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-birth- In practice, caloric intakes of 110 to 150 weight infants is to obtain a prompt postnatal kcal/kg/day enable most low-birth-weight in- resumption of growth to a rate approximating fants to achieve satisfactory rates of growth. If intrauterine growth because this is believed to infants fail to gain satisfactorily, a higher caloric provide the best possible conditions for subse- intake may be offered. quent normal development. This statement reviews current opinion and practices as well as Caloric Density of the Formula-Water earlier reviews1-5 of the feeding of the low-birth- Requirement weight infant. Although human milk or formulas that provide 67 kcal/dl (20 kcal/oz) are recommended for Caloric Requirement term infants, more concentrated formulas are The basal metabolic rate of low-birth-weight often used for low-birth-weight infants to facili- infants is lower than that of full-term infants tate increased caloric intakes in infants with during the first week of life, but it reaches and limited gastric capacity. Several studies have exceeds that of the full-term infant by the second shown that feeding low-birth-weight infants week. Daily caloric requirements reach 50 to 100 formulas with higher caloric densities results in kcal/kg by the end of the first week of life and faster rates of growth.8-13 Some nurseries now feed usually increase to 110 to 150 kcal/kg in subse- formulas of 81 kcal/dl (24 kcal/oz) and in some quent active growth. instances 91 kcal/dl (27 kcal/oz). The 81-kcal/dl A partition of the daily minimum energy re- concentration supplies most of the water required quirements is shown in Table 1.6 by the infant (150 ml/kg)14 and provides 120 There are considerable variations from these kcal/kg. average values, depending on both biological and The increased protein and mineral levels in environmental factors. Infants who are small for these more concentrated formulas increase the gestational age tend to have a higher basal renal solute load. With the limited capability of metabolic.rate than do premature infants of the the immature kidney for concentrating urine, same weight.7 The degree of physical activity sufficient water may not be supplied if the appears to be a characteristic of the individual formula is too concentrated. Infants consuming infant. Environmental factors may have a greater less than a normal volume of formula are particu- influence than biological variation in determining larly vulnerable because, under constant condi- the total caloric requirements. The maximal tions of extrarenal water loss, the lower the response to cold stress can increase the resting formula intake the greater the proportion of rate of heat production up to 21/2 times.6 Calories water required for renal excretion.'5 Infants expended for specific dynamic action and for whose water balance is threatened (e.g., infants fecal losses are dependent on the composition of exposed to heat, phototherapy, or cold stress, and the milk or formula fed, as well as on individual those with infection or diarrhea) should have variations in absorption of nutrients, particularly formulas of low renal solute load and should not fat. be fed formulas of caloric density greater than 81

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Vol. 60 No. 4 October 1977 519 TABLE I IV fluid is discontinued or hyperglycemia and ESTIMATED REQUIREMENTS FOR CALORIES IN A TYPICAL, hyperosmolality, which may be difficult to GROWING PREMATURE INFANT' control.4 Serum glucose levels should be regularly monitored and glucose infusion rates lowered to Item kcal/kg/Day 0.4 g/kg/hr, or less if the serum glucose level Resting caloric expenditure 50 exceeds 125 mg/dl.4 The first feeding should be Intermittent activity 15 distilled water to avoid excessive damage to the Occasional cold stress 10 lungs if vomiting occurs. Specific dynamic action 8 Fecal loss of calories 12 Protein Requirement Growth allowance 25 Total 120 The optimal protein intake for the low-birth- weight infant has not been precisely defined; 'Data from Sinclair et al.6 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, keal/dl (24 kcal/oz).15 Preterm infants excrete human milk supplies almost 2 g of protein per sodium well,16 17 and late metabolic acidosis seen kilogram per day. The feeding of human milk to in low-birth-weight infants may be related to low premature infants was the preferred practice mineral intake.16-19 Lactic acid-containing formu- until 25 years ago when Gordon et al.32 demon- las should not be fed because they may produce strated that premature infants gained more acidosis.20 weight and retained more nitrogen when fed cow's milk formulas of higher protein content. Alternate Feeding Procedures Subsequent reports have confirmed this, but in When conventional feedings every few hours some reports the increased weight gains with the do not result in the attainment of an adequate higher protein cow's milk formulas were nutrient intake, alternate methods of feeding such attributed in part to increased electrolyte intake as continuous nasogastric drip,21 nasojejunal feed- and subsequent water retention.33-37 However, ing,2223 intravenous (IV) administration of Babson and Bramhall38 found no increase in nutrients supplemented by oral feeding,24 and weight gain when only minerals were added to total IV alimentation25 27 may be tried. However, formula providing 1.8 g of protein per 100 kcal. the hazards and complexities of IV administration In studies designed to determine the protein preclude its use in routine practice.28 Parenteral requirement of low-birth-weight infants, protein administration of (1) 20% glucose and 2.5% amino has been given at levels ranging from 1.7 to 9 acid solution; (2) 12% glucose with 2.5% amino g/kg/day. The feedings have consisted of human acids and 10% soybean oil emulsion; and (3) 12% milk and cow's milk formulas, with the protein glucose, 2.5% amino acids, and 1% alcohol in a content varied by dilution with carbohydrate or volume of 125 to 150 ml/kg/day all provided by the addition of casein or deionized milk or positive nitrogen balance.29 Glucagon levels were whey. Because of the many variables in the lower and growth hormone levels higher in formulas, including types and levels of fat and infants given the fat-free mixtures. Parenteral carbohydrate and levels of vitamins and minerals, feedings appear to increase water retention.30 it is difficult to assess the nutritional adequacy of In a controlled study of the feeding of low- the various formulas used in the studies or to birth-weight infants by continuous nasogastric attribute the findings solely to dietary protein drip,21 satisfactory growth and clinical progress level. were reported with the feeding of human milk Infants fed 1.7 to 2.25 g of protein per kilogram and a simulated human milk formula (67 kcal/dl). per day either from human milk or a cow's milk Feeding was started at the fourth hour of life at formula did not increase in weight36-39 or the rate of 60 ml/kg/day and increased to 300 length38-39 as rapidly as those fed higher intakes, ml/kg/day (200 kcal/kg/day) by the ninth day. In and some developed low levels of serum practice, the latter intake is difficult to achieve. proteins. Although early administration of fluids is The feeding of relatively high levels of protein generally considered beneficial to prevent dehy- (6 to 9 g/kg/day) was associated with hyperpy- dration, excessive weight loss, hypoglycemia, and rexia and lethargy,40 high BUN levels,36 diar- excessive jaundice,4 5 use of 10% glucose parenter- rhea,39 high urinary excretion of phenols,39 clin- ally may cause reactive hypoglycemia when the ical edema,42 late metabolic acidosis, and

Downloaded from www.aappublications.org/news by guest on September 24, 2021 520 NUTRITION IN LOW-BIRTH-WEIGHT INFANTS increased mortality.39 The weight gains obtained breast milk had higher taurine levels than the with the feeding of the high intakes of protein did other formulas. This suggestive study requires not exceed those obtained by the feeding of confirmation. moderate levels.36'39.40 Elevated plasma amino A review of the literature led Cox and Filer53 to acid levels in low-birth-weight infants fed high- conclude that, with an adequate caloric intake, protein formulas suggest that the high protein most low-birth-weight infants will grow satisfac- intake may present an amino acid load that torily on cow's milk formulas supplying 2.25 to exceeds the metabolizing capability of the imma- 5.0 g/kg/day of cow's milk protein. Fomon and ture enzyme systems. Elevated levels of plasma co-workers estimated from hypothetical consider- tyrosine and phenylalanine are not uncommon, a ations that the premature infant requires 3.0 finding related to late maturing of p-hydroxy- g/kg/day or 2.54 g of protein per 100 kcal, phenylpyruvic oxidase.4344 High plasma levels of assuming an intake of 120 kcal/kg/day.54 proline and methionine are also associated with If further studies confirm these findings, high protein intake.45 consideration of protein quality along the lines The amino acid composition of formulas for discussed here may be important in defining the premature infants deserves special attention. optimal protein quantity for low-birth-weight Low-birth-weight infants require some amino infants. With adequate intakes, human milk may acids that are not essential for the term infant. In be the superior feeding for low-birth-weight the balance studies of Snyderman,46 the removal infants. of either cystine or tyrosine from the diet resulted in an impairment of growth and nitrogen reten- Fat tion, and a depression of the level of that partic- The ability of low-birth-weight infants to ular amino acid in the plasma. Infants requiring absorb fat, particularly saturated fat such as cystine also failed to show an increase in plasma butterfat, is relatively poor.55-58 This limitation is cystine level after a methionine load, a finding in associated with liver immaturity and decreased accord with the lack of cystathionase in the livers bile salt synthesis,59 and it is found to a lesser of fetuses and premature infants reported by extent in full-term infants during the first few Sturman et al.47'48 The high levels of cystathionine weeks of life.606' When palmitic acid-a long- in the plasma49 and urine50 of premature infants chain saturated fatty acid-is present in fat, its fed high-protein formulas also suggest that absorption depends on its position in the triglyc- conversion of methionine to cystine is not effi- eride molecule.6263 Early recommendations for cient until some time after birth. the feeding of low-birth-weight infants included Raiha et al.5152 fed low-birth-weight infants the feeding of low-fat formulas.64'65 However, the five formulas, including pooled breast milk. The recognition that the vegetable oils were much breast milk supplied approximately 1.7 g of better absorbed than butterfat and other satu- protein per kilogram per day, two formulas rated fats55 led to use in formulas of vegetable oils, supplied 2.25 g of protein per kilogram per day, or blends of vegetable oils and animal fats. These and two formulas supplied 4.50 g/kg/day. One are absorbed well, as is human milk fat.66 formula at each protein level had a 60:40 ratio of Including medium chain triglycerides as part of whey/casein proteins, and the other two had an the fat in the formula has been shown to improve 18:82 ratio of whey/casein proteins. All infants fat absorption in low-birth-weight infants.67'0 grew equally well when fed 117 kcal/kg/day; Medium-chain triglycerides have also been shown statistically, the breast-fed group gained at a to increase weight gain70 and to enhance calcium slightly lower rate. Significant differences in absorption69 and nitrogen retention.68 plasma amino acid and ammonia levels were Fat in human milk supplies a major proportion noted. The lower ammonia, tyrosine, and phenyl- of the caloric content. Formulas with 40% to 50% alanine levels were found in infants fed whey/ of calories from fat are recommended for the casein of 60:40, and the highest levels were in feeding of low-birth-weight infants because those fed the high-protein formula with casein formulas of a lower fat content may contain predominant. Those fed the high-protein, casein- higher levels of protein which increase renal predominant formula developed late metabolic solute load. acidosis. Serum protein levels were lowest in To meet the normal infant's requirement for infants fed breast milk. essential fatty acids, it is recommended71 that A major difference between the formulas was infant feedings supply 3% of the total calories in the higher content of cystine in the breast milk the form of linoleic acid or 300 mg of linoleic acid and high-whey protein formula. In addition, the per 100 kcal. Proprietary infant formulas with

Downloaded from www.aappublications.org/news by guest on September 24, 2021 AMERICAN ACADEMY OF PEDIATRICS 521 their high content of unsaturated fat supply a mineral contents of the bodies of premature and generous allowance of linoleic acid. term infants.80'81 Body composition data can provide a rough estimate, at best, of the increase Carbohydrate in minerals that the low-birth-weight infant The utilization of carbohydrate by the low- would have accrued had he remained in utero. birth-weight infant differs slightly from that of Because infants with low stores may retain 50% the full-term infant. Intestinal disaccharidases to 70% of the nutrients they are fed, the levels of develop early in fetal life72; maltase and sucrase nutrients supplied by formula must be 1.3 to 2 reach mature values by the sixth to eighth month, times those required to meet their needs. It and lactase reaches it at term. These data suggest appears that minimal levels in formula designed that the low-birth-weight infant can adequately for full-term infants could probably satisfy re- digest disaccharides, although there is some quirements of the low-birth-weight infant for evidence that lactose digestion may not be fully sodium, potassium, chloride, and zinc; would efficient for the first few days of life.73 Low-birth- probably be borderline in copper; and would weight infants develop satisfactorily when fed probably be deficient in iron, calcium, and phos- formulas in which the lactose of the milk has been phorus. Based on these calculations, some changes augmented with sucrose and when fed lactose- in mineral composition might be made in free formulas (i.e., formulas based on soy isolates, formulas intended for use by premature infants to meat or protein hydrolysates and containing achieve a mineral retention equivalent to that in sucrose and/or dextrose, maltose, and dextrins as utero. the carbohydrate). Lactose, sucrose, and maltose oral tolerance tests conducted on 2-week-old, low-birth-weight infants previously fed formulas Calcium and Phosphorus containing either lactose or sucrose as the sole Balance studies and roentgenographic findings carbohydrate revealed no significant differences in low-birth-weight infants suggest that formulas in the utilization of these three disaccharides, made from cow's milk with higher calcium and despite the presence or absence of the substrate phosphorus levels provide greater retention of sugar in the diet for the two weeks preceding the calcium and phosphorus and increased minerali- test.74 In another study of dietary sugars, infants zation of the skeleton than does human grew equally well on soy-isolate formulas milk.64'82-84 Although earlier studies85'86 suggested containing sucrose or dextrose,75 and a slightly that the low phosphorus content of human milk lesser rate with lactose. was the limiting factor in skeleton mineralization, Lactose, as the natural sugar of human milk, work by Day et al.87 suggests that the underminer- has been the usual choice for addition to a cow's alization of bone observed in premature infants milk formula to increase the carbohydrate fed human milk may also be caused by an content up to that of human milk. However, a inadequate calcium intake. In the Day et al.87 recent study with cow's milk formulas found that study of low-birth-weight infants (less than 1,300 the addition of sucrose rather than lactose to the g), infants fed a proprietary formula supple- milk base resulted in a lower incidence of diar- mented with calcium lactate (total calcium, 154 rhea and metabolic acidosis,76 which appears to mg/100 kcal) showed a better-defined bone support the findings of Boellner et al.73 Thus, the texture and wider cortices than infants fed unsup- slight delay in the maturation of intestinal lactase plemented formula containing 63 mg of calcium may be of physiological consequence in some per 100 kcal. Fomon et al.54 have calculated that infants. Usually lactose enhances calcium absorp- premature infants require 132 mg of calcium per tion in the small intestine77 and promotes a 100 kcal. fermentative, less putrefactive bacterial flora78'79 Infant formulas fed to low-birth-weight infants and reduces the incidence of constipation. in the United States (Table II) contain higher levels of calcium and phosphorus than those supplied by human milk, but they are generally Minerals lower than the level used by Day et al.87 or that Two thirds of the mineral content of the body recommended by Fomon et al.54 In clinical of the full-term infant is deposited during the last studies in which low-birth-weight infants were two months of gestation. The amounts of minerals fed current proprietary formulas88'89 or earlier the preterm infant must retain from the diet to formulas of comparable calcium and phosphorus achieve the mineral composition of the full-term content,36'90 no apparent abnormalities of cal- infant might be estimated from the differences in cium/phosphorus metabolism were noted, offer-

Downloaded from www.aappublications.org/news by guest on September 24, 2021 522 NUTRITION IN LOW-BIRTH-WEIGHT INFANTS TABLE II NUTRIENT COMPOSITION OF HUMAN MILK AND PROPRIETARY INFANT FORMULAS AND RECOMMENDED LEVELS FOR FULL-TERM AND LOW-BIRTH-WEIGHT INFANTS'

Nutrient Minimum Human Enfamil PM60/40 Premature Similac SMA Similac Level Milk60 Formula (13, 24, Recoin- or 27 Calo- mendedt riesloz) Protein, g 1.8t 1.3-1.6 2.3 2.3 2.8 2.3 2.3 2.7 Fat, g 3.3§ 5 5.5 5.2 5.1 5.3 5.3 5.3 Carbohydrate, g 10.3 10.3 11.1 11.5 10.6 10.7 10.3 Ash, mg 300 530 320 680 530 370 580 Vitamin A, IU 250 250 250 370 250 370 390 370 Vitamin D, IU 40 3 63 60 63 60 63 60 Vitamin E, IU 0.3(0.7)11 0.3 1.9 2.2 1.9 2.2 1.4 2.2 Vitamin K, jg 4 2 9 4 9 14 9 4 Vitamin C, mg 8 7.8 8.1 8.1 8.0 8.1 8.6 8.1 Thiamin, jig 40 25 78 96 78 96 105 96 Riboflavin, ,jg 60 60 94 147 94 147 156 147 Niacin, ,ug 250 250 1,250 1,074 1,250 1,030 780 1,000 Vitamin B6, Lg 35¶ 15 63 49 63 60 63 60 Folic acid, ug 4 4 16 7.3 16 7.3 8 7.3 Pantothenic acid, ,ug 300 300 470 440 470 440 310 440 Vitamin B12, lAg 0.15 0.15 0.3 0.22 0.3 0.22 0.16 0.22 Biotin, ,tg 1.5 1.0 2.5 1.7 2.5 1.5 3.0 1.5 Inositol, mg 4 20 5 7.5 6 5.0 5.5 Choline, mg 7 13 7 18.8 7 15 13 25 Calcium, mg 50 50 80 60 156 75 66 102 Phosphorus, mg 25# 25 70 30 78 57 49 79 Magnesium, mg 6 6 7 6 10 6 8 6 Iron, mg 0.1500 0.1 0.2tt 0.4 0.2 Tracett 1.9 Tracett Iodine, ,ug 5 4-9 10 6 8 15 10 15 Copper, ug 60 60 100 62 100 60 70 60 Zinc, mg 0.5 0.5 0.65 0.59 0.65 0.74 0.55 0.74 Manganese, ug 55 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 Renal solute load01 ... 11.3 16 14.3 18.1 16.2 13.6 18.4 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

Downloaded from www.aappublications.org/news by guest on September 24, 2021 AMERICAN ACADEMY OF PEDIATRICS 523 ing some assurance that current ranges of Without supplemental iron, the body stores of concentrations are not grossly inadequate for the iron will be depleted sometime after 2 months of feeding of low-birth-weight infants. age rather than after 4 to 6 months of age, as in The hypocalcemia-hyperphosphatemia syn- the normal, full-term infant.93 Orally adminis- drome seen in normal term neonates fed undi- tered iron is well absorbed.94 luted cow's milk has been attributed to immature Although the greater need for iron by the low- homeostatic control of serum phosphate.88 This birth-weight infant has been interpreted to indi- suggests that formulas for low-birth-weight cate that iron-fortified formulas be given as early infants should have a calcium/phosphorus ratio as possible, recent findings show that iron-supple- approaching that of human milk (2.0:1), or at least mented formulas increase the susceptibility of between 1.1:1 and 2.0:1, as recommended for infants to vitamin E deficiency and hemolytic formulas fed to full-term infants.7 anemia, especially when formulas are high in polyunsaturated fatty acids.5 95 (See discussion of Magnesium vitamin E.) These studies leave unresolved the The recommended minimum requirement for question of whether supplementary iron should magnesium in formula for the term infant was be started at 2 months of age or shortly after based on the amount present in human milk, 6 birth.93 They also suggest that formulas for low- mg/100 kcal.71 Clinical experience suggests that birth-weight infants containing more than 1 mg of this amount also suffices for the low-birth-weight iron per 100 kcal should contain moderate infant. Average serum magnesium levels of the amounts of polyunsaturated fats (and ample neonatal, low-birth-weight infant are similar to vitamin E in an absorbable form), and that those adult values.89 Low levels are not uncommon in with higher amounts of polyunsaturated fats the first few days of life, particularly in the small- should contain about 0.1 mg of iron per 100 kcal,' for-gestational-age group, but they rise to adult which is roughly equivalent to the iron present in values within days after feeding of conventional breast milk. formulas.89 Another, more speculative reason for tempo- Magnesium depletion has been observed in rarily delaying the use of iron-fortified formula in infants suffering from the gross malnutrition of low-birth-weight infants comes from recent kwashiorkor,9' and hypomagnesemia, as is true evidence that two iron-binding proteins in human with hypocalcemia, may result from high phos- milk (lactoferrin and transferrin) lose their bacte- phate feedings.92 But, there have been no reports riostatic action when saturated with iron.93 The of magnesium deficiency in healthy, low-birth- bacteriostatic properties of these proteins may be weight infants fed formulas of magnesium content especially important to low-birth-weight infants equal to or in moderate excess over that in human in the early weeks of life. milk. Low-birth-weight infants have been main- Thus, even though the Committee on Nutrition tained for prolonged periods on IV feeding continues to recommend that low-birth-weight containing 2 mg of magnesium per 100 kcal.2f If infants receive 2 mg of iron per kilogram per day the low-birth-weight infant can absorb 33% of the starting at age 2 months or earlier, one cannot magnesium in the formula-a reasonable as- categorically require that formulas provide this sumption-the 6 mg/100 kcal required in the level of iron from birth. Thus, formulas for low- formula would readily supply the 2 mg/ 100 kcal birth-weight infants may provide either 0.1 mg or given intravenously. 1.5 mg of iron per 100 kcal. If they provide the higher level of iron, they should contain ample Iron vitamin E and a moderate level of polyunsatu- The low-birth-weight infant is especially rated fatty acids. susceptible to the development of iron deficiency anemia because its stores of iron are much smaller Copper than those of a full-term infant, and they are The recommended level of copper in infant insufficient to last over a prolonged period when formulas is 60 pgg/100 kcal.71 This level is based on growth must be rapid. Erythrocyte and hemo- early data on human milk. Although copper globin levels are high at birth; the hemoglobin deficiency has not been noted in normal infants iron released by destruction of old RBCs is on customary feedings, several reports96-98 have salvaged and stored for future use. Active erythro- indicated that copper deficiency may develop in poiesis resumes between 1 and 2 months of age, small infants fed formulas not supplemented with and rapidly decreases the size of the iron reserve. copper. Recent data suggest that an intake of 90

Downloaded from www.aappublications.org/news by guest on September 24, 2021 524 NUTRITION IN LOW-BIRTH-WEIGHT INFANTS gtl100 kcal is desirable for low-birth-weight recommended for full-term infants71 until further infants.99 work confirms a higher, suggested need. Iodine Vitamins The recommended minimum requirement of Table II shows the levels of vitamins recom- normal infants (5 ,ug of iodine per 100 keal)71 was mended by the Committee as minimum levels for also based on the iodine content of human milk. infant formulas for full-term infants.7' These The uptake of radioactive iodine by the thyroid apply to formulas based on milk and milk substi- gland of premature infants has been found to be in tutes. The Committee recommends that the same the normal range for children and adults100; there- levels apply to formulas for low-birth-weight fore, we can assume that 5 ,ug of iodine per 100 infants, except for vitamin E. kcal is also adequate for the low-birth-weight However, even with proprietary formulas infant. containing adequate levels of vitamins, premature and low-birth-weight infants often consume much Zinc and Manganese less than 120 kcal/kg/day during the early weeks The Committee on Nutrition has recently of life, and they may not receive sufficient vita- proposed that infant formulas for full-term infants mins to prevent deficiency. For example, rickets supply 0.5 mg of zinc and 5 ,ug of manganese per has been found in premature infants fed proprie- 100 kcal.7' There is no basis for modifying these tary formulas containing 400 IU of vitamin D per recommended levels for low-birth-weight in- liter,104 and. folate and vitamin B1, deficiencies fants. have also been noted'05-'08 when the infants consumed a small volume of formula. Therefore, Other Trace Minerals the Committee recommends that low-birth- Although other minerals (such as cobalt, weight infants receive an intramuscular injection molybdenum, selenium, and chromium) are of 1 to 2 mg of vitamin K at birth and a daily, oral, probably essential in trace amounts for infants, multivitamin supplement providing the recom- there is no information on which to base recommended daily allowance of vitamins for infants as mendations at this time. Fluoride is usually established by the Food and Drug Administra- provided in supplements or as fluoridated tion.'09 water. The vitamin E requirement of low-birth-weight infants merits special consideration. Sodium, Chloride, and Potassium 1. Absorption of vitamin E by these infants is The daily requirements of low-birth-weight poor; Gordon et al.1"0 showed that the levels of infants for sodium, chloride, and potassium can vitamin E usually found in formulas-which are only be roughly estimated from tissue composi- adequate to maintain normal serum tocopherol tion (Table II), because obligatory losses in the levels in term infants-were not sufficient to do so urine and feces and from the skin vary consider- in premature infants. Recently, it was shown that ably. water-soluble forms of vitamin E improve absorp- Minimum levels of sodium, chloride, and potas- tion and result in higher' serum tocopherol sium recommended by the Committee on Nutri- levels."' tion for new formula standards were based on 2. The requirement for vitamin E increases as levels in human milk and should be sufficient for the level of polyunsaturated fats in the diet low-birth-weight infants. There have been a few increases.93 Thus, when formulas are high in reports'01-'03 of hyponatremia in low-birth-weight polyunsaturated fats, the infant needs more infants fed a formula with a concentration of vitamin E. sodium similar to that in human milk. Fomon et 3. When iron levels in the formula are high, al.54 also suggest that the level of sodium in the requirement for vitamin E by low-birth- human milk is not sufficient for the premature weight infants also increases. For example, low- infant; they recommend 30 mg of sodium per 100 birth-weight infants receiving a formula supple- kcal. mented with iron (12 mg/liter) and high in The Committee on Nutrition recommends that, polyunsaturated fats have a greater incidence of to prevent dehydration and disturbances of acid- RBC hemolysis and lower serum tocopherol levels base balances, minimum and maximum levels of than infants receiving formula that has a low level sodium, chloride, and potassium in formulas for of iron and is low in polyunsaturated fats.94 low-birth-weight infants be the same as those Therefore, the Committee on Nutrition recom-

Downloaded from www.aappublications.org/news by guest on September 24, 2021 AMERICAN ACADEMY OF PEDIATRICS 525 mends that formula fed to premature infants ml/kg/day will support the desired weight gain should provide 0.7 IU of vitamin E per 100 kcal in most infants. and at least 1.0 IU of vitamin E per gram of An appropriate requirement for protein equiv- linoleic acid. In addition, the multivitamin alent to casein for the low-birth-weight infant supplement given to low-birth-weight infants would appear to fall in the range of 2.5 to 5.0 should provide 5 IU of vitamin E, preferably in g/kg/day, or 2.25 to 4.5 g/100 kcal. A more water-soluble form. precise statement of optimal protein quantity awaits the definition of optimal protein quality Formula Compositions for low-birth-weight infants. Evidence has been Table II shows the composition of major accumulating that some amino acids considered proprietary formulas available for feeding full- nonessential for the normal infant are indispens- term and low-birth-weight infants, the average able to low-birth-weight infants. Thus, the composition of human milk, and the recent apparent normal growth of infants fed breast milk recommendations of the Committee on Nutri- supplying 1.7 g of protein per kilogram of body tion71 for proposed standards for infant formula. weight may be caused in part by its distribution of This information is presented in units per 100 amino acids. For the larger low-birth-weight kcal-which relate specific nutrient needs to infant, recommendations similar to those for the caloric requirements-and is particularly useful in term infant, including the desirability of breast discussing formulas for low-birth-weight infants feeding, apply.71 because it allows easy comparison of formulas of Fat mixtures in formulas currently in use differing caloric densities. include unsaturated vegetable oils and/or me- In many instances, formulas for term infants are dium-chain triglycerides, which are well ab- used for feeding low-birth-weight infants, and, in sorbed. Although good absorption of fat is impor- other instances, special formulas are available for tant-not only for energy requirements but also to premature and low-birth-weight infants. enhance the absorption of fat-soluble vitamins Discussions in this statement suggest that levels and certain minerals-other aspects must be of some nutrients in formulas for low-birth-weight considered in the selection of ideal formula fat infants should be somewhat higher than the compositions for low-birth-weight infants. The minimum levels proposed by the Committee for fatty acid composition of the diet influences the full-term infants; however, all of these recom- composition of body lipids, especially in low- mendations can be met within the proposed birth-weight infants who have meager stores of standards for infant formulas.7 body fat. Fat mixtures should not be too saturated or too unsaturated. The occurrence of hemolytic anemia in low- Conclusions birth-weight infants has been related to the The optimal diet for the low-birth-weight polyunsaturated fat, vitamin E, and iron content infant may be defined as one that supports a rate of the formula. The fortification of infant of growth approximating that of the third formulas with vitamin E, related to the polyunsat- trimester of intrauterine life, without imposing urated fatty acid content, is particularly impor- stress on the developing metabolic or excretory tant for the low-birth-weight infant because poor systems. Cell division and growth of all tissues in absorption of naturally occurring vitamin E by the infant should proceed at a rapid rate; undue low-birth-weight infants makes them more delay in the resumption of growth may have susceptible to a deficiency. This is especially serious and lasting consequences. The attainment important if iron-supplemented formulas are used of an adequate caloric intake is the primary in the early weeks of life. requirement, and this may be facilitated by the Recent evidence indicates that some mineral feeding of formulas of caloric density greater than requirements (e.g., calcium, sodium, copper) of that of human milk. However, the feeding of this the low-birth-weight infant may be greater per type of formula requires special attention to avoid 100 kcal than for full-term infants. This suggests too high an osmolar load and to provide sufficient that slightly higher levels of these minerals be water. The use of continuous intragastric or present in formulas for low-birth-weight infants intrajejunal drip with formulas providing 67 or 81 than the minimum levels proposed by the kcal/dl also may be a safe and practical means of Committee for full-term infants. increasing caloric intake. Caloric intakes of about Low body stores of vitamins, possible defects in 120 kcal/kg/day in formula volumes of 150 to 200 absorption (particularly of fat-soluble vitamins),

Downloaded from www.aappublications.org/news by guest on September 24, 2021 526 NUTRITION IN LOW-BIRTH-WEIGHT INFANTS and low intakes of formula in the first weeks of 9. Snyderman SE, Holt LE Jr: The effect of high caloric life necessitate the use of vitamin supplements, feeding on the growth of premature infants. J even though a formula adequate for full-term Pediatr 58:237, 1961. 10. Combes MA, Pratt EL: Premature infants and infants is used. A single injection of vitamin K1 at concentrated feeding. Am J Dis Child 102:610, birth and daily oral supplements of vitamins A, C, 1961. D, E, and all the B group are recommended. 11. Flakner F, Steigman AJ, Cruise MO: The physical The long-term effects of early nutrition are development of the premature infant: Some stan- important and challenging aspects of infant nutri- dards and certain relationships to caloric intake. J Pediatr 60:895, 1962. tion. Early feeding of low-birth-weight infants 12. Keitel HG, Chu E: Premature infant feeding: I. The entails a special responsibility because this is a clinical usefulness of caloric concentration of crucial period of development when inadequa- formulas, of early vs. late feeding and of low cies, excesses, or imbalances are most likely to stearic acid content formulas. Pediatr Clin North influence permanent changes. Long-term studies, Am 12:309, 1965. 13. Fomon SJ, Filer LJ Jr, Thomas LN, et al: Relationship still in progress, are attempting to relate feeding between formula concentration and rate of practices in the premature nursery to subsequent growth of normal infants. J Nutr 98:241, 1969. neurologic development, learning ability, behav- 14. Gordon HH, Levine SZ: The metabolic basis for the ioral characteristics, and mental development in individualized feeding of infants, premature and Other pathologic consequences full-term. J Pediatr 25:464, 1944. general. possible 15. Ziegler EE, Fomon SJ: Fluid intake, renal solute load, of improper early nutrition that are legitimate and water balance in infancy. J Pediatr 78:561, areas of concern for the pediatric nutritionist 1971. include atherosclerosis, obesity, hypertension, 16. Aperia A, Broberger 0, Thodenius K, Zetterstrom R: and renal disease. Developmental study of the renal response to an COMMITTEE ON NUTRITION oral salt load in preterm infants. Acta Paediatr Scand 63:517, 1974. 17. Aperia A, Broberger 0, Thodenius K, Zetterstrom R: Members: Lewis A. Barness, M.D., Chairman; Alvin M. Renal response to an oral sodium load in newborn Mauer, M.D., Vice-Chairman; Arnold S. Anderson, M.D.; full term infants. Acta Paediatr Scand 61:670, Peter R. Dallman, M.D.; Gilbert B. Forbes, M.D.; James C. 1972. Haworth, M.D.; Mary Jane Jesse, M.D.; Buford L. Nichols, 18. Radde IC, Chance GW, Bailey K, et al: Growth and Jr., M.D.; Nathan J. Smith, M.D.; Myron Winick, M.D. mineral metabolism in very low birth weight Consultants: William C. Heird, M.D.; 0. L. Kline, Ph.D.; infants: I. Comparison of the effects of two modes Donough O'Brien, M.D. of NaHCO3 treatment of late metabolic acidosis. Pediatr Res 9:564, 1975. 19. Suljok E: Sodium homoeostasis in preterm infants. Lancet 1:930, 1975. 20.. Ballabriga A, Conde C, Gallart-Catala A: Metabolic REFERENCES response of prematures to milk formulas with 1. Holt LE Jr, Snyderman SE: The feeding of premature different lactic acid isomers or citric acid. Helv and newborn infants. Pediatr Clin North Am Paediatr Acta 25:25, 1970. 13:1103, 1966. 21. Valman HB, Heath CD, Brown RJK: Continuous 2. Davidson M: Formula feeding of normal term and low intragastric milk feeds in infants of low birth birth weight infants. Pediatr Clin North Am weight. Br Med J 3:547, 1972. 17:913, 1970. 22. Rhea JW, Kilby JO: A nasojejunal tube for infant 3. Babson SG: Feeding the low-birth-weight infant. J feeding. Pediatrics 46:36, 1970. Pediatr 79:694, 1971. 23. Cheek JA Jr, Staub GF: Nasojejunal alimentation for 4. Dweck HS: Feeding the prematurely born infant: premature and full-term newborn infants. J Fluids, calories and methods of feeding during the Pediatr 82:955, 1973. period of extrauterine growth retardation. Clin 24. Benda GIM, Babson SG: Peripheral intravenous Perinatol 2:183, 1975. alimentation of the small premature infant. J 5. Barness LA: Nutrition for the low birth weight infant. Pediatr 79:494, 1971. Clin Perinatol 2:345, 1975. 25. Wilmore DW, Dudrick SJ: Growth and development 6. Sinclair JC, Driscoll JM Jr, Heird WC, Winters RW: of an infant receiving all nutrients exclusively by Supportive management of the sick neonate: vein. JAMA 203:860, 1968. Parenteral calories, water, and electrolytes. Pedi- 26. Peden VH, Karpel JT: Total parenteral nutrition in atr Clin North Am 17:863, 1970. premature infants. J Pediatr 81:137, 1972. 7. Hill JR, Robinson DC: Oxygen consumption in 27. Driscoll JM Jr, Heird WC, Schullinger JN, et al: Total normally grown, small-for-dates and large-for- intravenous alimentation in low-birth-weight dates new-born infants. J Physiol 199:685, 1968. infants: A preliminary report. J Pediatr 81:145, 8. Hardy JB, Goldstein EO: The feeding of premature 1972. infants: The value of high caloric diets in reducing 28. Committee on Nutrition: Parenteral feeding-A note the length of hospital stay. J Pediatr 38:154, of caution. Pediatrics 49:776, 1972. 1951. 29. Asch MJ, Sperling M, Fiser R, et al: Metabolic and

Downloaded from www.aappublications.org/news by guest on September 24, 2021 AMERICAN ACADEMY OF PEDIATRICS 527 hormonal studies comparing three parenteral content of plasma and red blood cells. Am J Clin nutrition regimens in infants. Ann Surg 182:62, Nutr 23:890, 1970. 1975. 46. Snyderman SE: The protein and amino acid require- 30. Brans YW, Sumners JE, Dweck HS, Cassady G: ments of the premature infant, in Jonxis JHP, Feeding the low birth weight infant: Orally or Vesser HRA, Troelstra JA (eds): Metabolic parenterally? Preliminary results of a comparative Processes in the Foetus and Newborn Infant. study. Pediatrics 54:15, 1974. Baltimore, Williams and Wilkins, 1971. 31. Lonnerdal B, Forsum E, Hambraeus L: The protein 47. Sturman JA, Gaull G, Raiha NCR: Absence of cysta- content of human milk: I. Transversal study of thionase in human fetal liver: Is cystine essential? Swedish normal material. Nutr Rep Int 13:125, Science 169:74, 1970. 1976. 48. Gaull G, Sturman JA, Raiha NCR: Development of 32. Gordon HH, Levine SZ, McNamara H: Feeding of mammalian sulfur metabolism: Absence of cysta- premature infants: A comparison of human and thionase in human fetal tissues. Pediatr Res 6:538, cow's milk. Am J Dis Child 73:442, 1947. 1972. 33. Kagan BM, Stanincova V, Felix NS, et al: Body 49. Valman HB, Brown RJK, Palmer T, et al: Protein composition of premature infants: Relation to intake and plasma amino acids of infants of low nutrition. Am J Clin Nutr 25:1153, 1972. birth weight. Br Med J 4:789, 1971. 34. Goldman HI, Karelitz S, Acs H, Seifter E: The 50. Przyrembel H, Bremer HJ: Cystathioninuria in prema- relationship of the sodium, potassium, and chlo- ture infants. Clin Chim Acta 41:95, 1972. ride concentration of the feeding to the weight 51. Raiha NCR, Heinonen K, Rassin DK, Gaull GE: Milk gain of premature infants. Pediatrics 30:909, protein quantity and quality in low-birthweight 1962. infants: I. Metabolic responses and effects on 35. Kagan BM, Felix N, Molander CW, et al: Body water growth. Pediatrics 57:659, 1976. changes in relation to nutrition of premature 52. Gaull GE, Rassin DK, Raiha NCR, Heinonen K: Milk infants. Ann NY Acad Sci 110:830, 1963. protein quantity and quality in low birth weight 36. Davidson M, Levine SZ, Bauer CH, Dann M: Feeding infants: III. Effects on sulfur amino acids in studies in low birth weight infants: Relationships plasma and urine. J Pediatr 90:348, 1977. of dietary protein, fat, and electrolyte to rates of 53. Cox WM Jr, Filer LJ Jr: Protein intake for low-birth weight gain, clinical courses and serum chemical weight infants. J Pediatr 74:1016, 1969. concentrations. J Pediatr 70:695, 1967. 54. Fomon S, Ziegler E, Vazquez H: Human milk and the 37. Levin B, Mackay HMM, Neill CA, et al: Weight small premature infant. Am J Dis Child 131:463, Gains, Serum Protein Levels and Health of Breast 1977. Fed and Artificially Fed Infants, special report 55. Tidwell HC, Holt LE Jr, Farrow HL, Neale S: Studies series No. 296. London, Medical Research Coun- in fat metabolism: III. Fat absorption in prema- cil, 1959. ture infants and twins. J Pediatr 6:481, 1935. 38. Babson SG, Bramhall JL: Diet and growth in the 56. Gordon HH, Levine SZ, Wheatley MA, Marples E: premature infant: The effect of different dietary Respiratory metabolism in infancy and in child- intakes of ash-electrolyte and protein on weight hood: XX. The nitrogen metabolism in premature gain and linear growth. J Pediatr 74:890, 1969. infants-comparative studies of human and cow's 39. Omans WB, Barness LA, Rose CS, Gyorgy P: milk. Am J Dis Child 54:1030, 1937. Prolonged feeding studies in premature infants. J 57. Soderhjelm L: Fat absorption studies in children: I. Pediatr 59:951, 1961. Influence of heat treatment of milk on fat reten- 40. Goldman HI, Freudenthal R, Holland B, Karelitz S: tion by premature infants. Acta Paediatr 41:207, Clinical effects of two different levels of protein 1952. intake on low birth weight infants. J Pediatr 58. Davidson M, Bauer CH: Patterns of fat excretion in 74:881, 1969. feces of premature infants fed various prepara- 41. Nichols MM, Danford BH: Feeding premature infants: tions of milk. Pediatrics 25:375, 1960. A comparison of effects on weight gain, blood and 59. Watkins JB, Szczepanik P, Gould JB, et al: Bile salt urine of two formulas with varying protein and metabolism in the human premature infant. ash composition. South Med J 59:1420, 1966. Gastroenterology 69:706, 1975. 42. Snyderman SE, Boyer A, Kogut MD, Holt LE Jr: The 60. Fomon SJ: Infant Nutrition, ed 2. Philadelphia, WB protein requirement of the premature infant: I. Saunders Co, 1974, p 101. The effect of protein intake on the retention of 61. Widdowson EM: Absorption and excretion of fat, nitrogen. J Pediatr 74:872, 1969. nitrogen and minerals from "filled" milks by 43. Levine SZ, Gordon HH, Marples E: Defect in the babies one week old. Lancet 2:1099, 1965. metabolism of tyrosine and phenylalanine in 62. Freeman CP, Jack EL, Smith LM: Intramolecular premature infants: II. Spontaneous occurrence fatty acid distribution in the milk fat triglycerides and eradication by vitamin C. J Clin Invest of several species. J Dairy Sci 48:853, 1965. 20:209, 1941. 63. Mattson FH, Volpenhein RA: Rearrangement of glyc- 44. Menkes JH, Welcher DW, Levi HS, et al: Relationship eride fatty acids during digestion and absorption. J of elevated blood tyrosine to the ultimate intellec- Biol Chem 237:53, 1962. tual performance of premature infants. Pediatrics 64. Gordon HH, McNamara H: Fat excretion of prema- 49:218, 1972. ture infants: I. Effect on fecal fat of decreasing fat 45. Snyderman SE, Holt LE Jr, Norton PM, Phansalkar intake. Am J Dis Child 62:328, 1941. SV: Protein requirement of the premature infant: 65. Powers GF: Some observations on the feeding of II. Influence of protein intake on free amino acid premature infants, based on twenty years' experi-

Downloaded from www.aappublications.org/news by guest on September 24, 2021 528 NUTRITION IN LOW-BIRTH-WEIGHT INFANTS ence at the New Haven hospital. Pediatrics 1:145, breast-fed babies on absorption and excretion of 1948. calcium, strontium, magnesium, and phosphorus. 66. Shaw JCL: Evidence for defective skeletal mineraliza- Lancet 2:1250, 1963. tion in low-birthweight infants: The absorption of 86. Von Sydow G: A study of the development of rickets in calcium and fat. Pediatrics 57:16, 1976. premature infants. Acta Paediatr Scand (Suppl) 67. Tantibhedhyangkul P, Hashim SA: Clinical and physi- 2:33, 1946. ologic aspects of medium-chain triglycerides: 87. Day GM, Chance GW, Radde IC, et al: Growth and Alleviation of steatorrhea in premature infants. mineral metabolism in very low birth weight Bull NY Acad Med 47:17, 1971. infants: II. Effects of calcium supplementation on 68. Tantibhedhyangkul P, Hashim SA: Medium-chain tri- growth and divalent cations. Pediatr Res 9:568, glyceride feeding in premature infants: Effects on 1975. fat and nitrogen absorption. Pediatrics 55:359, 88. Oppe TE, Redstone D: Calcium and phosphorus levels 1975. in healthy newborn infants given various types of 69. Andrews BF, Lorch V: Improved fat and Ca absorp- milk. Lancet 1:1045, 1968. tion in L.B.W. infants fed a medium chain trigly- 89. Tsang RC, Oh W: Serum magnesium levels in low ceride containing formula, abstracted. Pediatr Res birth weight infants. Am J Dis Child 120:44, 8:378, 1974. 1970. 70. Roy CC, Ste-Marie M, Chartrand L, et al: Correction 90. Barness LA, Omans WB, Rose CS, and Gyorgy P: of the malabsorption of the preterm infant with a Progress of premature infants fed a formula medium-chain triglyceride formula. J Pediatr containing demineralized whey. Pediatrics 32:52, 86:446, 1975. 1963. 71. Committee on Nutrition: Commentary on breast- 91. Caddell JL, Goddard DR: Studies in protein-calorie feeding and infant formulas, including proposed malnutrition: I. Chemical evidence of magnesium standards for formulas. Pediatrics 57:278, 1976. deficiency. N Engl J Med 276:533, 1967. 72. Auricchio S, Rubino A, Murset G: Intestinal glycosi- 92. Tsang RC: Neonatal magnesium disturbances. Am J dase activities in the human embryo, fetus and Dis Child 124:282, 1972. newborn. Pediatrics 35:944, 1965. 93. Dallman P: Iron, vitamin E, and folate in the preterm 73. Boellner SE, Beard AG, Panos TC: Impairment of infant. J Pediatr 85:742, 1974. intestinal hydrolysis of lactose in newborn infants. 94. Gorten MK, Cross ER: Iron metabolism in premature Pediatrics 36:542, 1965. infants: II. Prevention of iron deficiency. J Pediatr 74. Jarrett EC, Holman GH: Lactose absorption in the 64:509, 1964. premature infant. Arch Dis Child 41:525, 1966. 95. Williams ML, Shott RJ, O'Neal PL, Oski FA: Role of 75. Andrews BF, Cook LN: Low birth-weight infants fed a dietary irons and fat on vitamin E deficiency new carbohydrate-free formula with different anemia of infancy. N Engl J Med 292:887, 1975. sugars: Growth and clinical course. Am J Clin 96. Griscom NT, Craig JN, Neuhauser EBD: Systemic Nutr 22:845, 1969. bone disease developing in small premature 76. Fosbrooke AS, Wharton BA: "Added lactose" and infants. Pediatrics 48:883, 1971. "added sucrose" cow's milk formulae in nutrition 97. Seely JR, Humphrey GB, Matter BJ: Copper defi- of low birth-weight babies. Arch Dis Child 50:409, ciency in a premature infant fed an iron fortified 1975. formula, abstracted. Clin Res 20:107, 1972. 77. Duncan DL: The physiological effects of lactose. Nutr 98. Ashkenazi A, Levin S, Djaldetti M, et al: The Abst Rev 25:309, 1955. syndrome of neonatal copper deficiency. Pediat- 78. Barbero GJ, Runge G, Fischer D, et al: Investigations rics 52:525, 1973. on the bacterial flora, pH, and sugar content in 99. Cordano A: The role played by copper in the physio- the intestinal tract of infants. J Pediatr 40:152, pathology and nutrition of the infant and the 1952. child. Ann Nestle 33:2, 1974. 79. Cornely DA, Barness LA, Gyorgy P: Effect of lactose 100. Martmer EE, Corrigan KE, Charbeneau HP, Sosin A: on nitrogen metabolism and phenol excretion in A study of the uptake of iodine (1-131) by the infants. J Pediatr 51:40, 1957. thyroid of premature infants. Pediatrics 17:503, 80. Shohl AT: Mineral Metabolism. New York, Reinhold 1956. Publishing Co, 1939, p 19. 101. Honour JW, Shackleton CHL, Valman HB: Sodium 81. Widdowson E: Chemical analysis of the body, in homoeostasis in preterm infants. Lancet 2:1147, Brozek J (ed): Human Body Composition: 1974. Approaches and Applications. Oxford, England, 102. Willis DM, Roy NR, Chance GW, et al: Growth of Pergamon Press, 1965. very low birth weight (VLBW) infants: Effects of 82. Benjamin HR, Gordon HH, Marples E: Calcium and acidosis, caloric intake and hyponatremia, ab- phosphorus requirements of premature infants. stracted. Pediatr Res 8:452, 1974. Am J Dis Child 65:412, 1943. 103. Ackerman I, Chance G, Day G, et al: The association 83. Hoevels 0, Thilenius OG, Krafczyk S: Untersuchen of reduced growth with hyponatremia in very low zum Calcium und Phosphatstoffwechsel Fruhge- birth weight infants (VLBW) fed "improved" milk borener. Monatsschr Kinderheilkd 108:112, formula, abstracted. Clin Res 21:1020, 1973. 1960. 104. Levin PK, Reid M, Reilly BJ, et al: latrogenic rickets in 84. Eek S, Gabrielsen LH, Halvorsen S: Prematurity and low-birth-weight infants. J Pediatr 78:207, 1971. rickets. Pediatrics 20:63, 1957. 105. Strelling MK, Blackledge GD, Goodall HB, Walker 85. Widdowson EM, McCance RA, Harrison GE, Sutton CHM: Megaloblastic anaemia and whole-blood A: Effect of giving phosphate supplements to folate levels in premature infants. Lancet 1:898,

Downloaded from www.aappublications.org/news by guest on September 24, 2021 AMERICAN ACADEMY OF PEDIATRICS 529 1966. 50:584, 1972. 106. Vanier TM, Tyas JF: Folic acid status in premature 109. Federal Register 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 Child 44:637, 1969. 21:673, 1958. 108. Pathak A, Godwin HA, Prudent LM: Vitamin B,2 and 111. Gross S, Melhom DK: Vitamin E-dependent anemia in folic acid values in premature infants. Pediatrics the premature infants. J Pediatr 85:753, 1974.

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 post- mortem 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. Derby, Oct. 19, 1834 Saml W. Fearn Noted by T. E. C., Jr., M.D. From Feam SW: Sudden and unexplained death in children. Lancet 1:246, 1834.

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Downloaded from www.aappublications.org/news by guest on September 24, 2021 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 American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1977 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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