Feeding normal infants: rationale for recommendations.
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Biomedical subjects
Publications and source records attributed to S J Fomon.
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OBJECTIVE: In infants and children recovering from severe malnutrition, iron deficiency is common, and the ability to absorb iron during such recovery is uncertain. The objective of this study was to determine iron absorption during recovery from malnutrition. METHODS: During the later stages of recovery from malnutrition, erythrocyte incorporation of orally administered 58Fe was determined as a surrogate for iron absorption. Based on four indices, subjects were classified as iron-sufficient, iron-deficient or indeterminate. RESULTS: Of the 25 subjects, 9 were classified as iron sufficient, 5 as indeterminate and 11 as iron deficient; all but 5 had evidence of inflammation or infection. Geometric mean erythrocyte incorporation of 58Fe was 32.0% of the dose in the iron-deficient subjects, which was not significantly different (p = 0.073) than the 13.1% in the iron-sufficient subjects. Incorporation of 58Fe by the iron-sufficient subjects did not differ significantly from that by normal subjects in the same age range. Surprisingly, we found no correlation of erythrocyte incorporation of 58Fe and reticulocyte count. CONCLUSIONS: Even in the presence of infection or inflammation, iron absorption by children during a late stage of recovery from malnutrition is not impaired.
Erythrocyte incorporation of an administered iron isotope has been used as a surrogate for iron retention on the assumption (validated in normal and iron-deficient adults) that 80-100% of the retained isotope is promptly incorporated into circulating erythrocytes. This assumption has not been validated in infants or children. The purpose of our study was to determine concurrently in normal infants absorption and erythrocyte incorporation of the stable isotope, (58)Fe. In a preliminary study (Study 1), we demonstrated that fecal excretion of ingested isotope occurs predominantly during the first 4 d after administration but continues beyond 7 d after ingestion, that is, beyond the point at which isotope in feces can be explained either by excretion of isotope that failed to enter enterocytes or by exfoliation of isotope-enriched enterocytes. In Study 2, we administered (58)Fe to nine younger (age 20-69 d) and nine older (age 165-215 d) term infants and collected feces for 11 d. Geometric mean retention of (58)Fe by the younger infants was 31.2% of intake at 4 d and 26.9% at 11 d, and by the older infants, 35.0% at 4 d and 32.5% at 11 d. Erythrocyte incorporation of (58)Fe 14 d after ingestion was 5.2% of the dose by the younger infants and 12.5% by the older infants. Utilization of retained (11 d) isotope thus was 19.8% by the younger infants and 38.3% by the older infants. We conclude that far less than 80% of retained isotope is promptly incorporated into erythrocytes (utilized) by infants.
As a part of our effort to explore various aspects of ferrokinetics in infancy, the present study was designed to determine the timing of entry of an orally ingested iron isotope into circulating erythrocytes, and the effect of the level of dietary iron [0.3 mg/100 kcal (418.4 kJ) vs. 1.8 mg/100 kcal] after isotope administration on erythrocyte incorporation of the isotope. We administered the stable isotope, (58)Fe, orally to 56-d-old and 168-d-old infants. All infants were fed a low-iron formula (LF) before and until 5 h after isotope administration. Thereafter, half the infants were fed a formula high in iron (HF group) while the remaining infants continued to receive the LF (LF group) for an additional 28 d. The quantity of (58)Fe in circulating erythrocytes increased from 14 to 28 d after isotope administration was nearly constant from 28 through 84 d of age (plateau value) and decreased between 84 and 112 d. Erythrocyte incorporation of (58)Fe was greater by the 168-d-old infants than by the 56-d-old infants, presumably because of the lesser iron stores of the older infants. In the 56-d-old infants, erythrocyte incorporation of (58)Fe was greater by the LF than by the HF group, but this difference was not significant in the 168-d-old infants. Thus, at least in younger infants, the level of iron intake after administration of an iron isotope affects erythrocyte incorporation of the isotope. The fact that less isotope was present in erythrocytes 112 d than 84 d after administration indicates that the life span of erythrocytes of infants, even beyond the immediate newborn period, is less than the 120-d life span of erythrocytes in the adult.
BACKGROUND: Although the predominant beneficial effect of fluoride occurs locally in the mouth, the adverse effect, dental fluorosis, occurs by the systemic route. The caries attack rate in industrialized countries, including the United States and Canada, has decreased dramatically over the past 40 years. However, the prevalence of dental fluorosis in the United States has increased during the last 30 years both in communities with fluoridated water and in communities with nonfluoridated water. Dental fluorosis is closely associated with fluoride intake during the period of tooth development. METHODS: We reviewed the major changes in infant feeding practices that have occurred since 1930 and the changes in fluoride intakes by infants and young children associated with changes in feeding practices. RESULTS AND CONCLUSIONS: Based on this review, we conclude that fluoride intakes of infants and children have shown a rather steady increase since 1930, are likely to continue to increase, and will be associated with further increase in the prevalence of enamel fluorosis unless intervention measures are instituted. RECOMMENDATIONS: We believe the most important measures that should be undertaken are (1) use, when feasible, of water low in fluoride for dilution of infant formulas; (2) adult supervision of toothbrushing by children younger than 5 years of age; and (3) changes in recommendations for administration of fluoride supplements so that such supplements are not given to infants and more stringent criteria are applied for administration to children.
Throughout the world, the most common nutritional deficiency disorder of infants is iron deficiency. Developing effective strategies for preventing iron deficiency requires detailed knowledge of iron retention under ordinary living conditions. For the adult population, such knowledge is at an advanced stage, but relatively little is known about infants. Many reports of iron retention by infants have been based on the assumption that, as in normal and iron-deficient adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating erythrocytes, but this assumption is not supported by available data. This communication presents a review of iron retention by term and preterm infants, as determined by metabolic balance studies or (59)Fe whole-body counting studies, and it explores the relationship between iron retention and postnatal age, iron nutritional status, iron intake (or dose), and type of feeding.
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BACKGROUND: An adequate protein-energy ratio of infant formulas has been defined as one that permits growth similar to that of infants fed relatively generous protein-energy ratios, and serum concentrations of albumin and urea nitrogen no less than those observed in breast-fed infants. A safe ratio has been defined as one with no detectable adverse effects. The hypothesis was that a protein-energy ratio of 1.7 g/100 kcal is adequate and safe. METHODS: Healthy male infants were fed Formula 1.7, a milk-based formula, as the sole source of energy from the 8th to the 112th day of life. Weight, length, and energy intake were measured; serum albumin and urea nitrogen were determined; and the results were compared with data from appropriate reference groups of infants. RESULTS: Energy intake from 8 through 55 days was significantly higher than that of infants in the formula-fed reference group. Gain in weight was significantly more than that of the formula-fed reference group or of a breast-fed reference group, whereas gain in length was similar to that of the formula-fed reference group. Body mass index was significantly higher than that of either reference group, suggesting more fat accumulation in infants fed Formula 1.7. Plasma concentrations of albumin and urea nitrogen were similar to those of the breast-fed reference group. CONCLUSION: Infants fed Formula 1.7 received adequate intakes of protein. Because of the possibility that ad libitum feeding of diets with moderately inadequate protein-energy ratios is associated with increased food intake leading to excess weight gain, it is not possible to conclude that a protein-energy ratio of 1.7 g/100 kcal is safe.
Many infants are fully or partially breast fed during the early months of life; however, the percentage of such infants decreases to about 30 percent by 4 months of age. The majority of US infants are fed formulas for most of the first 10 months of life. Although fluoride (F) intakes by fully breast-fed infants are low, F intakes by partially breast-fed infants and by formula-fed infants are highly variable, depending primarily on the F content of the water used to dilute concentrated liquid or powdered infant formula products. In communities with F content of the drinking water less than 0.3 ppm, F consumption by many infants will be 30 to 40 micrograms.kg-1.d-1. The addition of a F supplement of 0.25 mg/d for a 4 kg infant would increase the F intake by 63 micrograms.kg-1.d-1, resulting in a total intake of about 100 micrograms.kg-1.d-1, an intake in the range believed to be associated with development of fluorosis of the permanent teeth. However, for the US infant population generally, many fewer infants are exposed to high F intakes from formula plus a supplement (recommended only for communities with water providing less than 0.3 ppm F) than from formula alone in communities with F content of 1 ppm in the drinking water. In assessing the possible effects of F intake during infancy on development of fluorosis, it is important to recognize that infant feeding practices have changed greatly during the past 30 years. In the 1960s, most infants over 4 months of age were fed fresh cow's milk and intakes of F were therefore low. By the mid 1970s a trend toward more extended feeding of formula was evident and this trend has continued into the 1990s. Prolonged exposure to high intakes of fluoride during infancy is much more common now than in the past.
Although feeding of formulas with iron concentration of 215 mumol/L (12 mg/L) is a reliable means of preventing iron deficiency, high intakes of iron may adversely affect absorption of copper and zinc. Because data are not available to establish whether fortification at a lower level would result in equivalent iron absorption, we tested the hypothesis that iron absorption is greater by infants fed formulas with an iron concentration of 215 mumol/L (12 mg/L) than by those fed formulas with an iron concentration of 143 mumol/L (8 mg/L). Fifty-two normal infants entered the study at 112 +/- 4 d of age, and 46 of these were successfully studied until 196 d of age. Using the stable isotope 58Fe, we determined erythrocyte incorporation of iron by infants fed Formula 8 [iron approximately 143 mumol/L (8 mg/L)] and by infants fed Similac with Iron [iron approximately 215 mumol/L (12 mg/L)]. On each of three test days beginning at 154 d of age, a major portion of the formula was labeled with 58Fe. Geometric mean erythrocyte incorporation of iron adjusted for plasma ferritin concentration at 168 d of age was 4.82 mumol/d (0.269 mg/d) by infants fed Formula 8 and 5.21 mumol/d (0.291 mg/d) by infants fed Similac with Iron. Corresponding values at 196 d of age were 5.12 and 5.41 mumol/d (0.286 and 0.302 mg/d). The differences in quantity of iron incorporated into erythrocytes by infants fed Formula 8 and Similac with Iron were not statistically significant (P = 0.66 at 168 d of age, P = 0.75 at 196 d of age) and were judged to be nutritionally trivial. Because we were unable to provide support for our hypothesis that iron absorption is greater by infants fed formulas providing 215 mumol (12 mg) of iron per liter than by those fed formulas providing 143 mumol (8 mg) of iron per liter, we conclude that, pending the results of further studies, It is reasonable to decrease the iron concentration of iron-fortified infant formulas.
Iron deficiency is the most prevalent nutrition deficiency among infants and young children in industrialized as well as developing countries. It is a condition that is preventable through appropriate dietary measures. The infant born at term is endowed with a sizable amount of iron, which allows the infant to be fed a nearly iron-free diet (e.g., breast milk) for 4-6 months without becoming overtly iron deficient. This has led some to conclude that depletion of iron stores in healthy infants is a normal and, hence, innocuous process that usually gives way to gradual repletion of iron stores as dietary diversification leads to greater iron intakes. Preservation of maternal iron stores at the expense of infant iron stores may have offered survival advantages to the human species during evolution. But there is no evidence that depletion of iron stores can offer advantages to infants in industrialized or developing countries. On the contrary, there is ample documentation of shortterm as well as long-term adverse effects from iron deficiency. Prudence therefore dictates that a high priority be assigned to the prevention of iron depletion and deficiency among infants and young children worldwide.
Infants eat primarily to satisfy energy needs and the safe amount of protein in infant formulas (ie, the amount adequate for nearly all infants) is therefore expressed as the protein-energy ratio. We studied male infants aged 8-112 d fed milk-based formulas. One group (experimental group) was fed formulas that provided protein-energy ratios of 3.73 g/MJ (1.56 g/100 kcal) from 8 to 27 d of age, gradually decreasing to 2.99 g/MJ (1.25 g/100 kcal) from 84 to 111 d of age. Growth rates and serum albumin and urea nitrogen of these infants were compared with those of a concurrently studied control group and a previously studied large reference group. Gains in weight and concentrations of serum albumin of the three groups were not significantly different. Gains in length were significantly less for the experimental group than for the reference group. Serum urea nitrogen was significantly less in the experimental group than in the control group or reference group. We conclude that the protein-energy ratios of the experimental formula diet were below the safe level. Because the decrease in growth rate of the experimental group was rather small (demonstrable only in comparison with the large reference group), and because serum albumin of the experimental group increased with age as in normally nourished infants, we suspect that the safe protein-energy ratio of infant formulas lies closer to the ratios fed to the experimental group than to the ratio [approximately 5.0 g/MJ (2.1 g/100 kcal)] in currently marketed milk-based formulas.
In an effort to obtain information about absorption of supplemental iron by breast-fed infants during the early months of life, we determined erythrocyte incorporation of a stable iron isotope, administered to 56-d-old breast-fed infants in the form of a 58Fe-labeled vitamin-iron supplement. Infants of similar age fed a milk-based formula low in iron (approximately 4 mg/L) were also studied. The 58Fe-labeled vitamin-iron supplement was given between feedings. Fourteen days after administration of 58Fe, mean erythrocyte incorporation of the isotope was 7.8% of the dose by breast-fed infants and 4.4% of the dose by formula-fed infants. The feeding-related difference was statistically significant, probably reflecting the greater quantities of inhibitors of iron absorption in the intestines of formula-fed infants. With mean iron intake from the 58Fe-labeled vitamin-iron supplement of 7.99 mg for the breast-fed infants, erythrocyte incorporation of 7.8% of the dose corresponded to 0.62 mg, a value in the range of the estimated requirement for absorbed iron. We conclude that 2-mo-old breast-fed infants are able to absorb nutritionally significant amounts of iron from an iron supplement.
There is a widespread belief that an adequate intake of fluoride during the pre-eruptive stage of enamel formation (i.e., from the diet in frequent small doses throughout the day) will be protective against caries in later life. To obtain data on bio-availability and retention of fluoride in one age group (infants), we studied 3 treatment regimens: In Regimen A, small amounts of fluoride were obtained from the diet in frequent doses throughout the day; in Regimen B, a fluoride supplement (0.25 mg) was given once each day with a feeding; Regimen C was similar to regimen B except that the fluoride supplement was given 1 h before a feeding. For the 3 regimens, the respective mean absorptions of fluoride were 90.1, 88.9, and 96.0% of intake, and the respective retentions were 12.5, 47.1, and 52.3% of intake. Neither the difference in absorption nor the difference in retention between regimens B and C was statistically significant. By subtracting the background urinary excretion of fluoride (i.e., excretion of fluoride while diet was the sole source of fluoride) from the excretion after administration of the fluoride supplement, we calculated that 68.1% of the supplement was retained in Regimen B and 73.0% of the supplement in Regimen C. The difference was not significant.
Fluoride pharmacokinetic data are presented for infants given a fluoride supplement. Seventeen infants participated in a total of 20 studies. On one day, 0.013 mmol (0.25 mg) fluoride was given as a supplement (fluoride supplement study), and on another day a placebo was given (control study). Samples of plasma and urine were collected for 5 h and analyzed for fluoride. During control studies fluoride intake averaged 0.15 mumol/kg (2.9 micrograms/kg), and plasma fluoride concentrations ranged from 0.05 to 0.11 mumol/L (10 to 20 micrograms/L). In nine instances, the quantity of fluoride excreted in the urine was more than twice that consumed. When the fluoride supplement was given, total fluoride intake averaged 1.93 mumol/kg (36.6 micrograms/kg). Plasma peak concentration was reached by 30 min in 14 studies and by 60 min in six studies. Mean plasma peak fluoride concentration was 3.3 mumol/L (63 ng/mL). Area under the plasma concentration curve averaged 236 nmol.m-1 x min (4479 ng.mL-1 x min) and was not related to the dose of fluoride. The rate of urinary excretion was significantly correlated with rate of urinary flow. When the dose of fluoride was expressed per unit of body weight, fluoride retention was strongly related to the dose. Retention of the fluoride absorbed from the fluoride dose ranged from 75.4 to 87.6%. Plasma clearance averaged 6.8 mL.kg-1 x min-1 and decreased significantly with age. Net fractional clearance (renal clearance of the fluoride dose/GFR) averaged 56.7%, which was significantly greater than the 29% observed during the control studies.(ABSTRACT TRUNCATED AT 250 WORDS)
As an index of iron absorption, erythrocyte incorporation of the stable isotope, 58Fe, was determined 14 and 42 d after the administration of 58Fe-labeled ferrous sulfate to 56-d-old exclusively breast-fed infants and to infants fed a low-iron (1.8 mg/L) formula. Each infant received a dose of 0.6 to 1.0 mg of iron with ascorbic acid between feedings on each of 3 consecutive d. Fourteen d after administration of the 58Fe-labeled iron doses (age 70 d), arithmetic mean incorporation of the 58Fe label into erythrocytes by breast-fed infants was 20.0% of the dose--only slightly less than that reported for erythrocyte incorporation of iron by fasting adults fed small quantities of 59Fe-labeled human milk. Erythrocyte incorporation of iron by the formula-fed infants was 6.9% of the dose, suggesting that, even between feedings, components of infant formula exerted a major inhibitory effect on iron absorption. For reasons that are not clear, the percentage of the administered label incorporated into erythrocytes was significantly greater in breast-fed (but not in formula-fed infants) at 112 d of age than at 70 d of age.