Download Nutritional Needs of Low-Birth-Weight Infants

AMERICAN ACADEMY OF PEDIATRICS
Committee on Nutrition
Nutritional Needs of Low-Birth-Weight Infants
The goal of feeding regimens for low-birthweight infants is to obtain a prompt postnatal
resumption of growth to a rate approximating
intrauterine growth because this is believed to
provide the best possible conditions for subsequent normal development. This statement
reviews current opinion and practices as well as
earlier reviews1-5 of the feeding of the low-birthweight infant.
Caloric Requirement
The basal metabolic rate of low-birth-weight
infants is lower than that of full-term infants
during the first week of life, but it reaches and
exceeds that of the full-term infant by the second
week. Daily caloric requirements reach 50 to 100
kcal/kg by the end of the first week of life and
usually increase to 110 to 150 kcal/kg in subsequent active growth.
A partition of the daily minimum energy requirements is shown in Table 1.6
There are considerable variations from these
average values, depending on both biological and
environmental factors. Infants who are small for
gestational age tend to have a higher basal
metabolic.rate than do premature infants of the
same weight.7 The degree of physical activity
appears to be a characteristic of the individual
infant. Environmental factors may have a greater
influence than biological variation in determining
the total caloric requirements. The maximal
response to cold stress can increase the resting
rate of heat production up to 21/2 times.6 Calories
expended for specific dynamic action and for
fecal losses are dependent on the composition of
the milk or formula fed, as well as on individual
variations in absorption of nutrients, particularly
fat.
In practice, caloric intakes of 110 to 150
kcal/kg/day enable most low-birth-weight infants to achieve satisfactory rates of growth. If
infants fail to gain satisfactorily, a higher caloric
intake may be offered.
Caloric Density of the Formula-Water
Requirement
Although human milk or formulas that provide
67 kcal/dl (20 kcal/oz) are recommended for
term infants, more concentrated formulas are
often used for low-birth-weight infants to facilitate increased caloric intakes in infants with
limited gastric capacity. Several studies have
shown that feeding low-birth-weight infants
formulas with higher caloric densities results in
faster rates of growth.8-13 Some nurseries now feed
formulas of 81 kcal/dl (24 kcal/oz) and in some
instances 91 kcal/dl (27 kcal/oz). The 81-kcal/dl
concentration supplies most of the water required
by the infant (150 ml/kg)14 and provides 120
kcal/kg.
The increased protein and mineral levels in
these more concentrated formulas increase the
renal solute load. With the limited capability of
the immature kidney for concentrating urine,
sufficient water may not be supplied if the
formula is too concentrated. Infants consuming
less than a normal volume of formula are particularly vulnerable because, under constant conditions of extrarenal water loss, the lower the
formula intake the greater the proportion of
water required for renal excretion.'5 Infants
whose water balance is threatened (e.g., infants
exposed to heat, phototherapy, or cold stress, and
those with infection or diarrhea) should have
formulas of low renal solute load and should not
be fed formulas of caloric density greater than 81
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PEDIATRICS
No. 4 October 1977
519
TABLE I
ESTIMATED REQUIREMENTS FOR CALORIES IN
GROWING PREMATURE INFANT'
Item
Resting caloric expenditure
Intermittent activity
Occasional cold stress
Specific dynamic action
TYPICAL,
kcal/kg/Day
50
15
Fecal loss of calories
Growth allowance
Total
'Data from
A
10
8
12
25
120
Sinclair et al.6
keal/dl (24 kcal/oz).15 Preterm infants excrete
sodium well,16 17 and late metabolic acidosis seen
in low-birth-weight infants may be related to low
mineral intake.16-19 Lactic acid-containing formulas should not be fed because they may produce
acidosis.20
Alternate Feeding Procedures
When conventional feedings every few hours
do not result in the attainment of an adequate
nutrient intake, alternate methods of feeding such
as continuous nasogastric drip,21 nasojejunal feeding,22 23 intravenous (IV) administration of
nutrients supplemented by oral feeding,24 and
total IV alimentation25 27 may be tried. However,
the hazards and complexities of IV administration
preclude its use in routine practice.28 Parenteral
administration of (1) 20% glucose and 2.5% amino
acid solution; (2) 12% glucose with 2.5% amino
acids and 10% soybean oil emulsion; and (3) 12%
glucose, 2.5% amino acids, and 1% alcohol in a
volume of 125 to 150 ml/kg/day all provided
positive nitrogen balance.29 Glucagon levels were
lower and growth hormone levels higher in
infants given the fat-free mixtures. Parenteral
feedings appear to increase water retention.30
In a controlled study of the feeding of lowbirth-weight infants by continuous nasogastric
drip,21 satisfactory growth and clinical progress
were reported with the feeding of human milk
and a simulated human milk formula (67 kcal/dl).
Feeding was started at the fourth hour of life at
the rate of 60 ml/kg/day and increased to 300
ml/kg/day (200 kcal/kg/day) by the ninth day. In
practice, the latter intake is difficult to achieve.
Although early administration of fluids is
generally considered beneficial to prevent dehydration, excessive weight loss, hypoglycemia, and
excessive jaundice,4 5 use of 10% glucose parenterally may cause reactive hypoglycemia when the
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IV fluid is discontinued or hyperglycemia and
hyperosmolality, which may be difficult to
control.4 Serum glucose levels should be regularly
monitored and glucose infusion rates lowered to
0.4 g/kg/hr, or less if the serum glucose level
exceeds 125 mg/dl.4 The first feeding should be
distilled water to avoid excessive damage to the
lungs if vomiting occurs.
Protein Requirement
The optimal protein intake for the low-birthweight infant has not been precisely defined;
however, it is between 2.25 and 5 g/kg/day for
cow's milk formulas. Human milk contains about
1.1 g of protein or less per deciliter, or 1.65 g/100
kcal.31 When fed at intakes of 120 kcal/kg/day,
human milk supplies almost 2 g of protein per
kilogram per day. The feeding of human milk to
premature infants was the preferred practice
until 25 years ago when Gordon et al.32 demonstrated that premature infants gained more
weight and retained more nitrogen when fed
cow's milk formulas of higher protein content.
Subsequent reports have confirmed this, but in
some reports the increased weight gains with the
higher protein cow's milk formulas were
attributed in part to increased electrolyte intake
and subsequent water retention.33-37 However,
Babson and Bramhall38 found no increase in
weight gain when only minerals were added to
formula providing 1.8 g of protein per 100 kcal.
In studies designed to determine the protein
requirement of low-birth-weight infants, protein
has been given at levels ranging from 1.7 to 9
g/kg/day. The feedings have consisted of human
milk and cow's milk formulas, with the protein
content varied by dilution with carbohydrate or
by the addition of casein or deionized milk or
whey. Because of the many variables in the
formulas, including types and levels of fat and
carbohydrate and levels of vitamins and minerals,
it is difficult to assess the nutritional adequacy of
the various formulas used in the studies or to
attribute the findings solely to dietary protein
level.
Infants fed 1.7 to 2.25 g of protein per kilogram
per day either from human milk or a cow's milk
formula did not increase in weight36-39 or
length38-39 as rapidly as those fed higher intakes,
and some developed low levels of serum
proteins.
The feeding of relatively high levels of protein
(6 to 9 g/kg/day) was associated with hyperpyrexia and lethargy,40 high BUN levels,36
diarrhea,39 high urinary excretion of phenols,39 clinical edema,42 late metabolic acidosis, and
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NUTRITION IN LOW-BIRTH-WEIGHT
INFANTS
increased mortality.39 The weight gains obtained
with the feeding of the high intakes of protein did
not exceed those obtained by the feeding of
moderate levels.36'39.40 Elevated plasma amino
acid levels in low-birth-weight infants fed highprotein formulas suggest that the high protein
intake may present an amino acid load that
exceeds the metabolizing capability of the immature enzyme systems. Elevated levels of plasma
tyrosine and phenylalanine are not uncommon, a
finding related to late maturing of p-hydroxyphenylpyruvic oxidase.43 44 High plasma levels of
proline and methionine are also associated with
high protein intake.45
The amino acid composition of formulas for
premature infants deserves special attention.
Low-birth-weight infants require some amino
acids that are not essential for the term infant. In
the balance studies of Snyderman,46 the removal
of either cystine or tyrosine from the diet resulted
in an impairment of growth and nitrogen retention, and a depression of the level of that particular amino acid in the plasma. Infants requiring
cystine also failed to show an increase in plasma
cystine level after a methionine load, a finding in
accord with the lack of cystathionase in the livers
of fetuses and premature infants reported by
Sturman et al.47'48 The high levels of cystathionine
in the plasma49 and urine50 of premature infants
fed high-protein formulas also suggest that
conversion of methionine to cystine is not efficient until some time after birth.
Raiha et al.5152 fed low-birth-weight infants
five formulas, including pooled breast milk. The
breast milk supplied approximately 1.7 g of
protein per kilogram per day, two formulas
supplied 2.25 g of protein per kilogram per day,
and two formulas supplied 4.50 g/kg/day. One
formula at each protein level had a 60:40 ratio of
whey/casein proteins, and the other two had an
18:82 ratio of whey/casein proteins. All infants
grew equally well when fed 117 kcal/kg/day;
statistically, the breast-fed group gained at a
slightly lower rate. Significant differences in
plasma amino acid and ammonia levels were
noted. The lower ammonia, tyrosine, and phenylalanine levels were found in infants fed whey/
casein of 60:40, and the highest levels were in
those fed the high-protein formula with casein
predominant. Those fed the high-protein, caseinpredominant formula developed late metabolic
acidosis. Serum protein levels were lowest in
infants fed breast milk.
A major difference between the formulas was
the higher content of cystine in the breast milk
and high-whey protein formula. In addition, the
breast milk had higher taurine levels than the
other formulas. This suggestive study requires
confirmation.
A review of the literature led Cox and Filer53 to
conclude that, with an adequate caloric intake,
most low-birth-weight infants will grow satisfactorily on cow's milk formulas supplying 2.25 to
5.0 g/kg/day of cow's milk protein. Fomon and
co-workers estimated from hypothetical considerations that the premature infant requires 3.0
g/kg/day or 2.54 g of protein per 100 kcal,
assuming an intake of 120 kcal/kg/day.54
If further studies confirm these findings,
consideration of protein quality along the lines
discussed here may be important in defining the
optimal protein quantity for low-birth-weight
infants. With adequate intakes, human milk may
be the superior feeding for low-birth-weight
infants.
Fat
The ability of low-birth-weight infants to
absorb fat, particularly saturated fat such as
butterfat, is relatively poor.55-58 This limitation is
associated with liver immaturity and decreased
bile salt synthesis,59 and it is found to a lesser
extent in full-term infants during the first few
weeks of life.606' When palmitic acid-a longchain saturated fatty acid-is present in fat, its
absorption depends on its position in the triglyceride molecule.6263 Early recommendations for
the feeding of low-birth-weight infants included
the feeding of low-fat formulas.64'65 However, the
recognition that the vegetable oils were much
better absorbed than butterfat and other saturated fats55 led to use in formulas of vegetable oils,
or blends of vegetable oils and animal fats. These
are absorbed well, as is human milk fat.66
Including medium chain triglycerides as part of
the fat in the formula has been shown to improve
fat absorption in low-birth-weight infants.67'0
Medium-chain triglycerides have also been shown
to increase weight gain70 and to enhance calcium
absorption69 and nitrogen retention.68
Fat in human milk supplies a major proportion
of the caloric content. Formulas with 40% to 50%
of calories from fat are recommended for the
feeding of low-birth-weight infants because
formulas of a lower fat content may contain
higher levels of protein which increase renal
solute load.
To meet the normal infant's requirement for
essential fatty acids, it is recommended71 that
infant feedings supply 3% of the total calories in
the form of linoleic acid or 300 mg of linoleic acid
per 100 kcal. Proprietary infant formulas with
AMERICAN
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OF PEDIATRICS
521
their high content of unsaturated fat supply a
generous allowance of linoleic acid.
Carbohydrate
The utilization of carbohydrate by the lowbirth-weight infant differs slightly from that of
the full-term infant. Intestinal disaccharidases
develop early in fetal life72; maltase and sucrase
reach mature values by the sixth to eighth month,
and lactase reaches it at term. These data suggest
that the low-birth-weight infant can adequately
digest disaccharides, although there is some
evidence that lactose digestion may not be fully
efficient for the first few days of life.73 Low-birthweight infants develop satisfactorily when fed
formulas in which the lactose of the milk has been
augmented with sucrose and when fed lactosefree formulas (i.e., formulas based on soy isolates,
meat or protein hydrolysates and containing
sucrose and/or dextrose, maltose, and dextrins as
the carbohydrate). Lactose, sucrose, and maltose
oral tolerance tests conducted on 2-week-old,
low-birth-weight infants previously fed formulas
containing either lactose or sucrose as the sole
carbohydrate revealed no significant differences
in the utilization of these three disaccharides,
despite the presence or absence of the substrate
sugar in the diet for the two weeks preceding the
test.74 In another study of dietary sugars, infants
grew equally well on soy-isolate formulas
containing sucrose or dextrose,75 and a slightly
lesser rate with lactose.
Lactose, as the natural sugar of human milk,
has been the usual choice for addition to a cow's
milk formula to increase the carbohydrate
content up to that of human milk. However, a
recent study with cow's milk formulas found that
the addition of sucrose rather than lactose to the
milk base resulted in a lower incidence of diarrhea and metabolic acidosis,76 which appears to
support the findings of Boellner et al.73 Thus, the
slight delay in the maturation of intestinal lactase
may be of physiological consequence in some
infants. Usually lactose enhances calcium absorption in the small intestine77 and promotes a
fermentative, less putrefactive bacterial flora78'79
and reduces the incidence of constipation.
Minerals
Two thirds of the mineral content of the body
of the full-term infant is deposited during the last
two months of gestation. The amounts of minerals
the preterm infant must retain from the diet to
achieve the mineral composition of the full-term
infant might be estimated from the differences in
522
mineral contents of the bodies of premature and
term infants.80'81 Body composition data can
provide a rough estimate, at best, of the increase
in minerals that the low-birth-weight infant
would have accrued had he remained in utero.
Because infants with low stores may retain 50%
to 70% of the nutrients they are fed, the levels of
nutrients supplied by formula must be 1.3 to 2
times those required to meet their needs. It
appears that minimal levels in formula designed
for full-term infants could probably satisfy requirements of the low-birth-weight infant for
sodium, potassium, chloride, and zinc; would
probably be borderline in copper; and would
probably be deficient in iron, calcium, and phosphorus. Based on these calculations, some changes
in mineral composition might be made in
formulas intended for use by premature infants to
achieve a mineral retention equivalent to that in
utero.
Calcium and Phosphorus
Balance studies and roentgenographic findings
in low-birth-weight infants suggest that formulas
made from cow's milk with higher calcium and
phosphorus levels provide greater retention of
calcium and phosphorus and increased mineralization of the skeleton than does human
milk.64'82-84 Although earlier studies85'86 suggested
that the low phosphorus content of human milk
was the limiting factor in skeleton mineralization,
work by Day et al.87 suggests that the undermineralization of bone observed in premature infants
fed human milk may also be caused by an
inadequate calcium intake. In the Day et al.87
study of low-birth-weight infants (less than 1,300
g), infants fed a proprietary formula supplemented with calcium lactate (total calcium, 154
mg/ 100 kcal) showed a better-defined bone
texture and wider cortices than infants fed unsupplemented formula containing 63 mg of calcium
per 100 kcal. Fomon et al.54 have calculated that
premature infants require 132 mg of calcium per
100 kcal.
Infant formulas fed to low-birth-weight infants
in the United States (Table II) contain higher
levels of calcium and phosphorus than those
supplied by human milk, but they are generally
lower than the level used by Day et al.87 or that
recommended by Fomon et al.54 In clinical
studies in which low-birth-weight infants were
fed current proprietary formulas88'89 or earlier
formulas of comparable calcium and phosphorus
content,36'90 no apparent abnormalities of calcium/phosphorus metabolism were noted, offer-
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INFANTS
NUTRITION IN LOW-BIRTH-WEIGHT
TABLE II
NUTRIENT COMPOSITION OF HUMAN MILK AND PROPRIETARY INFANT FORMULAS AND RECOMMENDED LEVELS FOR FULL-TERM
AND LOW-BIRTH-WEIGHT INFANTS'
Nutrient
Minimum
Level
Recoinmendedt
Human
Milk60
Enfamil
PM60/40
Premature
Formula
Similac
SMA
2.3
2.3
2.8
2.3
2.3
1.3-1.6
Protein, g
1.8t
5.3
5.3
5.1
5.2
5.5
5
Fat, g
3.3§
10.6
10.7
11.5
11.1
10.3
10.3
Carbohydrate, g
530
370
680
530
320
300
Ash, mg
370
390
250
250
370
250
250
Vitamin A, IU
60
63
63
60
63
3
40
Vitamin D, IU
2.2
1.4
1.9
1.9
2.2
0.3
Vitamin E, IU
0.3(0.7)11
14
9
4
9
2
4
9
Vitamin K, jg
8.1
8.6
8.0
8.1
8
Vitamin C, mg
8.1
7.8
105
96
78
96
25
40
78
Thiamin, jig
156
147
94
147
94
60
60
Riboflavin, ,jg
780
1,030
1,250
1,250
250
250
Niacin, ,ug
1,074
63
60
63
49
63
15
Vitamin B6, Lg
35¶
8
7.3
16
16
7.3
4
4
Folic acid, ug
310
440
470
440
470
300
300
Pantothenic acid, ,ug
0.22
0.16
0.3
0.3
0.22
0.15
0.15
Vitamin B12, lAg
1.5
3.0
2.5
2.5
1.7
1.0
1.5
Biotin, ,tg
5
5.5
5.0
6
7.5
4
20
Inositol, mg
13
15
7
7
18.8
13
7
Choline, mg
66
75
156
60
80
50
50
Calcium, mg
49
57
78
70
30
25
25#
Phosphorus, mg
8
6
10
7
6
6
6
Magnesium, mg
Tracett
1.9
0.2
0.4
0.1
0.1500
0.2tt
Iron, mg
10
15
8
10
6
4-9
5
Iodine, ,ug
100
70
60
100
62
60
60
Copper, ug
0.55
0.65
0.74
0.59
0.5
0.5
0.65
Zinc, mg
5
5
23
160
1.5
5
160
5
Manganese, ug
Sodium
32
24
24
42
23
40
20#
mg
1.7
1.0
1.0
1.8
1.0
1.6
0.9#
mEq
Potassium
83
102
85
110
103
80
81
mg
2.1
2.1
2.2
2.5
2.1
2.6
2.8
mEq
Chloride
66
79
55
55
55
80
85
mg
2.4
1.6
1.6
1.6
2.3
2.0
2.3
mEq
16.2
...
16
13.6
11.3
14.3
18.1
Renal solute load01
mOsm
°Per 100 kcal.
tCommittee on Nutrition recommendations7" for formula for full-term infants per 100 kcal.
VProtein of a nutritional quality equivalent to casein.
§Including a minimum of 300 mg of essential fatty acids.
IlCommittee on Nutrition recommendation different for low-birth-weight infants; also 1.0 IU/g linoleic acid.
Minimum of 15 ,ug of vitamin B6 per gram of protein.
*Some evidence for higher requirement for low-birth-weight infant.
@01.0 mg in iron-fortified formula.
ttl.5 mg in iron-fortified formula.
t$Calculated by the method of Ziegler and Fomon.?5
AMERICAN
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Similac
(13, 24,
or 27 Caloriesloz)
2.7
5.3
10.3
580
370
60
2.2
4
8.1
96
147
1,000
60
7.3
440
0.22
ACADEMY OF PEDIATRICS
1.5
25
102
79
6
Tracett
15
60
0.74
5
38
1.7
126
3.2
94
2.7
18.4
523
ing some assurance that current ranges of
concentrations are not grossly inadequate for the
feeding of low-birth-weight infants.
The hypocalcemia-hyperphosphatemia syndrome seen in normal term neonates fed undiluted cow's milk has been attributed to immature
homeostatic control of serum phosphate.88 This
suggests that formulas for low-birth-weight
infants should have a calcium/phosphorus ratio
approaching that of human milk (2.0:1), or at least
between 1.1:1 and 2.0:1, as recommended for
formulas fed to full-term infants.7
Magnesium
The recommended minimum requirement for
magnesium in formula for the term infant was
based on the amount present in human milk, 6
mg/100 kcal.71 Clinical experience suggests that
this amount also suffices for the low-birth-weight
infant. Average serum magnesium levels of the
neonatal, low-birth-weight infant are similar to
adult values.89 Low levels are not uncommon in
the first few days of life, particularly in the smallfor-gestational-age group, but they rise to adult
values within days after feeding of conventional
formulas.89
Magnesium depletion has been observed in
infants suffering from the gross malnutrition of
kwashiorkor,9' and hypomagnesemia, as is true
with hypocalcemia, may result from high phosphate feedings.92 But, there have been no reports
of magnesium deficiency in healthy, low-birthweight infants fed formulas of magnesium content
equal to or in moderate excess over that in human
milk. Low-birth-weight infants have been maintained for prolonged periods on IV feeding
containing 2 mg of magnesium per 100 kcal.2f If
the low-birth-weight infant can absorb 33% of the
magnesium in the formula-a reasonable assumption-the 6 mg/100 kcal required in the
formula would readily supply the 2 mg/ 100 kcal
given intravenously.
Iron
The low-birth-weight infant is especially
susceptible to the development of iron deficiency
anemia because its stores of iron are much smaller
than those of a full-term infant, and they are
insufficient to last over a prolonged period when
growth must be rapid. Erythrocyte and hemoglobin levels are high at birth; the hemoglobin
iron released by destruction of old RBCs is
salvaged and stored for future use. Active erythropoiesis resumes between 1 and 2 months of age,
and rapidly decreases the size of the iron reserve.
524
Without supplemental iron, the body stores of
iron will be depleted sometime after 2 months of
age rather than after 4 to 6 months of age, as in
the normal, full-term infant.93 Orally administered iron is well absorbed.94
Although the greater need for iron by the lowbirth-weight infant has been interpreted to indicate that iron-fortified formulas be given as early
as possible, recent findings show that iron-supplemented formulas increase the susceptibility of
infants to vitamin E deficiency and hemolytic
anemia, especially when formulas are high in
polyunsaturated fatty acids.5 95 (See discussion of
vitamin E.) These studies leave unresolved the
question of whether supplementary iron should
be started at 2 months of age or shortly after
birth.93 They also suggest that formulas for lowbirth-weight infants containing more than 1 mg of
iron per 100 kcal should contain moderate
amounts of polyunsaturated fats (and ample
vitamin E in an absorbable form), and that those
with higher amounts of polyunsaturated fats
should contain about 0.1 mg of iron per 100 kcal,'
which is roughly equivalent to the iron present in
breast milk.
Another, more speculative reason for temporarily delaying the use of iron-fortified formula in
low-birth-weight infants comes from recent
evidence that two iron-binding proteins in human
milk (lactoferrin and transferrin) lose their bacteriostatic action when saturated with iron.93 The
bacteriostatic properties of these proteins may be
especially important to low-birth-weight infants
in the early weeks of life.
Thus, even though the Committee on Nutrition
continues to recommend that low-birth-weight
infants receive 2 mg of iron per kilogram per day
starting at age 2 months or earlier, one cannot
categorically require that formulas provide this
level of iron from birth. Thus, formulas for lowbirth-weight infants may provide either 0.1 mg or
1.5 mg of iron per 100 kcal. If they provide the
higher level of iron, they should contain ample
vitamin E and a moderate level of polyunsaturated fatty acids.
Copper
The recommended level of copper in infant
formulas is 60 pgg/100 kcal.71 This level is based on
early data on human milk. Although copper
deficiency has not been noted in normal infants
on customary feedings, several reports96-98 have
indicated that copper deficiency may develop in
small infants fed formulas not supplemented with
copper. Recent data suggest that an intake of 90
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NUTRITION IN LOW-BIRTH-WEIGHT
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gtl100 kcal is desirable for low-birth-weight
infants.99
recommended for full-term infants71 until further
work confirms a higher, suggested need.
Iodine
Vitamins
The recommended minimum requirement of
normal infants (5 ,ug of iodine per 100 keal)71 was
also based on the iodine content of human milk.
The uptake of radioactive iodine by the thyroid
gland of premature infants has been found to be in
the normal range for children and adults100; therefore, we can assume that 5 ,ug of iodine per 100
kcal is also adequate for the low-birth-weight
infant.
Zinc and Manganese
The Committee on Nutrition has recently
proposed that infant formulas for full-term infants
supply 0.5 mg of zinc and 5 ,ug of manganese per
100 kcal.7' There is no basis for modifying these
recommended levels for low-birth-weight infants.
Other Trace Minerals
Although other minerals (such as cobalt,
molybdenum, selenium, and chromium) are
probably essential in trace amounts for infants,
there is no information on which to base recommendations at this time. Fluoride is usually
provided in supplements or as fluoridated
water.
Sodium, Chloride, and Potassium
The daily requirements of low-birth-weight
infants for sodium, chloride, and potassium can
only be roughly estimated from tissue composition (Table II), because obligatory losses in the
urine and feces and from the skin vary considerably.
Minimum levels of sodium, chloride, and potassium recommended by the Committee on Nutrition for new formula standards were based on
levels in human milk and should be sufficient for
low-birth-weight infants. There have been a few
reports'01-'03 of hyponatremia in low-birth-weight
infants fed a formula with a concentration of
sodium similar to that in human milk. Fomon et
al.54 also suggest that the level of sodium in
human milk is not sufficient for the premature
infant; they recommend 30 mg of sodium per 100
kcal.
The Committee on Nutrition recommends that,
to prevent dehydration and disturbances of acidbase balances, minimum and maximum levels of
sodium, chloride, and potassium in formulas for
low-birth-weight infants be the same as those
Table II shows the levels of vitamins recommended by the Committee as minimum levels for
infant formulas for full-term infants.7' These
apply to formulas based on milk and milk substitutes. The Committee recommends that the same
levels apply to formulas for low-birth-weight
infants, except for vitamin E.
However, even with proprietary formulas
containing adequate levels of vitamins, premature
and low-birth-weight infants often consume much
less than 120 kcal/kg/day during the early weeks
of life, and they may not receive sufficient vitamins to prevent deficiency. For example, rickets
has been found in premature infants fed proprietary formulas containing 400 IU of vitamin D per
liter,104 and. folate and vitamin B1, deficiencies
have also been noted'05-'08 when the infants
consumed a small volume of formula. Therefore,
the Committee recommends that low-birthweight infants receive an intramuscular injection
of 1 to 2 mg of vitamin K at birth and a daily, oral,
multivitamin supplement providing the recommended daily allowance of vitamins for infants as
established by the Food and Drug Administra-
tion.'09
The vitamin E requirement of low-birth-weight
infants merits special consideration.
1. Absorption of vitamin E by these infants is
poor; Gordon et al.1"0 showed that the levels of
vitamin E usually found in formulas-which are
adequate to maintain normal serum tocopherol
levels in term infants-were not sufficient to do so
in premature infants. Recently, it was shown that
water-soluble forms of vitamin E improve absorption and result in higher' serum tocopherol
levels."'
2. The requirement for vitamin E increases as
the level of polyunsaturated fats in the diet
increases.93 Thus, when formulas are high in
polyunsaturated fats, the infant needs more
vitamin E.
3. When iron levels in the formula are high,
the requirement for vitamin E by low-birthweight infants also increases. For example, lowbirth-weight infants receiving a formula supplemented with iron (12 mg/liter) and high in
polyunsaturated fats have a greater incidence of
RBC hemolysis and lower serum tocopherol levels
than infants receiving formula that has a low level
of iron and is low in polyunsaturated fats.94
Therefore, the Committee on Nutrition recom-
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AMERICAN ACADEMY OF PEDIATRICS
525
mends that formula fed to premature infants
should provide 0.7 IU of vitamin E per 100 kcal
and at least 1.0 IU of vitamin E per gram of
linoleic acid. In addition, the multivitamin
supplement given to low-birth-weight infants
should provide 5 IU of vitamin E, preferably in
water-soluble form.
Formula Compositions
Table II shows the composition of major
proprietary formulas available for feeding fullterm and low-birth-weight infants, the average
composition of human milk, and the recent
recommendations of the Committee on Nutrition71 for proposed standards for infant formula.
This information is presented in units per 100
kcal-which relate specific nutrient needs to
caloric requirements-and is particularly useful in
discussing formulas for low-birth-weight infants
because it allows easy comparison of formulas of
differing caloric densities.
In many instances, formulas for term infants are
used for feeding low-birth-weight infants, and, in
other instances, special formulas are available for
premature and low-birth-weight infants.
Discussions in this statement suggest that levels
of some nutrients in formulas for low-birth-weight
infants should be somewhat higher than the
minimum levels proposed by the Committee for
full-term infants; however, all of these recommendations can be met within the proposed
standards for infant formulas.7
Conclusions
The optimal diet for the low-birth-weight
infant may be defined as one that supports a rate
of growth approximating that of the third
trimester of intrauterine life, without imposing
stress on the developing metabolic or excretory
systems. Cell division and growth of all tissues in
the infant should proceed at a rapid rate; undue
delay in the resumption of growth may have
serious and lasting consequences. The attainment
of an adequate caloric intake is the primary
requirement, and this may be facilitated by the
feeding of formulas of caloric density greater than
that of human milk. However, the feeding of this
type of formula requires special attention to avoid
too high an osmolar load and to provide sufficient
water. The use of continuous intragastric or
intrajejunal drip with formulas providing 67 or 81
kcal/dl also may be a safe and practical means of
increasing caloric intake. Caloric intakes of about
120 kcal/kg/day in formula volumes of 150 to 200
526
ml/kg/day will support the desired weight gain
in most infants.
An appropriate requirement for protein equivalent to casein for the low-birth-weight infant
would appear to fall in the range of 2.5 to 5.0
g/kg/day, or 2.25 to 4.5 g/100 kcal. A more
precise statement of optimal protein quantity
awaits the definition of optimal protein quality
for low-birth-weight infants. Evidence has been
accumulating that some amino acids considered
nonessential for the normal infant are indispensable to low-birth-weight infants. Thus, the
apparent normal growth of infants fed breast milk
supplying 1.7 g of protein per kilogram of body
weight may be caused in part by its distribution of
amino acids. For the larger low-birth-weight
infant, recommendations similar to those for the
term infant, including the desirability of breast
feeding, apply.71
Fat mixtures in formulas currently in use
include unsaturated vegetable oils and/or medium-chain triglycerides, which are well absorbed. Although good absorption of fat is important-not only for energy requirements but also to
enhance the absorption of fat-soluble vitamins
and certain minerals-other aspects must be
considered in the selection of ideal formula fat
compositions for low-birth-weight infants. The
fatty acid composition of the diet influences the
composition of body lipids, especially in lowbirth-weight infants who have meager stores of
body fat. Fat mixtures should not be too saturated
or too unsaturated.
The occurrence of hemolytic anemia in lowbirth-weight infants has been related to the
polyunsaturated fat, vitamin E, and iron content
of the formula. The fortification of infant
formulas with vitamin E, related to the polyunsaturated fatty acid content, is particularly important for the low-birth-weight infant because poor
absorption of naturally occurring vitamin E by
low-birth-weight infants makes them more
susceptible to a deficiency. This is especially
important if iron-supplemented formulas are used
in the early weeks of life.
Recent evidence indicates that some mineral
requirements (e.g., calcium, sodium, copper) of
the low-birth-weight infant may be greater per
100 kcal than for full-term infants. This suggests
that slightly higher levels of these minerals be
present in formulas for low-birth-weight infants
than the minimum levels proposed by the
Committee for full-term infants.
Low body stores of vitamins, possible defects in
absorption (particularly of fat-soluble vitamins),
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NUTRITION IN LOW-BIRTH-WEIGHT INFANTS
and low intakes of formula in the first weeks of
life necessitate the use of vitamin supplements,
even though a formula adequate for full-term
infants is used. A single injection of vitamin K1 at
birth and daily oral supplements of vitamins A, C,
D, E, and all the B group are recommended.
The long-term effects of early nutrition are
important and challenging aspects of infant nutrition. Early feeding of low-birth-weight infants
entails a special responsibility because this is a
crucial period of development when inadequacies, excesses, or imbalances are most likely to
influence permanent changes. Long-term studies,
still in progress, are attempting to relate feeding
practices in the premature nursery to subsequent
neurologic development, learning ability, behavioral characteristics, and mental development in
general. Other possible pathologic consequences
of improper early nutrition that are legitimate
areas of concern for the pediatric nutritionist
include atherosclerosis, obesity, hypertension,
and renal disease.
COMMITTEE ON NUTRITION
Members: Lewis A. Barness, M.D., Chairman; Alvin M.
Mauer, M.D., Vice-Chairman; Arnold S. Anderson, M.D.;
Peter R. Dallman, M.D.; Gilbert B. Forbes, M.D.; James C.
Haworth, M.D.; Mary Jane Jesse, M.D.; Buford L. Nichols,
Jr., M.D.; Nathan J. Smith, M.D.; Myron Winick, M.D.
Consultants: William C. Heird, M.D.; 0. L. Kline, Ph.D.;
Donough O'Brien, M.D.
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51. Raiha NCR, Heinonen K, Rassin DK, Gaull GE: Milk
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58. Davidson M, Bauer CH: Patterns of fat excretion in
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59. Watkins JB, Szczepanik P, Gould JB, et al: Bile salt
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70. Roy CC, Ste-Marie M, Chartrand L, et al: Correction
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71. Committee on Nutrition: Commentary on breastfeeding and infant formulas, including proposed
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72. Auricchio S, Rubino A, Murset G: Intestinal glycosidase activities in the human embryo, fetus and
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73. Boellner SE, Beard AG, Panos TC: Impairment of
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74. Jarrett EC, Holman GH: Lactose absorption in the
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75. Andrews BF, Cook LN: Low birth-weight infants fed a
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76. Fosbrooke AS, Wharton BA: "Added lactose" and
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78. Barbero GJ, Runge G, Fischer D, et al: Investigations
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79. Cornely DA, Barness LA, Gyorgy P: Effect of lactose
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80. Shohl AT: Mineral Metabolism. New York, Reinhold
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81. Widdowson E: Chemical analysis of the body, in
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82. Benjamin HR, Gordon HH, Marples E: Calcium and
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84. Eek S, Gabrielsen LH, Halvorsen S: Prematurity and
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85. Widdowson EM, McCance RA, Harrison GE, Sutton
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88. Oppe TE, Redstone D: Calcium and phosphorus levels
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91. Caddell JL, Goddard DR: Studies in protein-calorie
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92. Tsang RC: Neonatal magnesium disturbances. Am J
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93. Dallman P: Iron, vitamin E, and folate in the preterm
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94. Gorten MK, Cross ER: Iron metabolism in premature
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96. Griscom NT, Craig JN, Neuhauser EBD: Systemic
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97. Seely JR, Humphrey GB, Matter BJ: Copper deficiency in a premature infant fed an iron fortified
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98. Ashkenazi A, Levin S, Djaldetti M, et al: The
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99. Cordano A: The role played by copper in the physiopathology and nutrition of the infant and the
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TWO CASES OF SUDDEN AND UNEXPLAINED DEATH OF CHILDREN DURING
SLEEP AS REPORTED IN 1834
Published case reports of unexpected deaths of infants during sleep prior to
the early decades of the 20th century routinely attributed the infant's death
either to overlaying of the mother or wet-nurse, or after the 1840s, to
suffocation by an enlarged thymus. The two cases in letter form reported
below are of historic interest because they are among the first to infer that
unexpected infant death during sleep might be due to natural causes.
To the Editor of THE LANCET.
Sir,-I have lately been called upon to examine two children, who, without having been
previously indisposed, were found'dead in bed.
In the first case the child was about six months old, and was lying in bed with its mother, who
discovered in the middle of the night that it was dead. An inquest was held upon the body, and I
was directed, in the absence of anything like testimony as to the cause of its dissolution, to make
a post-mortem investigation. I should mention that the mother stated positively that the child
had not lain near her, .and that it was impossible it could have been suffocated, either from its
mouth having been applied to any part of her person or to the bed linen.
I found nothing unusual in the cavity of the skull,-no engorgement of the vessels,-no
sanguineous or serous effusion. The viscera of the belly were in every respect of healthy
appearance, and there was nothing in the stomach to indicate that it had come by its death
unfairly. In the chest, however, I found, upon the surface of the thymus gland, numerous spots of
extravasated blood, similar spots upon the surface of the lower and back parts of each lung, and
many patches of ecchymosis upon the margin of the right ventricle of the heart, and along the
course of the trunk of the coronary vein. There was no engorgement, however, of the pulmonary
vessels, of the coronaries, or of the vessels of the thymus.
In the second case the child was five months old. It had been pretty well, had been suckled by
its mother, and laid in bed upon its side, and in about an hour and a half afterwards was
discovered to be dead. There was some frothy matter in and about the mouth, and its hands were
firmly clenched. From the position in which it was found it was impossible it could have been
smothered.
The appearances exhibited in the autopsy were strikingly the same as in the first case. The
contents of the skull and belly were in a perfectly natural condition. The extravasated spots upon
the thymus gland were more numerous than in the first case, and those upon the heart and the
surface of the lungs were fewer in number. There was about half an ounce of serous fluid in the
pericardium.
In these cases one naturally asks,-what was the cause of death? The similarity of the postmortem appearances would lead one to suppose that the cause must in each case have been the
same.
In the first case I was strongly disposed to think, in spite of the evidence of the mother, that
the child must have been destroyed by overlaying it; but after the occurrence of the last case,
where, from all the testimony that could be obtained, it seemed impossible that the child could
have been suffocated, as it was lying in bed by itself, and was not obstructed in its breathing by
the bed-clothes, I confess that the opinion I had formed was a good deal shaken, and that I
became almost entirely at a loss how to account for death in either. In both cases there seems to
have been, from some cause or other, a sudden and violent action of the heart,-and numerous
small vessels, from the increased force of its contraction, appear as a consequence to have given
way. But so trifling a lesion could hardly, in either instance, be supposed to be of itself sufficient
to produce death, and it is with the hope that some of your correspondents who may have seen
similar cases, and who may be better able to offer an explanation of the phenomena they present
than I am, will take the' trouble of enlightening me upon the subject, that I am induced to
forward you this communication.
Saml W. Fearn
Derby, Oct. 19, 1834
Noted by T. E. C., Jr., M.D.
From Feam SW: Sudden and unexplained death in children. Lancet 1:246, 1834.
530
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NUTRITION IN LOW-BIRTH-WEIGHT INFANTS
Nutritional Needs of Low-Birth-Weight Infants
Pediatrics 1977;60;519
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
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Nutritional Needs of Low-Birth-Weight Infants
Pediatrics 1977;60;519
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
/content/60/4/519
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,
it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked
by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,
Illinois, 60007. Copyright © 1977 by the American Academy of Pediatrics. All rights reserved. Print
ISSN: 0031-4005. Online ISSN: 1098-4275.
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