AMERICAN ACADEMY OF PEDIATRICS Committee on Nutrition
Nutritional
Needs
of Low-Birth-Weight Infants
The goal of feeding regimens for low-birth-weight 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 subse-quent normal development. This statement reviews current opinion and practices as well as earlier reviews1-5 ofthe feeding of the low-birth-weight 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 infantby the second week. Dailycaloricrequirements 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 subse-quent active growth.
A partition of the daily minimum energy re-quirements isshown inTable 1.6
There are considerable variations from these averagevalues, dependingonbothbiological 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 biologicalvariation indetermining 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, aswell as on individual variations inabsorption of nutrients, particularly fat.
In practice, caloric intakes of 110 to 150
kcal/kg/day enable most low-birth-weight in-fants 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 orformulas 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 facili-tate 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 Somenurseriesnowfeed formulas of 81 kcal/dl (24 kcal/oz) and in some
instances 91 kcal/dl (27 kcal/oz). The 81-kcal/dl concentrationsupplies 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 volumeof formula are particu-larly vulnerable because, under constant
condi-tions 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 exposedtoheat, phototherapy, orcoldstress, and those with infection or diarrhea) should have formulas of low renal solute load and should notbe fed formulas of caloricdensity greater than 81
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TABLE I
ESTIMATEDREQUIREMENTS FORCALORIES IN ATYPICAL,
GROWING PREMATUREINFANT'
Item kcal/kg/Day
Restingcaloric expenditure 50
Intermittentactivity 15
Occasional coldstress 10
Specificdynamicaction 8
Fecal loss ofcalories 12
Growth allowance 25
Total 120
'Data from Sinclairetal.6
keal/dl (24 kcal/oz).15 Preterm infants excrete sodium well,1617and late metabolic acidosis seen inlow-birth-weight infants may be related to low mineral
intake.16-19
Lactic acid-containing formu-las should not be fed because they may produceacidosis.20
Alternate Feeding Procedures
When conventional feedings every few hours do not result in the attainment of an adequate nutrientintake,alternatemethods offeeding such
ascontinuous nasogastric drip,21nasojejunal feed-ing,2223 intravenous (IV) administration of nutrients supplemented by oral feeding,24 and totalIValimentation2527 maybe tried. However, thehazards andcomplexities 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
positivenitrogenbalance.29 Glucagonlevelswerelower 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 low-birth-weight infants by continuous nasogastric
drip,21
satisfactory growth and clinical progresswere reported with the feeding of human milk andasimulatedhumanmilkformula (67kcal/dl). Feeding was started at the fourth hour oflife at
the rate of 60 ml/kg/day and increased to 300
ml/kg/day(200kcal/kg/day) bythe ninthday.In
practice, the latter intake is difficult to achieve. Although early administration of fluids is
generally considered beneficial to prevent dehy-dration,excessive weight loss, hypoglycemia, and
excessivejaundice,45useof10%glucose parenter-ally may cause reactive hypoglycemia when the
IV fluid is discontinued or hyperglycemia and hyperosmolality, which may be difficult to
control.4 Serumglucose levelsshould beregularly 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-birth-weight 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 perdeciliter, 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 demon-strated 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 feedingshave consisted of human milk and cow's milk formulas, with the protein content variedby 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 carbohydrateandlevelsofvitaminsand minerals, it isdifficult to assessthe nutritional adequacyof the various formulas used in the studies or to attribute the findings solely to dietary protein level.
Infantsfed 1.7to2.25 gofprotein perkilogram perday either from human milkor 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 serumproteins.
Thefeeding of relatively high levels of protein (6 to 9 g/kg/day) was associated with hyperpy-rexia and lethargy,40 highBUN levels,36 diar-rhea,39 high urinary excretion of phenols,39 clin-ical edema,42 late metabolic acidosis, and
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increasedmortality.39 The weight gains obtained with thefeeding 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 high-protein formulas suggest that the high protein intake may present an amino acid load that exceeds the metabolizingcapability of the imma-ture enzyme systems. Elevated levels of plasma tyrosine and phenylalanine are not uncommon, a finding related to late maturing of p-hydroxy-phenylpyruvic 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 reten-tion, and a depression of the level of that partic-ular 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 cystathionaseinthe livers
of fetuses and premature infants reported by
Sturman etal.47'48Thehigh levels of cystathionine in the plasma49 and urine50 ofpremature infants fed high-protein formulas also suggest that conversion of methionine to cystine is not effi-cient 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 formulaateach 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 phenyl-alanine 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 thehigh-protein,
casein-predominant 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 andFiler53 to conclude that, with an adequate caloric intake, most low-birth-weight infants will grow satisfac-torily 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 consider-ations 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, isrelatively 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 palmiticacid-a
long-chain saturated fatty acid-is present in fat, itsabsorption depends on itsposition in the triglyc-eride molecule.6263 Early recommendations for the feeding of low-birth-weight infants included thefeeding of low-fatformulas.64'65 However, the
recognition that the vegetable oils were much better absorbed than butterfat and other
satu-ratedfats55led to use informulasofvegetableoils,
orblends ofvegetable oilsand animal fats. These
are absorbedwell, as is human milk fat.66
Including medium chaintriglyceridesaspart of thefatinthe formula has been showntoimprove fat absorption in low-birth-weight infants.67'0 Medium-chaintriglycerideshave also been shown
to increase weightgain70and toenhance calcium absorption69and nitrogen retention.68
Fat inhuman milksupplies amajorproportion ofthe caloriccontent. 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 infantfeedings supply 3% of the total calories in theform of linoleic acid or 300 mg of linoleic acid per 100 kcal. Proprietary infant formulas with
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their high content of unsaturated fat supply a
generous allowance oflinoleic acid.
Carbohydrate
The utilization of carbohydrate by the low-birth-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, andlactase 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-birth-weight infants develop satisfactorily when fed formulasinwhich the lactose of the milk has been augmented with sucrose and when fed lactose-free 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 sugarin the dietfor 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, hasbeen 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 diar-rhea and metabolic acidosis,76 which appears to support the findings of Boellner et al.73 Thus, the slight delayinthe maturation of intestinal lactase may be of physiological consequence in some infants. Usually lactose enhances calcium
absorp-tion 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-terminfantisdeposited during the last
twomonthsof gestation. Theamountsofminerals 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
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 mayretain 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
re-quirements 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 phos-phorus. Basedonthesecalculations,somechanges in mineral composition might be made in
formulas intended foruseby prematureinfants to
achieve a mineral retention equivalent to that in
utero.
Calcium and Phosphorus
Balance studies and roentgenographic findings inlow-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 minerali-zation 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, workbyDayetal.87 suggests that the underminer-alization 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 oflow-birth-weight infants (less than 1,300 g), infants fed a proprietary formula supple-mented with calcium lactate (total calcium, 154
mg/100 kcal) showed a better-defined bone textureand widercortices thaninfants fed unsup-plemented formula containing 63 mg of calcium per 100kcal. Fomon et al.54 have calculated that premature infants require 132 mg of calcium per 100 kcal.
Infant formulas fedto 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 ofcomparable calcium and phosphorus content,36'90 no apparent abnormalities of cal-cium/phosphorus metabolism were noted,
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TABLE II
NUTRIENT COMPOSITION OFHUMAN MILKANDPROPRIETARY INFANT FORMULAS ANDRECOMMENDED LEVELS FORFULL-TERM
ANDLOW-BIRTH-WEIGHT INFANTS'
Nutrient Minimum Human Enfamil PM60/40 Premature Similac SMA Similac
Level Milk60 Formula (13, 24,
Recoin- or27
Calo-mendedt riesloz)
Protein, g Fat, g
Carbohydrate, g Ash, mg Vitamin A, IU Vitamin D, IU Vitamin E, IU Vitamin K,jg Vitamin C, mg Thiamin,jig
Riboflavin,
,jg
Niacin, ,ug VitaminB6, Lg Folicacid, ug Pantothenic acid,,ug VitaminB12, lAg Biotin, ,tg Inositol, mg Choline,mg Calcium, mg Phosphorus,mg Magnesium, mg Iron, mg Iodine,,ug Copper, ug Zinc, mg Manganese, ug Sodium mg mEq 1.8t 3.3§ 250 40 0.3(0.7)11 4 8 40 60 25035¶
4 300 0.15 1.5 4 7 50 25# 6 0.1500 5 60 0.5 5 1.3-1.6 5 10.3 300 250 3 0.3 2 7.8 25 60 250 15 4 300 0.15 1.0 20 13 50 25 6 0.1 4-9 60 0.5 1.5 2.3 5.5 10.3 530 250 63 1.9 9 8.1 78 94 1,250 63 16 470 0.3 2.5 5 7 80 70 7 0.2tt 10 100 0.65 160 2.3 5.2 11.1 320 370 60 2.2 4 8.1 96 147 1,074 49 7.3 440 0.22 1.7 7.5 18.8 60 30 6 0.4 6 62 0.59 5 2.8 5.1 11.5 680 250 63 1.9 9 8.0 78 94 1,250 63 16 470 0.3 2.5 6 7 156 78 10 0.2 8 100 0.65 160 2.3 5.3 10.6 530 370 60 2.2 14 8.1 96 147 1,030 60 7.3 440 0.22 1.5 5.0 15 75 57 6 Tracett 15 60 0.74 5 2.3 5.3 10.7 370 390 63 1.4 9 8.6 105 156 780 63 8 310 0.16 3.0 5.5 13 66 49 8 1.9 10 70 0.55 23 2.7 5.3 10.3 580 370 60 2.2 4 8.1 96 147 1,000 60 7.3 440 0.22 1.5 25 102 79 6 Tracett 15 60 0.74 5Manganese, ug 5 1.5 160 5 160 5 23 5
Sodium
mg 20# 24 42 23 40 32 24 38
mEq 0.9# 1.0 1.8 1.0 1.7 1.6 1.0 1.7
Potassium
mg 80 81 102 85 110 103 83 126
mEq 2.1 2.1 2.6 2.2 2.8 2.5 2.1 3.2
Chloride
mg 55 55 80 66 85 79 55 94
mEq 1.6 1.6 2.3 2.0 2.4 2.3 1.6 2.7
Renalsolute load01 ... 11.3 16 14.3 18.1 16.2 13.6 18.4
mOsm
°Per 100 kcal.
tCommitteeon Nutritionrecommendations7" for formula for full-term infants per 100kcal.
VProteinof a nutritional qualityequivalentto casein.
§Including aminimumof 300 mg of essentialfattyacids.
IlCommitteeonNutritionrecommendation different forlow-birth-weight infants;also 1.0IU/glinoleic acid. Minimum of15 ,ugofvitaminB6 per gram ofprotein.
*Some evidence forhigherrequirement forlow-birth-weight infant.
@01.0mginiron-fortified formula.
ttl.5mg iniron-fortified formula.
t$Calculatedbythemethod ofZieglerandFomon.?5
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ing some assurance that current ranges of concentrations are not grossly inadequate for the feeding of low-birth-weight infants.
The hypocalcemia-hyperphosphatemia syn-drome seen in normal term neonates fed undi-luted 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 atleast 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 alsosuffices 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 thefirstfewdays of life, particularly in the small-for-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 phos-phate feedings.92 But, there have been noreports of magnesium deficiency in healthy, low-birth-weight infants fedformulas of magnesium content equalto or inmoderate excess over that in human milk. Low-birth-weight infants have been main-tained for prolonged periods on IV feeding containing 2 mg of magnesium per 100 kcal.2f If thelow-birth-weight infant can absorb 33% of the magnesium in the formula-a reasonable as-sumption-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 tothe development of iron deficiency
anemiabecause itsstoresof 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 hemo-globin levels are high at birth; the hemoglobin iron released by destruction of old RBCs is salvaged and stored for future use. Active erythro-poiesis resumes between 1 and 2 months of age, and rapidly decreases thesize of the iron reserve.
Without supplemental iron, the body stores of iron will be depleted sometime after 2 months of age rather than after4 to 6 months of age, as in
the normal, full-term infant.93 Orally adminis-tered iron is well absorbed.94
Although the greater need for iron by the low-birth-weight infant has been interpreted to indi-catethat iron-fortified formulas be given as early aspossible, recent findings show that iron-supple-mented 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 low-birth-weight infants containingmorethan 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 ofiron per100kcal,' which is roughly equivalentto theiron presentin
breast milk.
Another, more speculative reason for tempo-rarily delayingthe use of iron-fortified formulain
low-birth-weight infants comes from recent evidence thattwoiron-bindingproteinsinhuman milk (lactoferrinandtransferrin) lose their bacte-riostatic 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,eventhough the Committee on Nutrition
continues to recommend that low-birth-weight infants receive 2mg 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 low-birth-weightinfantsmayprovideeither0.1mgor
1.5 mg ofiron per 100 kcal. Ifthey provide the higher level of iron, they should contain ample
vitamin E and a moderate level of polyunsatu-rated fatty acids.
Copper
The recommended level of copper in infant formulasis60
pgg/100
kcal.71 This levelisbasedon early data on human milk. Although copper deficiency has not been noted in normal infantson
customary
feedings, several reports96-98 have indicated that copper deficiency may develop insmall infants fedformulasnot
supplemented
with copper. Recent data suggest that an intake of 90gtl100 kcal is desirable for low-birth-weight infants.99
Iodine
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 glandof premature infants has been foundto be in the normal range for children andadults100; there-fore, 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 100kcal.7'
There is no basis for modifying these recommended levels for low-birth-weight in-fants.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 recom-mendations 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
composi-tion (Table II), because obligatory losses in the
urine and feces and from the skin vary consider-ably.
Minimumlevelsof sodium, chloride, and potas-sium recommended by the Committee on
Nutri-tion for new formula standards were based on levels inhuman milk andshould be
sufficient
for low-birth-weight infants. There have been a fewreports'01-'03
ofhyponatremiainlow-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.TheCommittee on Nutrition recommends that,
toprevent dehydration and disturbances of acid-base balances, minimum and maximum levels of sodium, chloride, and potassium in formulas for low-birth-weight infants be the same as those
recommended for full-term infants71 until further work confirms a higher, suggested need.
Vitamins
Table II shows the levels of vitamins recom-mended by theCommittee as minimum levels for infant formulas for full-term infants.7' These apply to formulas based on milk and milk substi-tutes. The Committee recommends that thesame
levels apply to formulas for low-birth-weight infants, except for vitamin E.
However, even with proprietary formulas containingadequate levelsof vitamins, premature andlow-birth-weight infants often consume much less than 120kcal/kg/day during theearly weeks of life, and they may not receive sufficient vita-mins to prevent deficiency. For example, rickets has been foundin premature infants fed proprie-taryformulas containing400 IUofvitaminDper 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-birth-weight infants receive anintramuscular injection of1to2mgof vitaminKatbirth andadaily, oral, multivitamin supplement providing the
recom-mendeddailyallowanceofvitaminsfor infantsas
established by the Food and Drug Administra-tion.'09
The vitamin Erequirement oflow-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 levelsinterminfants-were not sufficienttodoso
inprematureinfants. Recently, it was shown that water-soluble forms of vitamin E improve
absorp-tion and result in
higher'
serum tocopherol levels."'2. The requirement for vitaminE 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-birth-weight infants also increases. For example, low-birth-weight infants receiving a formula supple-mented with iron (12 mg/liter) and high in
polyunsaturated fats have a greater incidence of RBChemolysisand lowerserumtocopherollevels thaninfants receiving formula that hasalow level of iron and is low in polyunsaturated fats.94 Therefore, the Committee on Nutrition
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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 full-term and low-birth-weight infants, the average composition of human milk, and the recent recommendations of the Committee on Nutri-tion71 for proposed standards for infant formula. This information is presented in units per 100 kcal-which relate specific nutrient needs to caloric requirements-andisparticularlyuseful in discussing formulas for low-birth-weight infants because it allows easy comparison of formulas of differing caloric densities.
In manyinstances,formulas forterminfantsare
usedfor feedinglow-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 forlow-birth-weight infants should be somewhat higher than the minimum levels proposed by the Committee for full-term infants; however, all of these recom-mendations can be met within the proposed standards for infantformulas.7
Conclusions
The optimal diet for the low-birth-weight infant may be definedas onethat supports a rate
of growth approximating that of the third trimester of intrauterine life, without imposing stress on the developing metabolic or excretory systems. Celldivision andgrowth ofall tissues in
the infant should proceed at a rapidrate; undue delay in the resumption of
growth
may have seriousandlastingconsequences. Theattainmentof an adequate caloric intake is the primary requirement, and this may be facilitated by the feedingof formulas of caloricdensity greater than thatof human milk. However, the feedingof this typeofformula requiresspecialattentiontoavoid toohighanosmolarloadandtoprovide sufficient water. The use of continuous intragastric or
intrajejunal drip with formulasproviding67or 81
kcal/dlalso may be a safe andpracticalmeans of increasing caloric intake.Caloric intakesof about 120kcal/kg/dayinformula volumes of 150 to200
ml/kg/day will support the desired weight gain in most infants.
An appropriaterequirement forprotein equiv-alent 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 indispens-able to low-birth-weight infants. Thus, the apparentnormalgrowthof infants fed breast milk supplying 1.7 g of protein per kilogram ofbody weightmay becausedinpartbyitsdistribution 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
me-dium-chain
triglycerides, which are well ab-sorbed. Although good absorption of fat is impor-tant-notonly for energyrequirements
but alsotoenhance
the
absorption of fat-soluble vitaminsand 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 low-birth-weight infants who have meager stores of bodyfat. Fatmixturesshouldnotbe toosaturated
or too unsaturated.
The occurrence of hemolytic anemia in low-birth-weight infants has been related to the polyunsaturated fat, vitamin E, and iron content
of the formula. The fortification of infant formulaswithvitaminE, relatedtothe polyunsat-urated fatty acid content, is particularly
impor-tantfor thelow-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 ifiron-supplemented formulasareused in the early weeks oflife.
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 levelsproposed by
the Committee for full-term infants.Lowbodystoresof vitamins,possible defectsin absorption (particularly of fat-soluble vitamins),
526 NUTRITION IN LOW-BIRTH-WEIGHT INFANTS
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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 anddaily oral supplements of vitamins A, C, D, E, andall the B group are recommended.
The long-term effects of early nutrition are important andchallenging aspects of infant nutri-tion. Early feeding of low-birth-weight infants entails a special responsibility because this is a crucial period of development when inadequa-cies, 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, behav-ioral 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.; GilbertB.Forbes, M.D.; James C. Haworth, M.D.; Mary Jane Jesse, M.D.; BufordL. 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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44. MenkesJH,WelcherDW, Levi HS, etal:Relationship of elevated bloodtyrosine tothe ultimate intellec-tualperformanceofprematureinfants. Pediatrics
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contentof plasma andredbloodcells. Am JClin Nutr23:890, 1970.
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54. Fomon S,ZieglerE, VazquezH: Humanmilk and the small prematureinfant. Am JDisChild 131:463,
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SaundersCo, 1974,p 101.
61. Widdowson EM: Absorption and excretion of fat, nitrogen and minerals from "filled" milks by babiesoneweekold. Lancet2:1099, 1965. 62. Freeman CP, Jack EL, Smith LM: Intramolecular
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65. Powers GF: Some observations on the feeding of prematureinfants, basedontwentyyears'
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ence atthe New Haven hospital.Pediatrics 1:145, 1948.
66. Shaw JCL: Evidence for defective skeletal mineraliza-tioninlow-birthweight infants: The absorption of calcium and fat.Pediatrics 57:16, 1976.
67. Tantibhedhyangkul P, Hashim SA: Clinical and physi-ologic aspects of medium-chain triglycerides: Alleviation of steatorrhea in premature infants. Bull NY Acad Med 47:17, 1971.
68. TantibhedhyangkulP, Hashim SA: Medium-chain tri-glyceride feeding in premature infants: Effects on fat and nitrogen absorption. Pediatrics 55:359,
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69. Andrews BF, Lorch V: Improved fat and Ca absorp-tion inL.B.W.infants fed a medium chain trigly-ceride containing formula, abstracted. Pediatr Res 8:378, 1974.
70. Roy CC, Ste-Marie M,Chartrand L, et al: Correction of the malabsorption ofthe preterm infant with a medium-chain triglyceride formula. J Pediatr 86:446, 1975.
71. Committee on Nutrition: Commentary on breast-feeding and infant formulas, including proposed standards for formulas. Pediatrics 57:278, 1976. 72. Auricchio S, Rubino A, Murset G: Intestinal
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73. Boellner SE, Beard AG, Panos TC: Impairment of intestinalhydrolysis of lactose in newborn infants. Pediatrics36:542, 1965.
74. Jarrett EC, Holman GH: Lactose absorption in the premature infant. Arch Dis Child 41:525, 1966. 75. Andrews BF, Cook LN: Low birth-weight infants fed a
new carbohydrate-free formula with different sugars: Growth and clinical course. Am J Clin Nutr 22:845, 1969.
76. Fosbrooke AS, Wharton BA: "Added lactose" and "addedsucrose" cow'smilk formulae in nutrition of lowbirth-weightbabies. Arch Dis Child 50:409, 1975.
77. DuncanDL:Thephysiological effects of lactose. Nutr AbstRev 25:309, 1955.
78. BarberoGJ, Runge G,Fischer D, et al: Investigations
on the bacterial flora, pH, and sugar content in the intestinal tract of infants. J Pediatr 40:152, 1952.
79. CornelyDA, BarnessLA, GyorgyP: Effect of lactose
onnitrogen metabolism andphenol excretion in infants. J Pediatr 51:40, 1957.
80. Shohl AT: Mineral Metabolism. New York, Reinhold Publishing Co, 1939, p 19.
81. Widdowson E: Chemical analysis of the body, in Brozek J (ed): Human Body Composition: Approaches and Applications. Oxford, England, Pergamon Press, 1965.
82. Benjamin HR, Gordon HH, Marples E: Calcium and phosphorus requirements of premature infants.
AmJDis Child65:412, 1943.
83. Hoevels 0, Thilenius OG, Krafczyk S: Untersuchen
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84. Eek S, Gabrielsen LH,Halvorsen S: Prematurity and rickets. Pediatrics 20:63, 1957.
85. Widdowson EM, McCance RA, Harrison GE, Sutton
A: Effect of giving phosphate supplements to
breast-fedbabies on absorption andexcretion of calcium, strontium, magnesium, and phosphorus. Lancet2:1250, 1963.
86. VonSydowG:Astudy ofthedevelopmentof ricketsin
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88. Oppe TE, RedstoneD:Calciumandphosphoruslevels
inhealthynewborninfants givenvarioustypesof milk. Lancet 1:1045, 1968.
89. Tsang RC, Oh W: Serum magnesium levels in low birth weight infants. Am J Dis Child 120:44,
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90. Barness LA, Omans WB, Rose CS, and Gyorgy P:
Progress of premature infants fed a formula containingdemineralized whey.Pediatrics32:52, 1963.
91. Caddell JL, Goddard DR: Studies in protein-calorie
malnutrition: I.Chemical evidence ofmagnesium deficiency. NEnglJ Med276:533, 1967.
92. Tsang RC: Neonatal magnesium disturbances. Am J
DisChild 124:282, 1972.
93. DallmanP:Iron,vitaminE, and folateinthe preterm infant. JPediatr 85:742, 1974.
94. Gorten MK, CrossER: Iron metabolisminpremature infants:II.Preventionofirondeficiency.JPediatr 64:509, 1964.
95. Williams ML, ShottRJ, O'Neal PL, OskiFA: Role of dietary irons and fat on vitamin E deficiency anemiaofinfancy. NEnglJ Med292:887, 1975. 96. Griscom NT, Craig JN, Neuhauser EBD: Systemic
bone disease developing in small premature infants. Pediatrics48:883, 1971.
97. Seely JR, Humphrey GB, Matter BJ: Copper defi-ciency inaprematureinfant fedan ironfortified formula,abstracted. Clin Res 20:107, 1972.
98. Ashkenazi A, Levin S, Djaldetti M, et al: The syndrome of neonatal copper deficiency.
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99. CordanoA: The roleplayedby copperin the physio-pathology and nutrition of the infant and the child. AnnNestle 33:2, 1974.
100. MartmerEE, CorriganKE,Charbeneau HP, SosinA: A study of the uptake of iodine (1-131) by the thyroid of premature infants. Pediatrics 17:503, 1956.
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of reducedgrowthwithhyponatremiainverylow birthweightinfants(VLBW)fed"improved"milk formula, abstracted. Clin Res21:1020, 1973. 104. LevinPK,ReidM,ReillyBJ,etal:latrogenic ricketsin
low-birth-weight infants.J Pediatr78:207, 1971. 105. Strelling MK, Blackledge GD, Goodall HB, Walker
CHM: Megaloblastic anaemia and whole-blood folate levels inpremature infants. Lancet 1:898,
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1966. 50:584, 1972.
106. Vanier TM, Tyas JF: Folic acid status in premature 109. FederalRegister S125.1: 20717 (August 2) 1973. infants. Arch Dis Child 42:57, 1967. 110. Gordon HH, Nitowsky HM, Tildon JT, Levin S: 107. Roberts PM, Arrowsmith DE, Rau SM, Monk-Jones Studies of tocopherol deficiency in infants and ME: Folate state of premature infants. Arch Dis children: V. An interim summary. Pediatrics
Child44:637, 1969. 21:673, 1958.
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TWO CASES OF SUDDEN AND UNEXPLAINED DEATH OF CHILDREN DURING SLEEP AS REPORTED IN 1834
Published case reports of unexpected deathsof infants during sleep prior to the early decades of the 20th century routinely attributed the infant'sdeath 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.
Tothe EditorofTHELANCET.
Sir,-I have latelybeen called upon to examine two children, who, without having been previously indisposed, werefound'dead in bed.
Inthe firstcasethechildwasaboutsixmonthsold, andwaslyinginbedwith itsmother, who discoveredinthemiddleof the night thatit wasdead.Aninquest washelduponthebody, andI was directed, in the absenceof anything like testimony as to the cause of its dissolution, to make apost-mortem investigation. I should mention that the mother statedpositively that the child hadnotlainnearher,.and thatit wasimpossibleitcouldhavebeensuffocated, either fromits mouthhaving been applied to any part of herperson or to thebed 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, andthere was nothingin the stomach to indicate that it hadcome byitsdeath unfairly.Inthechest, however,Ifound,uponthe surface of thethymusgland,numerousspotsof extravasated blood, similarspotsupon the surfaceofthelowerand backpartsof eachlung, and manypatches of ecchymosisupon themargin oftheright ventricle oftheheart, and alongthe courseof the trunk of thecoronary vein.Therewas noengorgement,however, of thepulmonary vessels, ofthe coronaries, orof the vesselsofthe thymus.
Inthesecond case thechildwasfive months old.Ithad beenprettywell, hadbeensuckledby its mother, and laid in bed upon its side, and in about an hour and a half afterwards was discoveredtobe dead. Therewas somefrothymatter inandaboutthemouth, anditshandswere
firmlyclenched. From theposition in which it was found it was impossible itcouldhavebeen smothered.
Theappearancesexhibited in theautopsy werestrikingly the same as inthe firstcase. The contentsof the skull andbellywere in aperfectly natural condition. The extravasatedspots upon thethymus glandwere morenumerousthan in thefirstcase, and those upon the heartandthe surface of thelungswerefewerinnumber.There wasabout halfan ounceofserousfluidinthe
pericardium.
Inthese casesonenaturally asks,-what wasthe cause ofdeath? The similarity of the post-mortemappearanceswouldlead one to suppose that the cause must in each case have beenthe same.
Inthe firstcase Iwasstronglydisposedtothink,inspiteof the evidenceofthemother, that the childmusthave beendestroyed by overlaying it;but afterthe occurrence of thelastcase, where, from all the testimony that could beobtained,itseemedimpossiblethat thechild could have beensuffocated, as itwaslyinginbedbyitself,and was notobstructedinitsbreathingby thebed-clothes, I confessthat the opinion Ihad formed was agood deal shaken, and that I
became almost entirelyat alosshowtoaccountfor deathineither.Inbothcasesthereseems to
havebeen, fromsome cause orother,asuddenandviolentactionof the heart,-andnumerous smallvessels, from the increased force ofitscontraction, appear as aconsequence tohavegiven way. But sotriflingalesion could hardly, in either instance,be supposedtobeofitself sufficient toproduce death,and itiswiththehope thatsomeofyourcorrespondents whomayhaveseen
similar cases,and whomaybe better abletoofferanexplanation of thephenomena theypresent than I am, will take the'trouble ofenlightening me upon the subject, that I am induced to
forwardyou this communication.
Derby, Oct. 19, 1834 SamlW. Fearn
Noted byT. E. C., Jr., M.D.
From Feam SW: Sudden andunexplained death inchildren. Lancet 1:246, 1834.
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