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Hypochloremic alkalosis in infants associated with soy protein formula.

Thirteen infants, 2 to 10 months of age, developed hypochloremic alkalosis (serum chloride 59 to 92 mEq/l) while taking Neo-Mull-Soy (Syntex), a soy-based formula low in chloride (measured to be 0 to 2 mEq/l) but with considerable potassium citrate. Range of symptoms included lethargy, anorexia, mild spitting up, diarrhea, hematuria, and growth failure. Urine chloride excretion was less than 3 mEq/l. Plasma renin activity or aldosterone, measured in six infants, was elevated. All responded promptly to supplemental salt. One infant receiving Neo-Mull-Soy redeveloped alkalosis when supplemental salt was discontinued. Two of nine apparently normal infants receiving Neo-Mull-Soy also had hypochloremia (85, 86 mEq/l). Three of four receiving Prosobee (Mead Johnson; Cl content 7 mEq/l) had urine chloride concentration less than 20 mEq/l. The chloride content of some infant formulas is insufficient to offset salt losses following mild stress.

Alkalosis↗

Comparison of two regimens of feeding and oral electrolyte solutions in infants with diarrhea.

BACKGROUND: Glucose-based oral rehydration solutions (ORS) available in the United States do not appear to reduce the severity or duration of diarrhea. The use of cereal-derived ORS and cereal-based feedings appears to diminish the severity of illness in studies conducted in the developing world. To our knowledge, no controlled trials of cereal-derived ORS or cereal-based feedings have been performed in the United States. METHODS: We performed a randomized, double-blind trial of two ORS feeding regimens in outpatients with diarrhea. Patients aged 2-13 months with acute watery diarrhea were enrolled. Subjects received standard glucose-based ORS in alternation with soy-based, lactose-free infant formula (Group 1) or rice syrup solid containing ORS in alternation with rice-based, lactose-free infant formula (Group 2). Subjects were visited at home daily to determine the severity of illness and characteristics of the stool. RESULTS: After the first 2 days, significantly more Group 1 subjects continued to have diarrhea than did Group 2 subjects (median duration of diarrhea 3 vs. 2 days) as demonstrated by Kaplan-Meier survival curves (p = 0.04). CONCLUSION: We conclude that infants fed a regimen consisting of rice syrup solid containing ORS and rice formula resolved their diarrhea sooner than did infants fed a regimen of standard glucose-based ORS and formula. The relative contributions of ORS and formula to this more rapid recovery can be elucidated by further studies.

Diarrhea, Infantile↗

Sensitive periods for lead-induced behavioral impairment (nonspatial discrimination reversal) in monkeys.

A total of 52 nursery-reared monkeys (Macaca fascicularis) were dosed orally with 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): Group 1, vehicle only; Group 2, dosed with lead continuously from birth; Group 3, dosed with lead from birth to 400 days of age and vehicle thereafter; and Group 4, dosed with vehicle from birth to 300 days of age and lead thereafter. This dosing regimen allowed evaluation of differential infant vulnerability as well as reversibility of the behavioral toxicity of lead. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being exposed to lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl during lead exposure after weaning from infant formula. When monkeys were 5-6 years old, they were tested on a series of nonspatial discrimination reversal tasks: form, form with irrelevant color cues, color with irrelevant form cues, and alternating form and color. Group 2 exhibited the greatest degree of impairment compared to controls. Group 4 also exhibited impaired performance, although less marked than that of Group 2. Group 3 was not impaired on this series of tasks. These results confirm findings observed in other monkeys exposed continuously to lead and suggest that while exposure beginning after infancy produces impairment, exposure during infancy as well exacerbates the effect.

Aging↗

Fatty acid formula supplementation and neuromotor development in rhesus monkey neonates.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly concentrated in CNS tissues. Although breast milk contains the fatty acids DHA and arachidonic acid, infant formulas marketed in North America do not contain these nutrients. The potential deleterious effects of rearing infants with formulas devoid of these nutrients was assessed by comparing nursery-reared rhesus macaque infants (Macaca mulatta) fed standard formula with infants fed standard formula supplemented with physiologically relevant concentrations of DHA (1.0%) and arachidonic acid (1.0%). Neurobehavioral assessments were conducted on d 7, 14, 21, and 30 of life using blinded raters. The 30-min assessment consisted of 45 test items measuring orienting, temperament, reflex capabilities, and motor skills. Plasma concentrations of DHA in standard formula-fed infants were significantly lower than those fed supplemented formula or mother-raised (breast-fed) infants; however, infants fed the supplemented formula exhibited higher arachidonic acid levels than either mother-reared infants or infants fed standard formula. Infant monkeys fed the supplemented formula exhibited stronger orienting and motor skills than infants fed the standard formula, with the differences most pronounced during d 7 and 14. This pattern suggests an earlier maturation of specific visual and motor abilities in the supplemented infants. Supplementation did not affect measures of activity or state control, indicating no effect on temperament. These data support the assertion that preformed DHA and arachidonic acid in infant formulas are required for optimal development.

Animal Feed↗

Infant feeding in Nigeria.

A study by questionnaire of 1845 urban and 349 rural mothers in all regions of Nigeria is reported. 99% of all mothers commenced breastfeeding their infants. In urban areas most continued for at least 6 months and in rural areas for at least 12 months. In urban areas, 77% of the infants were given infant formula by the age of 3 months; in rural areas 40% were given infant formula. Cereals were also introduced early to many children. The reasons for and the effects of this pattern of infant feeding are not clear, but it presumably meets the overall needs of the population. Further investigation is needed before attempts are made to enforce change.

Africa↗

A comparative study of elemental composition of human breast milk and infant milk substitutes.

Instrumental neutron activation analysis (INAA) and proton-induced X-ray emission (PIXE) analysis have been employed to determine the concentration of 13 elements in human breast milk, various infant formulas, and locally produced cereals from Nigeria, as well as from various infant formulas and natural cow and goat milk available in the UK. The study shows that if the locally produced cereal is to be used on a regular basis for babies in Nigeria, then their diet must be supplemented with essential trace elements. Furthermore, parents should be discouraged from giving their infants cow and goat milk because of the high concentration of major elements compared to human breast milk.

Adult↗

Zinc status of breastfed and formula-fed infants of different gestational ages.

Zinc status in 186 full term and preterm infants was determined at birth, and 3, 6, 9, and 12 months of age along with determination of zinc levels in breast or formula milk to find out if routine zinc supplements are needed during infancy. The leukocyte and plasma zinc levels in all breastfed infants were high at birth and gradually declined reaching lowest values by 4-6 months of age, and improved to normal levels by 9 months following weaning. The preterm infants however, had significantly (P < 0.05) higher leukocyte zinc (213.6 +/- 46.91 micrograms/10(10) cells) at birth compared to term infants. Colostrum of all the mothers had higher zinc concentrations which declined to significantly lower levels in breastmilk by 4-6 months of lactation, corresponding to the age when the breastfed infants had lower zinc levels. The improvement of the levels to normal after weaning suggests that the fall in zinc status during early infancy could be a transient phenomenon which could be reversed by proper weaning, thus strengthening the plea for timely food supplements rather than the need for single nutrient supplements. Formula-fed full term infants had significantly lower leukocyte zinc levels (49.3 +/- 2.59 micrograms/10(10) cells) at 3 months of age compared to breastfed infants of the same age (92.8 +/- 14.04 micrograms/10(10) cells). Even these infants improved their zinc status after weaning on par with breastfed infants. The functional significance of their transient, but low zinc values during early infancy needs to be investigated.

Analysis of Variance↗

Minerals and trace elements in milk.

The nutritional roles, requirements, and metabolism and the quantitative relationship between dietary intakes and health for a number of the minerals and trace elements have been more clearly defined in recent years, but there are still considerable deficiencies in our understanding of these issues, e.g., the significance of calcium in the etiology and treatment of osteoporosis and hypertension. Reliable information is now available on the content, and the principal factors affecting it, of most of the minerals and trace elements in human and cow's milks. However, for some of the trace elements, there is still a wide variation in reported values in the literature, which is due, at least in part, to analytical difficulties. The contribution of cow milk and milk products to the diet in Western countries is significant for sodium, potassium, chloride, calcium, phosphorus, zinc, and iodine. Iodine is the only trace element for which there has been any suggestion of excessive amounts in cow milk. However, there is evidence of a decline in milk iodine concentrations in the United States in recent years, although the situation in other countries less clear. Breast milk usually has adequate mineral and trace element contents for feeding full-term infants, with the exceptions of fluoride, for which supplementation of infants is recommended, and of selenium in some countries, such as Finland and New Zealand, where maternal intakes are low. However, breast milk selenium contents have increased in these countries in recent years due to increased maternal selenium intakes. The concentrations of minerals and trace elements in infant formulas for full-term infants are generally higher than in human milk, and all appear to be more than adequate, with the possible exception of selenium, which may need to be increased in some formulas. Considerable changes in the mineral and trace element contents of formulas have been instituted in recent years in the light of improved knowledge of infant requirements. While the chemical forms of the macrominerals and some of the trace elements (iron, zinc, copper, and manganese) in milks are fairly well defined, the forms of many of the trace elements are unknown. Sodium, potassium, chloride, and iodine are believed to be almost totally absorbed from milks and infant formulas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of developmental changes and early nutrition on cholesterol metabolism in infancy: a review.

Plasma cholesterol levels usually range between 50 and 100 mg/dl at birth, with the cholesterol approximately equally distributed between low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Plasma cholesterol increases rapidly over the first days after birth, predominantly due to an increase in cholesterol with LDL, irrespective of whether the infant is breast fed or fed with infant formulas. With continued feeding, plasma cholesterol becomes progressively, and significantly, higher in infants who are breast fed compared to those fed low-cholesterol, polyunsaturated fatty acid-rich infant formula. Studies in the developing young of other species have suggested that up-regulation of cholesterol synthesis, or turnover and excretion, at stages when these pathways are acquiring functional maturity may have lasting effects on cholesterol metabolism. The information available, however, indicates the diet-related differences in plasma cholesterol of the more mature human newborn are temporal in nature and probably not of significance to adult cardiovascular disease. Infants born early in the third trimester of gestation, however, are at risk for marked elevations in plasma cholesterol, with stimulation of endogenous cholesterol biosynthesis, as a result of the intravenous nutrition required to sustain life. Whether this has long-term consequences for this group of infants is unknown. There is presently no reason to advocate diet modification to alter the plasma cholesterol of normal infants under the age of 2 years.

Animals↗

Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus.

Acute diarrhoea is a serious cause of infant morbidity and mortality, and the development of preventive measures remains an important goal. Bifidobacteria (which constitute the predominant intestinal flora of breastfed infants), as well as other lactic-acid-producing organisms such as Streptococcus thermophilus, are thought to have a protective effect against acute diarrhoeal disease. However, their efficacy has not been assessed in controlled trials. In a double-blind, placebo-controlled trial, infants aged 5-24 months who were admitted to a chronic medical care hospital were randomised to receive a standard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus. Patients were evaluated daily for occurrence of diarrhoea, and faecal samples, obtained weekly, were analysed for rotavirus antigen by enzyme immunoassay. Faecal samples were also obtained during an episode of diarrhoea for virological and bacteriological analyses. 55 subjects were evaluated for a total of 4447 patient-days during 17 months. 8 (31%) of the 26 patients who received the control formula and 2 (7%) of 29 who received the supplemented formula developed diarrhoea during the course of the study (p = 0.035, Fisher's exact test, two-tailed). 10 (39%) of the subjects who received the control formula and 3 (10%) of those who received the supplemented formula shed rotavirus at some time during the study (p = 0.025). The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital.

Acute Disease↗

Interaction of n-3 long-chain polyunsaturated fatty acids with n-6 fatty acids in suckled rat pups.

The addition of long-chain polyunsaturated fatty acids (LCP: C20, and C22) to infant formula may permit fatty acid accretion rates similar to breast-fed infants, and may have long-term outcome benefits, such as improved visual acuity and cognitive development. Although fish oil may provide a source of n-3 LCP, sources of n-6 LCP have been more difficult to identify. The present study evaluates the effects of n-3 and n-6 LCP derived from single-cell oils on liver, plasma, and brain fatty acid levels in a neonatal animal model. Newborn rat pups were suckled for 14 d by dams receiving diets containing n-3 LCP alone or combinations of n-3 LCP and increasing doses of linoleic acid (18:2n-6) or arachidonic acid (20:4n-6). Dietary groups received 2% n-3 LCP and 1, 2, or 5% of either 18:2n-6 or 20:4n-6. The 20:4n-6 source also contained modest levels of 18:2n-6. At the termination of the study, liver, plasma, and brain were obtained from the rat pups and the phospholipid fatty acid profiles determined. The results indicate complex interactions of n-3 and n-6 fatty acids. Groups receiving dietary 20:4n-6 incorporated higher levels of n-6 LCP into tissues than did the groups receiving 18:2n-6. The brain was relatively resistant to changes in fatty acid composition compared with the liver and plasma. As expected, tissue n-3 LCP levels were reciprocally related to n-6 levels. The present results document that single-cell LCP oils are bioavailable in a neonatal animal model. The use of 20:4n-6 is a more effective means of supporting n-6 status than the use of 18:2n-6. These results may have implications for the addition of LCP to infant formula.

Animals↗

Insulin in human milk and the prevention of type 1 diabetes.

Although controversial, exclusive breast milk feeding was shown to exert a protective effect in preventing type 1 diabetes. In contrast, an early introduction of cow's milk-based formula in young infants may enhance the risk of disease, especially in genetically susceptible children, presumably by an increase of intestinal permeability to macromolecules such as bovine serum albumin and beta-casein, which may arouse autoimmunity. We have shown that human milk contains insulin in substantial concentrations, while insulin is barely detectable (if at all) in infant formulas. Orally administered insulin was demonstrated to promote gut maturation and to reduce intestinal permeability to macromolecules. Furthermore, oral insulin may induce tolerance to insulin and protect against the development of type 1 diabetes. We herewith raise a hypothesis that human milk is protective against the development of type 1 diabetes by virtue of the effects of its substantial content of insulin.

Journal Article↗

Pesticide residues in the Canadian Market Basket Survey--1992 to 1996.

Market basket food samples from six Canadian cities collected from 1992 to 1996 were analysed for pesticide residues. One hundred and thirty-six composites were prepared for each city, representing 99% of the Canadian diet. Residues were found most frequently in peanut butter and butter. DDE, malathion and captan occurred most frequently, while the fungicides chlorothalonil, dicloran and captan were present in the highest concentrations. Processed commodities contained fewer residues and at lower concentrations than the raw products. No residues were detected in either milk or soy-based infant formula. Of the infant foods sampled, fruit contained both the greatest number and highest concentrations of pesticides.

Arachis↗

Bovine lactoferrin and lactoferricin derived from milk: production and applications.

Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk. The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies. In order to apply active lactoferrin to various products, a process for its pasteurization was developed. Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986. A pepsin hydrolysate of lactoferrin is also used in infant formula. This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion. Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography. Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin. Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans. The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system. Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products.

Animals↗

Methemoglobinemia caused by the ingestion of courgette soup given in order to resolve constipation in two formula-fed infants.

Methemoglobinemia is not a rare condition arising from the exposure to hemoglobin-oxidizing agents such as nitrates-nitrites present in well water or vegetables. Infants < 3 months of age are more susceptible than adults because of lower amounts of a key enzyme, NADH-cytochrome b5 reductase, which converts methemoglobin back to hemoglobin. We report 2 infants, aged respectively 2 and 1 months, suffering from methemoglobinemia, fed with a formula that was reconstituted with a high concentration of courgette soup to resolve constipation. They developed a severe cyanosis with methemoglobinemia (respectively 30.4 and 27%) and were hospitalized and treated with methylene blue at 1%. After 12 h the syndrome was completely resolved. Home-prepared infant foods containing vegetables are potential causes of methemoglobinemia. It is important not to feed infants with vegetables having a high nitrate content (e.g., courgette, spinach, beets and green beans) to resolve constipation since, particularly in the first months of life, they may cause severe methemoglobinemia.

Constipation↗

Commentary on the workshop statement. Essentiality of and recommended dietary intakes for Omega-6 and Omega-3 fatty acids.

The Workshop document is welcome and important in its content and objectives. My comments deal with three topics, and are intended to set the historical perspective and take the discussion further as regards attitudes to infant nutrition. 1. ADVERSE ARACHIDONIC EFFECTS. I have some difficulty with the statement on the need to reduce LA (linoleic acid) content of the diet because 'This is necessary to reduce adverse effects of excesses of arachidonic acid and its eicosanoid products.'I have no problem with suggesting a reduction in the present level of LA in the USA but consider the expression 'adverse effects of arachidonic acid ...' to be misleading. Linking LA and AA in this way also implies a direct conversion of LA to AA, which is not the case. In fact, a very high dietary LA will reduce membrane AA. 2. EFA RATIOS. I suspect that their choice of omega 3/omega 6 ratio of 5.7 for early life may be high. Their recommendation for adults gives the much lower ratio of about 1.4. In view of the high requirement for DHA during neural development, I would have thought the ratios would have been the other way round or the same for infants as adults but with AA included in the omega 6. Also, I have some difficulty with the concept of a unitary ratio when there is clear disunity in the biological activities of the different parent and LCP EFAs. Hence the concept of omega 6/omega 3 ratio based on activity equality does not reflect the biological reality. 3. FDA RECOMMENDATIONS ON INFANT FORMULA. The Workshop essentially disagrees with the recent FDA recommendations on inclusion of LCPs in infant formula. There is, in addition, a need to re-think the requirements of the preterm infant beyond their recommendation.

Arachidonic Acid↗

Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth-weight infants.

BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive enteral and parenteral nutriture that provides greater daily riboflavin (vitamin B2) than does term infant nutriture, and elevated plasma riboflavin develops in these infants after birth. The purpose of this study was to measure plasma and urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition. Our hypothesis was that elevated plasma riboflavin develops in VLBW infants because of high daily intake and immature renal riboflavin elimination. METHODS: Eighteen clinically healthy VLBW infants received parenteral nutrition and preterm infant formula during the first postnatal month. On postnatal days 10 and 28, the infants received specially prepared riboflavin-free enteral and parenteral nutrition for the 24-hour study period. Serial collections of plasma were made at time 0 and at 12 and 24 hours. Urine was collected continuously for the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin concentration. RESULTS: During the 24-hour riboflavin-free study period on postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/- SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the 24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5 hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased 40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral nutrition and preterm infant formula had elevated plasma riboflavin on postnatal days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin elimination was greater on postnatal day 28 than on postnatal day 10. Plasma riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of plasma and urine riboflavin in VLBW infants suggests a lower daily intake would maintain plasma riboflavin close to normal.

Aging↗