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Water requirements for renal excretion in full-term newborn infants and premature infants fed a variety of formulas
T H E JOURNAL OF
PEDIATRICS JUNE
1960
V o l u m e 56
Number 6
Water requirements for renal excretion in full-term newborn infants and premature infants fed a variety Philip L. Calcagno~ M.D., ~ and Mitchell I. Rubin, M.D. BUFFALO~
N.
Y.
as end products of protein metabolism and electrolytes. 1"4 There is sufficient documentation to show 5, 6 that the average renal concentrating capacity in healthy, newborn premature infants and in full-term infants in the first few weeks of life is below that which is obtained later in life. For the purposes of this. study, it is assumed to be 700 mOsm. per liter at a specific gravity approximating 1.021; this is about half the maximal renal concentrating capacity of the mature adult (1400 mOsm. per liter). Under usual circumstances of health and when the concentration of the solute load demanding renal excretion is below the maximal Concentrating capacity of the kidney, "expendable" renal water is available. Under
C u g g ~ N w L Y much emphasis is placed on the construction of infants' formulas with regard to their content of protein and solutes which are ultimately excreted by the kidney From the Statler Research Laboratories o[ the Children's Hospital of Buffalo and the Department of Pediatrics, University o[ Buffalo School o/Medicine. With the technical assistance of Dr. Phatick Mukherfi, Mary K. Wypych, and Margaret M. Stubbins and with the nursing assistance o[ Alberta Weaver, Sara PanzareUa, and Charlotte Garrett. Aided by grants from Ross Laboratories, Columbus, Ohio, and by Research Grant H-2290, National Institutes of Health, United States Public Health Service. ~Address, Department o[ Pediatrics, Tha University of Buffalo School o[ Medicine, 219 Bryant Street, Buffalo 22, N. Y.
717
7 18
Calcagno and Rubin
June 1960
Table I. Average values* per liter Sodium (mEq.)
Formula
Colostrum Transitional breast milk Low osmolar milk (Similac) Modified cow's milk Whole cow's milk
23.8 11.2 11.6 17.5 23.1
Potassium (mEq.)
Chloride (mEq.)
18.8 19.3 18.2 24.5 36.2
28.7 15.4 11.9 22.9 32.9
MiUiosmols
285 297 236 249 286
Nitrogen (Gin.)
5.4 3.0 2.1t 2.9 5.1
*Average values of all samples prepared in milk laboratory a n d obtained from mothers by hand expression (colostrum and transitional breast milk). t W h e n dilution of Similac is prepared in biochemical laboratory instead of in routine milk laboratory, this value is 2.7.
these circumstances, the solute load of the formula does not place a demand upon body water which m a y result in dehydration. In the presence of severe dehydration, whether produced by deprivation or loss of water or by fever or high environmental temperature, a maximal urinary concentration m a y be expected with a decrease in expendable renal water. Thus with formulas resulting in a urine osmolar concentration significantly below 700 mOsm. per liter in the newborn and in the very young infant, a surplus of water above that obligated for solute excretion must exist. Under such circumstances it can be assumed that the formula being given the infant is satisfactory from the viewpoint of the renal water requirement. In instances where urinary concentrating capacity is greater than 700 mOsm. per liter, the amount of obligated renal water would be less; in circumstances where the concentrating capacity is below 700 mOsm. per liter, the obligated renal water would be increased. This study is limited to full-term infants between the ages of 2 to 4 days and 6 to 9 days and to premature infants 10 to 56 days of age. These infants were fed a variety of formulas which contained different amounts of solutes demanding renal excretion to determine whether the resulting urine osmolarity was below the assumed maximal concentrating capacity for these infants. METHODS
AND
PROCEDURE
The urinary osmolar excretions during the second to fourth days of life on various formulas were studied in 39 full-term newborn
infants. The compositions of the formulas used are listed in Table I. Fourteen infants were fed modified whole cow's milk; 9, hum a n milk (colostrum); 4, equal parts of evaporated milk and water; and 12, low osmolar milk formulas.* Three additional fullterm newborn infants were studied during the sixth to ninth days of life while on human breast milk (transitional).t Seven premature infants varying in ages from 10 to 56 days were fed either low osmolar milk or equal parts of evaporated milk and water. In the bottle-fed infants, the intake of formula was determined by the difference in bottle weight before and after feeding. In the breast-fed infants, the difference in the infant's weight before and after feeding was recorded as the intake. T w o consecutive, separate 24-hour collections of urine were made for each period of study. T h e urine was collected in a container surrounded by ice to minimize bacterial growth. Daily analyses of the formulas were made with regard to their osmolar, sodium, potassium, chloride, and nitrogen contents. Osmotic pressures were determined with the Hill-Baldes apparatus#, s Sodium and potassium concentrations were determined with a Norelco flame photometer. Chloride was determined b y the method of Sendroy modified by Van Slyke and Heller, and nitrogen *Similac, Ross Laboratories. "~The formulas used in this study were prepared as follows : Whole cow's milk --150.0 ml. evaporated milk, 150.0 ml. water. Low osmolar milk (similac, Ross Laboratories)--8.5 Gin. dry milk, 60.0 ml. water. Modified cow's milk --150.0 ml. evaporated milk, 16.0 Gm. Dextri-Maltose No. 1, 480.0 ml. water.
Volume 56 Number 6
Water requirements [or renal excretion
was determined by a Micro-Parnass-Wagner apparatus with the use of a 2 per cent boric acid solution with mixed indicator (bromcresol green and methyl red) and titration of the ammonia with sulfuric acid. RESULTS
Table I lists the average composition of the various formulas used in the study. The data are derived from direct determinations. The values shown represent averages obtained from analyses of samples of the daily formulas as prepared in the hospital milk laboratory. It should be noted that the nitrogen value for the low osmolar milk is lower in the preparation made in the routine milk laboratory than the one prepared in the biochemical laboratory. The modified cow's milk formula fed the newborn infant was dilute when compared with the formula made of whole cow's milk. Whereas the carbohydrate in the various formulas adds to the total osmolar intake, it is not excreted in the urine and thus does not contribute to the total of solutes requiring renal excretion. The substances in the formula which contribute mainly to the renal solute load are derived from protein and electrolytes; the excreted end product of protein metabolism is largely urea, which in feedings of whole cow's milk consists of about 40 to 60 per cent of the total osmolar excretion. 9 Low concentrations of osmols as derived from
7 19
protein and electrolytes are found in transitional breast milk 1~ and are closely comparable to those of the low osmolar milk formulas used in this study; conversely, the whole cow's milk formula and colostrum have higher osmolar concentrations. T h e osmolar values of the modified cow's milk formula was between these two feedings. The actual osmolar intakes are listed in separate tables. Table I I lists the intake and urinary output of fluid, electrolyte, nitrogen, and total osmols in full-term infants fed a formula of equal parts of evaporated milk and water. Each infant had a larger intake on the second day of the study, which is a reflection of the larger intake as the infant aged. The average intake for the 2 days was 106 ml. per kilogram per day. The average urine output of these infants was 24 ml. per kilogram per day, with an average osmolar excretion of 7.6 mOsm. per kilogram per day. It should be noted that with the increased intake on the second day of the study, there is an associated increase in osmolar excretion. There is, however, no consistent increase in urinary concentration of osmoles. T h e highest osmolar concentration on any given day was 449 mOsm. per liter and the lowest was 184 mOsm. per liter, with an average of 318 mOsm. per liter for the group. These values are well below those found by Hansen and Smith s in full-term
Table II. Intake and urinary osmolar excretions in full-term infants fed whole cow's milk ~
Chloride Nitrogen Potassium Fluid Urine Sodium Urine (mEq.) (rag.) (mEq.) Milliosmols (mOsWeight Age intake output (mEq.) tlent (kg.) (days) (ml.) (ml.) IntakelOutput IntakelOutput Intake I Output Intake I Output intake[ Output rn./L.~ ea-
L.A.
4.1
3 4
73 110
11 22
1.69 2.54
0.14 0.17
2.58 3.95
0.39 0.91
2.31 3.58
0.19 0.32
361 534
71 107
20 31
3.8 6.2
355 280
P.R.
4.2
4 5
86 141
18 48
1.97 3.27
0.46 2.10
3.00 5.06
0.70 1.64
2.70 4.72
0.65 2.56
447 683
80 251
24 44
5.4 18.0
306 371
M.O.
2.8
3 4
75 155
21 35
1.74 3.57
0.20 1.32
2.72 5.63
0.62 0.32
2.36 4.89
0.51 1.66
391 820
57 147
21 45
3.9 11.0
184 304
T.E.
2.8
2 3
75 129
8 31
1.74 2.98
0.34 0.31
2.70 4.63
0.33 0.97
2.60 4.46
0.40 0.54
402 670
63 154
21 38
3.7 9.0
449 291
Average 106 24 2.43 *Per kilogram of body weight per day.
0.63
3.78
0.74
3.45
0.85
539
116
31
7.6
318
3.0
3.4
2.9
2.3
3.3
3.3
2.8
3.3
3.2
3.2
3.3
B.R.
M.A.
S.T.
Q.U.
B. R . Y .
M.O.
MeD.
L. A . N .
B. O . Y .
A.L.
P.E.
2 3
2 3
2 3
2 3
2 3
4 5
2 3
4
3 4
2 3
4 5
3 4
Age (days)
~Per kilogram of body weight per day.
Average
2.9
H. A . L .
Patient
Weight (kg.) 1 5 25 37 10 16 38 63 78 20 11 41 62 18 35 4 4 30 36 20 37 11 7 27
83 98
133 173
62 91
126 135
222
73 96
146 148
52 89
76 83
110 163
137 169
120 127
118
1.30
1.39 .
1.59 1.96
1.28 1.89
0.88 0.97
0.60 1.04
1.60 1.57
0.86 0.99
.
1.71 1.49
0.73 1.05
1.52 1.83
0.99 1.22
0.20
0.04 .
0.14 0.16
0.09 0.07
0.06 0.05
0.06 0.04
0.12 0.80
0.08 0.07
.
0.38 0.75
0.24 0.19
0.20 0.56
0.01 0.11
.
. 2.20
2.18
2.49 2.88
2.00 2.97
-
0.94 1.65
2.68 2.55
1.41 1.66
.
3.03 2.48
1.26 1.70
2.45 3.18
1.52 2.01
.
0.40
0.13 .
0.34 0.37
0.39 0.50
-
0.44 0.46
0.33 0.62
0.22 0.08
.
0.68 1.01
0.21 0.33
0.31 0.34
0.02 0.10
.
1.30
. .
1.63 2.01
1.31 1.94
0.90 0.99
0.62 1.06
1.59 1.72
1.15 1.16
1.79 1.61
0.78 1.08
1.52 1.80
1.00 1.17
.
0.20
.
0.10 0.07
0.09 0.22
0.09 0.10
0.44 0.49
0.33 0.43
0.12 0.09
0.42 0.63
0.39 0.25
0.15 0.41
0.01 0.03
. .
258
.
-
-
-
93 197
261 265
188 204
364
315 308
-
209 432
-
77
-
-
-
81 112
74 106
70 46
89
81 50
-
81 61
-
27
29 30
22 28
19 27
27 28
14 17
32 34
19 22
51
42 30
15 23
31 43
22 25
3.2
1.5 0.8
3.0 3.8
3.0 3.6
2.0 1.8
4.6 7.9
3.7 4.3
1.9 2.2
6.8
157
141 112
150 102
101 101
465 492
252 225
90 70
91 199
87
117 100
175
2.7 4.4 6.3
213
77 79
117 170
Urine (mOsm./L.)
2.1
2.0 3.0
0.1 0.9
Potassium Chloride Fluid Urine Nitrogen (mg.) Milliosrnols (rnEq.) (mEq.) intake output Sodium (mEq.) Intake IOutput Intake [Output Intake IOutput Intake [Output Intake [ Output (ml.) (ml.)
Table I l L Intake and urinary osmolar excretions in full-term infants fed a low osmolar milk*
ro o~
3"
g~
g~
gl
0~
g~
Volume 56 Number 6
infants at this age during thirsting (approximately 600 mOsm. per liter). Table I I I lists the intake and urinary o.utput of a similar group of substances presented in Table I I for full-term infants fed a low osmolar milk. The average total intake of this formula is slightly larger than that of whole cow's milk: 118 ml. per kilogram per day with an average osmolar excretion of 3.2 mOsm. per kilogram per day, about half o$ that observed with the infants fed equal parts of evaporated milk and water. The urinary osmolar concentrations average 157 mOsm. per liter; the lowest value is 77 mOsm. per liter and the highest is 492 mOsm. per liter. The average urinary concentration of 157 mOsm. per liter is significantly below that of infants fed equal parts of evaporated milk and water, 318 mOsm. per liter (p < 0.05). As with whole cow's milk feedings, these urinary osmolar values are considerably below the maximal renal concentrating capacity of normal full-term infants. Table I V lists similar data for intake and urinary output of full-term infants fed a modified cow's milk formula. The average intake was 107 ml. per kilogram per day with an osmolar excretion of 5.2 mOsm. per kilogram per day. The average urinary osmolar concentration was 204 mOsm. per liter, which is significantly different from that in the infants fed whole cow's milk. The lowest value in this group is 114 mOsm. per liter and the highest is 446 mOsm. per liter. These values are also well under the maximal renal concentrating capacity of the normal fullterm infant for this age. Table V lists similar data for intake and urinary output for full-term infants fed human breast milk (colostrum). It is evident that the average total intake is significantly smaller in these infants than in the artificially fed infants; the average intake is 72.0 ml. per kilogram per day, with an osmolar excretion of 3.2 mOsm. per kilogram per day. The average urinary osmolar concentration was 273 mOsm. per liter, with a high value of 408. Again, these values are considerably below the maximal renal concen-
Water requirements for renal excretion
721
trating capacity for an infant of this age. Table V I lists similar data for intake and urinary output of full-term infants fed human breast milk (transitional). The average intake is 162 ml. per kilogram per day, the largest of all the groups. These infants were 3 to 4 days older than the infants given the feedings listed above. The average osmolar excretion is 8.8 mOsm. per kilogram per day. The average osmolar urinary concentration of 122 mOsm. per liter is the lowest of the entire group. The lowest value obtained in this group is 77 and the highest is 194. The second part of this study presents data on the patterns of excretion of premature infants from 10 to 56 days of age, whose weights varied from 1.4 to 2.1 kilograms. Table V I I lists the intake and urinary output of fluid, electrolytes, nitrogen, and osmols in premature infants fed evaporated milk and water. The data in this chart come from a previous study. 9 The infants were maintained on this diet from 5 to 7 days prior to a 6-day study period. The data presented are average daily values. The average total intake is 149 ml. per kilogram per day, with an average urinary osmolar excretion of 26.5 mOsm. per kilogram per day, the average urinary concentration is 410 mOsm. per liter. These urinary o smolar concentrations are considerably below the maximal renal concentrating capacity of premature infants of this age. Table V I I I lists similar data for intake and urinary output of premature infants fed a low osmolar milk formula. The intake was 168 ml. per kilogram per day, with an average o.smolar output of 8.7 mOsm. per kilogram per day, and an average urinary osmolar concentration of 104 mOsm. per liter, with a low of 81 and a high of 147. These values are well below the maximal renal concentrating capacity for these infants. DISCUSSION
The nutritive value of the infant's formula is of paramount consideration in feeding. The purpose of this study, however, was primarily to determine whether constituents
2.3
2.3
3.2
2.9
2.8
2.8
3.2
2.3
3.2
2.8
3.4
3.3
3.2
McK.
T. I-I.
M.U.
W.H.
B.E.
B. E. C.
B.O.
H.A.
E.U.
j.A.
S.E.
L.I.
D.E.
2 3
2 3
107
109 141
105 13,3
66 102
31
13 20
35 67
20 22
3
2 3
6 19
7O
86
2
46 55
5 31
24 15
7 13
104 148
94 106
54 116
40
107 154
27
51 40
37 66
37 32
41 74
9
86 104
141 141
122 131
124 163
36
66 80
3 4
3 4
3 4
2 3
3
2
2 3
3 4
2 3
3 4
2
Age (days)
Average ~Per kilogram of body weight per day,
3.3
Weight (kg.)
S.I.
Patient
2.00
1.93 2.70
1.84 2.48
1.14 1.92
1.22 1.50
1.15 1.40
1.83 1.68
1.64 1.86
0.81 2.11
2.01 3.44
1.14 1.81
2.81 2.63
2.38 2.54
2.48 2.93
0.49
0.40
0.08 0.14
0.35 0.73
0.26 0.26
0.12 0.25
0.04 0.15
0.38 0.82
0.04 0.43
0.48 0.39
0.24 0.21
0.46 0.20
0.16 0.66
0.62 0.55
0.49 0.96
-
2.80
2.76 4.05
2.55 3.81
1.59 2.50
2.10
1.61 1.95
2.59 3.62
2.30 2.60
1.18 3.20
2.44 4.05
2.07 2.54
3.71 3.32
2.93 3.13
3.12 3.98
0.84
0.60
0.15 0.12
0.72 0.67
0.43 0.46
0.56
0.13 0.19
0.64 0.99
0.07 0.86
0.50 0.26
0.48 0.33
0.92 0.88
0.63 1.12
0.66 0.64
0.74 1.11
-
2.40
2.51 3.22
2.39 3.06
1.52 2.32
1.59 1.96
1.50 1.73
2.39 3.39
2.15 2.43
1.23 2.66
1.61 3.91
1.23 2.37
3.35 3.40
3.01 3.04
3.10 3.60
1.0'9
0.50
0.14 0.20
0.21 0.52
0.30 0.20
0.06 0.27
0.20 0.21
0.46 0.99
0.06 0.89
0.41 0.23
0.40 0.30
0.87 0.60
0.56 1.31
0.77 0.74
0.25 0.74
-
116
-
409
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
98 74
-
-
-
185 300
130 188
81 122
400 419 568 482
70 169
-
381 535
-
5.2
3.1 27
2.4
38
10.5
5.6
4.0
3.1
5.8
2.5
2.6
2.1
7.2
5.2
4.4
1.7
2.8
5.1
3.6
5.8
6.2 5.0
6.7 11.1
5.3 7.4
5.1 9.9
3.9
24
36
23
25
16
21
19
22
16
37
26
29
20
32
13
40
27
22 28
39 34
34 35
32 41
8
204
189 156
162 158
158 184
446 302
299 201
114 131
323 145
212 180
145 132
122 124
180 169
144 230
125 134
454
Chloride Fluid I Urine Sodium (mEq.) Potassium (mEq.) (mEq.) Nitrogen (mg.) Milliosmols Urine intake output (ml.) (ml.) Intake t Output Intake l Output Intake ]Output Intake IOutput Intake [Output (mOsm./L.)
Table IV. Intake and urinary osmolar excretions in full-term infants fed a modified evaporated milk and carbohydrate formula e
o
7,
ct~
t~
ro
Volume 56
Table
V.
Number 6
Intake
and
Water requirements [or renal excretion
urinary
723
o s m o l a r e x c r e t i o n in f u l l - t e r m i n f a n t s fed h u m a n
milk (colostrum) *
9 9 Sodium Potassium Chloride Nitrogen Urine Fluzd Umne " E ' Milliosmols (mOs(mEq.) (mEq.) (rag.) Weight Age ]intake]output I (m:~q.) Patient (kg.) (days) (ml.) (ml.) Intake[Output Intake[Output IntakelOutput IntakelOutput IntakelOutput m./L.) A.V.
3.2
2 3 4
33 63 66
3 9 18
0.80 1.49 1.56
0.07 0.22 0.54
0.63 1.19 1.23
. . .
G.I.
39
3 4
28 81
16 9
0.67 1.93
0.08 0.09
0.53 1.53
0.08 0.15
0.53 2.33
0.21 0.04
-
L.Y.
3.3
3 4
36 82
5 4
0.87 1.95
0.04 0.04
0.74 1.56
0.83 0.62
0.68 2.35
0.03 0.05
S.T.A.
3.3
3
64
46
1.50
-
0.90
-
-
K. E . L .
2.9
2
48
4
1.15
-
0.79
-
M. A . R .
2.0
2 3
I00
7 34
2.38 -
0.11 0.30
-
T.O.
3.2
4 5
103 134
32 12
1.96 2.36
0.16 0.19
S.H.
2.8
3 4
96 73
19 32
2.61 1.75
3
78
34
72
18
G.R.
2.3
Average
. . .
. . .
. . .
. . .
9 18 19
1.7 4.5 6.5
361
-
8 23
3.4 0.9
211 97
174 -
-
11 24
1.3 1.1
242 278
-
340
59
-
3.0
70
-
-
258
25
-
1.2
328
-
2.87 -
0.08 0.30
864 -
51 139
29 28
2.7 7.0
408 208
1.85 2.41
0.28 0.13
-
-
405 541
78 35
30 39
4.1 2.1
127 170
0.27 0.33
1.44 0.88
0.22 0.29
.
1629 .
269
28 21
4.3 4.6
223 -
2.05
-
2.56
0.39
.
1.60
0.20
1.30
0.30
1.80
.
. .
.
0.12
.
.
602
. 94
143 22
3.2
273
~Per kiloglam of body weight per day.
T a b l e V I . I n t a k e a n d u r i n a r y o s m o l a r e x c r e t i o n in f u l l - t e r m i n f a n t s f e d t r a n s i t i o n a l human milk*
9 Urzne . Sodium Fluzd Weight Age intake output (mEq.) Patient (kg.) /days)(ml.) (ml.) Intake Output L.A.S
3.2
P. O . S .
3.4
G. L . D .
3.2
6 7
117 152
86 72
7
79
6 7
244 220 162
Average
Potassium (mEq.)
I
Nitrogen (me.)
Chloride (mEq.)
MilIiosmols
Intake]Output IntakelOutput ZntakelOutput 1I~7~kdOutput
Urine (mOsm./L.)
2.2 2.4
1.0 0.7
342 444
167 104
34 44
14.1 10.4
164 145
0.3
1.4
0.l
335
90
23
5.0
194
0.6 0.7
5.2 5.1
0.6 1.2
703 635
63 112
78 64
5.9 8.6
77 80
1.1
3.2
0.7
492
107
49
8.8
122
1.5 2.1
3.4 2.2
26
1.0
70 108
2.0 1.7
72
1.7
~Per kilogram of body weight per day.
in
formulas
would
put
commonly undue
offered
demands
to
infants
on body water
do not become
a part
of t h e o s m o l a r l o a d
excreted in the urine. On
the other hand,
for the r e n a l e x c r e t i o n of the m e t a b o l i c e n d
ingested but nonretained
p r o d u c t s o f t h e diet. A m o n g
p o se d largely to u r e a a n d o t h e r o s m o t i c a l l y
young
infants
p r o t e i n is d e c o m -
t h e r e is a v a r i a b i l i t y i n t h e c a p a c i t y of t h e
active substances; their excretion by the kid-
k i d n e y to e x c r e t e a solute load at a given
ney requires water. The
rate
f o r m u l a w h i c h are not r e t a i n e d also exert a n
and
concentration.
In
the
course
metabolism, the absorbed carbohydrate
of and
fat in the diet are utilized by the body and
osmotic effect and excretion. Thus
e l e c t r o l y t e s of t h e
require water
the protein
for renal
and electrolyte
724
Calcagno and Rubin
June 1960
T a b l e V I I . I n t a k e a n d u r i n a r y o s m o l a r excretion in p r e m a t u r e infants fed whole cow's milk*
Fluid I Urine Sodium Potassium C h l o r i d e Nitrogen I Pa- Weight Age intake output (mEq.) (mEq.) (mEq.) (rag.) Milliosmols (mOsUrine tlent (kg.) (days) (ml.) (ml.) IntakelOutput IntakelOutput lntakelOutput lntakelOutput ~ t ra./L.) B.R. C.L. B.A.
2.1 1.8 1.6
56 38 28
Average
151 146 150
67 59 68
4.50 4.38 4,50
2.78 2.59 1.07
5.28 2.98 5 . 1 1 2.43 5.25 2.69
-
-
900 880 900
475 457 403
50 48 49
36.2 24.2 19.1
540 410 281
149
65
4.45
2.48
5 . 2 1 2.70
-
-
890
445
49
26.5
410
*Per kilogram of body weight per day.
T a b l e V I I I . I n t a k e an d u r i n a r y osmolar excretion in p r e m a t u r e infants fed a low osmolar milk*
Nitrogen Fluid Urine[ Sodium Potassium Chloride e (mg.) Milliosmols U~in (mEq.) (mEq.) (mEq.) (mOs. Pa- Weight Age intake output tient (kg.) (days) (ml.) (ml.) lntakelOutput IntakelOutput IntakelOutput IntakelOutput IntakelOutput m./L.~ G.H.
1.4
20 21
161 186
90 91
3,83 4,43
0.66 0.51
3.03 3.50
2.36 4.16
4.62 5.34
1.20 0.94
86 100
77 104
46 54
10.0 9.7
112 106
K.E.
1.4
15 16
103 113
76 89
1,28 1,33
0.35 0.41
2.26 2.48
1.69 1.89
2.01 1.87
0.94 0.91
256 286
86 101
33 33
6.8 8.0
90 90
C.L.
2.1
14 15
143 172
49 62
1,63 2.09
0.80 0.89
3.26 3.71
1.14 1.83
3.46 2.70
1.05 1.35
357 441
73 102
43 49
5.9 9.1
121 147
L.A.
1.9
10 11
229 234
113 130
2,66 2.72
0.27 0.39
5.22 5.76
2.63 2.79
3.84 3.98
1.41 1.45
381 400
97 120
66 67
9.2 10.9
81 84
168
88
2.50
0.54
3.65
2.31
3.45
1.16
288
95
49
8.7
104
Average
*Per kilogram of body weight per day.
T a b l e I X . T h e av erag e intake of the respective formulas
Age 2 2 2 2 6 10 28
to to to to to to to
4 days 4 days 4 days 4 days 9 days 20 days 56 days
I
I (full-term) (full-term) (full-term) (full-term) (full-term) (premature) (premature)
contents of t h e diet are the essential substances w h i c h m u s t be considered in estim a t i n g t h e w a t e r needs of the i n f a n t for renal excretion. T h e d a t a h e r e presented i n d i c a t e t h a t the f u l l - t e r m n e w b o r n a n d older p r e m a t u r e i n f a n t w i t h an assumed r e na l c o n c e n t r a t i n g c a p a c i t y of 700 m O s m . p e r liter in an e n v i r o n m e n t of 70 ~ to 80 ~ F. are qu i t e capable of e x c r e t in g the renal
Milk feedings Whole cow's milk Low osmolar milk Modified cow's milk Colostrum Transitional milk Low osmolar milk Whole cow's milk
I
ml./kg./day 106 118 107 72 162 168 149
solutes derived f r o m a v a r i e t y of formulas, w i t h o u t r e q u i r i n g additional fluid i n t a k e or d r a w i n g u p o n stores of body water. T a b l e I X indicates the a v e r a g e intake of t h e respective formulas. Fig. 1 is a composite of the d a t a presented in T a b l e s I I to V I I I . T h e a m o u n t designated as obligatory renal w a t e r in the figure is p r e d i c a t e d on the ass u m p t i o n t h a t these infants can co n cen t r at e
Volume 56 Number 6
their urine to 700 mOsm. per liter. The columns depict the urine output as a percentage of the intake. Each block represents an average of the percentage of urinary water excretion of all the infants in a single group. It is interesting that the renal water excretion in the full-term infants on the various diets was approximately 25 per cent of the intake (23 to 29 ml. per kilogram per day). Hansen and Smith 6 showed that infants of the same age, when thirsted, excreted about 10 to 15 ml. per kilogram per day. In the older full-term and premature infants, the urinary volume was 44 to 52 per cent of the intake. In these infants the actual total fluid intake per kilogram of body weight was larger than that of the younger ones. The figures in the solid portion of each column represent the amount of water in the urine unobligated by the excreted solutes (expendable renal water), indicating that this amount of water could have been reabsorbed by the renal tubules if needed for body economy. Thus in newborn infants fed whole cow's milk ad libitum with an average intake of 106 ml. per kilogram per day at 66 calories per kilogram per day, there was no drain upon body fluids and the renal excretion of water was beyond that demanded for the excretion of solutes. Those infants ingesting formulas with the smallest amount of osmols requiring renal excretion had a larger volume of expendable renal water. With the older full-term breastfed infants ingesting an average of 162 ml. per kilogram per day, containing 105 calories per kilogram per day, there was a larger amount of unobligated water in the urine which could have been saved by the body if needed. In the 2 groups of older premature infants, those on the low osmolar milk had an average intake of 168 ml. per kilogram per day, while those on whole cow's milk had an average intake of 151 ml. per kilogram per day. There was a larger amount of unobligated or expendable renal water in the infants fed the low osmolar milk than in those fed whole cow's milk, yet even in the latter group, 45 per cent of the renal water was unobligated.
Water requirements for renal excretion
PERCENT 3 0 2 0 10
0
OF
725
INTAKE
10 2 0 3 0 4 0 5 0 WHOLE COWS MILK LOW OSMOLAll MILK
2 - 4 DAY OLD FULL TERM INFANTS
MODIFIED COWS MILK COLOST|UM
6 - 9 DAY OLD FULL T E R M INFANTS
TIANSITIOHAL MILK
LOW OSMOLAll MILK
10-56 DAY OLD PREMATURE INFANTS
WHOLE COWS MILK
OBL RENAL WATER
Fig. I. The number in the solid area o f each column represents the percentage of expendable renal water of the total urine output.
It must be emphasized that we do not recommend the feeding of undiluted, unmodified cow's milk to newborn infants. The margin of safety with such a formula with regard to the water requirements could be greatly reduced under adverse circumstances, when extra losses of renal water may be excessively large. In a previous study in premature infants 9 and in keeping with other data in the literature, 11, 12 it was demonstrated that the addition of a carbohydrate to an isonitrogenous diet increases the nitrogen retention and decreases the urea nitrogen excretion as well as the total renal osmolar excretion. These latter studies were short-term experiments, as have been most of the other studies on the protein-sparing effect of carbohydrate feedings. Nevertheless, they indicate that the addition of carbohydrate to the formula may be of value in sparing water during periods when the water balance of the individual is critical, when there may be depression of renal concentrating capacity, when there is a decreased intake of fluid or excessive losses of water. Whereas there is a variation in the total osmolar intake with various sugars in the diet, they do not have a variable effect on the amount of
7 26
Calcagno and Rubin
water required for renal excretion unless they appear in the urine. The above conclusions regarding unobligated renal water in the newborn infant during feeding with various formulas are predicated upon an assumed optimal renal concentrating capacity of approximately 700 mOsm. per liter and when extra renal water losses are not excessive. I t is known, however, that some full-term newborn infants and older premature infants may concentrate to much higher levels? I t is also known that urinary concentrating capacity may be influenced by variations in the intake of dietary protein 16, 1~; it is reduced on a low protein intake and increased on a high one. Infants beyond the second month of life may give concentrations to adult levels of 1400 mOsm. per liter? U n d e r these circumstances when renal concentrating capacity is greater, the obligatory renal water volume will be smaller, resulting in a larger volume of expendable renal water. I n those instances where extra renal water losses are larger than usual, there will be a gradual diminution o f unobligated renal water, and finally body stores will be drawn upon to meet the obligatory renal water needs. Cooke and co-workers ~3 and Darrow and colleagues x4 have demonstrated that the extra renal water losses may be large when the infant is exposed to high environmental temperatures. There are conditions which may result in reduced renal concentrating capacity such as severe dehydration, potassium deficiency, infections, sickle cell anemia, primary renal disorders, etc. Under these circumstances, obligatory renal water demands would increase, and, when concentrating capacity is greatly reduced, the stores of body water m a y be depleted for renal solute excretion. CONCLUSIONS 1. Full-term infants 2 to 4 days of age fed whole cow's milk, low osmolar milk, modified cow's milk, and human milk ad libitum and kept in an environment of 70 ~ to 80 ~ F., had a urine volume which meas-
lune 1960
ured approximately 25 per cent of the fluid intake. Fifty-seven per cent of the urinary water excretion of the infants fed whole cow's milk was expendable water; the highes t amount of expendable water (82 per cent) was found in the infants fed low osmolar milk. These data indicate that in normal infants in this age period when extra renal water losses are not excessive, the ad libitum intake of the formulas studied do not impose a drain on the stores of body water. 2. I n the 6- to 9-day-old full-term infants fed transitional h u m a n milk ad libitum, the urinary volume was approximately 45 per cent of the fluid intake; the intake of these infants was considerably larger than that of the 2- to 4-day-old infants. On this feeding, the expendable renal water was 82 per cent of the total urine volume. 3. Premature infants 10 to 20 days of age who weighed between 1.4 and 2.1 kilograms and who were fed low osmolar milk, excreted 52 per cent of their fluid intake, 86 per cent of which was expendable urinary water. 4. Even though a large proportion of the urinary water excretion of full-term newborn infants and 10- to 56-day-old premature infants when fed a formula of whole cow's milk is expendable, the margin of safety with such a formula with regard to water requirements would be greatly reduced w h e n extra renal water losses are excessive. We, therefore, do not recommend the feeding of undiluted whole cow's milk at this age period.
REFERENCES 1. Pratt, E. L., and Snyderman, S. E.: Renal
Water Requirements of Infants Fed Evaporated Milk With and Without Added Carbohydrate, Pediatrics l h 65, 1953. 2. Colle, E., Ayoub, E., and Raile, R.: Hypertonic Dehydration (Hypernatremia). The Role of Feedings High in Solutes, Pediatrics 22: 5, 1958. 3. Pratt, E. L., Bienvenu, B., and Whyte, M. M.: Concentration of Urine Solutes by Young Infants, Pediatrics 1: 181, 1948. 4. Report of Committee on Nutrition: Water Requirements in Relation to Osmolar Load as It Applies to Infant Feeding, Pediatrics 19: 339, 1957.
Volume 56 Number 6
5. Thomson, J.: Observations on the Urine of the Newborn Infant, Arch. Dis. Childhood 19: 169, 1944. 6. Hansen, J. D. L., and Smith, C. A.: Effects of Withholding Fluid in the Immediate Postnatal Period, Pediatrics 12: 99, 1953. 7. Hill, A. V.: Thermal Method of Measuring Vapour Pressure of Aqueous Solution, Proc. Roy. Soc. London A. 127: 9, 1930. 8. Baldes, E. J.: Micromethod of Measuring Osmotic Pressure, J. So. Inst. 11: 223, 1934. 9. Calcagn% P. L., and Rubin, M. I.: Effect of Added Carbohydrate on Growth, Nitrogen Retention and Renal Water Excretion in Premature Infants, Pediatrics 13: 193, 1954. 10. Spector, W. S.: Handbook of Biological Data, Philadelphia, 1956, W. B. Saunders Company, p. 50. 11. Cuthbertson, D. P., and Munro, H. N.: Protein-Saving Effect of Carbohydrate and Fat When Superimposed on Diet Adequate for Maintenance, Biochem. J. 31: 694, 1937.
Water requirements for renal excretion
727
12. Gamble, J. L.: Physiological Information Gained From Studies on Life Raft Ration, Harvey Lect. 42: 247, 1946 to 1947. 13. Cooke, R. E., Pratt, E. L., and Darrow, D. C.: Metabolic Response of Infants to Heat Stress, Yale J. Biol. & Med. 22: 227, 1950. 14. Darrow, D. C., Cooke, R. E., and Segar, W. E.: Water and Electrolyte Metabolism in Infants Fed Cow's Milk Mixture During Heat Stress, Pediatrics 14: 602, 1954. 15. Calcagno, P. L., and Rubin, M. I.: Effect of Dehydration Produced by Water Deprivation, Diarrhea and Vomiting on Renal Function in Infants, Pediatrics 7: 328, 1951. 16. Epstein, F. H., Kleeman, C. R., Pursel, S., and Hendrikx, A.: The Effect of Feeding Protein and Urea on the RenM Concentrating Process, J. Clin. Invest. 36: 635, 1957. 17. Edelmann, C. M., Troupkou, V., and Barnett, H. L.: Renal Concentrating Ability in Newborn Infants, Fed. Proc. 18: 637, 1959.
PEDIATRICS JUNE
1960
V o l u m e 56
Number 6
Water requirements for renal excretion in full-term newborn infants and premature infants fed a variety Philip L. Calcagno~ M.D., ~ and Mitchell I. Rubin, M.D. BUFFALO~
N.
Y.
as end products of protein metabolism and electrolytes. 1"4 There is sufficient documentation to show 5, 6 that the average renal concentrating capacity in healthy, newborn premature infants and in full-term infants in the first few weeks of life is below that which is obtained later in life. For the purposes of this. study, it is assumed to be 700 mOsm. per liter at a specific gravity approximating 1.021; this is about half the maximal renal concentrating capacity of the mature adult (1400 mOsm. per liter). Under usual circumstances of health and when the concentration of the solute load demanding renal excretion is below the maximal Concentrating capacity of the kidney, "expendable" renal water is available. Under
C u g g ~ N w L Y much emphasis is placed on the construction of infants' formulas with regard to their content of protein and solutes which are ultimately excreted by the kidney From the Statler Research Laboratories o[ the Children's Hospital of Buffalo and the Department of Pediatrics, University o[ Buffalo School o/Medicine. With the technical assistance of Dr. Phatick Mukherfi, Mary K. Wypych, and Margaret M. Stubbins and with the nursing assistance o[ Alberta Weaver, Sara PanzareUa, and Charlotte Garrett. Aided by grants from Ross Laboratories, Columbus, Ohio, and by Research Grant H-2290, National Institutes of Health, United States Public Health Service. ~Address, Department o[ Pediatrics, Tha University of Buffalo School o[ Medicine, 219 Bryant Street, Buffalo 22, N. Y.
717
7 18
Calcagno and Rubin
June 1960
Table I. Average values* per liter Sodium (mEq.)
Formula
Colostrum Transitional breast milk Low osmolar milk (Similac) Modified cow's milk Whole cow's milk
23.8 11.2 11.6 17.5 23.1
Potassium (mEq.)
Chloride (mEq.)
18.8 19.3 18.2 24.5 36.2
28.7 15.4 11.9 22.9 32.9
MiUiosmols
285 297 236 249 286
Nitrogen (Gin.)
5.4 3.0 2.1t 2.9 5.1
*Average values of all samples prepared in milk laboratory a n d obtained from mothers by hand expression (colostrum and transitional breast milk). t W h e n dilution of Similac is prepared in biochemical laboratory instead of in routine milk laboratory, this value is 2.7.
these circumstances, the solute load of the formula does not place a demand upon body water which m a y result in dehydration. In the presence of severe dehydration, whether produced by deprivation or loss of water or by fever or high environmental temperature, a maximal urinary concentration m a y be expected with a decrease in expendable renal water. Thus with formulas resulting in a urine osmolar concentration significantly below 700 mOsm. per liter in the newborn and in the very young infant, a surplus of water above that obligated for solute excretion must exist. Under such circumstances it can be assumed that the formula being given the infant is satisfactory from the viewpoint of the renal water requirement. In instances where urinary concentrating capacity is greater than 700 mOsm. per liter, the amount of obligated renal water would be less; in circumstances where the concentrating capacity is below 700 mOsm. per liter, the obligated renal water would be increased. This study is limited to full-term infants between the ages of 2 to 4 days and 6 to 9 days and to premature infants 10 to 56 days of age. These infants were fed a variety of formulas which contained different amounts of solutes demanding renal excretion to determine whether the resulting urine osmolarity was below the assumed maximal concentrating capacity for these infants. METHODS
AND
PROCEDURE
The urinary osmolar excretions during the second to fourth days of life on various formulas were studied in 39 full-term newborn
infants. The compositions of the formulas used are listed in Table I. Fourteen infants were fed modified whole cow's milk; 9, hum a n milk (colostrum); 4, equal parts of evaporated milk and water; and 12, low osmolar milk formulas.* Three additional fullterm newborn infants were studied during the sixth to ninth days of life while on human breast milk (transitional).t Seven premature infants varying in ages from 10 to 56 days were fed either low osmolar milk or equal parts of evaporated milk and water. In the bottle-fed infants, the intake of formula was determined by the difference in bottle weight before and after feeding. In the breast-fed infants, the difference in the infant's weight before and after feeding was recorded as the intake. T w o consecutive, separate 24-hour collections of urine were made for each period of study. T h e urine was collected in a container surrounded by ice to minimize bacterial growth. Daily analyses of the formulas were made with regard to their osmolar, sodium, potassium, chloride, and nitrogen contents. Osmotic pressures were determined with the Hill-Baldes apparatus#, s Sodium and potassium concentrations were determined with a Norelco flame photometer. Chloride was determined b y the method of Sendroy modified by Van Slyke and Heller, and nitrogen *Similac, Ross Laboratories. "~The formulas used in this study were prepared as follows : Whole cow's milk --150.0 ml. evaporated milk, 150.0 ml. water. Low osmolar milk (similac, Ross Laboratories)--8.5 Gin. dry milk, 60.0 ml. water. Modified cow's milk --150.0 ml. evaporated milk, 16.0 Gm. Dextri-Maltose No. 1, 480.0 ml. water.
Volume 56 Number 6
Water requirements [or renal excretion
was determined by a Micro-Parnass-Wagner apparatus with the use of a 2 per cent boric acid solution with mixed indicator (bromcresol green and methyl red) and titration of the ammonia with sulfuric acid. RESULTS
Table I lists the average composition of the various formulas used in the study. The data are derived from direct determinations. The values shown represent averages obtained from analyses of samples of the daily formulas as prepared in the hospital milk laboratory. It should be noted that the nitrogen value for the low osmolar milk is lower in the preparation made in the routine milk laboratory than the one prepared in the biochemical laboratory. The modified cow's milk formula fed the newborn infant was dilute when compared with the formula made of whole cow's milk. Whereas the carbohydrate in the various formulas adds to the total osmolar intake, it is not excreted in the urine and thus does not contribute to the total of solutes requiring renal excretion. The substances in the formula which contribute mainly to the renal solute load are derived from protein and electrolytes; the excreted end product of protein metabolism is largely urea, which in feedings of whole cow's milk consists of about 40 to 60 per cent of the total osmolar excretion. 9 Low concentrations of osmols as derived from
7 19
protein and electrolytes are found in transitional breast milk 1~ and are closely comparable to those of the low osmolar milk formulas used in this study; conversely, the whole cow's milk formula and colostrum have higher osmolar concentrations. T h e osmolar values of the modified cow's milk formula was between these two feedings. The actual osmolar intakes are listed in separate tables. Table I I lists the intake and urinary output of fluid, electrolyte, nitrogen, and total osmols in full-term infants fed a formula of equal parts of evaporated milk and water. Each infant had a larger intake on the second day of the study, which is a reflection of the larger intake as the infant aged. The average intake for the 2 days was 106 ml. per kilogram per day. The average urine output of these infants was 24 ml. per kilogram per day, with an average osmolar excretion of 7.6 mOsm. per kilogram per day. It should be noted that with the increased intake on the second day of the study, there is an associated increase in osmolar excretion. There is, however, no consistent increase in urinary concentration of osmoles. T h e highest osmolar concentration on any given day was 449 mOsm. per liter and the lowest was 184 mOsm. per liter, with an average of 318 mOsm. per liter for the group. These values are well below those found by Hansen and Smith s in full-term
Table II. Intake and urinary osmolar excretions in full-term infants fed whole cow's milk ~
Chloride Nitrogen Potassium Fluid Urine Sodium Urine (mEq.) (rag.) (mEq.) Milliosmols (mOsWeight Age intake output (mEq.) tlent (kg.) (days) (ml.) (ml.) IntakelOutput IntakelOutput Intake I Output Intake I Output intake[ Output rn./L.~ ea-
L.A.
4.1
3 4
73 110
11 22
1.69 2.54
0.14 0.17
2.58 3.95
0.39 0.91
2.31 3.58
0.19 0.32
361 534
71 107
20 31
3.8 6.2
355 280
P.R.
4.2
4 5
86 141
18 48
1.97 3.27
0.46 2.10
3.00 5.06
0.70 1.64
2.70 4.72
0.65 2.56
447 683
80 251
24 44
5.4 18.0
306 371
M.O.
2.8
3 4
75 155
21 35
1.74 3.57
0.20 1.32
2.72 5.63
0.62 0.32
2.36 4.89
0.51 1.66
391 820
57 147
21 45
3.9 11.0
184 304
T.E.
2.8
2 3
75 129
8 31
1.74 2.98
0.34 0.31
2.70 4.63
0.33 0.97
2.60 4.46
0.40 0.54
402 670
63 154
21 38
3.7 9.0
449 291
Average 106 24 2.43 *Per kilogram of body weight per day.
0.63
3.78
0.74
3.45
0.85
539
116
31
7.6
318
3.0
3.4
2.9
2.3
3.3
3.3
2.8
3.3
3.2
3.2
3.3
B.R.
M.A.
S.T.
Q.U.
B. R . Y .
M.O.
MeD.
L. A . N .
B. O . Y .
A.L.
P.E.
2 3
2 3
2 3
2 3
2 3
4 5
2 3
4
3 4
2 3
4 5
3 4
Age (days)
~Per kilogram of body weight per day.
Average
2.9
H. A . L .
Patient
Weight (kg.) 1 5 25 37 10 16 38 63 78 20 11 41 62 18 35 4 4 30 36 20 37 11 7 27
83 98
133 173
62 91
126 135
222
73 96
146 148
52 89
76 83
110 163
137 169
120 127
118
1.30
1.39 .
1.59 1.96
1.28 1.89
0.88 0.97
0.60 1.04
1.60 1.57
0.86 0.99
.
1.71 1.49
0.73 1.05
1.52 1.83
0.99 1.22
0.20
0.04 .
0.14 0.16
0.09 0.07
0.06 0.05
0.06 0.04
0.12 0.80
0.08 0.07
.
0.38 0.75
0.24 0.19
0.20 0.56
0.01 0.11
.
. 2.20
2.18
2.49 2.88
2.00 2.97
-
0.94 1.65
2.68 2.55
1.41 1.66
.
3.03 2.48
1.26 1.70
2.45 3.18
1.52 2.01
.
0.40
0.13 .
0.34 0.37
0.39 0.50
-
0.44 0.46
0.33 0.62
0.22 0.08
.
0.68 1.01
0.21 0.33
0.31 0.34
0.02 0.10
.
1.30
. .
1.63 2.01
1.31 1.94
0.90 0.99
0.62 1.06
1.59 1.72
1.15 1.16
1.79 1.61
0.78 1.08
1.52 1.80
1.00 1.17
.
0.20
.
0.10 0.07
0.09 0.22
0.09 0.10
0.44 0.49
0.33 0.43
0.12 0.09
0.42 0.63
0.39 0.25
0.15 0.41
0.01 0.03
. .
258
.
-
-
-
93 197
261 265
188 204
364
315 308
-
209 432
-
77
-
-
-
81 112
74 106
70 46
89
81 50
-
81 61
-
27
29 30
22 28
19 27
27 28
14 17
32 34
19 22
51
42 30
15 23
31 43
22 25
3.2
1.5 0.8
3.0 3.8
3.0 3.6
2.0 1.8
4.6 7.9
3.7 4.3
1.9 2.2
6.8
157
141 112
150 102
101 101
465 492
252 225
90 70
91 199
87
117 100
175
2.7 4.4 6.3
213
77 79
117 170
Urine (mOsm./L.)
2.1
2.0 3.0
0.1 0.9
Potassium Chloride Fluid Urine Nitrogen (mg.) Milliosrnols (rnEq.) (mEq.) intake output Sodium (mEq.) Intake IOutput Intake [Output Intake IOutput Intake [Output Intake [ Output (ml.) (ml.)
Table I l L Intake and urinary osmolar excretions in full-term infants fed a low osmolar milk*
ro o~
3"
g~
g~
gl
0~
g~
Volume 56 Number 6
infants at this age during thirsting (approximately 600 mOsm. per liter). Table I I I lists the intake and urinary o.utput of a similar group of substances presented in Table I I for full-term infants fed a low osmolar milk. The average total intake of this formula is slightly larger than that of whole cow's milk: 118 ml. per kilogram per day with an average osmolar excretion of 3.2 mOsm. per kilogram per day, about half o$ that observed with the infants fed equal parts of evaporated milk and water. The urinary osmolar concentrations average 157 mOsm. per liter; the lowest value is 77 mOsm. per liter and the highest is 492 mOsm. per liter. The average urinary concentration of 157 mOsm. per liter is significantly below that of infants fed equal parts of evaporated milk and water, 318 mOsm. per liter (p < 0.05). As with whole cow's milk feedings, these urinary osmolar values are considerably below the maximal renal concentrating capacity of normal full-term infants. Table I V lists similar data for intake and urinary output of full-term infants fed a modified cow's milk formula. The average intake was 107 ml. per kilogram per day with an osmolar excretion of 5.2 mOsm. per kilogram per day. The average urinary osmolar concentration was 204 mOsm. per liter, which is significantly different from that in the infants fed whole cow's milk. The lowest value in this group is 114 mOsm. per liter and the highest is 446 mOsm. per liter. These values are also well under the maximal renal concentrating capacity of the normal fullterm infant for this age. Table V lists similar data for intake and urinary output for full-term infants fed human breast milk (colostrum). It is evident that the average total intake is significantly smaller in these infants than in the artificially fed infants; the average intake is 72.0 ml. per kilogram per day, with an osmolar excretion of 3.2 mOsm. per kilogram per day. The average urinary osmolar concentration was 273 mOsm. per liter, with a high value of 408. Again, these values are considerably below the maximal renal concen-
Water requirements for renal excretion
721
trating capacity for an infant of this age. Table V I lists similar data for intake and urinary output of full-term infants fed human breast milk (transitional). The average intake is 162 ml. per kilogram per day, the largest of all the groups. These infants were 3 to 4 days older than the infants given the feedings listed above. The average osmolar excretion is 8.8 mOsm. per kilogram per day. The average osmolar urinary concentration of 122 mOsm. per liter is the lowest of the entire group. The lowest value obtained in this group is 77 and the highest is 194. The second part of this study presents data on the patterns of excretion of premature infants from 10 to 56 days of age, whose weights varied from 1.4 to 2.1 kilograms. Table V I I lists the intake and urinary output of fluid, electrolytes, nitrogen, and osmols in premature infants fed evaporated milk and water. The data in this chart come from a previous study. 9 The infants were maintained on this diet from 5 to 7 days prior to a 6-day study period. The data presented are average daily values. The average total intake is 149 ml. per kilogram per day, with an average urinary osmolar excretion of 26.5 mOsm. per kilogram per day, the average urinary concentration is 410 mOsm. per liter. These urinary o smolar concentrations are considerably below the maximal renal concentrating capacity of premature infants of this age. Table V I I I lists similar data for intake and urinary output of premature infants fed a low osmolar milk formula. The intake was 168 ml. per kilogram per day, with an average o.smolar output of 8.7 mOsm. per kilogram per day, and an average urinary osmolar concentration of 104 mOsm. per liter, with a low of 81 and a high of 147. These values are well below the maximal renal concentrating capacity for these infants. DISCUSSION
The nutritive value of the infant's formula is of paramount consideration in feeding. The purpose of this study, however, was primarily to determine whether constituents
2.3
2.3
3.2
2.9
2.8
2.8
3.2
2.3
3.2
2.8
3.4
3.3
3.2
McK.
T. I-I.
M.U.
W.H.
B.E.
B. E. C.
B.O.
H.A.
E.U.
j.A.
S.E.
L.I.
D.E.
2 3
2 3
107
109 141
105 13,3
66 102
31
13 20
35 67
20 22
3
2 3
6 19
7O
86
2
46 55
5 31
24 15
7 13
104 148
94 106
54 116
40
107 154
27
51 40
37 66
37 32
41 74
9
86 104
141 141
122 131
124 163
36
66 80
3 4
3 4
3 4
2 3
3
2
2 3
3 4
2 3
3 4
2
Age (days)
Average ~Per kilogram of body weight per day,
3.3
Weight (kg.)
S.I.
Patient
2.00
1.93 2.70
1.84 2.48
1.14 1.92
1.22 1.50
1.15 1.40
1.83 1.68
1.64 1.86
0.81 2.11
2.01 3.44
1.14 1.81
2.81 2.63
2.38 2.54
2.48 2.93
0.49
0.40
0.08 0.14
0.35 0.73
0.26 0.26
0.12 0.25
0.04 0.15
0.38 0.82
0.04 0.43
0.48 0.39
0.24 0.21
0.46 0.20
0.16 0.66
0.62 0.55
0.49 0.96
-
2.80
2.76 4.05
2.55 3.81
1.59 2.50
2.10
1.61 1.95
2.59 3.62
2.30 2.60
1.18 3.20
2.44 4.05
2.07 2.54
3.71 3.32
2.93 3.13
3.12 3.98
0.84
0.60
0.15 0.12
0.72 0.67
0.43 0.46
0.56
0.13 0.19
0.64 0.99
0.07 0.86
0.50 0.26
0.48 0.33
0.92 0.88
0.63 1.12
0.66 0.64
0.74 1.11
-
2.40
2.51 3.22
2.39 3.06
1.52 2.32
1.59 1.96
1.50 1.73
2.39 3.39
2.15 2.43
1.23 2.66
1.61 3.91
1.23 2.37
3.35 3.40
3.01 3.04
3.10 3.60
1.0'9
0.50
0.14 0.20
0.21 0.52
0.30 0.20
0.06 0.27
0.20 0.21
0.46 0.99
0.06 0.89
0.41 0.23
0.40 0.30
0.87 0.60
0.56 1.31
0.77 0.74
0.25 0.74
-
116
-
409
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
98 74
-
-
-
185 300
130 188
81 122
400 419 568 482
70 169
-
381 535
-
5.2
3.1 27
2.4
38
10.5
5.6
4.0
3.1
5.8
2.5
2.6
2.1
7.2
5.2
4.4
1.7
2.8
5.1
3.6
5.8
6.2 5.0
6.7 11.1
5.3 7.4
5.1 9.9
3.9
24
36
23
25
16
21
19
22
16
37
26
29
20
32
13
40
27
22 28
39 34
34 35
32 41
8
204
189 156
162 158
158 184
446 302
299 201
114 131
323 145
212 180
145 132
122 124
180 169
144 230
125 134
454
Chloride Fluid I Urine Sodium (mEq.) Potassium (mEq.) (mEq.) Nitrogen (mg.) Milliosmols Urine intake output (ml.) (ml.) Intake t Output Intake l Output Intake ]Output Intake IOutput Intake [Output (mOsm./L.)
Table IV. Intake and urinary osmolar excretions in full-term infants fed a modified evaporated milk and carbohydrate formula e
o
7,
ct~
t~
ro
Volume 56
Table
V.
Number 6
Intake
and
Water requirements [or renal excretion
urinary
723
o s m o l a r e x c r e t i o n in f u l l - t e r m i n f a n t s fed h u m a n
milk (colostrum) *
9 9 Sodium Potassium Chloride Nitrogen Urine Fluzd Umne " E ' Milliosmols (mOs(mEq.) (mEq.) (rag.) Weight Age ]intake]output I (m:~q.) Patient (kg.) (days) (ml.) (ml.) Intake[Output Intake[Output IntakelOutput IntakelOutput IntakelOutput m./L.) A.V.
3.2
2 3 4
33 63 66
3 9 18
0.80 1.49 1.56
0.07 0.22 0.54
0.63 1.19 1.23
. . .
G.I.
39
3 4
28 81
16 9
0.67 1.93
0.08 0.09
0.53 1.53
0.08 0.15
0.53 2.33
0.21 0.04
-
L.Y.
3.3
3 4
36 82
5 4
0.87 1.95
0.04 0.04
0.74 1.56
0.83 0.62
0.68 2.35
0.03 0.05
S.T.A.
3.3
3
64
46
1.50
-
0.90
-
-
K. E . L .
2.9
2
48
4
1.15
-
0.79
-
M. A . R .
2.0
2 3
I00
7 34
2.38 -
0.11 0.30
-
T.O.
3.2
4 5
103 134
32 12
1.96 2.36
0.16 0.19
S.H.
2.8
3 4
96 73
19 32
2.61 1.75
3
78
34
72
18
G.R.
2.3
Average
. . .
. . .
. . .
. . .
9 18 19
1.7 4.5 6.5
361
-
8 23
3.4 0.9
211 97
174 -
-
11 24
1.3 1.1
242 278
-
340
59
-
3.0
70
-
-
258
25
-
1.2
328
-
2.87 -
0.08 0.30
864 -
51 139
29 28
2.7 7.0
408 208
1.85 2.41
0.28 0.13
-
-
405 541
78 35
30 39
4.1 2.1
127 170
0.27 0.33
1.44 0.88
0.22 0.29
.
1629 .
269
28 21
4.3 4.6
223 -
2.05
-
2.56
0.39
.
1.60
0.20
1.30
0.30
1.80
.
. .
.
0.12
.
.
602
. 94
143 22
3.2
273
~Per kiloglam of body weight per day.
T a b l e V I . I n t a k e a n d u r i n a r y o s m o l a r e x c r e t i o n in f u l l - t e r m i n f a n t s f e d t r a n s i t i o n a l human milk*
9 Urzne . Sodium Fluzd Weight Age intake output (mEq.) Patient (kg.) /days)(ml.) (ml.) Intake Output L.A.S
3.2
P. O . S .
3.4
G. L . D .
3.2
6 7
117 152
86 72
7
79
6 7
244 220 162
Average
Potassium (mEq.)
I
Nitrogen (me.)
Chloride (mEq.)
MilIiosmols
Intake]Output IntakelOutput ZntakelOutput 1I~7~kdOutput
Urine (mOsm./L.)
2.2 2.4
1.0 0.7
342 444
167 104
34 44
14.1 10.4
164 145
0.3
1.4
0.l
335
90
23
5.0
194
0.6 0.7
5.2 5.1
0.6 1.2
703 635
63 112
78 64
5.9 8.6
77 80
1.1
3.2
0.7
492
107
49
8.8
122
1.5 2.1
3.4 2.2
26
1.0
70 108
2.0 1.7
72
1.7
~Per kilogram of body weight per day.
in
formulas
would
put
commonly undue
offered
demands
to
infants
on body water
do not become
a part
of t h e o s m o l a r l o a d
excreted in the urine. On
the other hand,
for the r e n a l e x c r e t i o n of the m e t a b o l i c e n d
ingested but nonretained
p r o d u c t s o f t h e diet. A m o n g
p o se d largely to u r e a a n d o t h e r o s m o t i c a l l y
young
infants
p r o t e i n is d e c o m -
t h e r e is a v a r i a b i l i t y i n t h e c a p a c i t y of t h e
active substances; their excretion by the kid-
k i d n e y to e x c r e t e a solute load at a given
ney requires water. The
rate
f o r m u l a w h i c h are not r e t a i n e d also exert a n
and
concentration.
In
the
course
metabolism, the absorbed carbohydrate
of and
fat in the diet are utilized by the body and
osmotic effect and excretion. Thus
e l e c t r o l y t e s of t h e
require water
the protein
for renal
and electrolyte
724
Calcagno and Rubin
June 1960
T a b l e V I I . I n t a k e a n d u r i n a r y o s m o l a r excretion in p r e m a t u r e infants fed whole cow's milk*
Fluid I Urine Sodium Potassium C h l o r i d e Nitrogen I Pa- Weight Age intake output (mEq.) (mEq.) (mEq.) (rag.) Milliosmols (mOsUrine tlent (kg.) (days) (ml.) (ml.) IntakelOutput IntakelOutput lntakelOutput lntakelOutput ~ t ra./L.) B.R. C.L. B.A.
2.1 1.8 1.6
56 38 28
Average
151 146 150
67 59 68
4.50 4.38 4,50
2.78 2.59 1.07
5.28 2.98 5 . 1 1 2.43 5.25 2.69
-
-
900 880 900
475 457 403
50 48 49
36.2 24.2 19.1
540 410 281
149
65
4.45
2.48
5 . 2 1 2.70
-
-
890
445
49
26.5
410
*Per kilogram of body weight per day.
T a b l e V I I I . I n t a k e an d u r i n a r y osmolar excretion in p r e m a t u r e infants fed a low osmolar milk*
Nitrogen Fluid Urine[ Sodium Potassium Chloride e (mg.) Milliosmols U~in (mEq.) (mEq.) (mEq.) (mOs. Pa- Weight Age intake output tient (kg.) (days) (ml.) (ml.) lntakelOutput IntakelOutput IntakelOutput IntakelOutput IntakelOutput m./L.~ G.H.
1.4
20 21
161 186
90 91
3,83 4,43
0.66 0.51
3.03 3.50
2.36 4.16
4.62 5.34
1.20 0.94
86 100
77 104
46 54
10.0 9.7
112 106
K.E.
1.4
15 16
103 113
76 89
1,28 1,33
0.35 0.41
2.26 2.48
1.69 1.89
2.01 1.87
0.94 0.91
256 286
86 101
33 33
6.8 8.0
90 90
C.L.
2.1
14 15
143 172
49 62
1,63 2.09
0.80 0.89
3.26 3.71
1.14 1.83
3.46 2.70
1.05 1.35
357 441
73 102
43 49
5.9 9.1
121 147
L.A.
1.9
10 11
229 234
113 130
2,66 2.72
0.27 0.39
5.22 5.76
2.63 2.79
3.84 3.98
1.41 1.45
381 400
97 120
66 67
9.2 10.9
81 84
168
88
2.50
0.54
3.65
2.31
3.45
1.16
288
95
49
8.7
104
Average
*Per kilogram of body weight per day.
T a b l e I X . T h e av erag e intake of the respective formulas
Age 2 2 2 2 6 10 28
to to to to to to to
4 days 4 days 4 days 4 days 9 days 20 days 56 days
I
I (full-term) (full-term) (full-term) (full-term) (full-term) (premature) (premature)
contents of t h e diet are the essential substances w h i c h m u s t be considered in estim a t i n g t h e w a t e r needs of the i n f a n t for renal excretion. T h e d a t a h e r e presented i n d i c a t e t h a t the f u l l - t e r m n e w b o r n a n d older p r e m a t u r e i n f a n t w i t h an assumed r e na l c o n c e n t r a t i n g c a p a c i t y of 700 m O s m . p e r liter in an e n v i r o n m e n t of 70 ~ to 80 ~ F. are qu i t e capable of e x c r e t in g the renal
Milk feedings Whole cow's milk Low osmolar milk Modified cow's milk Colostrum Transitional milk Low osmolar milk Whole cow's milk
I
ml./kg./day 106 118 107 72 162 168 149
solutes derived f r o m a v a r i e t y of formulas, w i t h o u t r e q u i r i n g additional fluid i n t a k e or d r a w i n g u p o n stores of body water. T a b l e I X indicates the a v e r a g e intake of t h e respective formulas. Fig. 1 is a composite of the d a t a presented in T a b l e s I I to V I I I . T h e a m o u n t designated as obligatory renal w a t e r in the figure is p r e d i c a t e d on the ass u m p t i o n t h a t these infants can co n cen t r at e
Volume 56 Number 6
their urine to 700 mOsm. per liter. The columns depict the urine output as a percentage of the intake. Each block represents an average of the percentage of urinary water excretion of all the infants in a single group. It is interesting that the renal water excretion in the full-term infants on the various diets was approximately 25 per cent of the intake (23 to 29 ml. per kilogram per day). Hansen and Smith 6 showed that infants of the same age, when thirsted, excreted about 10 to 15 ml. per kilogram per day. In the older full-term and premature infants, the urinary volume was 44 to 52 per cent of the intake. In these infants the actual total fluid intake per kilogram of body weight was larger than that of the younger ones. The figures in the solid portion of each column represent the amount of water in the urine unobligated by the excreted solutes (expendable renal water), indicating that this amount of water could have been reabsorbed by the renal tubules if needed for body economy. Thus in newborn infants fed whole cow's milk ad libitum with an average intake of 106 ml. per kilogram per day at 66 calories per kilogram per day, there was no drain upon body fluids and the renal excretion of water was beyond that demanded for the excretion of solutes. Those infants ingesting formulas with the smallest amount of osmols requiring renal excretion had a larger volume of expendable renal water. With the older full-term breastfed infants ingesting an average of 162 ml. per kilogram per day, containing 105 calories per kilogram per day, there was a larger amount of unobligated water in the urine which could have been saved by the body if needed. In the 2 groups of older premature infants, those on the low osmolar milk had an average intake of 168 ml. per kilogram per day, while those on whole cow's milk had an average intake of 151 ml. per kilogram per day. There was a larger amount of unobligated or expendable renal water in the infants fed the low osmolar milk than in those fed whole cow's milk, yet even in the latter group, 45 per cent of the renal water was unobligated.
Water requirements for renal excretion
PERCENT 3 0 2 0 10
0
OF
725
INTAKE
10 2 0 3 0 4 0 5 0 WHOLE COWS MILK LOW OSMOLAll MILK
2 - 4 DAY OLD FULL TERM INFANTS
MODIFIED COWS MILK COLOST|UM
6 - 9 DAY OLD FULL T E R M INFANTS
TIANSITIOHAL MILK
LOW OSMOLAll MILK
10-56 DAY OLD PREMATURE INFANTS
WHOLE COWS MILK
OBL RENAL WATER
Fig. I. The number in the solid area o f each column represents the percentage of expendable renal water of the total urine output.
It must be emphasized that we do not recommend the feeding of undiluted, unmodified cow's milk to newborn infants. The margin of safety with such a formula with regard to the water requirements could be greatly reduced under adverse circumstances, when extra losses of renal water may be excessively large. In a previous study in premature infants 9 and in keeping with other data in the literature, 11, 12 it was demonstrated that the addition of a carbohydrate to an isonitrogenous diet increases the nitrogen retention and decreases the urea nitrogen excretion as well as the total renal osmolar excretion. These latter studies were short-term experiments, as have been most of the other studies on the protein-sparing effect of carbohydrate feedings. Nevertheless, they indicate that the addition of carbohydrate to the formula may be of value in sparing water during periods when the water balance of the individual is critical, when there may be depression of renal concentrating capacity, when there is a decreased intake of fluid or excessive losses of water. Whereas there is a variation in the total osmolar intake with various sugars in the diet, they do not have a variable effect on the amount of
7 26
Calcagno and Rubin
water required for renal excretion unless they appear in the urine. The above conclusions regarding unobligated renal water in the newborn infant during feeding with various formulas are predicated upon an assumed optimal renal concentrating capacity of approximately 700 mOsm. per liter and when extra renal water losses are not excessive. I t is known, however, that some full-term newborn infants and older premature infants may concentrate to much higher levels? I t is also known that urinary concentrating capacity may be influenced by variations in the intake of dietary protein 16, 1~; it is reduced on a low protein intake and increased on a high one. Infants beyond the second month of life may give concentrations to adult levels of 1400 mOsm. per liter? U n d e r these circumstances when renal concentrating capacity is greater, the obligatory renal water volume will be smaller, resulting in a larger volume of expendable renal water. I n those instances where extra renal water losses are larger than usual, there will be a gradual diminution o f unobligated renal water, and finally body stores will be drawn upon to meet the obligatory renal water needs. Cooke and co-workers ~3 and Darrow and colleagues x4 have demonstrated that the extra renal water losses may be large when the infant is exposed to high environmental temperatures. There are conditions which may result in reduced renal concentrating capacity such as severe dehydration, potassium deficiency, infections, sickle cell anemia, primary renal disorders, etc. Under these circumstances, obligatory renal water demands would increase, and, when concentrating capacity is greatly reduced, the stores of body water m a y be depleted for renal solute excretion. CONCLUSIONS 1. Full-term infants 2 to 4 days of age fed whole cow's milk, low osmolar milk, modified cow's milk, and human milk ad libitum and kept in an environment of 70 ~ to 80 ~ F., had a urine volume which meas-
lune 1960
ured approximately 25 per cent of the fluid intake. Fifty-seven per cent of the urinary water excretion of the infants fed whole cow's milk was expendable water; the highes t amount of expendable water (82 per cent) was found in the infants fed low osmolar milk. These data indicate that in normal infants in this age period when extra renal water losses are not excessive, the ad libitum intake of the formulas studied do not impose a drain on the stores of body water. 2. I n the 6- to 9-day-old full-term infants fed transitional h u m a n milk ad libitum, the urinary volume was approximately 45 per cent of the fluid intake; the intake of these infants was considerably larger than that of the 2- to 4-day-old infants. On this feeding, the expendable renal water was 82 per cent of the total urine volume. 3. Premature infants 10 to 20 days of age who weighed between 1.4 and 2.1 kilograms and who were fed low osmolar milk, excreted 52 per cent of their fluid intake, 86 per cent of which was expendable urinary water. 4. Even though a large proportion of the urinary water excretion of full-term newborn infants and 10- to 56-day-old premature infants when fed a formula of whole cow's milk is expendable, the margin of safety with such a formula with regard to water requirements would be greatly reduced w h e n extra renal water losses are excessive. We, therefore, do not recommend the feeding of undiluted whole cow's milk at this age period.
REFERENCES 1. Pratt, E. L., and Snyderman, S. E.: Renal
Water Requirements of Infants Fed Evaporated Milk With and Without Added Carbohydrate, Pediatrics l h 65, 1953. 2. Colle, E., Ayoub, E., and Raile, R.: Hypertonic Dehydration (Hypernatremia). The Role of Feedings High in Solutes, Pediatrics 22: 5, 1958. 3. Pratt, E. L., Bienvenu, B., and Whyte, M. M.: Concentration of Urine Solutes by Young Infants, Pediatrics 1: 181, 1948. 4. Report of Committee on Nutrition: Water Requirements in Relation to Osmolar Load as It Applies to Infant Feeding, Pediatrics 19: 339, 1957.
Volume 56 Number 6
5. Thomson, J.: Observations on the Urine of the Newborn Infant, Arch. Dis. Childhood 19: 169, 1944. 6. Hansen, J. D. L., and Smith, C. A.: Effects of Withholding Fluid in the Immediate Postnatal Period, Pediatrics 12: 99, 1953. 7. Hill, A. V.: Thermal Method of Measuring Vapour Pressure of Aqueous Solution, Proc. Roy. Soc. London A. 127: 9, 1930. 8. Baldes, E. J.: Micromethod of Measuring Osmotic Pressure, J. So. Inst. 11: 223, 1934. 9. Calcagn% P. L., and Rubin, M. I.: Effect of Added Carbohydrate on Growth, Nitrogen Retention and Renal Water Excretion in Premature Infants, Pediatrics 13: 193, 1954. 10. Spector, W. S.: Handbook of Biological Data, Philadelphia, 1956, W. B. Saunders Company, p. 50. 11. Cuthbertson, D. P., and Munro, H. N.: Protein-Saving Effect of Carbohydrate and Fat When Superimposed on Diet Adequate for Maintenance, Biochem. J. 31: 694, 1937.
Water requirements for renal excretion
727
12. Gamble, J. L.: Physiological Information Gained From Studies on Life Raft Ration, Harvey Lect. 42: 247, 1946 to 1947. 13. Cooke, R. E., Pratt, E. L., and Darrow, D. C.: Metabolic Response of Infants to Heat Stress, Yale J. Biol. & Med. 22: 227, 1950. 14. Darrow, D. C., Cooke, R. E., and Segar, W. E.: Water and Electrolyte Metabolism in Infants Fed Cow's Milk Mixture During Heat Stress, Pediatrics 14: 602, 1954. 15. Calcagno, P. L., and Rubin, M. I.: Effect of Dehydration Produced by Water Deprivation, Diarrhea and Vomiting on Renal Function in Infants, Pediatrics 7: 328, 1951. 16. Epstein, F. H., Kleeman, C. R., Pursel, S., and Hendrikx, A.: The Effect of Feeding Protein and Urea on the RenM Concentrating Process, J. Clin. Invest. 36: 635, 1957. 17. Edelmann, C. M., Troupkou, V., and Barnett, H. L.: Renal Concentrating Ability in Newborn Infants, Fed. Proc. 18: 637, 1959.