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The effect of various supplements to the diet on the iron balance of the anemic infant
The Journal of Pediatrics VOL. 10
FE~aVARY, 1937
NO. 2
Original Communications T H E E F F E C T OF V A R I O U S S U P P L E M E N T S TO T H E D I E T ON T H E IRON B A L A N C E OF T t I E A N E M I C I N F A N T
FREDERIC W. SCIILUTZ, M.D., MINERVA MORSE, PE.D., AND HELEN
0LDHA~
CI:iICAGO, IDL.
I N uponAN
earlier report on the influence of fruit and vegetable feeding the iron metabolism of the infant we included a study of the iron balance of one infant suffering from nutritional anemia. The results showed that, while addition of dried spinach to a~ milk diet caused a lowered retention of iron, the f u r t h e r addition of apricots caused a m a r k e d increase in the retention of iron. The iron retention was also increased b y feeding large amounts of iron in the form of ferric ammonium citrate. I t showed a f u r t h e r increase when an additional supplement of liver was made to the diet. In spite of the increased retention of iron, the hemoglobin concentration of the blood was not improved until the iron salt in the diet w a s supplemented by liver. To determine w h e t h e r these results were peculiar to the individual ease or typical also of other eases of secondary anemia in infants, we have continued the s t u d y of the effects of these foods on the iron retentions of three other anemic infal~ts.
The three infants, J. tI., G. K., and R. K. were thirteen, eight, and eight months old, respectively, when the metabolism s t u d y was begun. EXPERIMENTAL,
PROCEDURE
The same general plan was followed in the s t u d y of these cases as in the case r e p o r t e d previously. W i t h the exception of the control periods on p o w d e r e d milk, v cane sugar, and cod liver oil, the infants :From the Department of Pediatrics, University of Chicago. This work was supported in part by a grant from the Douglas Smith Foundation f o r M e d i c a l R e s e a r c h of t h e U n i v e r s i t y o f C h i c a g o . * P o w d e r e d m i l k i n t h e f o r m o f d r y c o w a s f u r n i s h e d t h r o u g h t h e c o u r t e s y of t h e D r y IV[ilk C o m p a n y .
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received each diet for a period of at least fifteen days before an additional supplement to the diet was made. Care was t a k e n to keep the supplements as u n i f o r m as possible, and the daily a m o u n t of each, ~:' with the exception of the iron salts, was constant for all three cases. A f t e r the i n f a n t had received a given diet f o r a fore period of at least five days, the urine and feces were collected for two consecutive periods of five days each, aliquots of food, urine, and feces w e r e analyzed f o r iron content and the iron balance calculated. Supplements to the diets were not made in the same order for each infant. In every ease the first period was a control on powdered milk, cane sugar, and cod liver oil formula. Following the control period, J. H. and G. K. were given purged spinach for periods 2 and 3. This p a r t i c u l a r f o r m of spinach was used as it had been found to be utilized slightly better by normal infants t h a n either the dried or raw form. 1 D u r i n g periods 4 and 5 J. H. and G. K. received both spinach and apricots. 1%. K. was given apricots d u r i n g periods 2 and 3 and apricots and pur6ed spinach in periods 4 and 5. I t was felt that, if a g r e a t e r percentage of the iron of apricots t h a n of spinach were retained, it would be reflected in his iron balance when compared with t h a t of the other two infants. An intestinal disturbance, accompanied b y diarrhea, occurred in the case of i n f a n t J. H. a f t e r period 5 and the s t u d y was discontinued for a Short time. I t was not felt t h a t the diet had caused this disturbance as the same foods had been given to several other infants with no evidence of diarrhea. A f t e r recovery, J. tI. was given a basic f o r m u l a of powdered milk, cane sugar, orange juice, and cod liver oil d u r i n g period 6. This diet was supplemented with liver d u r i n g periods 7 and 8 and f u r t h e r supplemented with varying' amounts of iron salts (111 to 199 rag,) in the f o r m of ferrous sulphate in glucose solution d u r i n g the f o u r periods following. I t seemed of interest to compare the effect of the ferrous salt with t h a t of the ferric form, since L o t t r u p 2,a and Parsons and H a w k s l e y ~ had f o u n d ferrous salts more effective in curing secondary anemias. In periods 13 and 14 copper in the f o r m of cupric sulphate was given as an additional supplement to the liver and the iron saIts. Spinach and apricots were continued in the diet of G. K. and R. K. t h r o u g h o u t the remainder of the study. In the ease of G. K. f u r t h e r supplements of ferric ammonium citrate (132 to 146 nag'. Fe), cupric sulphate, and liver were given in the order mentioned. In the diet o f 1%. K. the same supplements were given, but the order was cupric sulphate, ferric ammonium citrate, and, finally, liver. * P u r O e d s p i n a c h w a s s u p p l i e d t h r o u g h t h e c o u r t e s y of V a n C a m p ' s Inc. D a i l y s u p p l e m e n t s o f 70 gin. w e r e g i v e n . D a i l y s u p p l e m e n t s of a p r i c o t s w e r e e q u i v a l e n t to 40 g'm. o f t h e d r i e d f r u i t . D a i l y s u p p l e m e n t s of c a l f ' s l i v e r a m o u n t e d to 20 gin. T w e l v e m i l l i g r a m s of copper, as copper sulphate, w e r e g i v e n daily.
S C E L U T Z ET AL. :
IRON BALANCE IN ANElV[IA
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Details concerning the p r e p a r a t i o n of food, the collection of excreta and the methods used f o r determining iron and hemoglobin h a t e been given in the previous communication. All three infants were in positive nitrogen balance and each showed consistent weight gains d u r i n g every period studied. Feedings were t a k e n well, and w i t h the exception of the anemia the infants seemed to be quite normal, In all cases the anemias were t h o u g h t to have been caused b y inadequate diets and were t h e r e f o r e believed to be comparable. ttISTOI%u OF CASES CASE ] . - - J . It., a m a l e i n f a n t , w a s a f u l l - t e r m b a b y , delivered b y low forceps with no compllcatlons. B i r t h w e i g h t w a s 3,790 gin. T h e b a b y was n o r m a l except f o r a b i l a t e r a l h a r e l i p a n d a u n i l a t e r a l cleft palate. F e e d i n g c o n s i s t e d o f b r e a s t milk a n d dryc% b y g a r a g e . Cod liver oil a n d viosterol were g i v e n r e g u l a r l y . He was first b r o u g h t to t h i s clinic at %he a g e of one m o n t h , in good n u t r i t i v e s t a t e . A n operation w a s p e r f o r m e d , a n d t h e h a r e l i p w a s repaired. D u r i n g his first y e a r he h a d m e a s l e s a n d two a c u t e a t t a c k s of otltls m e d i a ( ] e f t ) . IIe w a s r e a d m i t t e d to t h e h o s p i t a l at "~he a g e Of one y e a r , a well-nourished a n d well-developed child, for repair of t h e c l e f t palate. H i s h e m o g l o b i n a t t h e t i m e o f a d m i t t a n c e w a s 70 per cent. D u r i n g his convalescence, h i s h e m o g l o b i n fell to 40 per cent, a n d at t h e a g e of t h i r t e e n m o n t h s he w a s d i a g n o s e d as h a v i n g s e c o n d a r y a n e m i a . CASE 2 . - - G . K . , a m a l e i n f a n t , w a s one of identical, f u l l - t e r m twins. H i s b i r t h h i s t o r y w a s n o r m a l , a n d h i s b i r t h w e i g h t was 2,~55 gin. t i e w a s first seen a t this clinic at t h e a g e o f e i g h t m o n t h s , w h e n he w a s b r o u g h t i n b e c a u s e o f i r r i t a b i l i t y a n d paleness, l i e h a d b e e n b r e a s t f e d for t h e first two m o n t h s o f life a n d t h e n w a s g i v e n complemen%ary f e e d i n g s u n t i l t h e f o u r t h m o n t h , at which t i m e he was g i v e n a f o r m u l a c o n s i s t i n g o f whole milk, cane s u g a r , a n d water. Cod liver oil a n d o r a n g e juice were g i v e n r e g u l a r l y a f t e r t h e second m o n t h , b u t cereals and vegetables were n o t i n t r o d u c e d i n t o his diet u n t i l h e w a s seven m o n t h s old. The child h a d b e e n in f a i r h e a l t h a n d h a d suffered f r o m no c o n t a g i o u s diseases. U p o n a d m i s s i o n h i s h e m o g l o b i n w a s f o u n d to be 44 per cent, a n d t h e case w a s d i a g n o s e d as s e c o n d a r y a n e m i a . CASE 3.--I~. K., a m a l e i n f a n t , w a s first seen at t h i s clinic at t h e a g e of eight m o n t h s . H e w a s t h e i d e n t i c a l t w i n of G. K., a n d b i r t h h a d been n o r m a l . B i r t h w e i g h t was 2,540 g m . H i s f e e d i n g since b i r t h h a d been t h e s a m e as t h a t of G. t{:. which h a s b e e n described p r e v i o u s l y , l i e h a d always b e e n i n a p p a r e n t good h e a l t h a n d h a d s u f f e r e d f r o m no c o n t a g i o u s diseases, t i e w a s b r o u g h t to t h e clinic b e c a u s e of a n o t i c e a b l e pallor a n d a n aeu%e u p p e r r e s p i r a t o r y i n f e c t i o n . A h e m o g l o b i n value o f 37 p e r cent w a s f o u n d , a n d t h e case was d i a g n o s e d as one of secondary anemia.
DISCUSSION OF ~ESULTS The iron intakes and retentions and the corresponding hemoglobin values for these cases as influenced by the various supplements to the diets will be f o u n d in Charts 1 and 2.
Effect of Sp~nach.--The addition of pur6ed spinach to the control diet of infants J. H. and G. K. caused a v e r y small increase in the retention of iron in one case and a very slight decrease in the other.
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W h e n added to the control diet supplemented with apricots, in the ease of tL K., the retention remained the same as on the milk-apricot diet. The hemoglobin showed no appreciable change in any ease. The addition of dried spinach resulted in a negative iron balance in the ease of secondary anemia r e p o r t e d previously. No negative balances were f o u n d in these cases when the purged form was used. However, the additional iron given in this f o r m did not a p p e a r to be retained. I t would seem that anemic infants are not able to utilize the iron of spinach.
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C h a r t 1 . - - T h e effect of s p i n a c h a n d a p r i c o t f e e d i n g on t h e r e t e n t i o n of i r o n a n d t h e f o r m a t i o n os h e m o g l o b i n . * C o n t r o l d i e t : P o w d e r e d m i l k , can'e s u g a r , a n d cod l i v e r oil.
Effect of Apricots.--When apricots were added to a milk-spinach diet (J. H. and G. K.), the retentions were slightly higher t h a n on either the control or the milk-spinach diet. The addition of apricots to the control diet (R. K.) caused a slightly increased retention which was n o t increased f u r t h e r by the addition of s p i n a c h . The retentions in all cases were small, and the hemoglobin values were not appreciably affected. In no case was there a decrease in the fecal o u t p u t or a m a r k e d increase in the retention as occurred in the ease of the i n f a n t reported previously.
SCHLUTZ
ET
AL. :
IRON
BALANCE
IN
151
ANEIWIIA
Since the r e t e n t i o n of iron showed a slight increase in all eases when apricots were fed, it would seem t h a t the iron of a p r i c o t s is more readily available to the anemic i n f a n t t h a n t h a t of spinach. This m a y
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2 . - - E f f e c t os iror~ a n c l c o p p e r s a l t s a n d l i v e r o n t h e r e t e n t i o n o f i r o n a n d t h e formation of hemoglobin. *Determined by average results of periods 4 and 5 for each case. ?Control diet (1) : Powdered milk, cane sugar, orange juice, and cod liver oil $Control diet (2) : Powdered m i l k , c a n e s u g a r , c o d l i v e r oil, s p i n a c h a n d a p r i c o t s .
be due to the f a c t t h a t a much higher p e r c e n t a g e of the iron of apricots t h a n of spinach is in the inorganic form. While we ~ find no conclusive
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evidence t h a t a normal child utilizes iron in the inorganic f o r m more readily t h a n in the organic, it is possible t h a t the anemic child might utilize the inorganic p o r t i o n ' m o r e easily.
E~ect of Iron and Copper Salts Alone and in Combination.--When iron salts in the form of ferric ammonium citrate were added to a diet containing spinach and apricots (G. K.), the retention of iron was increased markedly, and the hemoglobin showed consistent gains. Supplementing this diet f u r t h e r with cupric sulphate did n o t affect any additional increase in the retention or a more r a p i d gain in the hemoglobin. It would appear, then, t h a t this i n f a n t had been receiving an adequate amount of copper in his previous diets and t h a t iron r a t h e r t h a n copper had been the limiting factor. On the other hand, the addition of copper salts to a diet containing spinach and apricots (R. K.) caused no change in either retention or hemoglobin. At this level of iron intake additional copper had no beneficial effect. It is quite probable t h a t the copper content of the spinach-apricot diet was adequate as was shown in the case of G. K. W h e n the diet was f u r t h e r supplemented with iron salts, there was a m a r k e d increase in the retention, comparable to the increase shown when G. K. first received iron salts. The hemoglobin values d u r i n g these periods showed a decided gain. These results as in the case of G. K. indicate a definite need of i n f a n t R. K. for iron. These infants were able to store large quantities of iron and to convert it to hemoglobin when it was supplied to them in an easily available f o r m and in amounts which greatly exceeded normal intake. In the case r e p o r t e d previously, no rise in hemoglobin occurred on a similar diet, although there was a decided increase in retention. The iron intake was somewhat lower in this case (100 rag. daily), and the possibility must not be overlooked t h a t the h i g h e r iron intake m a y have accounted for the hemoglobin rises and the higher retentions in the cases of G. X. and 1%. K. The Effect of Liver Alone and in Combination With Other Supplements. Liver, when added to a control diet of milk (J. H.), caused a slight increase in the r e t e n t i o n similar to the increase f o u n d when a p p r o x i m a t e l y the same a m o u n t of iron in the f o r m of apricots was added to a milk-spinach diet (J. tI.). As in the case of the apricots, there was no gain in hemoglobin. The addition of iron salts in the f o r m of ferrous sulphate to a milkliver diet (J. It.) b r o u g h t a b o u t a decided increase in retention f o r three of the f o u r periods studied. The a m o u n t of iron given varied from period to period, and the t r e n d of the retention followed the general t r e n d of the intake. The hemoglobin also showed a significant gain d u r i n g this time. The retention of iron by J. It. when receiving ferrous sulphate was of the same order of m a g n i t u d e as those of G. K.
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and R. I~. when given ferric ammonium citrate. There was no evidence f r o m either the iron retention or the hemoglobin f o r m a t i o n t h a t ferrous salts "were p r e f e r a b l e to ferric salts in the ease of our infants. W h e n a f u r t h e r addition of copper salts was made to the liver-iron diet (J. H.), the iron retention during the first period was h i g h e r than it has been at previous times, and the rate of gain of hemoglobin was also increased. D u r i n g the second period on this d i e t the retention was much lower, while the hemoglobin continued to gain at approxim a t e l y the same rate. The lowered r e t e n t i o n d u r i n g t h a t period m a y have been due to a lessened need for iron, since at t h a t time the hemoglobin was approaching a normal value. There was a definite decrease in the retention in two cases (G. K. and R. I~.) when liver was given in conjunction with iron and copper salts, apricots, and spinach. The hemoglobin values at that time, however, were r a p i d l y approaching normal, and again it m a y be that the lessened need f o r iron was the real cause f o r the lowered retention. The hemoglobin continued to rise during these periods at a p p r o x i m a t e l y the same rate as formerly. Our results with J. It., G. K., and R. K. show no evidence that liver was of value in the t r e a t m e n t of their secondary anemias, either when fed alone or in addition to a diet containing spinach, apricots, and iron and copper salts. In the ease of the anemic i n f a n t previously reported, liver had a p p e a r e d to be of great benefit since immediately on supplementing the spinach, apricot, and irQn and copper salt diet with liver, an increased iron retention and a m a r k e d rise in hemoglobin occurred. I t m a y be i m p o r t a n t in this connection to note t h a t this i n f a n t was older (twenty-three months) at the time the metabolism s t u d y was begun. His anemia was a p p a r e n t l y of much longer standing, and he showed a m a r k e d anorexia which was not characteristic of the other infants. The elimination of large h a r d stools at a p p r o x i m a t e l y twod a y intervals indicated an intestinal disturbance which m a y have complicated the results. W e believe that the results on J. H., G. K. and R.. K. shown in this r e p o r t represent more n e a r l y the reactions of a simple case of s e c o n d a r y anemia caused by malnutrition. SU~k~ARu
The effect of various supplements to the diet on the iron retention and hemoglobin of three cases of secondary anemia has been shown. Additional iron, w h e n supplied b y pur6ed spinach, was not utilized by these infants. The iron of apricots, although utilized somewhat better t h a n t h a t of spinach, affected no change in hemoglobin and only a slight increase in retention. Iron salts, when given in large amounts either in the f o r m of ferrous sulphate or ferric ammonium citrate caused a m a r k e d increase in the
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retention and a rise in hemoglobin. There was no evidence shown that the ferrous salt was more efficacious t h a n the ferric salt. Copper salts, given in conjunction with either a low or a high iron intake, did not seem to have a n y effect on the iron retention or the hemoglobin level. The copper contents of the previous diets were app a r e n t l y adequate. The i n t r o d u c t i o n of liver into a diet of low iron content caused a slight increase in retention, but no gain in hemoglobin. W i t h a high iron intake, a decreased retention of iron occurred coincident with the addition of liver to the diet. I t is suggested t h a t this lowered retention was due not to the liver per se, but to a lessened need of the infant for iron at t h a t time. R~FERENCES J. 2. 3. 4. 5.
Schlutz~ Lottrup, Imttrup, Parsons, Old]lam,
F. W., Morse, M., and Oldham, H.: J. PEDIAT. 3: 225, ]933. M. C.: Ugeskr. f. Laeger. 94: 584~ 1932. ~. C.: Am. J. Dis. Child. 47: ], 1934. L. G., and IIawksley~ J. C.: Arch. ])is. Child. 8: ]]7, 1933. I-I., Schlutz, F. W., and Morse, IV[.: Am. J. Dis. Child. (In press.)
FE~aVARY, 1937
NO. 2
Original Communications T H E E F F E C T OF V A R I O U S S U P P L E M E N T S TO T H E D I E T ON T H E IRON B A L A N C E OF T t I E A N E M I C I N F A N T
FREDERIC W. SCIILUTZ, M.D., MINERVA MORSE, PE.D., AND HELEN
0LDHA~
CI:iICAGO, IDL.
I N uponAN
earlier report on the influence of fruit and vegetable feeding the iron metabolism of the infant we included a study of the iron balance of one infant suffering from nutritional anemia. The results showed that, while addition of dried spinach to a~ milk diet caused a lowered retention of iron, the f u r t h e r addition of apricots caused a m a r k e d increase in the retention of iron. The iron retention was also increased b y feeding large amounts of iron in the form of ferric ammonium citrate. I t showed a f u r t h e r increase when an additional supplement of liver was made to the diet. In spite of the increased retention of iron, the hemoglobin concentration of the blood was not improved until the iron salt in the diet w a s supplemented by liver. To determine w h e t h e r these results were peculiar to the individual ease or typical also of other eases of secondary anemia in infants, we have continued the s t u d y of the effects of these foods on the iron retentions of three other anemic infal~ts.
The three infants, J. tI., G. K., and R. K. were thirteen, eight, and eight months old, respectively, when the metabolism s t u d y was begun. EXPERIMENTAL,
PROCEDURE
The same general plan was followed in the s t u d y of these cases as in the case r e p o r t e d previously. W i t h the exception of the control periods on p o w d e r e d milk, v cane sugar, and cod liver oil, the infants :From the Department of Pediatrics, University of Chicago. This work was supported in part by a grant from the Douglas Smith Foundation f o r M e d i c a l R e s e a r c h of t h e U n i v e r s i t y o f C h i c a g o . * P o w d e r e d m i l k i n t h e f o r m o f d r y c o w a s f u r n i s h e d t h r o u g h t h e c o u r t e s y of t h e D r y IV[ilk C o m p a n y .
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received each diet for a period of at least fifteen days before an additional supplement to the diet was made. Care was t a k e n to keep the supplements as u n i f o r m as possible, and the daily a m o u n t of each, ~:' with the exception of the iron salts, was constant for all three cases. A f t e r the i n f a n t had received a given diet f o r a fore period of at least five days, the urine and feces were collected for two consecutive periods of five days each, aliquots of food, urine, and feces w e r e analyzed f o r iron content and the iron balance calculated. Supplements to the diets were not made in the same order for each infant. In every ease the first period was a control on powdered milk, cane sugar, and cod liver oil formula. Following the control period, J. H. and G. K. were given purged spinach for periods 2 and 3. This p a r t i c u l a r f o r m of spinach was used as it had been found to be utilized slightly better by normal infants t h a n either the dried or raw form. 1 D u r i n g periods 4 and 5 J. H. and G. K. received both spinach and apricots. 1%. K. was given apricots d u r i n g periods 2 and 3 and apricots and pur6ed spinach in periods 4 and 5. I t was felt that, if a g r e a t e r percentage of the iron of apricots t h a n of spinach were retained, it would be reflected in his iron balance when compared with t h a t of the other two infants. An intestinal disturbance, accompanied b y diarrhea, occurred in the case of i n f a n t J. H. a f t e r period 5 and the s t u d y was discontinued for a Short time. I t was not felt t h a t the diet had caused this disturbance as the same foods had been given to several other infants with no evidence of diarrhea. A f t e r recovery, J. tI. was given a basic f o r m u l a of powdered milk, cane sugar, orange juice, and cod liver oil d u r i n g period 6. This diet was supplemented with liver d u r i n g periods 7 and 8 and f u r t h e r supplemented with varying' amounts of iron salts (111 to 199 rag,) in the f o r m of ferrous sulphate in glucose solution d u r i n g the f o u r periods following. I t seemed of interest to compare the effect of the ferrous salt with t h a t of the ferric form, since L o t t r u p 2,a and Parsons and H a w k s l e y ~ had f o u n d ferrous salts more effective in curing secondary anemias. In periods 13 and 14 copper in the f o r m of cupric sulphate was given as an additional supplement to the liver and the iron saIts. Spinach and apricots were continued in the diet of G. K. and R. K. t h r o u g h o u t the remainder of the study. In the ease of G. K. f u r t h e r supplements of ferric ammonium citrate (132 to 146 nag'. Fe), cupric sulphate, and liver were given in the order mentioned. In the diet o f 1%. K. the same supplements were given, but the order was cupric sulphate, ferric ammonium citrate, and, finally, liver. * P u r O e d s p i n a c h w a s s u p p l i e d t h r o u g h t h e c o u r t e s y of V a n C a m p ' s Inc. D a i l y s u p p l e m e n t s o f 70 gin. w e r e g i v e n . D a i l y s u p p l e m e n t s of a p r i c o t s w e r e e q u i v a l e n t to 40 g'm. o f t h e d r i e d f r u i t . D a i l y s u p p l e m e n t s of c a l f ' s l i v e r a m o u n t e d to 20 gin. T w e l v e m i l l i g r a m s of copper, as copper sulphate, w e r e g i v e n daily.
S C E L U T Z ET AL. :
IRON BALANCE IN ANElV[IA
]49
Details concerning the p r e p a r a t i o n of food, the collection of excreta and the methods used f o r determining iron and hemoglobin h a t e been given in the previous communication. All three infants were in positive nitrogen balance and each showed consistent weight gains d u r i n g every period studied. Feedings were t a k e n well, and w i t h the exception of the anemia the infants seemed to be quite normal, In all cases the anemias were t h o u g h t to have been caused b y inadequate diets and were t h e r e f o r e believed to be comparable. ttISTOI%u OF CASES CASE ] . - - J . It., a m a l e i n f a n t , w a s a f u l l - t e r m b a b y , delivered b y low forceps with no compllcatlons. B i r t h w e i g h t w a s 3,790 gin. T h e b a b y was n o r m a l except f o r a b i l a t e r a l h a r e l i p a n d a u n i l a t e r a l cleft palate. F e e d i n g c o n s i s t e d o f b r e a s t milk a n d dryc% b y g a r a g e . Cod liver oil a n d viosterol were g i v e n r e g u l a r l y . He was first b r o u g h t to t h i s clinic at %he a g e of one m o n t h , in good n u t r i t i v e s t a t e . A n operation w a s p e r f o r m e d , a n d t h e h a r e l i p w a s repaired. D u r i n g his first y e a r he h a d m e a s l e s a n d two a c u t e a t t a c k s of otltls m e d i a ( ] e f t ) . IIe w a s r e a d m i t t e d to t h e h o s p i t a l at "~he a g e Of one y e a r , a well-nourished a n d well-developed child, for repair of t h e c l e f t palate. H i s h e m o g l o b i n a t t h e t i m e o f a d m i t t a n c e w a s 70 per cent. D u r i n g his convalescence, h i s h e m o g l o b i n fell to 40 per cent, a n d at t h e a g e of t h i r t e e n m o n t h s he w a s d i a g n o s e d as h a v i n g s e c o n d a r y a n e m i a . CASE 2 . - - G . K . , a m a l e i n f a n t , w a s one of identical, f u l l - t e r m twins. H i s b i r t h h i s t o r y w a s n o r m a l , a n d h i s b i r t h w e i g h t was 2,~55 gin. t i e w a s first seen a t this clinic at t h e a g e o f e i g h t m o n t h s , w h e n he w a s b r o u g h t i n b e c a u s e o f i r r i t a b i l i t y a n d paleness, l i e h a d b e e n b r e a s t f e d for t h e first two m o n t h s o f life a n d t h e n w a s g i v e n complemen%ary f e e d i n g s u n t i l t h e f o u r t h m o n t h , at which t i m e he was g i v e n a f o r m u l a c o n s i s t i n g o f whole milk, cane s u g a r , a n d water. Cod liver oil a n d o r a n g e juice were g i v e n r e g u l a r l y a f t e r t h e second m o n t h , b u t cereals and vegetables were n o t i n t r o d u c e d i n t o his diet u n t i l h e w a s seven m o n t h s old. The child h a d b e e n in f a i r h e a l t h a n d h a d suffered f r o m no c o n t a g i o u s diseases. U p o n a d m i s s i o n h i s h e m o g l o b i n w a s f o u n d to be 44 per cent, a n d t h e case w a s d i a g n o s e d as s e c o n d a r y a n e m i a . CASE 3.--I~. K., a m a l e i n f a n t , w a s first seen at t h i s clinic at t h e a g e of eight m o n t h s . H e w a s t h e i d e n t i c a l t w i n of G. K., a n d b i r t h h a d been n o r m a l . B i r t h w e i g h t was 2,540 g m . H i s f e e d i n g since b i r t h h a d been t h e s a m e as t h a t of G. t{:. which h a s b e e n described p r e v i o u s l y , l i e h a d always b e e n i n a p p a r e n t good h e a l t h a n d h a d s u f f e r e d f r o m no c o n t a g i o u s diseases, t i e w a s b r o u g h t to t h e clinic b e c a u s e of a n o t i c e a b l e pallor a n d a n aeu%e u p p e r r e s p i r a t o r y i n f e c t i o n . A h e m o g l o b i n value o f 37 p e r cent w a s f o u n d , a n d t h e case was d i a g n o s e d as one of secondary anemia.
DISCUSSION OF ~ESULTS The iron intakes and retentions and the corresponding hemoglobin values for these cases as influenced by the various supplements to the diets will be f o u n d in Charts 1 and 2.
Effect of Sp~nach.--The addition of pur6ed spinach to the control diet of infants J. H. and G. K. caused a v e r y small increase in the retention of iron in one case and a very slight decrease in the other.
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W h e n added to the control diet supplemented with apricots, in the ease of tL K., the retention remained the same as on the milk-apricot diet. The hemoglobin showed no appreciable change in any ease. The addition of dried spinach resulted in a negative iron balance in the ease of secondary anemia r e p o r t e d previously. No negative balances were f o u n d in these cases when the purged form was used. However, the additional iron given in this f o r m did not a p p e a r to be retained. I t would seem that anemic infants are not able to utilize the iron of spinach.
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C h a r t 1 . - - T h e effect of s p i n a c h a n d a p r i c o t f e e d i n g on t h e r e t e n t i o n of i r o n a n d t h e f o r m a t i o n os h e m o g l o b i n . * C o n t r o l d i e t : P o w d e r e d m i l k , can'e s u g a r , a n d cod l i v e r oil.
Effect of Apricots.--When apricots were added to a milk-spinach diet (J. H. and G. K.), the retentions were slightly higher t h a n on either the control or the milk-spinach diet. The addition of apricots to the control diet (R. K.) caused a slightly increased retention which was n o t increased f u r t h e r by the addition of s p i n a c h . The retentions in all cases were small, and the hemoglobin values were not appreciably affected. In no case was there a decrease in the fecal o u t p u t or a m a r k e d increase in the retention as occurred in the ease of the i n f a n t reported previously.
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Since the r e t e n t i o n of iron showed a slight increase in all eases when apricots were fed, it would seem t h a t the iron of a p r i c o t s is more readily available to the anemic i n f a n t t h a n t h a t of spinach. This m a y
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2 . - - E f f e c t os iror~ a n c l c o p p e r s a l t s a n d l i v e r o n t h e r e t e n t i o n o f i r o n a n d t h e formation of hemoglobin. *Determined by average results of periods 4 and 5 for each case. ?Control diet (1) : Powdered milk, cane sugar, orange juice, and cod liver oil $Control diet (2) : Powdered m i l k , c a n e s u g a r , c o d l i v e r oil, s p i n a c h a n d a p r i c o t s .
be due to the f a c t t h a t a much higher p e r c e n t a g e of the iron of apricots t h a n of spinach is in the inorganic form. While we ~ find no conclusive
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evidence t h a t a normal child utilizes iron in the inorganic f o r m more readily t h a n in the organic, it is possible t h a t the anemic child might utilize the inorganic p o r t i o n ' m o r e easily.
E~ect of Iron and Copper Salts Alone and in Combination.--When iron salts in the form of ferric ammonium citrate were added to a diet containing spinach and apricots (G. K.), the retention of iron was increased markedly, and the hemoglobin showed consistent gains. Supplementing this diet f u r t h e r with cupric sulphate did n o t affect any additional increase in the retention or a more r a p i d gain in the hemoglobin. It would appear, then, t h a t this i n f a n t had been receiving an adequate amount of copper in his previous diets and t h a t iron r a t h e r t h a n copper had been the limiting factor. On the other hand, the addition of copper salts to a diet containing spinach and apricots (R. K.) caused no change in either retention or hemoglobin. At this level of iron intake additional copper had no beneficial effect. It is quite probable t h a t the copper content of the spinach-apricot diet was adequate as was shown in the case of G. K. W h e n the diet was f u r t h e r supplemented with iron salts, there was a m a r k e d increase in the retention, comparable to the increase shown when G. K. first received iron salts. The hemoglobin values d u r i n g these periods showed a decided gain. These results as in the case of G. K. indicate a definite need of i n f a n t R. K. for iron. These infants were able to store large quantities of iron and to convert it to hemoglobin when it was supplied to them in an easily available f o r m and in amounts which greatly exceeded normal intake. In the case r e p o r t e d previously, no rise in hemoglobin occurred on a similar diet, although there was a decided increase in retention. The iron intake was somewhat lower in this case (100 rag. daily), and the possibility must not be overlooked t h a t the h i g h e r iron intake m a y have accounted for the hemoglobin rises and the higher retentions in the cases of G. X. and 1%. K. The Effect of Liver Alone and in Combination With Other Supplements. Liver, when added to a control diet of milk (J. H.), caused a slight increase in the r e t e n t i o n similar to the increase f o u n d when a p p r o x i m a t e l y the same a m o u n t of iron in the f o r m of apricots was added to a milk-spinach diet (J. tI.). As in the case of the apricots, there was no gain in hemoglobin. The addition of iron salts in the f o r m of ferrous sulphate to a milkliver diet (J. It.) b r o u g h t a b o u t a decided increase in retention f o r three of the f o u r periods studied. The a m o u n t of iron given varied from period to period, and the t r e n d of the retention followed the general t r e n d of the intake. The hemoglobin also showed a significant gain d u r i n g this time. The retention of iron by J. It. when receiving ferrous sulphate was of the same order of m a g n i t u d e as those of G. K.
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and R. I~. when given ferric ammonium citrate. There was no evidence f r o m either the iron retention or the hemoglobin f o r m a t i o n t h a t ferrous salts "were p r e f e r a b l e to ferric salts in the ease of our infants. W h e n a f u r t h e r addition of copper salts was made to the liver-iron diet (J. H.), the iron retention during the first period was h i g h e r than it has been at previous times, and the rate of gain of hemoglobin was also increased. D u r i n g the second period on this d i e t the retention was much lower, while the hemoglobin continued to gain at approxim a t e l y the same rate. The lowered r e t e n t i o n d u r i n g t h a t period m a y have been due to a lessened need for iron, since at t h a t time the hemoglobin was approaching a normal value. There was a definite decrease in the retention in two cases (G. K. and R. I~.) when liver was given in conjunction with iron and copper salts, apricots, and spinach. The hemoglobin values at that time, however, were r a p i d l y approaching normal, and again it m a y be that the lessened need f o r iron was the real cause f o r the lowered retention. The hemoglobin continued to rise during these periods at a p p r o x i m a t e l y the same rate as formerly. Our results with J. It., G. K., and R. K. show no evidence that liver was of value in the t r e a t m e n t of their secondary anemias, either when fed alone or in addition to a diet containing spinach, apricots, and iron and copper salts. In the ease of the anemic i n f a n t previously reported, liver had a p p e a r e d to be of great benefit since immediately on supplementing the spinach, apricot, and irQn and copper salt diet with liver, an increased iron retention and a m a r k e d rise in hemoglobin occurred. I t m a y be i m p o r t a n t in this connection to note t h a t this i n f a n t was older (twenty-three months) at the time the metabolism s t u d y was begun. His anemia was a p p a r e n t l y of much longer standing, and he showed a m a r k e d anorexia which was not characteristic of the other infants. The elimination of large h a r d stools at a p p r o x i m a t e l y twod a y intervals indicated an intestinal disturbance which m a y have complicated the results. W e believe that the results on J. H., G. K. and R.. K. shown in this r e p o r t represent more n e a r l y the reactions of a simple case of s e c o n d a r y anemia caused by malnutrition. SU~k~ARu
The effect of various supplements to the diet on the iron retention and hemoglobin of three cases of secondary anemia has been shown. Additional iron, w h e n supplied b y pur6ed spinach, was not utilized by these infants. The iron of apricots, although utilized somewhat better t h a n t h a t of spinach, affected no change in hemoglobin and only a slight increase in retention. Iron salts, when given in large amounts either in the f o r m of ferrous sulphate or ferric ammonium citrate caused a m a r k e d increase in the
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retention and a rise in hemoglobin. There was no evidence shown that the ferrous salt was more efficacious t h a n the ferric salt. Copper salts, given in conjunction with either a low or a high iron intake, did not seem to have a n y effect on the iron retention or the hemoglobin level. The copper contents of the previous diets were app a r e n t l y adequate. The i n t r o d u c t i o n of liver into a diet of low iron content caused a slight increase in retention, but no gain in hemoglobin. W i t h a high iron intake, a decreased retention of iron occurred coincident with the addition of liver to the diet. I t is suggested t h a t this lowered retention was due not to the liver per se, but to a lessened need of the infant for iron at t h a t time. R~FERENCES J. 2. 3. 4. 5.
Schlutz~ Lottrup, Imttrup, Parsons, Old]lam,
F. W., Morse, M., and Oldham, H.: J. PEDIAT. 3: 225, ]933. M. C.: Ugeskr. f. Laeger. 94: 584~ 1932. ~. C.: Am. J. Dis. Child. 47: ], 1934. L. G., and IIawksley~ J. C.: Arch. ])is. Child. 8: ]]7, 1933. I-I., Schlutz, F. W., and Morse, IV[.: Am. J. Dis. Child. (In press.)