kansas State Beard Uf‘Hgalth. Division of Sanitation. «311 water supplies. (1947) 2“d Ed° lcpeka, Kansas, 229' (Enqinecrina Bulletin No 22) A . 22. KRUEQER, g, u. a method for the removal of nitrates from Water prior to use in infant formula, (1949) g;_£ggigt. (to be published) ,. ' I 23- LEDERER, J. A. Contribution a l'étude pharmacodynamique do Is thicnino, (1937) Arch. -internat. Pharmacogxn- 55. 357 24. MARCUS, H. & JOFFE, J. a. Nitrate methemopiobinamia, (1949) . New Ennln J. Méd. 240, 599 > '25. MARRIOTT, u. M. HAR'MANN h. F. &. SBNN, M. G. E. Observations on nature and treatment of diarrhoea and associated systemic disturbances (1933) J. Pediat. 3. 181 26. MATTHEwS, G. F. & SELLNER, E. P.. Infant cyanosis and nitrates, (1947) J Oklahoma med. Ass. 40, 444 27. MEDOVI, H. GUEST, 'u. C. & VICTOR I. Cyanosis in infants in rural aroaS‘,‘(l947) Canad. med. Ass. J. 56, 505 28. MICHEL, H. O. & HARRIS, J. S. dlood pigments, properties and quantitative determination with Special reference to . _ spectrophotometric methods, (1940) J. Lab. clin. Med. 25, 445 29; Minnesota Department of Health. Section on Environmental Sanitation (1947) Manual of water supply sanitation. Small powar pump installations. Section VII, paragrqahs 701-799 St. Pavia-1,. Minnr 32 p. ' C30.‘-Minnesota Deportnent of Health. Section on Environmental ' Sanitation (1948) Manual of water supply sanitation.- Hand pump installations. Section V, paragraphs 501-599 ‘St. Paul, Minn, 21 p. 31. Nitrates in rural we11 waters (1949) Amer. J, publ. filth, 39, 1033 32. Nitrite poisoning recognized in Plattsburg infants (11 July 1949) . N. Y. State Dept. of Health Bull. 2, 31 BBL “FEULL;BF;D-.& KEHP, 0‘ R- “ethemozlobin: a'nprmal-constituent 5f "Eflbod“ (1944) Free. Soc. exp. Biol. N. Y. 56, 55 34.. ROBERTSON, H- E. .8: RIDDELL,‘a. A. Cyancsis' of infants produced . by hinh nitrate‘ concentration in ruraI waters of SaSKatChe"a (1949) Canad. J. pub1.H1t.h, 40, 72 35- ROCHE, J- Sur 1'30t10n Ph¥51010gique de la méthémoalobinisation du sang (1930) Arch internat. Pharmacodyn. 3?, 358 - 36. 37. 405 41. 42. 43. 45. 46. HHO/MCH/lB page 7 303, H. E. Methemovlobinemia £0113winq the administration of bismuth subnitrate: report cf a fatal case (1933) J. nmer. med. Ass. 101, 352 """— Sanitary Standards f0? hand-pumped wells (1942) Bull. ICwa State ”f DeEt cf Health ..._...__.___.... SCHWARTZ: A- 5‘ & RECTOR, 3- J. tethemc~lcbincmia of unknown criflin in a twc week old infant (1940) Amer. J. Dis. Child. 60, 652 W SCOTT, E. P. Cyanrsis caused by nothemcrlobin, (1949) Amer. J. Dis. Child. '78, 77 STLFFORD, G. 3. Methemcvlcbinenia in infants from water Containing high concentraticns of nitrates (1947) Nebraska Med. J. 32, 392 VAN DEN BERGH, A. A. H. antnrogem cyanosc (1905) Dtsch. Arch. klin. Lied. 83, 86 WALLACE, W. M. nethemoylcbinemia in an infant as the result of the administration 3f bismuth subnitrate (1947) J. Amer. med. Ass. 133, 1280 WEART, J. J. Effect of nitrates in rural water supplies cn infant health (1948) Illinois med. J. 93, 131 WENDEL,W. B. The control of nethemoplobinaemia with methylene blue (1939) J. clin. Invest. 18, 179 WILLIAMS, J. R. & CHALLIS, F. E. Methylene blue as antidote for aniline dye poisoning (1933) J. Lab. clin. Med. 19, 166 20 BELL, C. E. Factors influencinv the reduction of nitrates and nitrites by bacteria in semisolid media (1932) J. East. 24, 273
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Cyanosis of infants produced by high concentration in rural wells: a summary of recent literature
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