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Transplacental naphthalene poisoning
TRANSPLACENTAL NAPHTHALENE POISONING
J.
JoHN A. ANZIULEwrcz,* HERMAN DrcK, M.D., AND EuGENE E. CHIARULLI, M.D., SYRAcusE, N.Y.
(From the Departments of Pathology and Obstetrics, St. Joseph's Hospital)
WELVE cases of hemolytic anemia in children secondary to the ingestion of naphthalene have been reported within the last ten years in the American literature.l-9 The first 4 cases of fulminating hemolytic anemia in children were presented by Zuelzer and Apt 1 in 1949. The ages of these children ranged between 2 and 2Vz years. Each child had either sucked or swallowed moth balls. These authors experimentally produced and verified in dogs the hemolytic anemia caused by naphthalene. Mackell and associates/ Abelson and Henderson, 3 Bregman,4 MacGregor, 5 Chusid and Fried, 6 and Haggerty 7 all have reported hemolytic anemia in children secondary to naphthalene ingestion. Acute hemolytic anemia due to absorption of naphthalene through the skin of a newborn infant has been reported by Schafer. 8 This 6-day-old infant had been dressed in diapers which had been stored in moth balls. Oil, which had been rubbed on the child's skin, was believed to have facilitated the absorption of naphthalene. Cock9 also reported a case of naphthalene poisoning due to absorption of naphthalene through the skin of a newborn infant. This 11-day-old infant had also been clothed in diapers and clothes which had been stored in moth balls. This child recovered after receiving type-specific whole blood transfusions. The exact mechanism by which naphthalene induces hemolysis of red blood cells is not entirely clear. After ingestion, naphthalene is absorbed into the blood stream and transported to the liver where it is detoxified. Naphthalene combines with cysteine to form naphthalenemercapturic acid in which the S is linked to the alpha position of naphthalene. 10 It is also oxidized to alphaphenol, betaphenol, y-naphthoquinone, and ~-naphthoquinone within the body. Naphthalenemercapturic acid, oxidation products of naphthalene, and naphthalene which has not been detoxified are all excreted in the urine. Blood seen in naphthalene poisoning generally shows a reduced hematocrit and erythrocyte count as well as a severely reduced hemoglobin. The leukocyte count, reticulocytes, and icteric index are elevated. The case reported here we believe to be the first reported case of transplacental naphthalene poisoning.
T
•Second year Medical Student, State University of New York College of Medicine at Syracuse, N. Y.
519
520
.. \m.
ANZIULEWICZ, DICK, AND CHIARULLI
Ob:\t. & Gvnec September, 19SIJ
1.
Mrs. E. J. W., a 26-year-old gravida ii, para i, was admitted to St. Joseph's Hospital .Tune 18, 1951, 4 days prior to delivery, complaining of bleeding hemorrhoids. Houtine blood studies at this time reveale ounces.
NORMAL WOMAN, NINTH MONTH OF PREGNANCY
MOTHER, NINTH MONTH OF PREG· NANCY
NORMAL INFANT, FIRST DAY (AI,·
10.8-14.4
5.2
1 i.i-26.5
3.7-5.0
1.79
4.7-7.0
(AL· L)
( Gm./1 Oil ml.)
c.
( thousand/mm,3) N eutrophils (%) Stab forms (%) Lymphocytes (%) Monoeytes (%) Eosinophils (%) Basophils (% ) Nucleated red Cells /100 white cells Coombs test (direct) Coombs test (indirect) Jaundice
i
I
5.5-15.5 69 25.5 4.0 1.5 0.2
l)
~H-.34.0
15.6 74 11 9 5 1 0
5.0-21.0 1.75 2Jl-11.5 0.20-3.1 ~ 0.05·1.00 0-0.3
INF'ANT_, F'IRST DAY PORT PAR TUM
13.0 1l.56
13.1
47
8 37 5 3 0 35
4
Negative
Negative Negative
INFANT, THIRD DAY POST PAR TUM
13.5 4.39
18.8 42 8 46 1 2
TNF'AK:P,
F'IRR'J' WEEK (ALBRITTONll)
] 6.2-25.5 4.:)-6.4
.).0-21.0 1.5-10.0 0.8:1 2.0-17.0 0.30-2.7? O.Oi-1.10 00.25
:1
Negativn Ncg·atiw Po~itive
Initial hematological stm'lies on the infant along with the normal hematological values of Albrittonu are also presented in Table I. Direct and indirect Coomb~ tests on the infant were negative. By the third day post partum, the chiltl wa~ noticeably jaundiced, lethargic, and anorexic. At this time hematological studies were also made (Table I). Moderate anisocytosis, poikilocytosis, and fragmentation of red cells were seen. On being questioned further, the mother at1mittPr1 having "sucked on moth halls" .luring the last trimester of her pregmmcy.
Comment Moth ball poisoning is most common in children between the ages o£ 2 and 4 years, since this group on finding moth balls are prone to put them into their mouths. The resulting hemolytic anemia seen in naphthalene poisoning resembles that seen in Lederer's anemia or acute hemolytic anemia of unknown origin. In cases of parental Rh incompatibility, the firstborn child generally does not show severe erythroblastotic changes unless the mother has been sensitized earlier by transfusion. The acute hemolytic anemia seen in the child presented resembled that seen in erythroblastosis fetalis. Rh incompatibility was ruled out as the causative factor, however, since no antibodies were demonstrated by the Coombs test. It is believed that the ingestion of moth balls led directly to the hemolytic anemia seen in Mrs. E. J. W. It is further believed that naphthalene and/or its oxidation products traversed the placenta and caused intrauterine hemolytic anemia of the fetus.
\"olume 78 .1\.T:llnher 3
TRANSPLACENTAL NAPHTHALENE POISONING
521
Naphthalene ha.s a molecular weight of 128 and its various oxidation products may vary in weight up to 160. Even assuming that they may be combined (degraded) with cysteine, the maximum molecular weight would be in the neighborhood of 400 which could readily pentrate the placental barrier. Hematological studies on the infant during the first day post partum showed that he had acute hemolytic anemia. By the third day post partum, the red blood cells and hemoglobin had increased. At this time nucleated red cells were markedly decreased. These changes occmTed spontaneously without any therapeutic attempts to correct the acute hemolytic anemia. This spontam~ous change is in accord with that seen in hemolytic anemia ser.ondary to naphthalene intoxication. Heinz bodies arc often found in acute hemolytic anemia due to naphthalene poisoning. Failure to demonstrate Heinz bodies in the erythrocytes of this newborn child may be due to the fact that the anemia had developed and been present in utero for some time prior to delivery. Variation in the rate of gastrointestinal absorption and liver detoxification of naphthalene may account for the degree of severity of the anemia in both the mother and child. The mother and child presented here show the classical features of naphthalene poisoning: ( 1) a history of maternal ingestion of moth balls, ( 2) fragmentation of red blood cells, anisocytosis, and poikilocytosis, (3) lethargy, icterus (in the infant) and anorexia, (4) severe anemia \Vith nucleated red cells and leukocytosis, and ( 5) decreased hemoglobin and erythrocyte count. Six weeks after discharge from St. Joseph's Hospital, the mother and child were reported as fully recovered. Summary
The diagnosis of hemolytic anemia in a newborn infant secondary to maternal ingestion of moth balls is reported. The acute hemolytic anemia seen in this child apparently originated in utero due to transplacental migration of naphthalene and/or its oxidation products. Often the diagnosis of naphthalene poisoning depends primarily on an accurate history as it did in this case. Addendum.-vVhile this article was in press, Dawson and associatest2 reported 2 cases of acute hemolytic anemia of the newborn in which they demonstrated familial glutathione instability of the red blood cells to acetyl phenylhydrazine and naphthol. They also noted that there is a diminished glutathione reuuctase (1) in the newborn period, (2) in these familial cases, and (3) in "sensitive" individuals, and that conjuga· tion of naphthalene with glucuroni
References Zuelzer, W. W., and Apt, L.: J. A. M.A. 141: 185, 1949. Mackell, J. V., Rieders, F., Brieger, H., and Bauer, E. L.: Pediatrics 7: 722, 1951. Abelson, S. M., and Henderson, A. T.: U.S. Armeu Forces M. J. 2: 491, 1951. Bregman, R.: Olin. Proc. Children's Hosp. (Washington) 10: 1, 1954. MacGregor, R. R.: Canad. M. A. J. 70: 313, 1954. Chusid, E., and Fried, C. T.: A. M. A. Am. J. Dis. Child. 89: 612, 1955. Haggerty, R. J.: New England J. Med. 255: 919, 1956. Schafer, W. B.: Pediatrics 7: 172, 1951. Cock, T. C.: A. M. A. Am. J. Dis. Child. 94: 77, 1957. West. E. S .. and Todd. W. R.: Textbook of BiochemistrY. ed. 2. New York. 1956. The Macmillan Company. •' ' ' ' 11. Albritton, E. C.: Standard Values in Blood, Philadelphia, 1952, W. B. Saunders Co. 12. Dawson et a!.: Blood 13: 1113, 19511.
1. 2. 3. 4. 5. 6. 7. 8. D. 10.
J.
JoHN A. ANZIULEwrcz,* HERMAN DrcK, M.D., AND EuGENE E. CHIARULLI, M.D., SYRAcusE, N.Y.
(From the Departments of Pathology and Obstetrics, St. Joseph's Hospital)
WELVE cases of hemolytic anemia in children secondary to the ingestion of naphthalene have been reported within the last ten years in the American literature.l-9 The first 4 cases of fulminating hemolytic anemia in children were presented by Zuelzer and Apt 1 in 1949. The ages of these children ranged between 2 and 2Vz years. Each child had either sucked or swallowed moth balls. These authors experimentally produced and verified in dogs the hemolytic anemia caused by naphthalene. Mackell and associates/ Abelson and Henderson, 3 Bregman,4 MacGregor, 5 Chusid and Fried, 6 and Haggerty 7 all have reported hemolytic anemia in children secondary to naphthalene ingestion. Acute hemolytic anemia due to absorption of naphthalene through the skin of a newborn infant has been reported by Schafer. 8 This 6-day-old infant had been dressed in diapers which had been stored in moth balls. Oil, which had been rubbed on the child's skin, was believed to have facilitated the absorption of naphthalene. Cock9 also reported a case of naphthalene poisoning due to absorption of naphthalene through the skin of a newborn infant. This 11-day-old infant had also been clothed in diapers and clothes which had been stored in moth balls. This child recovered after receiving type-specific whole blood transfusions. The exact mechanism by which naphthalene induces hemolysis of red blood cells is not entirely clear. After ingestion, naphthalene is absorbed into the blood stream and transported to the liver where it is detoxified. Naphthalene combines with cysteine to form naphthalenemercapturic acid in which the S is linked to the alpha position of naphthalene. 10 It is also oxidized to alphaphenol, betaphenol, y-naphthoquinone, and ~-naphthoquinone within the body. Naphthalenemercapturic acid, oxidation products of naphthalene, and naphthalene which has not been detoxified are all excreted in the urine. Blood seen in naphthalene poisoning generally shows a reduced hematocrit and erythrocyte count as well as a severely reduced hemoglobin. The leukocyte count, reticulocytes, and icteric index are elevated. The case reported here we believe to be the first reported case of transplacental naphthalene poisoning.
T
•Second year Medical Student, State University of New York College of Medicine at Syracuse, N. Y.
519
520
.. \m.
ANZIULEWICZ, DICK, AND CHIARULLI
Ob:\t. & Gvnec September, 19SIJ
1.
Mrs. E. J. W., a 26-year-old gravida ii, para i, was admitted to St. Joseph's Hospital .Tune 18, 1951, 4 days prior to delivery, complaining of bleeding hemorrhoids. Houtine blood studies at this time reveale
NORMAL WOMAN, NINTH MONTH OF PREGNANCY
MOTHER, NINTH MONTH OF PREG· NANCY
NORMAL INFANT, FIRST DAY (AI,·
10.8-14.4
5.2
1 i.i-26.5
3.7-5.0
1.79
4.7-7.0
(AL· L)
( Gm./1 Oil ml.)
c.
( thousand/mm,3) N eutrophils (%) Stab forms (%) Lymphocytes (%) Monoeytes (%) Eosinophils (%) Basophils (% ) Nucleated red Cells /100 white cells Coombs test (direct) Coombs test (indirect) Jaundice
i
I
5.5-15.5 69 25.5 4.0 1.5 0.2
l)
~H-.34.0
15.6 74 11 9 5 1 0
5.0-21.0 1.75 2Jl-11.5 0.20-3.1 ~ 0.05·1.00 0-0.3
INF'ANT_, F'IRST DAY PORT PAR TUM
13.0 1l.56
13.1
47
8 37 5 3 0 35
4
Negative
Negative Negative
INFANT, THIRD DAY POST PAR TUM
13.5 4.39
18.8 42 8 46 1 2
TNF'AK:P,
F'IRR'J' WEEK (ALBRITTONll)
] 6.2-25.5 4.:)-6.4
.).0-21.0 1.5-10.0 0.8:1 2.0-17.0 0.30-2.7? O.Oi-1.10 00.25
:1
Negativn Ncg·atiw Po~itive
Initial hematological stm'lies on the infant along with the normal hematological values of Albrittonu are also presented in Table I. Direct and indirect Coomb~ tests on the infant were negative. By the third day post partum, the chiltl wa~ noticeably jaundiced, lethargic, and anorexic. At this time hematological studies were also made (Table I). Moderate anisocytosis, poikilocytosis, and fragmentation of red cells were seen. On being questioned further, the mother at1mittPr1 having "sucked on moth halls" .luring the last trimester of her pregmmcy.
Comment Moth ball poisoning is most common in children between the ages o£ 2 and 4 years, since this group on finding moth balls are prone to put them into their mouths. The resulting hemolytic anemia seen in naphthalene poisoning resembles that seen in Lederer's anemia or acute hemolytic anemia of unknown origin. In cases of parental Rh incompatibility, the firstborn child generally does not show severe erythroblastotic changes unless the mother has been sensitized earlier by transfusion. The acute hemolytic anemia seen in the child presented resembled that seen in erythroblastosis fetalis. Rh incompatibility was ruled out as the causative factor, however, since no antibodies were demonstrated by the Coombs test. It is believed that the ingestion of moth balls led directly to the hemolytic anemia seen in Mrs. E. J. W. It is further believed that naphthalene and/or its oxidation products traversed the placenta and caused intrauterine hemolytic anemia of the fetus.
\"olume 78 .1\.T:llnher 3
TRANSPLACENTAL NAPHTHALENE POISONING
521
Naphthalene ha.s a molecular weight of 128 and its various oxidation products may vary in weight up to 160. Even assuming that they may be combined (degraded) with cysteine, the maximum molecular weight would be in the neighborhood of 400 which could readily pentrate the placental barrier. Hematological studies on the infant during the first day post partum showed that he had acute hemolytic anemia. By the third day post partum, the red blood cells and hemoglobin had increased. At this time nucleated red cells were markedly decreased. These changes occmTed spontaneously without any therapeutic attempts to correct the acute hemolytic anemia. This spontam~ous change is in accord with that seen in hemolytic anemia ser.ondary to naphthalene intoxication. Heinz bodies arc often found in acute hemolytic anemia due to naphthalene poisoning. Failure to demonstrate Heinz bodies in the erythrocytes of this newborn child may be due to the fact that the anemia had developed and been present in utero for some time prior to delivery. Variation in the rate of gastrointestinal absorption and liver detoxification of naphthalene may account for the degree of severity of the anemia in both the mother and child. The mother and child presented here show the classical features of naphthalene poisoning: ( 1) a history of maternal ingestion of moth balls, ( 2) fragmentation of red blood cells, anisocytosis, and poikilocytosis, (3) lethargy, icterus (in the infant) and anorexia, (4) severe anemia \Vith nucleated red cells and leukocytosis, and ( 5) decreased hemoglobin and erythrocyte count. Six weeks after discharge from St. Joseph's Hospital, the mother and child were reported as fully recovered. Summary
The diagnosis of hemolytic anemia in a newborn infant secondary to maternal ingestion of moth balls is reported. The acute hemolytic anemia seen in this child apparently originated in utero due to transplacental migration of naphthalene and/or its oxidation products. Often the diagnosis of naphthalene poisoning depends primarily on an accurate history as it did in this case. Addendum.-vVhile this article was in press, Dawson and associatest2 reported 2 cases of acute hemolytic anemia of the newborn in which they demonstrated familial glutathione instability of the red blood cells to acetyl phenylhydrazine and naphthol. They also noted that there is a diminished glutathione reuuctase (1) in the newborn period, (2) in these familial cases, and (3) in "sensitive" individuals, and that conjuga· tion of naphthalene with glucuroni
References Zuelzer, W. W., and Apt, L.: J. A. M.A. 141: 185, 1949. Mackell, J. V., Rieders, F., Brieger, H., and Bauer, E. L.: Pediatrics 7: 722, 1951. Abelson, S. M., and Henderson, A. T.: U.S. Armeu Forces M. J. 2: 491, 1951. Bregman, R.: Olin. Proc. Children's Hosp. (Washington) 10: 1, 1954. MacGregor, R. R.: Canad. M. A. J. 70: 313, 1954. Chusid, E., and Fried, C. T.: A. M. A. Am. J. Dis. Child. 89: 612, 1955. Haggerty, R. J.: New England J. Med. 255: 919, 1956. Schafer, W. B.: Pediatrics 7: 172, 1951. Cock, T. C.: A. M. A. Am. J. Dis. Child. 94: 77, 1957. West. E. S .. and Todd. W. R.: Textbook of BiochemistrY. ed. 2. New York. 1956. The Macmillan Company. •' ' ' ' 11. Albritton, E. C.: Standard Values in Blood, Philadelphia, 1952, W. B. Saunders Co. 12. Dawson et a!.: Blood 13: 1113, 19511.
1. 2. 3. 4. 5. 6. 7. 8. D. 10.