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Studies on the growth and development of malechildren receiving evaporated milk
STUDIES ON THE GROWTH AND DEVELOPMENT OF MALE CHILDREN EECEIVING EVAPORATED MILK I. THE EFFECT OF VARIOUS VITAMIN SUPPLEMENTS ON GROWTH IN LENGTH AND INCIDENC~E OF RICKETS DURING THE FIRST TWO YEARS OF LIFE
TERESA FOLIN RHOADS, M.D., MILTON RAPOPORT, ~.D., RUTH KENNEDY, AND JOSEPH STOKES, JR., 1Vi.D., PHILADELPHIA, PA.
acceptance and use of irradiated evaporated milk in infant feedT HE ing has become so general that it prompts an inquiry into the suitability of this food in the dietary of older children. The metabolic studies of Souders, Hunscher, I-Iumme], and Macy1 indicate that there is excellent assimilation of the organic and inorganic elements of irradiated evaporated milk in young children. However, there is no body of data available concerning the growth and development of children who have received irradiated evaporated milk from infancy through the preschool years. Almost all of the studies concerning irradiated evaporated milk have been with infants for relatively short periods of observation, usually of six months' duration. This report presents data obtained from 233 male children who have received evaporated milk as their sole source of milk since early infancy, viz., an average beginning age of 42 days. It has been the purpose of this outpatient study to observe the growth and development of these children receiving" eva.porated milk, to evaluate the protection against rickets afforded by the vitamin D content of the irradiated evaporated milk, and to study comparatively the influence of supplements of vitamins A, D, and B complex: The children have been in this study for periods varying from two and one-half to four years, and we are presenting data concerning selected aspects of their growth and development for a continuous two-year period of observation of each child. The majority of these children come from homes where there is financial difficulty and therefore m a y b e considered to be representative of many children in t h e lower income groups of our cities. The organization of the study and methods used will be described first, and the results will then be discussed under the sections of consumption of evaporated milk, growth in length, incidence of rickets, and incidence of infections. Subsequent reports will be made concerning the weight of these children, other anthropometrie measurements , development including psychometric tests, laboratory findings, and photoelectric examination of roentgenograms of the forearm. ORGANIZATION A:ND METHODS
The study was undertaken in November,-1936, in the Out-Patient Department of the Children's Hospital of Philadelphia. The personnel From
the Children's
Hospital
of Philadelphia. 169
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THE
J O U R N A L OF P E D I A T R I C S
consisted of two part-time physicians, a part-time technician, a fulltime nurse and a full-time social worker. X-ray examinations were carried out in the X-ray Department of the Children's IIospitalP In~ants were enrolled with the cooperation of the maternity departments of the Pennsylvania, the Philadelphia General, and tile University of Pennsylvania Hospitals. Also some infants were referred from the Child Hygiene Division of the Department of Public Health of Philadelphia, others from the Children's Hospital, and a few through personal contact. The criteria set up for the selection of infants for this study were as follows: 1. All infants selected were males in order to eliminate sex as a variable. 2. All infants selected had birth weights of 5 pounds or more in order to eliminate prematurity as a factor. 3. All but four of the infants were under 3 months of age when they were enrolled. These four were under 3.5 months. The average age of the entire group was 42 days. 4. No infants were receiving any breast milk when they were referred for the study. The last criterion eliminated so many infants that twenty-two months were required for the enrollment of the entire group. The racial distribution of the children was 42 per cent negro and 58 per cent white. Among the white infants 25 per cent were of Italian extraction, 25 per cent of Irish, 12 per cent of British, 10 per cent of German, 7 per cent o.f Slavic, 11 per cent of mixed northern and southern European, and 10 per cent of mixed German and British extraction. FOr the purposes of the study the 233 infants were divided into three groups according to the vitamin content of the diet they received. The colored and white infants comprising each group were considered separately in the statistical analysis. The diets were as follows: Group I. Eighty infants received 110 U.S.P. units of vitamin D daily in the form of irradiated evaporated milk. Group II. Seventy-three infants received approximately 1,500 U.S.P. units of vitamin D and 15,000 U. S. P. units of vitamin A daily in three teaspoons of cod-liver oil.f This group received nonirradiated evaporated milk. Group III. Eighty infants received 110 U.S.P. units of vitamin D in the form of irradiated evaporated milk daily and 10 drops of carotenes (equivalent to approximately 2,250 U.S.P. units of vitamin A). A subgroup (thirty-nine infants), referred to as Group IV, received 0.5 tablespoonful of brewer's yeast powder daily (approximately 250 units of vitamin B1 and 250 Sherman units of vitamin B2). *All r o e n t g e n o g r a m s w e r e r e a d b y Dr. R a l p h S. ] ~ r o m e r , r o e n t g e n o l o g i s t of t h e C h i l d r e n ' s YrIospital of :Philadelphia. t T h e c o d - l i v e r oil a n d y e a s t u s e d in t h i s s t u d y w e r e m a d e a v a i l a b l e b y t h e g e n e r o s i t y of M e a d J o h n s o n a n d Co. $ C a r o t e n e w a s o b t a i n e d f r o m t h e S.M.A. C o r p o r a t i o n .
R H O A D S E T AL. :
M A L E CI-IILDREN R E C E I V I N G EVAPORATED M I L K
171
All children received vitamin C in the form of orange juice or tomato juice in adequate amounts daily from the time of the first visit. In all groups the daily formula, contained one 14.5 ounce Can of evaporated milk (13 fluid o u n e e s ) a t or before the age of 4 months. Five per cent carbohydrate was added, usually in the form of dark corn syrup. As the children grew older, additional calories were given in solid food and the intake of evaporated milk remained the same. Banana and cereal were started at 3 to 4 months, pur~ed vegetables and fruits at 5 to 6 months, and potato and meat at 8 to 10 months.. Egg yolk was not recommended earlier than 10 months but was given in some cases. Before the age of 1 year, the added carbohydrate was eliminated and transition from bottle to cup feeding was advised at this time. Iron ammonium citrate (18 grains daily) or a solution of ferrous sulfate (6 grains daily) was given when the hemoglobin was below ]3 Gin. per 100 e.e. In assessing the physical development of the children a definite pro~ gram was followed. At the first visit the history was taken, and a cornplete physical examination was made. The child was weighed, and the following anthropometrie measurements 2 were taken : (1) crownheel length, (2) crown-rump length, (3) intereristal diameter, (4) width of the head, (5) length of the head, (6) circumference of the head, (7) width or the chest, (8) depth of the chest, and (9) circumference of the chest. Clinical evidences of rickets (eraniotabes, bossing, beading, Harrison's groove) were noted. A roentgenogram of the left forearm was made, and blood was taken for determination of hemoglobin and serum protein concentrations. The children were brought to the clinic at short intervals until well established on the formula and then every month during the first year, and every two months thereafter. At each regular visit the child was weighed and measured. A complete medical record was kept, including illnesses, evidence of rickets, developmental history, amount of regurgitation, and number of stools per day. Determinations of hemoglobin and serum protein were done at every second visit, and x-ray examinations of the left forearm were made ten times during the first two years, at intervals of two months from November to May and of three months during the remainder of the year. The milk and the vitamin supplements were delivered at the homes every two weeks b y the nurse and by the social worker. The n u m b e r of cans of milk left was calculated so that, when the child was due for a r e t u r n visit, the supply of milk was exhausted. This method was fairly effective in assuring the regularity of visits to the clinic. The supply of milk was maintained during infectious diseases and when it was temporarily impossible for the mother to bring the child to the hospital. In families where there were younger brothers and sisters, milk was supplied for them also so that there was no question of whether or not the children included in this s t u d y had had milk available. Most of the
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hospitalization that was necessary was provided at the Children's Hospital where the feeding could be continued as at home. ACCEPTABILITY
OF
EVAPORATED
MILK
AT
2
YEARS
When the children stopped drinking milk from bottles, most of the mothers put a can of milk in a quart jar and filled it up to the top with water, making a di]ution of 13 fluid ounces of evaporated milk to 19 ounces of water. W h e n the child did not finish his milk, it was recommended that 13 or 11 ounces of w a t e r should be added. I n one case the milk was well taken when only 4 ounces of water were added. To obtain an a p p r o x i m a t e idea of how much milk each child was consuming, the mothers were asked f r o m time to time if the child took a whole can daily. Although the replies to these questions m a y not be entirely truthful, they seemed f a i r l y reliable and were tabulated. TABLE I PERCENTAGE DISTRIBUTION OF 2-YEAI~-OLD CHILDREN ACCORDING TO DAILY CONSUMPTION 0P EVAPORATED ~]:ILK N0. GROUP
Group I (irradiated evaporated milk) Group I I (~onirradiat~4 evaporated milk plus codliver oil) Group I I I (irradiated evaporated milk plus carotene) Group I V (irradiated evaporated milk plus carotene and yeast) Total
mACE
OF CHILDIZEN
I
CAN (%)
~4
CAN
(%)
-~ CAN
(%)
OAIq
(%)
White Colored
48 32
83.3 90.6
14.6 6.3
2.1 3.1
0 0
White Colored
4~2 31
90.4 83.9
2.4 12.9
4.8 3.2
2.4 0
White I Colored
24 17
75.0 82.4
]2.5 5.9
8.3 11.7
4.2 0
White Colored
20 19
70.0 94.7
10.0 5.3
20.0 O
White Colored
J34 99
82.1 87.9
9.7 8.1
6.7 4.0
1.5 0
Table I shows that the evaporated milk was well taken by the colored children and slightly less well by the white. T h a t the carotene and yeast group of white children took less milk t h a n the others is perhaps due to the presence of yeast in the milk; when tile yeast was disliked, the best method of giving it seemed to be to sprinkle it on cereal. GROWTH IN LENGTH
Since the children were measured at different chronological ages, at the suggestion of Dr. J. H. Austin the following method was used to determine their probable lengths at the ages which were to be tabulated. Charts were p r i n t e d with a straight line representing the average rate of growth for boys f r o m birth to 2 years, based on the average figures given by K o r n f e l d ) This line was straight instead of being the usual
30
~0
90
V'LO
i5]
IBI
~12
'z43 Zl3
304
334
JYEAR
t YEAR 3r=.S 395
4"z5
~55
,48.~
51G
5A,F, 577
(,O,B &38 66"~ r
Z YEARS
"L"(E AE S" 7~0
~ig. 1.~Sample chart used in plotting" lengths of children. I~leavy straight line represents average length of boys f r o m birth to 2 Ty~ears, from data os KornfeId3 Note that ordinates representing clays of age are spaced at decreasing intervals to achieve a straight line f o r growth in length. ~/~easurements taken in these studies were plotted on appropriate ordinates and connected by straight lines. Length at any age between two actual meaBuremerits may be read directly from the chart.
AGE II't PAY5
co
C~
z
c~
F~
9
]74
THE
JOURNAL
OF P E D I A T R I C S
curve because the time intervals were spaced at decreasing distances (Fig. 1). The measurements for each child and the ages in days when he had been measured were plotted on one of these charts, and the successive points were connected by straight lines. The lengths of a child at the particulal; ages (3, 6, 9, 12, 15, 18, 21, 24 months) were obtained directly f r o m the intersections of the child's length line and the age ordinates. This method avoided the subjective element which enters into the interpolation of curves. -Lcn~t/~
Croop
./rr~dl'~fed
Z. ~HH-e
~pora+e$l
-IV~ilk
rnn3, 9~0 -
850 .
"250 -
@50 '
550
4=o q~--'] ~ir~t3
I-~ n3o,
@ roD,
I
I-
I
~ too,
) ~j n
15 m e
I I~ t o o .
2.1 t o o ,
I ~ qn
F i g s . 2 - 9 . - - G r o w t h in l e n g t h c o m p a r e d w i t h I ~ o r n f e l d s t a n d a r d s f o r b o y s . S t i p p l e d a r e a s r e p r e s e n t a v e r a g e r a n g e of 14:ornfeld s t a n d a r d s f o r b o y s . U p p e r l i n e s c o r r e s p o n d to u p p e r l i m i t of h e i g h t g i v e n b y K o r n f e l d , a n d l o w e r l i n e s c o r r e s p o n d to l o w e r l i m i t of l e n g t h . H e a v y l i n e s a r e a v e r a g e l e n g t h c u r v e s of e a c h g r o u p . Fig.
2.--Group
I, f o r t y - e i g h t
white
children
on i r r a d i a t e d
evaporated
milk.
When the growths of the children on each of the f o u r feeding regimes were compared, the white and colored children on each diet were considered separately since it has been n0ted that colored children show a tendency toward more r a p i d growth t h a n white children. ~ The more rapid growth o~ colored children was also noted in this ~tudy and warrants this division. The average lengths of the white and colored children in each o2 the four groups were determined at the above stated intervals and were plotted against the K o r n f e l d standards. These are shown in Figs. 2-9. E x a m i n a t i o n of these figures shows t h a t the average lengths of the different groups at 3 months of age were all below
RHOADS E T AL. :
M A L E C H I L D R E N R E C E I V I N G EVAPORATED M I L K
175
- - Groap X- Colored-.~enq+h mtn. gSO
l r r a d iof~e d "~pca p o r a ~ e d
IV)ilk
~
850~
~50-
650
9
550
-
.45o t" ~ir+h
I
I
I
I
I
S too.
6 too,
9 too.
I bit.
15 toO.
I 18 r~qo.
I
I
~1 rt3o.
~.qt%
Fig. 3 . - - G r o u p I, t h i r t y - t w o c o l o r e d c h i l d r e n on i r r a d i a t e d e v a p o r a t e d m i l k .
-- Groop Tr-Mhi~e-/~on-lrrodl'a§ ~Cva~orar Cod-Liver Oil
.l.,en~§ rnrn 950-
850
Iv)ilk
-
~50"!
650
"
550
-
"F~iI"~'~ ~ig.
4.~Group
~mo. II,
bin0. ~orty-two
9 rno. white
|qr,
children
15 m 0 .
on nonirradiated
liver oil
18 m0. evaporated
~I m 0 ; milk
~.~ plus
cod-
176
T I I E J O U R N A L OF P E D I A T R I C ~ G.roup.~
- -
Colored - -
-
IMon-lrrad~a+eol
E~apora~ed
pl~s
rnPD.
Iv]ilk
Cool-Liver Oil
8301 ~501 ~50
350 *50 [ ]Sit-+h
1 5 too.
I 6too.
I g too,
I
I
1 qr,
15 t o o ,
I
Fig. 5 . - - T h i r t y - o n e c o l o r e d c h i l d r e n on n o n i r r a d i a t e d oil.
Irrad/a~r
1~e n g t h
850
JEva~ora'keel
18 rnO.
l s
I too.
P~ q r ,
e v a p o r a t e d m i l k plus c o d - l i v e r
M i l k
plus Caro§
P
750
650
~0
~-5o J" ]~irtb
I
3 too.
I
bmo,
I
9 too,
I
I qr,
I
15 t o o .
'I
I~ too.
' I
s
too.
'
I
~qr',
Fig. 6 . - - T w e n t y - f o u r w h i t e c h i l d r e n on i r r a d i a t e d e v a p o r a t e d m i l k plus c a r o t e n e .
RHOADS ET AL. :
~MALE C H I L D R E N R E C E I V I N G EVAPORATED IViILK
--
Len~[+h
177
Gro~l~ . ~ 9 C o l o r e d - -
Irr~dla§
rD,,~,
:By,pomaded p/as
Mi/k
950
8501
?501 650550
,~o,["
....
:Bir§ ~ig.
I D too.
,1
I 6 too.
I
I
I
9 too.
I q r.
i5 rno.
-
', =8 too.
"
I 21 too.
I ~_qr.
7 . - - S e v e n t e e n c o l o r e d c h i l d r e n on i r r a d i a t e d ~ e v a p o r a t e d m i l k p l u s c a r o t e n e . --~roap~-
s
Sqhi'~e--
Irradiated
~vaporo~ed IV/ilk p/aS C ~ r o f e n e onal Ye~S~
mm.
950 -
650 -
950 --
550
,*so ~ - - - ~ 1 ~irth
~mO.
I
[
I
1
6too.
9rno,
IC~r.
15too,
'
I
I
18too.
P~t~o,
I ~qr,
Fig. 8 . - - T w e n t y w h i t e c h i l d r e n on i r r a d i a t e d e v a p o r a t e d m i l k plus c a r o t e n e a n d y e a s t .
178
THE
JOURNAL
OF
PEDIATRICS
the average figures given by Kornfeld. At 2 years of age M1 groups had bettered their position and were within the average range of the Kornfeld standards. The K o r n f e l d standards correspond to those of Stuart 5 until the age of 18 months when they become definitely lower, and they are s l i g h t l y l o w e r at 1 y e a r t h a n those of Bakwin and Bakwin2 I t is interesting to note that the average increment in length of the 134~ white children f r o m 3 months to I year was 149 mm., 1 mm. below the average increase in length of thirty-seven white children in New York, who had received fresh milk, dextrimaltose formulas plus 3 teaspoons o~ cod-liver oil daily f r o m October to May and who were followed for one year by Elias and Turner. 7 - - C - r o a p 2:~". C o l o r e ~ -
.E~,~po~'a~'ed M i D < D/as Coro't-ene a n d >'eosf"
I. ens"i'h
Irradia§
From.
gSOT 6501 ?.50@ 650-
550 -
"P~ir'H'~ 5 rno Fig. 9.--Nineteen
6too. colored
9
children
rno.
on
I qn
irradiated yeast.
15rno,
evaporated
~8 too,
milk
plus
El too.
~.q~..
carotene
and
A s u m m a r y of the average lengths at three-month intervals for the white and colored children is presented in Table I I . The average lengths at 3, 12, and 24 months of both white and colored children on the four different feeding regimes were compared statistically to determine whether there were a n y significant differences among them. Table I I I summarizes the statistical data used in these comparisons. I t is obvious that there was no statistical difference in the average length of either white or colored children on any of the f o u r dietaries at 3, 12, and 24 months.
II
~
Grqup llI White 1 ~ (irra,diatedrated milk evap(plus C~176 / 17 carotene) ~ Group IV " (Irradiated evap- Colored 19 orated milk plus carotene and yeast)
/
665 657
_+61.2 / •
586
~ ]
657 660
665 664
661 665
/ •
/ +_35.8
+38.f ] ~44.1
_+42.7 / _+69.1
58S
593
TION
(hiM.)
LENGTH
6 MO.
~ / 591
I 31 ]
Whit-e--/TlT
(nonirradiatedpluseVaporatedcod.l~vermflkC~ oil
Group
G r ~ p -I White ~ (irradias 3 2 omilk) revap a t Colored e d /
GROUP
I
3 MONTHS --" j STAND RACE I CHIL- I LENGTt:[ I ARD DREN (NIIVf.) DEVIA"
I
1oNO.1
TABLE II
711 706
709 713
7O4 712
710 711
]NG~
751 748
743 747
739 750
745
744
~-+51.7 •
• •
• •
•
•
TION
DEWA
AKD
MONTHS STAND
LENG'?II (~M ,)
]2
18 M e .
21 MO.
784 776
776 782
774 785
776 778 846
--s4--~-837
816 808
840
--83~
I
817 807 815
i~
8o3
8o7 ) ~ 808 [ 835
LENGTH LENGTH ] LENGTH (MM.) (M~.) / (MM.)
15 ~0.
AVERAGELENGTH IN I~[ILLISfETERSACCORDINGTO AGE AND GROUP
862
864
870
858
(MM.)
LENGTH
•
-
•
•
•
• •
•
DEVIATION •
ARD
STAND
24 MONTHS
}-a
F
9N
4
N
F
c~
>
V ,~
9
LENGTHS
il and III II and IV III and IV
I and I V II and III II and Y V III and I V I and II I and III I and I V
I and Ir I a n d III
GROUPS COIV~PAI~D
OF
]2.2 4.5 4.4 8.7 7.8 0.9 5.4 2.5 7.3 2.9 1.9 4.8
MONTHS
OF
THE
+-7.9 +_10.5 +_15.1 +_10.5 +15.1 +-16.6 +_12.5 +_9.6 +_13.1 +12.0 +14.2 +11.8
STANDAI~D DEVIATION OF DIFFERENCE OF TIlE MEANS
3
IV[ILLIMETERS
DIFFERENCE OF MEANS
IN
-
SIGNIFICANCE
DIEFERENT
4.6 0.9 7.1 3.7 11.7 8.0 4.6 2.0 2.4 2.6 2.2 0.4
DIFEERENOE OF MEANS
GROUPS
AGES
MONTHS
T}IE
OF
+_14.5 +19.8 +_16.7 +_21.1 +_18.2 +22.6
-+7.5 +_9.9 +_13.0 +_9.9 +13.0 +_14.5
STANDARD DEVIATION OF DIFFERENCE OF T~IE MEANS
]2
AT
-
NIFINOE
3 MONTHS,
1.4
12.5 5.8 4.4 6.7 8.1
10.1
10.9
0.1 0.7 I0.8 0.8
DIFFERENCE O~ MEANS
AND
24 ~r
+8.9 +12.6 +18:4 +12.6 +18.3 +20.4 +17.1 _+29.2 +23.1 _+30.9 +_25.2 +34.6
MONTIIS STANDARD DEVIATION~ OF DIFFEREN0] ~] OF THE MEANS
2~
12 IV[ONTHSj
SIGNIFI" CANCE
s i g n i f i c a n t d i f f e r e n c e b e t w e e n t w o g r o u p s is p r e s e n t w h e n t h e d i f f e r e n c e o f t h e m e a n s is t w o o r m o r e t i m e s t h e s t a n d a r d d e v i a t i o n of t h e d i f ference of the means. G r o u p s I r e c e i v e d i r r a d i a t e d e v a p o r a t e d m i l k ; G r o u p s II, n o n i r r a d i a t e d e v a p o r a t e d m i l k p l u s c o d - l i v e r o i l ; G r o u p s III, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e ; G r o u p s IV, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e a n d :Feast.
The difference in the average lengths of the two groups compared is listed in the column headed "difference of means." The standard deviat i o n of t h e d i f f e r e n c e o f t h e m e a n s w a s c a l c u l a t e d f r o m t h e s t a n d a r d d e v i a t i o n s of t h e a v e r a g e l e n g t h s of t h e t w o g r o u p s u s i n g t h e f o r m u l a . A
~Colored
White
RACE
COMPARISON
TABLE III
9
>
9
Oo
RHOADS ET AL. :
]MALE C H I L D R E N R E C E I V I N G E V A P O R A T E D M I L K
181
The a~erage increases in length for the white and colored children of the four groups from 3 to 24 months and their statistical attributes (namely, standard deviation of the mean and standard deviation) are tabulated in Table IV. The simple analysis of the gain in length on the four diets appeared to show significant superiority of the white children in Groups II and IV over those in Group i, and of the colored children in Group I I over those in Group I. (Table IV summarizes the statistical data employed in this analysis.) TABLE I V SUIvilv/AI~Y OF ~TATISTICAL
~DATA USED IN COMPARISON OF THE BETWEEN 3 AND 2~- MONTHS
4
RACE
MEAI'.I INCI~EASE IN LENGTH ( STANDAI~D DEVIATION OF ~{EAN STANDARD ~Eu )
~
5
256.7J_ +_3.38 +_23.5
p
6
DIFFERENCE OF h{EANS (STANDAI~D DEVIATION OF DIFFERENCE OF lViEAN S SIGNIFICANCE)
II
White
IN LENGTH
INCREASES
12.19 +_5.09 Significant
IiI
~.83 +5:47 Not significant
7.36
268.90
_+5.73 Not significant
+3.80 +_24.6
IV
i5.29 +7.30 Significant
3.10 +_7.50 /~ot signitlcant
10.~6
261.5,,5_
+_7.76 1Vot s i g n i f i c a n t
+_4.29 +_21.0
g72.00 +6.46 +28.9 Colored
26d.72 +3.36 +_19.0
282.64 +4.45 +24.8
273.0'0 _+8.77 _+36.1
17.89 +5.58 Significant
8.28 +9.39 :Not s i g n i f i c a n t
9.62 +9.83 Not significant
11.70 +7.82 1VOt s i g n i f i c a n t
~.19 +8.35 1Vot s i g n i f i c a n t
kd2 +11.29 Not significant
276,d2 _+7.07 +30.8 T h e m e a n i n c r e a s e in l e n g t h , t h e s t a n d a r d d e v i a t i o n of t h e m e a n , a n d t h e s t a n d a r d d e v i a t i o n a r e t a b u l a t e d f o r e a c h g r o u p i n c o l u m n 3. I n c o l u m n s 4, 5, a n d 6 r e a d i n g a c r o s s a r e t h e d i f f e r e n c e s o f t h e m e a n s a n d t h e s t a n d a r d d e v i a t i o n s of t h e d i f f e r e n c e s of t h e m e a n s of t h e g r o u p s c o m p a r e d . ~Vhen t h e d i f f e r e n c e o f t h e m e a n s is m o r e t h a n t w i c e t h e s t a n d a r d d e v i a t i o n of t h e d i f f e r e n c e o f t h e m e a n s , t h e i n c r e a s e s in l e n g t h of t h e t w o g r o u p s u n d e r c o m p a r i s o n a r e c o n s i d e r e d to b e s i g n i f i c a n t l y d i f f e r e n t . G r o u p s I r e c e i v e d i r r a d i a t e d e v a p o r a t e d m i l k ; G r o u p s II, n o n i r r a d i a t e d e v a p o r a t e d m i l k p l u s c o d - l i v e r o i l ; G r o u p s III, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e ; G r o u p s IV, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e a n d y e a s t .
However, plotting gain o f length against initial length in each of the eight groups showed that in the white children of GrOups I , II, and IV there was greater gain oi length on die same diet when the initial length was less. This correlation was not evident in white children in Group I I I nor in any of the colored groups. The existence of the cor-
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relation in the white children in Groups I, II, and IV suggested correcting the gain in these three groups to a common initial length. The regression coefficient from the data of these three groups pooled was A gain in length ~ 0.371 A initiM length. Correcting the gain of these three groups by use of the regression coefficient to any a r b i t r a r y initial length reduced the difference between Groups I and I I and between Groups I and I V so that the differences were no longer clearly significant. Table V summarizes the data for these corrected increases in length in Groups-I, II, and IV and the values used in determining statistical differences. While the average lengths attained at 1 and 2 years by the white or colored children in any of the four groups were not significantly different, there were some differences in the amount of growth between 3 and 24 months because of the differences in the average initial lengths at 3 months of age. Thus it is apparent that the colored children receiving 3 teaspoonfuls of cod-liver oil daily (1,500 units of vitamin D) grew significantly more than colored children receiving 110 units of vitamin TABLE V
CORRECTED
MEAN
INCREASES
IN LENGTI-I
FOE WHITE
CIIILDREN
IN GROUPS
I~ II,
AND, ~ V AND T t I E I E ~OMPARISON
GROUP
MEAN LENGTH AT 3 MONTHS
I
599
II
587
IV
595
INCREASE FROM 3 TO 24 MONT~S CORRECTED FOE AN I N I T I A L L E N G T H OF 5 9 4 MM. 258.57 +1.86 266.30 -2.60 272.37 +0.37
DIFFERENCE OF MEANS (STANDARD DEVIATION OP DII~I~EI~ENCE OF MEANS) 2
4
7.73
13.80
+-5.09
-+7.30
6.07 +-7.50
T h e c o r r e c t e d v a l u e f o r t h e m e a n i n c r e a s e in l e n g t h b e t w e e n t h e a g e s of 3 a n d 24 m o n t h s w a s c a l c u l a t e d in t h e f o l l o w i n g m a n n e r . A n a r b i t r a r y i n i t i a l l e n g t h a t 3 m o n t h s of 594 r a m . w a s t a k e n . The difference between the actual initial mean l e n g t h s a n d t h i s a r b i t r a r y m e a n i n i t i a l l e n g t h w a s m u l t i p l i e d b y t h e r e g r e s s i o n coefficient (A g a i n i n l e n g t h z 0.371 A i n i t i a l l e n g t h ) . T h e v a l u e t h u s o b t a i n e d w a s a d d e d o r s u b t r a c t e d ( d e p e n d i n g on w h e t h e r t h e a c t u a l i n i t i a l m e a n l e n g t h w a s g r e a t e r o r l e s s t h a n t h e a s s u m e d v a l u e of 594 r a m . ) f r o m t h e a c t u a l i n c r e a s e in l e n g t h f r o m 3 to 24 m o n t h s .
D in irradiated evaporated milk. Administration of 10 drops of carotene daily (2,250 units of vitamin A activity) to colored children rec.eiving irradiated evaporated milk did not increase their rate of growth. Similarly daily supplements o3 10 drops of carotene and 0.5 tablespoonful (5 Gin.) of powdered brewer's yeast had no added effect on the linear growth of the colored children receiving the same milk. With the correction derived from the correlation mentioned for initial length, there were no significant differences in the amounts of growth in length from 3 to 24 months of the white children in the four groups. Although the difference was not significant, there was still a suggestive tendency for white children receiving 1,500 units of vitamin D in codliver oil or 110 units of vitamin D in irradiated evaporated milk plus carotene and yeast to grow more rapidly than those receiving irradiated
RHOADS ET AL. :
lVIALE C H I L D R E N RECEIVING EVAPORATED M I L K
183
milk without other supplements.
While the addition of vitamin A to the dietary of white children was without influence on growth in length, the administration of a supplement of B complex (yeast) had the same effect on growth in length as an increased intake of vitamin D (1,500 units). RICKETS
For the consideration of the incidence of rickets the groups receiving irradiated evaporated milk plus carotene and those receiving irradiated evaporated milk plus carotene and yeast were combined, making groups comparable in size to those receiving irradiated evaporated milk alone and those receiving nonirradiated evaporated milk plus cod-liver oil. TABLE
VI
I~EI%CENTAGE DISTI%IBUTION OF ~{AXIMUM. X-:RAY DIAGNOSIS OF t~ICKETS AOCOB,DING TO GROUP AND RACE
DAILY NO.
GROUP
OF UNITS OF VITA-
RACE
I~IIN D
Group I (irradiated evaporated milk) Group II (nonirradlated evaporated milk p l u s codliver o i l ) Group III (irradiated evaporated
NO. OF CElLDIZEN
NORA{AL MILD CHANGES IVIILD lVs ENCON- II:[EALED EAIgL~ ATE TII%EL" SIDEI%ED I%ICKETS lgICKE'I P~ICKETS
No~ [ (%)
NOR~A (%) aACm~ic (%)
VChite Colored
--35.3 47.0
43.8 43.7
1,500
White Colored
40.4 35.5
45.2 51.6
]I0
Rite Colored
38.6 41.7
50.0 47.2
Ii0
-/--8A--6.2
7.2 9.7
(%)
(%)
3.1
4.8 3.2
2.4 0
milk plus
carotene) Children receiving irradiated evaporated milk and carotene are combined with those receiving irradiated l~oentgenographic heading of normal.
evaporated milk plus carotene and yeast, to make Group III. bone changes considered nonrachitie are classified under the
The diagnosis of rickets was based on roentgenograms of the bones of the left forearm. 8 There is very little correlation possible between the clinical findings of rickets (craniotabes, bossing, flaring of the costal margins, beading of the costochondral junctions, and enlargement of the wrists) and the x-ray findings at the wrist. 9 The maximmn amount of rachitic change found in the course of ten routine roentgenological examinations is used as the basis for the rating given to each child in Table VI.
No instance of marked rickets occurred in any group. One case of moderate rickets (0.4 per cent of the totali occurred in the group receiving nonirradiated evaporated milk and cod-liver oil. This patient was a small white child of German and Irish extraction, who grew at
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an average rate. His mother, a reliable person now doing social service work, is sure that the cod-liver oil was given regularly. He was born March 29, 1937, and was first, seen on April 20 when the administration of cod-liver oil was begun. At the first visit the x-ray examination was normal; at 3 ~ months it showed mild healing rickets and at 6 months very definite moderate healing rickets; at 8 months there was no change; and from 9 to 16 months the diagnosis was healed rickets. From 19 months on the roentgenograms have been normal. The incidence o~ mild rickets in the '233 children was 13.3 per cent. Mild rickets already showing evidences of healing occurred in 6 per cent of both the white and colored groups. Mild rickets without healing was present in 7.3 per cent of the entire group (8.9 per cent of the white children and 5 per cent of the colored). The total incidence of rickets in the two groups receiving 110 units of vitamin D was 13.8 per cent as compared with 15.5 per cent in a study of ninety-seven initially nonrachitic infants receiving irradiated evaporated milk previously reported from this hospital by Rapoport, Krick, and Stokes2 In Table VI it is seen that, of the children receiving irradiated evaporated milk alone, 20.9 per cent of the white and 9.3 per cent of the colored had rickets. In the cod-liver oil groups 14.4 per cent of the white and 12.9 per cent of the colored children had rickets. In the carotene groups 11.4 per cent of the white and 11.1 per cent of the colored had rickets. Findings indicate that there was no appreciable difference in the antirachitic effectiveness of 1,500 units of vitamin D in the form of cod-liver oil as compared to 110 units of vitamin D in irradiated evaporated milk. Included in the normal groups were children whose roentgenograms showed bone changes from the normal which were not definitely rachitic. These changes consisted, for the most part, of slight cupping of the distal end of the ulna, but included slightly increased density in the zones of temporary calcification, slight decalcificas slight " s p r e a d , " slight fuzziness of the distal ends of the radius and ulna, slight osteoid deposition along the inner border of the radius, etc. They occurred (Table VI) in 43.8 per cent of the white and 43.7 per cent of the colored children receiving irradiated evaporated milk, in 45.2 per cent of the white and 51.6 per cent of the colored children receiving nonirradiated evaporated milk and cod-liver oil, and in 50.0 per cent of the white and 47.2 per cent of the colored children receiving irradiated evaporated milk and carotene. The nature of these Changes is not clear. Eliot and her co-workers4 consider them as doubtful rickets, and it certainly is true that often they precede or follow an x-ray diagnosis of actual rick~ ets. Hood and Raviteh ~~ question their being rachitic, since in their study of irradiated cholesterol they found the highest percentage of these changes (37.0 per cent) in the group of white children receiving the greatest amount of vitamin D (950 to 1,200 units), while none
RHOADS ET AL. :
M A L E C H I L D R E N R E C E I V I N G E V A P O R A T E D ~VIILK
185
occurred in the colored children of that group. Jeans 11 has referred to them as "concomitants of rapid normal g r o w t h " ; Robinson 1~ questions this since she f o u n d them in a much smaller proportion (9.0 per cent) of the breast-fed group in her series. In this study these changes are classified as normal. The roentgenograms of all the children were normal a t 2 years with the following exceptions: three cases of slight cupping, two cases of marked, increased density of the zones of temporary calcification, and one case of marked increase in width of the zones of temporary calcification. These were all preceded by normal roentgenograms at the previous examination. That rickets occurs more frequently in the white than in the colored ~ was borne out by this study: 15.6 per cent of the white children and 11.1 per cent of the colored having rickets. However, in the carotene group the incidence was nearly equal (11.4 per cent for the white and 11.1 per cent for the colored). In the series of children given irradiated evaporated milk studied by l~apoport, Krick, and Stokes 9 twelve of forty-seven white children developed mild rickets and three of fifty negro children developed mild rickets. Eliot and her co-workers 4 found that the incidence of slight rickets was greater in infants who were growing rapidly than in those growing slowly when 400 units or more of vitamhl D were given daily, but that this relationship was absent when the dosage was lower than 400 units. In this s t u d y no such correlation appeared when the infants were classified according to rate of growth as :follows: a child was rated as growing at the average rate when his increase in length between 3 and 9 months was within 5 ram. of the average increase of his entire group for that period. When his increase in length was greater than this, he was considered to be growing faster, and, when it was less, he was considered to be growing more slowly. Table V I I shows that in the cod-liver oil group rickets occurred slightly more f r e q u e n t l y in those children who were growing at a rate slower than ~he average of their group. The incidence of roentgenographie bone changes not considered rachitic in this group showed almost no difference according to rate of growth. In the group receiving irradiated evaporated milk alone, the distribution of rickets and of these changes was practically the same in the fast and in the slow growing groups. In the group receiving irradiated evaporated milk plus carotene, there were somewhat more rickets and fewer questionable roentgenographic bone changes in the faster growing children. Many studies of rickets are not continued after the infants reach the age of 6 months, and therefore some cases of rickets occur Which are not reported. In this series three cases oR mild healed rickets appeared at 7 to 9 months. Two of them were in the i r r a d i a t e d evaporated milk group; one of these was preceded by roentgenographic bone: changes,
186
T H E J O U R N A L OF PEDIATRICS
and the other was not. The third case was in the colored group receiving cod-liver oil and was preceded by the changes at only one examination. Roentgenographic bone changes considered not rachitie occurring f o r the first time at 7 months or later were as follows : irradiated evaporated milk group, white 10.4 per cent, colored 9.4 p e r cent; cod-liver oil group, w h i t e 19.0 per cent, colored 22.6 per cent; i r r a d i a t e d evaporated milk plus carotene, white 13.6 per cent, colored 5.6 per cent. No conclusions are drawn f r o m the fact t h a t the greater percentage of delayed changes occurred in the groups receiving the larger amount of vitamin D. TABL~ V I I INCIDENCE
OF I~ICKETS
-~CC'DRI)II'TG TO CxI~OUP AND 3 AND 9 :~r
I~ATE
OF GROWT~I
BETWEEN
r GROUP
RACE
Group I
White
irradiated evaporated milk) Colored
Group II nonirradiated evapor a t e d m i l k p l u s codl i v e r oil)
White
Colored
R A T E OF GI~OWTI~I
Faster Av. Slower
Faster _A_v. Slower Faster 2~v. Slower Faster Au Slower Faster Av. Slower Faster Av. Slower
16 15 17 11 9 12 13 15 14 13 8 10 14 16 14 14 7 15
8 7 6 5 3 6 5 10 5 8 3 6
2 2 2
1 2 1 1 1
1 1 2
1 2 5 Group III Whit~ 8 2 9 irradiated evaporated milk plus carotene) 2 6 Colored 5 1 1 6 A child w a s c l a s s i f i e d a s g r o w i n g a t t h e a v e r a g e r a t e w h e n h i s i n c r e a s e in l e n g t h between 3 a n d 9 m o n t h s w a s w i t h i n 5 ram. of t h e a v e r a g e i n c r e a s e of his e n t i r e g r o u p . W h e n t h e i n c r e a s e w a s g r e a t e r , h e w a s r a t e d a s g r o w i n g f a s t e r ; and, w h e n i t w a s less, he w a s r a t e d a s g r o w i n g m o r e s l o w l y .
The total incidence of rickets in this series was 13.7 per cent, r a t h e r lower than that f o u n d in m a n y studies. Eliot and her co-workers, 4 in Detroit, using 135 units to 735 units of v i t a m i n D in various antirachitie agents, found rickets, exclusive of doubtful rickets (corresponding to those in this study reported as roentgenographic bone changes considered nonrachitir in 36 per cent of white males and 28 per cent of colored males. Robinson 1~ found the incidence of definite rickets to be 33 per cent in St. Louis. R o d d y and his co-workers, ~3 in Philadelphia, f o u n d 25 per cent rickets occurring in e i g h t y - f o u r initially nonrachitic infants followed for four and a half months on 2,140 or 1,070 units of vitamin D in the f o r m of pereomorph-liver oil. Other studies find lower
]
[
7 [
[
[
__1__
Colored
I ~
RACE
" Group II White (nonirradiated evapo[ Colored ' rated milk plus co d liver oil) 9 Group I I I ......~ ] (irradiated evaporated [ Colored milk plus carotene) [ " Group I V - - I ~ (irradiated evaporated I Colored milk plus carotene and yeast)
ilk)
" Group I (irradiated evaporated
GROUP
19
17
42 31
32
DREN
cOIL -
NO.
6.05
--Egg--
4.25 5.12
4.10 5.32
4.42 6.19
MILD
VIII
0.84
~ 0.53
0.79
0.59
1.25
0.76
0.44
0.58
~
~
SEVERE
0.77
0.62
0.73 1.0
ATE
5~ODER-
0.32
0.40
0.24
0.29
0.35
0.33--
0.35 0.28
OTITIS MEDIA
0.05 0.0
0.08 0.0
D.07 0.07
0.47
3.06 D.03
0.05 0.21
0.33 0.24
~
I
0.42
o.13
0.06
~
0.0
/o . - - ~ 6 - - - ~
0.02 0.03
_ _ 1 _
L~ZMPHADENITIS
CERVICAL
o.x4
0.38
SPECIEIC INFECTIONS
NEUONIA
CHILD ~q~ROM 3 TO 2 4 ~V~ONTHS .A_COOKDING TO GROUP
COLDS
N U M B E R OF INFECTIONS ~ E R
TABLE
~
O.ll
0.24
0.07
0.04 0.13
ECZEMA '
~
~ 0.05
0.35
'
0.29
~ J
0.17 0.28
TION
0.35
o.17
0.42
o.26
0.25 0.34
I
,- o.4o [0.47
I ]
INFEC-TION
TEEAL
OUT PAREN-
WITDI:ARRHEA WITHPAttENT~RAL INEEC-
~ - - E "
I
b-a DO --1
9 ~V
7~
z
a:
>
5~
O >
188
THE
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incidences of rickets, but it seems to be true that a certain amount of clinically insignificant rickets is bound to occur with usual doses of customary antirachitic agents, and in this study ~rradiated evap~)rated milk has been essentially as efficacious! as large amounts of cod-liver oil. INCIDEi'~CE OF I N F E C T I O N S
In Table V I I I the incidence of infections is reported according to the number of infections occurring in each group per child in that group. It will be noticed that there were more mild colds among the colored children than among the white. Diarrhea without parenteral infection was slightly more frequent in the groups receiving yeast. The white group receiving irradiated evaporated milk plus carotene had more severe colds, slightly less otitismedia, and more diarrhea with parenteral infection and less without parenteral infection. Obviously carotene had no beneficial influence on the number or severity of respiratory tract or other infections. There were four eases of lipoid pneumonia which are not included in Table VIII. One occurred in a colored child receiving irradiated evaporated milk; it was learned that he had received cod-liver oil for ten days early in infancy. T w o occurred in the cod-liver oil group, one white and one colored. The fourth ease occurred in a white child receiving carotene. All have done well except the colored one who received cod-liver oil and who has remained small and thin with poor musculature. In general, there was littledifference between the groups in the incidence of infections. CONCLUSIONS
Longitudinal observation has been made of 233 male infants receiving diets containing evaporated milk as the sole source of milk from an average initial age of 6 weeks until the age of 2: years. The acceptability of evaporated milk by children beyond the period of infancy was noted. The infants were divided into four groups according to vitamin supplements. Group I received irradiated evaporated milk; Group II, nonirradiated evaporated milk plus cod-liver oil; Group III, irradiated evaporated milk plus carotene; Group IV, irradiated evaporated milk plus carotene and yeast. The average growth in length of all groups was better than would have been expected according to the Kornfeld standards of normal growth of boys, and there was no significant difference in length between any of the groups at 3 months, 1 year, or 2 years. White children receiving 1,500 units of vitamin D in the form of cod-liver oil between the ages of 3 months and 2 years, increased in length by a suggestively, although not clearly significantly, greater amount than:the childre n receiving 110 units of vitamin D in irradiated
RHOADS E T AL. :
M A L E C H I L D R E N R E C E I V I N G EVAPORATED M I L K
189
e v a p o r a t e d m i l k w i t h o u t a d d e d v i t a m i n s A a n d B. Colored c h i l d r e n r e c e i v i n g cod-liver oil i n c r e a s e d i n l e n g t h a s i g n i f i c a n t l y g r e a t e r a m o u n t t h a n those r e c e i v i n g i r r a d i a t e d e v a p o r a t e d milk. A d d i t i o n of 2,250 u n i t s of v i t a m i n A i n the f o r m of carotene prod u c e d no s i g n i f i c a n t effect on r a t e of g r o w t h i n l e n g t h of either the white or colored c h i l d r e n . W h i t e c h i l d r e n r e c e i v i n g carotene a n d a p p r o x i m a t e l y 250 u n i t s of v i t a m i n s B~ a n d B~ i n p o w d e r e d b r e w e r ' s y e a s t b e t w e e n the ages of 3 a n d 24 m o n t h s i n c r e a s e d i n l e n g t h b y a suggestively, a l t h o u g h n o t d e a r l y significantly, g r e a t e r a m o u n t t h a n the c h i l d r e n o n the same milk n o t r e c e i v i n g these v i t a m i n s u p p l e m e n t s . F o r the colored c h i l d r e n , a d d i t i o n of yeast p r o d u c e d no s i g n i f i c a n t increase i n length. The i n c i d e n c e of r o e n t g e n o g r a p h i e rickets was p r a c t i c a l l y the same at b o t h levels of v i t a m i n D i n t a k e (110 a n d 1,500 u n i t s d a i l y ) . T h e v a r i o u s v i t a m i n s u p p l e m e n t s h a d no i n f l u e n c e on the i n c i d e n c e or s e v e r i t y of i n f e c t i o n s of the u p p e r r e s p i r a t o r y t r a c t . We wish to express our thanks to Dr. J. H. Austin, Professor of Research Madlcine, School of Medicine of the IYniversity of Pennsylvania, for his generous and invaluable aid with the statistical analyses in this paper. REFERENCES
1. Souders, tI. J., Hunscher, H. A., Hummel, t ~. C., and Macy, I. G.: Am. J. Dis. Child. 58: 529, 1939. 2. Dawson, H. I~.: J. PEDIAT. 9: 187, 1936. 3. Kornfeld, W.: Ztschr. f. E:inderh. 48: 188, 1929. 4. Eliot, IV[. M., Nelson, E. M., Barnes, I). J., Browne, F. A., and Jenss, R. M. : J-. PEDIAT. 9: 355, 1936. 5. Stuart, If. C.: J. PEDIAT. 51 194, 1934. 6. Bakwin, II., and Bakwin, R. l~I.: J. PEJ)IAT. 8: 177, 1936. 7. Elias, H. L., and Turner) R.: J. PEDIAT. 8" 352, 1936. 8. Eliot, M. M., and Powers, G. !~.:. J. A. M. A. 102: 1823, ]934. 9. Rapoport, !Yr., Kriek, E., and Stokes, 5., Jr.: J. PEDIAT. 11: 782, 1937. 10. Hood, J-. S., and Ravitch, I.: J. PE~)IA~. 11'. 521, 1937. 11. Jeans, P . C . : J . A . ~/f. A. 106: 2066, 1936. 12. Robinson, E. C.: Am. J. Dis: Child. 59: 816, 1940. 13. Roddy, R. L., Rose, E. K., No.des, P. J., and Gittings, 3-. C. : Am. J. Dis. Child. 55: 526, 1938.
TERESA FOLIN RHOADS, M.D., MILTON RAPOPORT, ~.D., RUTH KENNEDY, AND JOSEPH STOKES, JR., 1Vi.D., PHILADELPHIA, PA.
acceptance and use of irradiated evaporated milk in infant feedT HE ing has become so general that it prompts an inquiry into the suitability of this food in the dietary of older children. The metabolic studies of Souders, Hunscher, I-Iumme], and Macy1 indicate that there is excellent assimilation of the organic and inorganic elements of irradiated evaporated milk in young children. However, there is no body of data available concerning the growth and development of children who have received irradiated evaporated milk from infancy through the preschool years. Almost all of the studies concerning irradiated evaporated milk have been with infants for relatively short periods of observation, usually of six months' duration. This report presents data obtained from 233 male children who have received evaporated milk as their sole source of milk since early infancy, viz., an average beginning age of 42 days. It has been the purpose of this outpatient study to observe the growth and development of these children receiving" eva.porated milk, to evaluate the protection against rickets afforded by the vitamin D content of the irradiated evaporated milk, and to study comparatively the influence of supplements of vitamins A, D, and B complex: The children have been in this study for periods varying from two and one-half to four years, and we are presenting data concerning selected aspects of their growth and development for a continuous two-year period of observation of each child. The majority of these children come from homes where there is financial difficulty and therefore m a y b e considered to be representative of many children in t h e lower income groups of our cities. The organization of the study and methods used will be described first, and the results will then be discussed under the sections of consumption of evaporated milk, growth in length, incidence of rickets, and incidence of infections. Subsequent reports will be made concerning the weight of these children, other anthropometrie measurements , development including psychometric tests, laboratory findings, and photoelectric examination of roentgenograms of the forearm. ORGANIZATION A:ND METHODS
The study was undertaken in November,-1936, in the Out-Patient Department of the Children's Hospital of Philadelphia. The personnel From
the Children's
Hospital
of Philadelphia. 169
170
THE
J O U R N A L OF P E D I A T R I C S
consisted of two part-time physicians, a part-time technician, a fulltime nurse and a full-time social worker. X-ray examinations were carried out in the X-ray Department of the Children's IIospitalP In~ants were enrolled with the cooperation of the maternity departments of the Pennsylvania, the Philadelphia General, and tile University of Pennsylvania Hospitals. Also some infants were referred from the Child Hygiene Division of the Department of Public Health of Philadelphia, others from the Children's Hospital, and a few through personal contact. The criteria set up for the selection of infants for this study were as follows: 1. All infants selected were males in order to eliminate sex as a variable. 2. All infants selected had birth weights of 5 pounds or more in order to eliminate prematurity as a factor. 3. All but four of the infants were under 3 months of age when they were enrolled. These four were under 3.5 months. The average age of the entire group was 42 days. 4. No infants were receiving any breast milk when they were referred for the study. The last criterion eliminated so many infants that twenty-two months were required for the enrollment of the entire group. The racial distribution of the children was 42 per cent negro and 58 per cent white. Among the white infants 25 per cent were of Italian extraction, 25 per cent of Irish, 12 per cent of British, 10 per cent of German, 7 per cent o.f Slavic, 11 per cent of mixed northern and southern European, and 10 per cent of mixed German and British extraction. FOr the purposes of the study the 233 infants were divided into three groups according to the vitamin content of the diet they received. The colored and white infants comprising each group were considered separately in the statistical analysis. The diets were as follows: Group I. Eighty infants received 110 U.S.P. units of vitamin D daily in the form of irradiated evaporated milk. Group II. Seventy-three infants received approximately 1,500 U.S.P. units of vitamin D and 15,000 U. S. P. units of vitamin A daily in three teaspoons of cod-liver oil.f This group received nonirradiated evaporated milk. Group III. Eighty infants received 110 U.S.P. units of vitamin D in the form of irradiated evaporated milk daily and 10 drops of carotenes (equivalent to approximately 2,250 U.S.P. units of vitamin A). A subgroup (thirty-nine infants), referred to as Group IV, received 0.5 tablespoonful of brewer's yeast powder daily (approximately 250 units of vitamin B1 and 250 Sherman units of vitamin B2). *All r o e n t g e n o g r a m s w e r e r e a d b y Dr. R a l p h S. ] ~ r o m e r , r o e n t g e n o l o g i s t of t h e C h i l d r e n ' s YrIospital of :Philadelphia. t T h e c o d - l i v e r oil a n d y e a s t u s e d in t h i s s t u d y w e r e m a d e a v a i l a b l e b y t h e g e n e r o s i t y of M e a d J o h n s o n a n d Co. $ C a r o t e n e w a s o b t a i n e d f r o m t h e S.M.A. C o r p o r a t i o n .
R H O A D S E T AL. :
M A L E CI-IILDREN R E C E I V I N G EVAPORATED M I L K
171
All children received vitamin C in the form of orange juice or tomato juice in adequate amounts daily from the time of the first visit. In all groups the daily formula, contained one 14.5 ounce Can of evaporated milk (13 fluid o u n e e s ) a t or before the age of 4 months. Five per cent carbohydrate was added, usually in the form of dark corn syrup. As the children grew older, additional calories were given in solid food and the intake of evaporated milk remained the same. Banana and cereal were started at 3 to 4 months, pur~ed vegetables and fruits at 5 to 6 months, and potato and meat at 8 to 10 months.. Egg yolk was not recommended earlier than 10 months but was given in some cases. Before the age of 1 year, the added carbohydrate was eliminated and transition from bottle to cup feeding was advised at this time. Iron ammonium citrate (18 grains daily) or a solution of ferrous sulfate (6 grains daily) was given when the hemoglobin was below ]3 Gin. per 100 e.e. In assessing the physical development of the children a definite pro~ gram was followed. At the first visit the history was taken, and a cornplete physical examination was made. The child was weighed, and the following anthropometrie measurements 2 were taken : (1) crownheel length, (2) crown-rump length, (3) intereristal diameter, (4) width of the head, (5) length of the head, (6) circumference of the head, (7) width or the chest, (8) depth of the chest, and (9) circumference of the chest. Clinical evidences of rickets (eraniotabes, bossing, beading, Harrison's groove) were noted. A roentgenogram of the left forearm was made, and blood was taken for determination of hemoglobin and serum protein concentrations. The children were brought to the clinic at short intervals until well established on the formula and then every month during the first year, and every two months thereafter. At each regular visit the child was weighed and measured. A complete medical record was kept, including illnesses, evidence of rickets, developmental history, amount of regurgitation, and number of stools per day. Determinations of hemoglobin and serum protein were done at every second visit, and x-ray examinations of the left forearm were made ten times during the first two years, at intervals of two months from November to May and of three months during the remainder of the year. The milk and the vitamin supplements were delivered at the homes every two weeks b y the nurse and by the social worker. The n u m b e r of cans of milk left was calculated so that, when the child was due for a r e t u r n visit, the supply of milk was exhausted. This method was fairly effective in assuring the regularity of visits to the clinic. The supply of milk was maintained during infectious diseases and when it was temporarily impossible for the mother to bring the child to the hospital. In families where there were younger brothers and sisters, milk was supplied for them also so that there was no question of whether or not the children included in this s t u d y had had milk available. Most of the
172
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PEDIATRICS
hospitalization that was necessary was provided at the Children's Hospital where the feeding could be continued as at home. ACCEPTABILITY
OF
EVAPORATED
MILK
AT
2
YEARS
When the children stopped drinking milk from bottles, most of the mothers put a can of milk in a quart jar and filled it up to the top with water, making a di]ution of 13 fluid ounces of evaporated milk to 19 ounces of water. W h e n the child did not finish his milk, it was recommended that 13 or 11 ounces of w a t e r should be added. I n one case the milk was well taken when only 4 ounces of water were added. To obtain an a p p r o x i m a t e idea of how much milk each child was consuming, the mothers were asked f r o m time to time if the child took a whole can daily. Although the replies to these questions m a y not be entirely truthful, they seemed f a i r l y reliable and were tabulated. TABLE I PERCENTAGE DISTRIBUTION OF 2-YEAI~-OLD CHILDREN ACCORDING TO DAILY CONSUMPTION 0P EVAPORATED ~]:ILK N0. GROUP
Group I (irradiated evaporated milk) Group I I (~onirradiat~4 evaporated milk plus codliver oil) Group I I I (irradiated evaporated milk plus carotene) Group I V (irradiated evaporated milk plus carotene and yeast) Total
mACE
OF CHILDIZEN
I
CAN (%)
~4
CAN
(%)
-~ CAN
(%)
OAIq
(%)
White Colored
48 32
83.3 90.6
14.6 6.3
2.1 3.1
0 0
White Colored
4~2 31
90.4 83.9
2.4 12.9
4.8 3.2
2.4 0
White I Colored
24 17
75.0 82.4
]2.5 5.9
8.3 11.7
4.2 0
White Colored
20 19
70.0 94.7
10.0 5.3
20.0 O
White Colored
J34 99
82.1 87.9
9.7 8.1
6.7 4.0
1.5 0
Table I shows that the evaporated milk was well taken by the colored children and slightly less well by the white. T h a t the carotene and yeast group of white children took less milk t h a n the others is perhaps due to the presence of yeast in the milk; when tile yeast was disliked, the best method of giving it seemed to be to sprinkle it on cereal. GROWTH IN LENGTH
Since the children were measured at different chronological ages, at the suggestion of Dr. J. H. Austin the following method was used to determine their probable lengths at the ages which were to be tabulated. Charts were p r i n t e d with a straight line representing the average rate of growth for boys f r o m birth to 2 years, based on the average figures given by K o r n f e l d ) This line was straight instead of being the usual
30
~0
90
V'LO
i5]
IBI
~12
'z43 Zl3
304
334
JYEAR
t YEAR 3r=.S 395
4"z5
~55
,48.~
51G
5A,F, 577
(,O,B &38 66"~ r
Z YEARS
"L"(E AE S" 7~0
~ig. 1.~Sample chart used in plotting" lengths of children. I~leavy straight line represents average length of boys f r o m birth to 2 Ty~ears, from data os KornfeId3 Note that ordinates representing clays of age are spaced at decreasing intervals to achieve a straight line f o r growth in length. ~/~easurements taken in these studies were plotted on appropriate ordinates and connected by straight lines. Length at any age between two actual meaBuremerits may be read directly from the chart.
AGE II't PAY5
co
C~
z
c~
F~
9
]74
THE
JOURNAL
OF P E D I A T R I C S
curve because the time intervals were spaced at decreasing distances (Fig. 1). The measurements for each child and the ages in days when he had been measured were plotted on one of these charts, and the successive points were connected by straight lines. The lengths of a child at the particulal; ages (3, 6, 9, 12, 15, 18, 21, 24 months) were obtained directly f r o m the intersections of the child's length line and the age ordinates. This method avoided the subjective element which enters into the interpolation of curves. -Lcn~t/~
Croop
./rr~dl'~fed
Z. ~HH-e
~pora+e$l
-IV~ilk
rnn3, 9~0 -
850 .
"250 -
@50 '
550
4=o q~--'] ~ir~t3
I-~ n3o,
@ roD,
I
I-
I
~ too,
) ~j n
15 m e
I I~ t o o .
2.1 t o o ,
I ~ qn
F i g s . 2 - 9 . - - G r o w t h in l e n g t h c o m p a r e d w i t h I ~ o r n f e l d s t a n d a r d s f o r b o y s . S t i p p l e d a r e a s r e p r e s e n t a v e r a g e r a n g e of 14:ornfeld s t a n d a r d s f o r b o y s . U p p e r l i n e s c o r r e s p o n d to u p p e r l i m i t of h e i g h t g i v e n b y K o r n f e l d , a n d l o w e r l i n e s c o r r e s p o n d to l o w e r l i m i t of l e n g t h . H e a v y l i n e s a r e a v e r a g e l e n g t h c u r v e s of e a c h g r o u p . Fig.
2.--Group
I, f o r t y - e i g h t
white
children
on i r r a d i a t e d
evaporated
milk.
When the growths of the children on each of the f o u r feeding regimes were compared, the white and colored children on each diet were considered separately since it has been n0ted that colored children show a tendency toward more r a p i d growth t h a n white children. ~ The more rapid growth o~ colored children was also noted in this ~tudy and warrants this division. The average lengths of the white and colored children in each o2 the four groups were determined at the above stated intervals and were plotted against the K o r n f e l d standards. These are shown in Figs. 2-9. E x a m i n a t i o n of these figures shows t h a t the average lengths of the different groups at 3 months of age were all below
RHOADS E T AL. :
M A L E C H I L D R E N R E C E I V I N G EVAPORATED M I L K
175
- - Groap X- Colored-.~enq+h mtn. gSO
l r r a d iof~e d "~pca p o r a ~ e d
IV)ilk
~
850~
~50-
650
9
550
-
.45o t" ~ir+h
I
I
I
I
I
S too.
6 too,
9 too.
I bit.
15 toO.
I 18 r~qo.
I
I
~1 rt3o.
~.qt%
Fig. 3 . - - G r o u p I, t h i r t y - t w o c o l o r e d c h i l d r e n on i r r a d i a t e d e v a p o r a t e d m i l k .
-- Groop Tr-Mhi~e-/~on-lrrodl'a§ ~Cva~orar Cod-Liver Oil
.l.,en~§ rnrn 950-
850
Iv)ilk
-
~50"!
650
"
550
-
"F~iI"~'~ ~ig.
4.~Group
~mo. II,
bin0. ~orty-two
9 rno. white
|qr,
children
15 m 0 .
on nonirradiated
liver oil
18 m0. evaporated
~I m 0 ; milk
~.~ plus
cod-
176
T I I E J O U R N A L OF P E D I A T R I C ~ G.roup.~
- -
Colored - -
-
IMon-lrrad~a+eol
E~apora~ed
pl~s
rnPD.
Iv]ilk
Cool-Liver Oil
8301 ~501 ~50
350 *50 [ ]Sit-+h
1 5 too.
I 6too.
I g too,
I
I
1 qr,
15 t o o ,
I
Fig. 5 . - - T h i r t y - o n e c o l o r e d c h i l d r e n on n o n i r r a d i a t e d oil.
Irrad/a~r
1~e n g t h
850
JEva~ora'keel
18 rnO.
l s
I too.
P~ q r ,
e v a p o r a t e d m i l k plus c o d - l i v e r
M i l k
plus Caro§
P
750
650
~0
~-5o J" ]~irtb
I
3 too.
I
bmo,
I
9 too,
I
I qr,
I
15 t o o .
'I
I~ too.
' I
s
too.
'
I
~qr',
Fig. 6 . - - T w e n t y - f o u r w h i t e c h i l d r e n on i r r a d i a t e d e v a p o r a t e d m i l k plus c a r o t e n e .
RHOADS ET AL. :
~MALE C H I L D R E N R E C E I V I N G EVAPORATED IViILK
--
Len~[+h
177
Gro~l~ . ~ 9 C o l o r e d - -
Irr~dla§
rD,,~,
:By,pomaded p/as
Mi/k
950
8501
?501 650550
,~o,["
....
:Bir§ ~ig.
I D too.
,1
I 6 too.
I
I
I
9 too.
I q r.
i5 rno.
-
', =8 too.
"
I 21 too.
I ~_qr.
7 . - - S e v e n t e e n c o l o r e d c h i l d r e n on i r r a d i a t e d ~ e v a p o r a t e d m i l k p l u s c a r o t e n e . --~roap~-
s
Sqhi'~e--
Irradiated
~vaporo~ed IV/ilk p/aS C ~ r o f e n e onal Ye~S~
mm.
950 -
650 -
950 --
550
,*so ~ - - - ~ 1 ~irth
~mO.
I
[
I
1
6too.
9rno,
IC~r.
15too,
'
I
I
18too.
P~t~o,
I ~qr,
Fig. 8 . - - T w e n t y w h i t e c h i l d r e n on i r r a d i a t e d e v a p o r a t e d m i l k plus c a r o t e n e a n d y e a s t .
178
THE
JOURNAL
OF
PEDIATRICS
the average figures given by Kornfeld. At 2 years of age M1 groups had bettered their position and were within the average range of the Kornfeld standards. The K o r n f e l d standards correspond to those of Stuart 5 until the age of 18 months when they become definitely lower, and they are s l i g h t l y l o w e r at 1 y e a r t h a n those of Bakwin and Bakwin2 I t is interesting to note that the average increment in length of the 134~ white children f r o m 3 months to I year was 149 mm., 1 mm. below the average increase in length of thirty-seven white children in New York, who had received fresh milk, dextrimaltose formulas plus 3 teaspoons o~ cod-liver oil daily f r o m October to May and who were followed for one year by Elias and Turner. 7 - - C - r o a p 2:~". C o l o r e ~ -
.E~,~po~'a~'ed M i D < D/as Coro't-ene a n d >'eosf"
I. ens"i'h
Irradia§
From.
gSOT 6501 ?.50@ 650-
550 -
"P~ir'H'~ 5 rno Fig. 9.--Nineteen
6too. colored
9
children
rno.
on
I qn
irradiated yeast.
15rno,
evaporated
~8 too,
milk
plus
El too.
~.q~..
carotene
and
A s u m m a r y of the average lengths at three-month intervals for the white and colored children is presented in Table I I . The average lengths at 3, 12, and 24 months of both white and colored children on the four different feeding regimes were compared statistically to determine whether there were a n y significant differences among them. Table I I I summarizes the statistical data used in these comparisons. I t is obvious that there was no statistical difference in the average length of either white or colored children on any of the f o u r dietaries at 3, 12, and 24 months.
II
~
Grqup llI White 1 ~ (irra,diatedrated milk evap(plus C~176 / 17 carotene) ~ Group IV " (Irradiated evap- Colored 19 orated milk plus carotene and yeast)
/
665 657
_+61.2 / •
586
~ ]
657 660
665 664
661 665
/ •
/ +_35.8
+38.f ] ~44.1
_+42.7 / _+69.1
58S
593
TION
(hiM.)
LENGTH
6 MO.
~ / 591
I 31 ]
Whit-e--/TlT
(nonirradiatedpluseVaporatedcod.l~vermflkC~ oil
Group
G r ~ p -I White ~ (irradias 3 2 omilk) revap a t Colored e d /
GROUP
I
3 MONTHS --" j STAND RACE I CHIL- I LENGTt:[ I ARD DREN (NIIVf.) DEVIA"
I
1oNO.1
TABLE II
711 706
709 713
7O4 712
710 711
]NG~
751 748
743 747
739 750
745
744
~-+51.7 •
• •
• •
•
•
TION
DEWA
AKD
MONTHS STAND
LENG'?II (~M ,)
]2
18 M e .
21 MO.
784 776
776 782
774 785
776 778 846
--s4--~-837
816 808
840
--83~
I
817 807 815
i~
8o3
8o7 ) ~ 808 [ 835
LENGTH LENGTH ] LENGTH (MM.) (M~.) / (MM.)
15 ~0.
AVERAGELENGTH IN I~[ILLISfETERSACCORDINGTO AGE AND GROUP
862
864
870
858
(MM.)
LENGTH
•
-
•
•
•
• •
•
DEVIATION •
ARD
STAND
24 MONTHS
}-a
F
9N
4
N
F
c~
>
V ,~
9
LENGTHS
il and III II and IV III and IV
I and I V II and III II and Y V III and I V I and II I and III I and I V
I and Ir I a n d III
GROUPS COIV~PAI~D
OF
]2.2 4.5 4.4 8.7 7.8 0.9 5.4 2.5 7.3 2.9 1.9 4.8
MONTHS
OF
THE
+-7.9 +_10.5 +_15.1 +_10.5 +15.1 +-16.6 +_12.5 +_9.6 +_13.1 +12.0 +14.2 +11.8
STANDAI~D DEVIATION OF DIFFERENCE OF TIlE MEANS
3
IV[ILLIMETERS
DIFFERENCE OF MEANS
IN
-
SIGNIFICANCE
DIEFERENT
4.6 0.9 7.1 3.7 11.7 8.0 4.6 2.0 2.4 2.6 2.2 0.4
DIFEERENOE OF MEANS
GROUPS
AGES
MONTHS
T}IE
OF
+_14.5 +19.8 +_16.7 +_21.1 +_18.2 +22.6
-+7.5 +_9.9 +_13.0 +_9.9 +13.0 +_14.5
STANDARD DEVIATION OF DIFFERENCE OF T~IE MEANS
]2
AT
-
NIFINOE
3 MONTHS,
1.4
12.5 5.8 4.4 6.7 8.1
10.1
10.9
0.1 0.7 I0.8 0.8
DIFFERENCE O~ MEANS
AND
24 ~r
+8.9 +12.6 +18:4 +12.6 +18.3 +20.4 +17.1 _+29.2 +23.1 _+30.9 +_25.2 +34.6
MONTIIS STANDARD DEVIATION~ OF DIFFEREN0] ~] OF THE MEANS
2~
12 IV[ONTHSj
SIGNIFI" CANCE
s i g n i f i c a n t d i f f e r e n c e b e t w e e n t w o g r o u p s is p r e s e n t w h e n t h e d i f f e r e n c e o f t h e m e a n s is t w o o r m o r e t i m e s t h e s t a n d a r d d e v i a t i o n of t h e d i f ference of the means. G r o u p s I r e c e i v e d i r r a d i a t e d e v a p o r a t e d m i l k ; G r o u p s II, n o n i r r a d i a t e d e v a p o r a t e d m i l k p l u s c o d - l i v e r o i l ; G r o u p s III, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e ; G r o u p s IV, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e a n d :Feast.
The difference in the average lengths of the two groups compared is listed in the column headed "difference of means." The standard deviat i o n of t h e d i f f e r e n c e o f t h e m e a n s w a s c a l c u l a t e d f r o m t h e s t a n d a r d d e v i a t i o n s of t h e a v e r a g e l e n g t h s of t h e t w o g r o u p s u s i n g t h e f o r m u l a . A
~Colored
White
RACE
COMPARISON
TABLE III
9
>
9
Oo
RHOADS ET AL. :
]MALE C H I L D R E N R E C E I V I N G E V A P O R A T E D M I L K
181
The a~erage increases in length for the white and colored children of the four groups from 3 to 24 months and their statistical attributes (namely, standard deviation of the mean and standard deviation) are tabulated in Table IV. The simple analysis of the gain in length on the four diets appeared to show significant superiority of the white children in Groups II and IV over those in Group i, and of the colored children in Group I I over those in Group I. (Table IV summarizes the statistical data employed in this analysis.) TABLE I V SUIvilv/AI~Y OF ~TATISTICAL
~DATA USED IN COMPARISON OF THE BETWEEN 3 AND 2~- MONTHS
4
RACE
MEAI'.I INCI~EASE IN LENGTH ( STANDAI~D DEVIATION OF ~{EAN STANDARD ~Eu )
~
5
256.7J_ +_3.38 +_23.5
p
6
DIFFERENCE OF h{EANS (STANDAI~D DEVIATION OF DIFFERENCE OF lViEAN S SIGNIFICANCE)
II
White
IN LENGTH
INCREASES
12.19 +_5.09 Significant
IiI
~.83 +5:47 Not significant
7.36
268.90
_+5.73 Not significant
+3.80 +_24.6
IV
i5.29 +7.30 Significant
3.10 +_7.50 /~ot signitlcant
10.~6
261.5,,5_
+_7.76 1Vot s i g n i f i c a n t
+_4.29 +_21.0
g72.00 +6.46 +28.9 Colored
26d.72 +3.36 +_19.0
282.64 +4.45 +24.8
273.0'0 _+8.77 _+36.1
17.89 +5.58 Significant
8.28 +9.39 :Not s i g n i f i c a n t
9.62 +9.83 Not significant
11.70 +7.82 1VOt s i g n i f i c a n t
~.19 +8.35 1Vot s i g n i f i c a n t
kd2 +11.29 Not significant
276,d2 _+7.07 +30.8 T h e m e a n i n c r e a s e in l e n g t h , t h e s t a n d a r d d e v i a t i o n of t h e m e a n , a n d t h e s t a n d a r d d e v i a t i o n a r e t a b u l a t e d f o r e a c h g r o u p i n c o l u m n 3. I n c o l u m n s 4, 5, a n d 6 r e a d i n g a c r o s s a r e t h e d i f f e r e n c e s o f t h e m e a n s a n d t h e s t a n d a r d d e v i a t i o n s of t h e d i f f e r e n c e s of t h e m e a n s of t h e g r o u p s c o m p a r e d . ~Vhen t h e d i f f e r e n c e o f t h e m e a n s is m o r e t h a n t w i c e t h e s t a n d a r d d e v i a t i o n of t h e d i f f e r e n c e o f t h e m e a n s , t h e i n c r e a s e s in l e n g t h of t h e t w o g r o u p s u n d e r c o m p a r i s o n a r e c o n s i d e r e d to b e s i g n i f i c a n t l y d i f f e r e n t . G r o u p s I r e c e i v e d i r r a d i a t e d e v a p o r a t e d m i l k ; G r o u p s II, n o n i r r a d i a t e d e v a p o r a t e d m i l k p l u s c o d - l i v e r o i l ; G r o u p s III, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e ; G r o u p s IV, i r r a d i a t e d e v a p o r a t e d m i l k p l u s c a r o t e n e a n d y e a s t .
However, plotting gain o f length against initial length in each of the eight groups showed that in the white children of GrOups I , II, and IV there was greater gain oi length on die same diet when the initial length was less. This correlation was not evident in white children in Group I I I nor in any of the colored groups. The existence of the cor-
182
THE
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relation in the white children in Groups I, II, and IV suggested correcting the gain in these three groups to a common initial length. The regression coefficient from the data of these three groups pooled was A gain in length ~ 0.371 A initiM length. Correcting the gain of these three groups by use of the regression coefficient to any a r b i t r a r y initial length reduced the difference between Groups I and I I and between Groups I and I V so that the differences were no longer clearly significant. Table V summarizes the data for these corrected increases in length in Groups-I, II, and IV and the values used in determining statistical differences. While the average lengths attained at 1 and 2 years by the white or colored children in any of the four groups were not significantly different, there were some differences in the amount of growth between 3 and 24 months because of the differences in the average initial lengths at 3 months of age. Thus it is apparent that the colored children receiving 3 teaspoonfuls of cod-liver oil daily (1,500 units of vitamin D) grew significantly more than colored children receiving 110 units of vitamin TABLE V
CORRECTED
MEAN
INCREASES
IN LENGTI-I
FOE WHITE
CIIILDREN
IN GROUPS
I~ II,
AND, ~ V AND T t I E I E ~OMPARISON
GROUP
MEAN LENGTH AT 3 MONTHS
I
599
II
587
IV
595
INCREASE FROM 3 TO 24 MONT~S CORRECTED FOE AN I N I T I A L L E N G T H OF 5 9 4 MM. 258.57 +1.86 266.30 -2.60 272.37 +0.37
DIFFERENCE OF MEANS (STANDARD DEVIATION OP DII~I~EI~ENCE OF MEANS) 2
4
7.73
13.80
+-5.09
-+7.30
6.07 +-7.50
T h e c o r r e c t e d v a l u e f o r t h e m e a n i n c r e a s e in l e n g t h b e t w e e n t h e a g e s of 3 a n d 24 m o n t h s w a s c a l c u l a t e d in t h e f o l l o w i n g m a n n e r . A n a r b i t r a r y i n i t i a l l e n g t h a t 3 m o n t h s of 594 r a m . w a s t a k e n . The difference between the actual initial mean l e n g t h s a n d t h i s a r b i t r a r y m e a n i n i t i a l l e n g t h w a s m u l t i p l i e d b y t h e r e g r e s s i o n coefficient (A g a i n i n l e n g t h z 0.371 A i n i t i a l l e n g t h ) . T h e v a l u e t h u s o b t a i n e d w a s a d d e d o r s u b t r a c t e d ( d e p e n d i n g on w h e t h e r t h e a c t u a l i n i t i a l m e a n l e n g t h w a s g r e a t e r o r l e s s t h a n t h e a s s u m e d v a l u e of 594 r a m . ) f r o m t h e a c t u a l i n c r e a s e in l e n g t h f r o m 3 to 24 m o n t h s .
D in irradiated evaporated milk. Administration of 10 drops of carotene daily (2,250 units of vitamin A activity) to colored children rec.eiving irradiated evaporated milk did not increase their rate of growth. Similarly daily supplements o3 10 drops of carotene and 0.5 tablespoonful (5 Gin.) of powdered brewer's yeast had no added effect on the linear growth of the colored children receiving the same milk. With the correction derived from the correlation mentioned for initial length, there were no significant differences in the amounts of growth in length from 3 to 24 months of the white children in the four groups. Although the difference was not significant, there was still a suggestive tendency for white children receiving 1,500 units of vitamin D in codliver oil or 110 units of vitamin D in irradiated evaporated milk plus carotene and yeast to grow more rapidly than those receiving irradiated
RHOADS ET AL. :
lVIALE C H I L D R E N RECEIVING EVAPORATED M I L K
183
milk without other supplements.
While the addition of vitamin A to the dietary of white children was without influence on growth in length, the administration of a supplement of B complex (yeast) had the same effect on growth in length as an increased intake of vitamin D (1,500 units). RICKETS
For the consideration of the incidence of rickets the groups receiving irradiated evaporated milk plus carotene and those receiving irradiated evaporated milk plus carotene and yeast were combined, making groups comparable in size to those receiving irradiated evaporated milk alone and those receiving nonirradiated evaporated milk plus cod-liver oil. TABLE
VI
I~EI%CENTAGE DISTI%IBUTION OF ~{AXIMUM. X-:RAY DIAGNOSIS OF t~ICKETS AOCOB,DING TO GROUP AND RACE
DAILY NO.
GROUP
OF UNITS OF VITA-
RACE
I~IIN D
Group I (irradiated evaporated milk) Group II (nonirradlated evaporated milk p l u s codliver o i l ) Group III (irradiated evaporated
NO. OF CElLDIZEN
NORA{AL MILD CHANGES IVIILD lVs ENCON- II:[EALED EAIgL~ ATE TII%EL" SIDEI%ED I%ICKETS lgICKE'I P~ICKETS
No~ [ (%)
NOR~A (%) aACm~ic (%)
VChite Colored
--35.3 47.0
43.8 43.7
1,500
White Colored
40.4 35.5
45.2 51.6
]I0
Rite Colored
38.6 41.7
50.0 47.2
Ii0
-/--8A--6.2
7.2 9.7
(%)
(%)
3.1
4.8 3.2
2.4 0
milk plus
carotene) Children receiving irradiated evaporated milk and carotene are combined with those receiving irradiated l~oentgenographic heading of normal.
evaporated milk plus carotene and yeast, to make Group III. bone changes considered nonrachitie are classified under the
The diagnosis of rickets was based on roentgenograms of the bones of the left forearm. 8 There is very little correlation possible between the clinical findings of rickets (craniotabes, bossing, flaring of the costal margins, beading of the costochondral junctions, and enlargement of the wrists) and the x-ray findings at the wrist. 9 The maximmn amount of rachitic change found in the course of ten routine roentgenological examinations is used as the basis for the rating given to each child in Table VI.
No instance of marked rickets occurred in any group. One case of moderate rickets (0.4 per cent of the totali occurred in the group receiving nonirradiated evaporated milk and cod-liver oil. This patient was a small white child of German and Irish extraction, who grew at
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an average rate. His mother, a reliable person now doing social service work, is sure that the cod-liver oil was given regularly. He was born March 29, 1937, and was first, seen on April 20 when the administration of cod-liver oil was begun. At the first visit the x-ray examination was normal; at 3 ~ months it showed mild healing rickets and at 6 months very definite moderate healing rickets; at 8 months there was no change; and from 9 to 16 months the diagnosis was healed rickets. From 19 months on the roentgenograms have been normal. The incidence o~ mild rickets in the '233 children was 13.3 per cent. Mild rickets already showing evidences of healing occurred in 6 per cent of both the white and colored groups. Mild rickets without healing was present in 7.3 per cent of the entire group (8.9 per cent of the white children and 5 per cent of the colored). The total incidence of rickets in the two groups receiving 110 units of vitamin D was 13.8 per cent as compared with 15.5 per cent in a study of ninety-seven initially nonrachitic infants receiving irradiated evaporated milk previously reported from this hospital by Rapoport, Krick, and Stokes2 In Table VI it is seen that, of the children receiving irradiated evaporated milk alone, 20.9 per cent of the white and 9.3 per cent of the colored had rickets. In the cod-liver oil groups 14.4 per cent of the white and 12.9 per cent of the colored children had rickets. In the carotene groups 11.4 per cent of the white and 11.1 per cent of the colored had rickets. Findings indicate that there was no appreciable difference in the antirachitic effectiveness of 1,500 units of vitamin D in the form of cod-liver oil as compared to 110 units of vitamin D in irradiated evaporated milk. Included in the normal groups were children whose roentgenograms showed bone changes from the normal which were not definitely rachitic. These changes consisted, for the most part, of slight cupping of the distal end of the ulna, but included slightly increased density in the zones of temporary calcification, slight decalcificas slight " s p r e a d , " slight fuzziness of the distal ends of the radius and ulna, slight osteoid deposition along the inner border of the radius, etc. They occurred (Table VI) in 43.8 per cent of the white and 43.7 per cent of the colored children receiving irradiated evaporated milk, in 45.2 per cent of the white and 51.6 per cent of the colored children receiving nonirradiated evaporated milk and cod-liver oil, and in 50.0 per cent of the white and 47.2 per cent of the colored children receiving irradiated evaporated milk and carotene. The nature of these Changes is not clear. Eliot and her co-workers4 consider them as doubtful rickets, and it certainly is true that often they precede or follow an x-ray diagnosis of actual rick~ ets. Hood and Raviteh ~~ question their being rachitic, since in their study of irradiated cholesterol they found the highest percentage of these changes (37.0 per cent) in the group of white children receiving the greatest amount of vitamin D (950 to 1,200 units), while none
RHOADS ET AL. :
M A L E C H I L D R E N R E C E I V I N G E V A P O R A T E D ~VIILK
185
occurred in the colored children of that group. Jeans 11 has referred to them as "concomitants of rapid normal g r o w t h " ; Robinson 1~ questions this since she f o u n d them in a much smaller proportion (9.0 per cent) of the breast-fed group in her series. In this study these changes are classified as normal. The roentgenograms of all the children were normal a t 2 years with the following exceptions: three cases of slight cupping, two cases of marked, increased density of the zones of temporary calcification, and one case of marked increase in width of the zones of temporary calcification. These were all preceded by normal roentgenograms at the previous examination. That rickets occurs more frequently in the white than in the colored ~ was borne out by this study: 15.6 per cent of the white children and 11.1 per cent of the colored having rickets. However, in the carotene group the incidence was nearly equal (11.4 per cent for the white and 11.1 per cent for the colored). In the series of children given irradiated evaporated milk studied by l~apoport, Krick, and Stokes 9 twelve of forty-seven white children developed mild rickets and three of fifty negro children developed mild rickets. Eliot and her co-workers 4 found that the incidence of slight rickets was greater in infants who were growing rapidly than in those growing slowly when 400 units or more of vitamhl D were given daily, but that this relationship was absent when the dosage was lower than 400 units. In this s t u d y no such correlation appeared when the infants were classified according to rate of growth as :follows: a child was rated as growing at the average rate when his increase in length between 3 and 9 months was within 5 ram. of the average increase of his entire group for that period. When his increase in length was greater than this, he was considered to be growing faster, and, when it was less, he was considered to be growing more slowly. Table V I I shows that in the cod-liver oil group rickets occurred slightly more f r e q u e n t l y in those children who were growing at a rate slower than ~he average of their group. The incidence of roentgenographie bone changes not considered rachitic in this group showed almost no difference according to rate of growth. In the group receiving irradiated evaporated milk alone, the distribution of rickets and of these changes was practically the same in the fast and in the slow growing groups. In the group receiving irradiated evaporated milk plus carotene, there were somewhat more rickets and fewer questionable roentgenographic bone changes in the faster growing children. Many studies of rickets are not continued after the infants reach the age of 6 months, and therefore some cases of rickets occur Which are not reported. In this series three cases oR mild healed rickets appeared at 7 to 9 months. Two of them were in the i r r a d i a t e d evaporated milk group; one of these was preceded by roentgenographic bone: changes,
186
T H E J O U R N A L OF PEDIATRICS
and the other was not. The third case was in the colored group receiving cod-liver oil and was preceded by the changes at only one examination. Roentgenographic bone changes considered not rachitie occurring f o r the first time at 7 months or later were as follows : irradiated evaporated milk group, white 10.4 per cent, colored 9.4 p e r cent; cod-liver oil group, w h i t e 19.0 per cent, colored 22.6 per cent; i r r a d i a t e d evaporated milk plus carotene, white 13.6 per cent, colored 5.6 per cent. No conclusions are drawn f r o m the fact t h a t the greater percentage of delayed changes occurred in the groups receiving the larger amount of vitamin D. TABL~ V I I INCIDENCE
OF I~ICKETS
-~CC'DRI)II'TG TO CxI~OUP AND 3 AND 9 :~r
I~ATE
OF GROWT~I
BETWEEN
r GROUP
RACE
Group I
White
irradiated evaporated milk) Colored
Group II nonirradiated evapor a t e d m i l k p l u s codl i v e r oil)
White
Colored
R A T E OF GI~OWTI~I
Faster Av. Slower
Faster _A_v. Slower Faster 2~v. Slower Faster Au Slower Faster Av. Slower Faster Av. Slower
16 15 17 11 9 12 13 15 14 13 8 10 14 16 14 14 7 15
8 7 6 5 3 6 5 10 5 8 3 6
2 2 2
1 2 1 1 1
1 1 2
1 2 5 Group III Whit~ 8 2 9 irradiated evaporated milk plus carotene) 2 6 Colored 5 1 1 6 A child w a s c l a s s i f i e d a s g r o w i n g a t t h e a v e r a g e r a t e w h e n h i s i n c r e a s e in l e n g t h between 3 a n d 9 m o n t h s w a s w i t h i n 5 ram. of t h e a v e r a g e i n c r e a s e of his e n t i r e g r o u p . W h e n t h e i n c r e a s e w a s g r e a t e r , h e w a s r a t e d a s g r o w i n g f a s t e r ; and, w h e n i t w a s less, he w a s r a t e d a s g r o w i n g m o r e s l o w l y .
The total incidence of rickets in this series was 13.7 per cent, r a t h e r lower than that f o u n d in m a n y studies. Eliot and her co-workers, 4 in Detroit, using 135 units to 735 units of v i t a m i n D in various antirachitie agents, found rickets, exclusive of doubtful rickets (corresponding to those in this study reported as roentgenographic bone changes considered nonrachitir in 36 per cent of white males and 28 per cent of colored males. Robinson 1~ found the incidence of definite rickets to be 33 per cent in St. Louis. R o d d y and his co-workers, ~3 in Philadelphia, f o u n d 25 per cent rickets occurring in e i g h t y - f o u r initially nonrachitic infants followed for four and a half months on 2,140 or 1,070 units of vitamin D in the f o r m of pereomorph-liver oil. Other studies find lower
]
[
7 [
[
[
__1__
Colored
I ~
RACE
" Group II White (nonirradiated evapo[ Colored ' rated milk plus co d liver oil) 9 Group I I I ......~ ] (irradiated evaporated [ Colored milk plus carotene) [ " Group I V - - I ~ (irradiated evaporated I Colored milk plus carotene and yeast)
ilk)
" Group I (irradiated evaporated
GROUP
19
17
42 31
32
DREN
cOIL -
NO.
6.05
--Egg--
4.25 5.12
4.10 5.32
4.42 6.19
MILD
VIII
0.84
~ 0.53
0.79
0.59
1.25
0.76
0.44
0.58
~
~
SEVERE
0.77
0.62
0.73 1.0
ATE
5~ODER-
0.32
0.40
0.24
0.29
0.35
0.33--
0.35 0.28
OTITIS MEDIA
0.05 0.0
0.08 0.0
D.07 0.07
0.47
3.06 D.03
0.05 0.21
0.33 0.24
~
I
0.42
o.13
0.06
~
0.0
/o . - - ~ 6 - - - ~
0.02 0.03
_ _ 1 _
L~ZMPHADENITIS
CERVICAL
o.x4
0.38
SPECIEIC INFECTIONS
NEUONIA
CHILD ~q~ROM 3 TO 2 4 ~V~ONTHS .A_COOKDING TO GROUP
COLDS
N U M B E R OF INFECTIONS ~ E R
TABLE
~
O.ll
0.24
0.07
0.04 0.13
ECZEMA '
~
~ 0.05
0.35
'
0.29
~ J
0.17 0.28
TION
0.35
o.17
0.42
o.26
0.25 0.34
I
,- o.4o [0.47
I ]
INFEC-TION
TEEAL
OUT PAREN-
WITDI:ARRHEA WITHPAttENT~RAL INEEC-
~ - - E "
I
b-a DO --1
9 ~V
7~
z
a:
>
5~
O >
188
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incidences of rickets, but it seems to be true that a certain amount of clinically insignificant rickets is bound to occur with usual doses of customary antirachitic agents, and in this study ~rradiated evap~)rated milk has been essentially as efficacious! as large amounts of cod-liver oil. INCIDEi'~CE OF I N F E C T I O N S
In Table V I I I the incidence of infections is reported according to the number of infections occurring in each group per child in that group. It will be noticed that there were more mild colds among the colored children than among the white. Diarrhea without parenteral infection was slightly more frequent in the groups receiving yeast. The white group receiving irradiated evaporated milk plus carotene had more severe colds, slightly less otitismedia, and more diarrhea with parenteral infection and less without parenteral infection. Obviously carotene had no beneficial influence on the number or severity of respiratory tract or other infections. There were four eases of lipoid pneumonia which are not included in Table VIII. One occurred in a colored child receiving irradiated evaporated milk; it was learned that he had received cod-liver oil for ten days early in infancy. T w o occurred in the cod-liver oil group, one white and one colored. The fourth ease occurred in a white child receiving carotene. All have done well except the colored one who received cod-liver oil and who has remained small and thin with poor musculature. In general, there was littledifference between the groups in the incidence of infections. CONCLUSIONS
Longitudinal observation has been made of 233 male infants receiving diets containing evaporated milk as the sole source of milk from an average initial age of 6 weeks until the age of 2: years. The acceptability of evaporated milk by children beyond the period of infancy was noted. The infants were divided into four groups according to vitamin supplements. Group I received irradiated evaporated milk; Group II, nonirradiated evaporated milk plus cod-liver oil; Group III, irradiated evaporated milk plus carotene; Group IV, irradiated evaporated milk plus carotene and yeast. The average growth in length of all groups was better than would have been expected according to the Kornfeld standards of normal growth of boys, and there was no significant difference in length between any of the groups at 3 months, 1 year, or 2 years. White children receiving 1,500 units of vitamin D in the form of cod-liver oil between the ages of 3 months and 2 years, increased in length by a suggestively, although not clearly significantly, greater amount than:the childre n receiving 110 units of vitamin D in irradiated
RHOADS E T AL. :
M A L E C H I L D R E N R E C E I V I N G EVAPORATED M I L K
189
e v a p o r a t e d m i l k w i t h o u t a d d e d v i t a m i n s A a n d B. Colored c h i l d r e n r e c e i v i n g cod-liver oil i n c r e a s e d i n l e n g t h a s i g n i f i c a n t l y g r e a t e r a m o u n t t h a n those r e c e i v i n g i r r a d i a t e d e v a p o r a t e d milk. A d d i t i o n of 2,250 u n i t s of v i t a m i n A i n the f o r m of carotene prod u c e d no s i g n i f i c a n t effect on r a t e of g r o w t h i n l e n g t h of either the white or colored c h i l d r e n . W h i t e c h i l d r e n r e c e i v i n g carotene a n d a p p r o x i m a t e l y 250 u n i t s of v i t a m i n s B~ a n d B~ i n p o w d e r e d b r e w e r ' s y e a s t b e t w e e n the ages of 3 a n d 24 m o n t h s i n c r e a s e d i n l e n g t h b y a suggestively, a l t h o u g h n o t d e a r l y significantly, g r e a t e r a m o u n t t h a n the c h i l d r e n o n the same milk n o t r e c e i v i n g these v i t a m i n s u p p l e m e n t s . F o r the colored c h i l d r e n , a d d i t i o n of yeast p r o d u c e d no s i g n i f i c a n t increase i n length. The i n c i d e n c e of r o e n t g e n o g r a p h i e rickets was p r a c t i c a l l y the same at b o t h levels of v i t a m i n D i n t a k e (110 a n d 1,500 u n i t s d a i l y ) . T h e v a r i o u s v i t a m i n s u p p l e m e n t s h a d no i n f l u e n c e on the i n c i d e n c e or s e v e r i t y of i n f e c t i o n s of the u p p e r r e s p i r a t o r y t r a c t . We wish to express our thanks to Dr. J. H. Austin, Professor of Research Madlcine, School of Medicine of the IYniversity of Pennsylvania, for his generous and invaluable aid with the statistical analyses in this paper. REFERENCES
1. Souders, tI. J., Hunscher, H. A., Hummel, t ~. C., and Macy, I. G.: Am. J. Dis. Child. 58: 529, 1939. 2. Dawson, H. I~.: J. PEDIAT. 9: 187, 1936. 3. Kornfeld, W.: Ztschr. f. E:inderh. 48: 188, 1929. 4. Eliot, IV[. M., Nelson, E. M., Barnes, I). J., Browne, F. A., and Jenss, R. M. : J-. PEDIAT. 9: 355, 1936. 5. Stuart, If. C.: J. PEDIAT. 51 194, 1934. 6. Bakwin, II., and Bakwin, R. l~I.: J. PEJ)IAT. 8: 177, 1936. 7. Elias, H. L., and Turner) R.: J. PEDIAT. 8" 352, 1936. 8. Eliot, M. M., and Powers, G. !~.:. J. A. M. A. 102: 1823, ]934. 9. Rapoport, !Yr., Kriek, E., and Stokes, 5., Jr.: J. PEDIAT. 11: 782, 1937. 10. Hood, J-. S., and Ravitch, I.: J. PE~)IA~. 11'. 521, 1937. 11. Jeans, P . C . : J . A . ~/f. A. 106: 2066, 1936. 12. Robinson, E. C.: Am. J. Dis: Child. 59: 816, 1940. 13. Roddy, R. L., Rose, E. K., No.des, P. J., and Gittings, 3-. C. : Am. J. Dis. Child. 55: 526, 1938.