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Inhibition of beta-glucuronidase by casein hydrolysate formula.

BACKGROUND: A casein hydrolysate infant formula has been shown to be associated with lower levels of neonatal jaundice than are standard infant formulas. Because beta-glucuronidase is related to neonatal jaundice, this study examined the effect of a casein hydrolysate formula on beta-glucuronidase. METHODS: Beta-glucuronidase activity was measured with or without added dietary components. The beta-glucuronidase sources used were meconium, breast milk, and the purified bovine liver enzyme. The dietary components assayed for their effect on beta-glucuronidase activity included casein hydrolysate formula (Nutramigen), whey-predominant formula (Enfamil), breast milk; enzymatically hydrolyzed casein, and other constituents of the casein hydrolysate formula. Stool samples of 6-day-old infants, who were exclusively fed one of the two formulas or breast milk, were also assayed for inhibition of beta-glucuronidase. RESULTS: Only Nutramigen, enzymatically hydrolyzed casein, and stool from Nutramigen-fed infants consistently demonstrated significant inhibition of beta-glucuronidase activity, ranging from 45% to 85% of that in controls. The inhibition of beta-glucuronidase in purified bovine liver demonstrates a dose response in a pH range from 4 to 7.3. CONCLUSIONS: Hydrolyzed casein contains a beta-glucuronidase inhibitor that, in casein hydrolysate-fed infants, persists after passage through the digestive tract. These data are consistent with the possibility that inhibition of beta-glucuronidase is a mechanism by which infants fed casein hydrolysate have lower jaundice levels than infants fed routine formulas or breast milk. Further study of this mechanism is needed.

Animals↗

The effects of dietary nucleotides on intestinal blood flow in preterm infants.

Nucleotides (NT) are reported to affect development of the immune and gastrointestinal systems, and they are currently added to most term infant formulas. In the present study, dietary NT effects on superior mesenteric artery blood flow were investigated. Formula-fed preterm infants were studied once with a 20 kcal/oz. term infant formula containing 80.6 mg/L of NT (NT+), and once with the same formula with no added NT (NT-) (n = 20, gestational age 28.0 +/- 2.2 wk). A reference group of preterm infants fed human milk was also studied (n = 20, gestational age 29.0 +/- 1.6 wk). Superior mesenteric artery blood flow velocities (BFV) were measured by Doppler ultrasound 15 min before and 30, 60, and 90 min after the start of the feed. BFV rose in all infants from baseline to 30 min after feed initiation, and progressively declined thereafter in infants fed NT- or human milk. However, NT+ feedings were associated with a minimal change in BFV between 60 and 90 min. As a result, the difference in blood flow velocities between baseline and 90 min was significantly greater with the NT+ versus the NT- feedings for the mean, peak systolic, and end diastolic velocities (p = 0.03, 0.05, and 0.03, respectively). BFV after the NT- and human milk feedings were similar. These data suggest that orally administered NT are associated with effects on the intestinal vasculature.

Blood Flow Velocity↗

Growth, fatty acid composition of plasma lipid classes, and plasma retinol and alpha-tocopherol concentrations in full-term infants fed formula enriched with omega-6 and omega-3 long-chain polyunsaturated fatty acids.

Full-term infants fed formula without dietary long-chain polyunsaturated fatty acids (LCF) exhibit significantly lower plasma LCP values than breast-fed infants. We studied prospectively two groups of healthy full-term infants fed conventional infant formula without LCP (F, n = 10) or the same formula enriched with both omega-6 and omega-3 LCP (LCP-F, n = 12). Anthropometric data were obtained and fatty acid (FA) compositions of plasma phospholipids, triglycerides and sterol esters as well as plasma retinol and alpha-tocopherol concentrations were determined at 5 days and 1, 2, 3 and 4 months of age. Gains in weight, length and head circumference did not differ between the two groups throughout the study period. Plasma FA values did not differ at 5 days of age. Between 1 and 4 months of age, plasma phospholipids of infants fed LCP-F consistently had significantly (p < 0.05) higher percentages of arachidonic acid (1 month: 9.7 (0.8) versus 7.0 (1.3) %wt/wt, 4 months: 8.7 (0.5) versus 6.6 (1.0) %wt/wt, median (interquartile range), LCP-F versus F) and docosahexaenoic acid (1 month: 2.9 (0.5) versus 1.6 (0.3) %wt/wt; 4 months: 2.9 (0.4) versus 0.9 (0.3) %wt/wt). Plasma retinol and alpha-tocopherol concentrations did not differ between the two groups throughout the study. We conclude that this form of LCP enrichment of formula for full-term infants effectively enhances plasma LCP contents without detectable adverse effects. The potential effects on functional outcome need to be studied carefully in prospective clinical trials.

Age Factors↗

Tolerance of a soy formula by infants and children.

For a minimum of one month (mean, 54 days), 287 infants and children less than 8 years of age were fed an isolated soy-protein formula. Prior to entry into the study, a cow's milk formula was being fed to 71%, a soy formula to 9%, and cow's milk or other formulas to 20%. Intolerance to cow's milk was reported in 35% of the patients, symptoms indicative of cow's milk intolerance in 23%, diarrhea or gastroenteritis in 18%, a family history of allergy in 13%, and insufficient weight gain, intolerance to other formulas, or constipation in 11%. The patients showed normal increases in weight and length during the study. A significant decrease in the following symptoms were reported in the patients from before to after treatment: abdominal cramps, bloating or gas, colic, diarrhea, fussiness, rashes or eczema, spitting up, waking up crying at night, wheezing, and vomiting. It is concluded that, while receiving soy formula, infants and children continued to thrive normally and that the formula was well tolerated. After receiving soy formula, the frequency of undesirable feeding-related symptoms was reduced in the majority of infants and children.

Body Height↗

Comparison of the oestrogenic effects of infant milk formulae, oestradiol and the phytoestrogen coumestrol delivered continuously in the drinking water to ovariectomised mice.

The potential oestrogenic effects of infant milk formulae, coumestrol and oestradiol delivered in the drinking water were investigated in ovariectomised mice. None of the infant formulae tested (three soya, two cow's milk) produced any uterotrophic or mitotic responses in the reproductive tract, although the soya milks displayed weak oestrogenic activity in vitro. Studies of the interactions between coumestrol and oestradiol were undertaken to investigate claims that phytoestrogens may act as oestrogen antagonists. The responses to coumestrol (100 g/ml drinking water) and 17-oestradiol (100 ng/ml) given separately were similar. Combined administration begun simultaneously produced only additive effects on uterine weight and cell proliferation in the vagina and uterus. While pretreatment with coumestrol for 24 h reduced the mitotic response of the uterus 48 h after placement of an oestradiol implant, the uterine weight increase was unaffected and the apparent reduction in mitoses reflected the natural fluctuations in the underlying cycle of cell proliferation. These studies indicate that coumestrol acts as a typical oestrogen and shows only additive effects with oestradiol. The results also indicate that infant soya milk formulae do not constitute a large enough source of oestrogenic compounds to invoke oestrogenic effects in the reproductive tract of mature mice.

Animals↗

Decreased thymus size in formula-fed infants compared with breastfed infants.

The objective of this research was to investigate if breastfeeding affects the size of the thymus. Ultrasound assessment of the thymic index (a volume estimate) at birth and age 4 months in 47 healthy infants born in the hospital were used. History of feeding mode, body size and illness were registered. At 4 months the geometric mean thymic index (range) was 38.3 (16.2-83.2) in exclusively breastfed infants (n = 21), 27.3 (15.6-50.0) in partially breastfed infants (n = 13) and 18.3 (12.2-32.6) in formula fed infants (n = 13; p = 0.0001, ANOVA). This finding was independent of weight, length, sex and previous or current illness. There was no significant difference in mean thymic index at birth between the three feeding groups and mean thymic index had increased in all three groups from birth to 4 months. For the formula-fed infants it seems that the thymus remains large for a period and then decreases in size after breastfeeding has been terminated. We conclude that the thymus is considerably larger in breastfed than in formula-fed infants at the age of 4 months. The cause of this difference is unknown but human milk contains many immune modulating factors that might cause this effect.

Analysis of Variance↗

Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development.

UNLABELLED: This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC-PUFA) in maternal and child health. The attending investigators involved in the majority of randomized trials examining LC-PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base. CONCLUSIONS: For healthy infants we recommend and strongly support breastfeeding as the preferred method of feeding, which supplies preformed LC-PUFA. Infant formulas for term infants should contain at least 0.2% of total fatty acids as docosahexaenoic acid (DHA) and 0.35% as arachidonic acid (AA). Since preterm infants are born with much less total body DHA and AA, we suggest that preterm infant formulas should include at least 0.35% DHA and 0.4% AA. Higher levels might confer additional benefits and should be further investigated because optimal dietary intakes for term and preterm infants remain to be defined. For pregnant and lactating women we consider it premature to recommend specific LC-PUFA intakes. However, it seems prudent for pregnant and lactating women to include some food sources of DHA in their diet in view of their assumed increase in LC-PUFA demand and the relationship between maternal and foetal DHA status.

Animals↗

Breast-feeding patterns in a Nigerian maternity center.

The immediate postpartum feeding practices and the expected time of introducing infant formula to newborn infants at three maternity wards in Ile-Ife, Oyo State, Nigeria are described. Questionnaires and interview schedules were used to collect the data. Less than 3 per cent of the mothers introduced breast-milk to the infants within one hour after delivery, while the rest did not only feed the infants glucose water, but did so with feeding bottles. The time of initiating breast-feeding by the majority of the mothers ranged from 10 to 18 hours after delivery. The higher the level of education of the mothers, the earlier the expected time of introducing infant formula (p less than 0.05). Essentially, no mothers who had primary or greater education expected to nurse longer than 3 months.

Adolescent↗

Growth patterns of breast fed and formula fed infants in the first 12 months of life: an Italian study.

AIM: To compare the growth patterns of breast fed and formula fed Italian infants in the first 12 months of life using World Health Organisation (WHO) reference data. METHODS: The growth patterns of 73 breast fed infants (36 male, 37 female) and 65 formula fed infants (35 male, 30 female) were compared. Solid foods were introduced with the same weaning schedules from the 5th month in both groups. The weight for age (WA), length for age (LA), and weight for length (WL) z scores (National Center for Health Statistics-WHO data) were calculated at birth, 1, 2, 3, 4, 6, 9, and 12 months. RESULTS: Breast fed infants had the highest z scores (WA, WL) at birth. Breast fed groups had significantly higher growth indices at 1 month (WA, LA), 2 months (WA) and 3 months (WA, LA) of age. Compared to breast fed groups, formula fed infants showed significantly higher WA z score changes in the 1-2, 2-3, 3-4, and 4-6 month intervals. LA z score changes were higher for breast fed infants at 0-1 month and for the formula fed infants at 4-6 months. In the 6-12 month interval growth indices progressively increased for the formula fed infants and declined for infants breast fed for longer (12 months). The 0-12 month changes in WA, LA, and WL z scores were positive for formula fed infants and negative for the 12 month breast fed group. Nevertheless, the 12 month breast fed group showed an absolute WA z score just below 0 (mean (SEM) -0.04 (0.26)) at 12 months. CONCLUSION: The growth pattern of breast fed and formula fed Italian infants differs in the first 12 months of life. This questions the validity of current reference values for monitoring the growth of breast fed infants. Growth indices in breast fed groups, high at birth and closer than expected to the reference at 12 months, may reflect differences in genetic factors, intrauterine conditions, or both.

Body Height↗

Aluminium content in milk powders by inductively-coupled argon plasma--optical emission spectrometry.

Forty-four brands of milk powders and simulated milk powders were analysed for aluminium content using Inductively Coupled Plasma Spectroscopy (ICP-OES) technique. The samples covered the full range of infant food items available in Singapore--full-cream milk formula, infant formula, fortified infant formula and milk-free soy protein formula. ICP-OES technique was employed for the analysis. Most samples analysed were found to contain less than 1 mg aluminium per kg powder. The highest aluminium content found was 15.0 mg aluminium per kg powder in a milk-free soy protein formula. The study found that ICP-OES is a convenient and accurate technique for trace metal analysis. However, considerable care needs to be exercised in the selection of emission lines of the metal under analysis to avoid error caused by emission from other metal present in the sample.

Aluminum↗

Cholesterol metabolism in adult baboons is influenced by infant diet.

We tested the hypothesis that preweaning diet alters cholesterol metabolism in adult baboons. Eighty baboons, progeny of 6 sires and 80 dams, were either breast-fed or fed one of three infant formulas containing 2, 30 or 60 mg cholesterol/100 mL. At 16 wk of age the baboons were weaned to one of four diets containing 1.0 or 0.01 mg cholesterol/kcal with 40% of energy from saturated [polyunsaturated fat/saturated fat [P/S) = 0.37] or unsaturated fat [P/S = 2.1] and maintained on these diets until they were necropsied as young adults at 7-8 yr of age. We observed no significant effects of formula cholesterol content on serum lipid or lipoprotein concentrations measured at 6-8 yr of age, but formula cholesterol intake influenced the cholesterol turnover rate and several variables of cholesterol metabolism in the adult. At 6-8 yr, baboons that were breast-fed during infancy, compared with those that were formula-fed, had lower high-density lipoprotein cholesterol (HDL-C) concentrations and higher ratios of very-low-density plus low-density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C. Breast-fed baboons, as adults, had lower cholesterol production rates, masses of the rapidly exchanging cholesterol compartment (pool A) and neutral steroid excretion rates than did those fed formula as infants. Breast and formula feeding differentially influenced the adult metabolic responses to dietary cholesterol or fat saturation. These results demonstrate that breast vs. formula feeding in infancy alters cholesterol metabolism and serum lipoprotein concentrations in adult baboons.

Aging↗

[Clinical consequences of replacing milk with yogurt in persistent infantile diarrhea].

Persistent diarrhea is an episode of diarrhea that begins acutely but lasts longer than expected for this usually self-limited disease. Treatment of this ill-defined syndrome is not well standardized but immediate intervention is required to minimize the risk of malnutrition with its various consequences. This randomized clinical trial was undertaken to evaluate the clinical efficacy of substituting yogurt for milk, as the only treatment. After a one to two-day observation period during which a standard milk diet was given, 78 children aged 3 to 36 months with confirmed persistent diarrhea of more than 15 days but less than one month duration and negative tests for fecal blood were fed either milk (infant formula) or yogurt (infant formula fermented with Lactobacillus bulgaricus and Streptococcus thermophilus). At inclusion both groups were comparable for age, nutritional status, diarrhea, and lactose hydrogen breath test results. Clinical treatment failure (weight loss greater than 5% in one day or persistent diarrhea after 5 days) was significantly less common in children fed yogurt (15 +/- 6%) than in children fed milk (45 +/- 8%). The beneficial effects of feeding yogurt were apparent within 48 hours in 67 +/- 8% of infants. In conclusion, these data confirm the clinical efficacy of substituting yogurt for milk in young children with persistent diarrhea. They also suggest that yogurt may be a good alternative for the initial treatment of persistent diarrhea.

Algeria↗

Breath hydrogen responses in infants using lactose-rice formula and regular lactose formula.

Starch thickened infant formulas have been shown to relieve regurgitation and increase caloric retention. We compared the completeness of digestion of the carbohydrates in lactose-rice formula (study formula) with routine infant formula in infants with GER. A prospective open study of 30 normal, well-nourished infants with simple regurgitation was conducted. The clinical history on regurgitation, stool pattern and baseline breath hydrogen (bH2) test were obtained at entry, with the infants still using their original routine infant formula, and after a wash out period of 7 days, during which they were fed only with study formula. Analysis of bH2 results showed lower levels of bH2 at 1, 2 and 3 hours with study formula compared with the original formula at the 2nd and 3rd hour (p<0.05). The effectiveness of the study formula in managing GER was demonstrated by the fact that 26 out of 30 had either "some improvement" or a "good response." Hardening of the stool pattern was reported in 13 of the 30 infants after 1 week of study formula. The mean of peak bH2 in study formula fed subjects with formed and firm/hard stool was significantly lower than in those with soft and pasty stool. In conclusion, this study has shown the effectiveness of rice thickened infant formulas in managing infants with GER. Rice-starch has an additional advantage of ease of digestion. The hardening of stool pattern was also frequently observed.

Breath Tests↗

Selenium levels in infant milk formula.

Twenty-four brands of commercial infant milk formula were collected and analysed for selenium by inductively coupled plasma spectrometry with the hydride t-system after an acid digestion procedure. The mean selenium concentration was 49.0 +/- 11.55 micrograms l-1, with a range from 26-68 micrograms l-1, resulting in an adequate daily selenium intake for infants aged from zero to six months consuming 0.75 l milk daily as set by the US National Research Council in 1989.

Animals↗

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.

BACKGROUND: The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS: In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS: Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS: The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Aging↗

[In vitro availability of minerals in infant foods with different protein source].

As the result of the digestion process, it is produced at gastrointestinal level interactions between proteins-minerals and minerals-minerals that might modify the bioavailability of the nutrients initially designed for an adequate nutrition in infant formulas. The aim of the present study is to compare the in vitro availability of some minerals and trace elements (calcium, phosphorus, magnesium, iron and zinc) in infant formulas of initiation elaborated with different protein sources: formulas based on cow milk protein (whey-casein) versus vegetal protein (soy-based infant formulas). Also, for evaluating the effects of the different mineral supplementation in the availability of minerals, it was used infant formulas from two different manufacturers. Milk-protein based infant formulas showed for both manufacturers higher dialysis percentage (%) of phosphorus and zinc than the soy-protein based formulas. The availability of iron in the soy formula of the manufacturer A lowered significantly (P < 0.05) respect to the whey-casein based formula (9.6 +/- 2.3 versus 4.6 +/- 0.8), but not respect to the whey-casein formula of manufacturer B (9.6 +/- 1.1 versus 9.0 +/- 0.7), which might be due to the lowest proportion of phytic acid in this last commercial formula. Dialysability of all the minerals analysed from soy-protein based formulas showed significant differences depending on the manufacturer. The purification processes of the soy protein have a high repercussion in the mineral availability of soy-based infant formulas. It could be more interesting to use soy proteins more purified, with low level of phytic acid, in the elaboration of soy infants formulas, than the supplementation them with high amounts of minerals.

Dietary Proteins↗

Blood lipid docosahexaenoic and arachidonic acid in term gestation infants fed formulas with high docosahexaenoic acid, low eicosapentaenoic acid fish oil.

The effect of fish oil high in docosahexaenoic acid (22:6n-3) and low in eicosapentaenoic acid (20:5n-3) in formula on blood lipids and growth of full-term infants was studied. Infants were fed formula with about 15% oleic acid (18:1), 32% linoleic acid (18:2n-6), 4.9% linolenic acid (18:3n-3) and 0, 0.10, or 0.22% 22:6n-3, or 35% 18:1, 20% 18:2n-6, 2.1% 18:3n-3 and 0, 0.11, or 0.24% 22:6n-3 from 3 d to 16 wk of age (n = 16,18,17,21,17,16, respectively). The formulae had < 0.1% 20:5n-3 and no arachidonic acid (20:4n-6). Breast-fed infants (n = 26) were also studied. Plasma phospholipid and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fatty acids were determined at 3 d and 4, 8, and 16 wk of age. These longitudinal analyses showed differences in blood lipid 22:6n-3 between breast-fed and formula-fed infants depending on the feeding duration. At 16 wk, infants fed formula with 0.10, 0.11% 22:6n-3, or 0.22% 22:6n-3 had similar 22:6n-3 levels in the plasma phospholipid and RBC PC and PE compared with breast-fed infants, and higher 22:6n-3 than infants fed formula without 22:6n-3. Formula with 0.24% 22:6n-3, however, resulted in higher plasma phospholipid 22:6n-3 than in breast-fed infants at 16, but not 4 or 8 wk of age. Plasma and RBC phospholipid 20:4n-6 was lower in formula-fed than breast-fed infants, but no differences in growth were found. Higher blood lipid C20 and C22 n-6 and n-3 fatty acids in infants fed formula with 20% 18:2n-6 and 2.4% 18:3n-3 compared with 32% 18:2n-6 and 4.9% 18:3n-3 show the increase in blood lipid 22:6n-3 in response to dietary 22:6n-3 depending on other fatty acids in the formula.

Arachidonic Acid↗

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5&#x2009;kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans↗