Low Protein Formula Research Articles

Early Life Factors Influencing the Risk of Obesity.

The obesity epidemic is a worldwide problem. Factors predisposing to obesity include genetics, race, socioeconomic conditions, birth by cesarean section, and perinatal antibiotic use. High protein (HP) content in infant formulas has been identified as a potential culprit predisposing to rapid weight gain in the first few months of life and leading to later obesity. In a large multicountry study the effects of lower protein (LP) formula (1.77 and 2.2 g protein/100 kcal, before and after the 5th month, respectively) were compared to those of higher protein (2.9 and 4.4 g protein/100 kcal, respectively). Results indicated that at 24 months, the weight-for-length z score of infants in the LP formula group was 0.20 (0.06, 0.34) lower than that of the HP group and was similar to that of the breastfed reference group. The authors concluded that a HP content of infant formula is associated with higher weight in the first 2 years of life but has no effect on length. LP intake in infancy might diminish the later risk of overweight and obesity. At 6 years of age HP children had a significantly higher body mass index (by 0.51; 95% confidence interval [CI], 0.13-0.90; p=0.009) and a 2.43 (95% CI, 1.12-5.27; p=0.024) fold greater risk of becoming obese than those who received the LP. In conclusion, several factors may influence development of metabolic syndrome and obesity. Breastfeeding should always be encouraged. An overall reduction of protein intake in formula non breastfed infants seems to be an additional way to prevent obesity.

PO-0598 The Economic Impact Of Low Protein Formula For The Children Of Overweight And Obese Mothers

<h3>Background and aims</h3> Global prevalence of obesity has doubled the last 30 years, with WHO estimating that 10% of men and 14% of women worldwide are obese. The corresponding health risk is associated with a significant health system cost, loss of health related quality of life, and economic costs such as reduced productivity. Obesity in adulthood is the result of several factors, including weight gain during infanthood. The objective of this paper is to demonstrate the impact on infant weight gain and economic value of low protein nutritional formula compared with standard protein nutritional formula. <h3>Methods</h3> A double blind, randomised, controlled trial of 252 healthy infants born of overweight or obese mothers estimated the impact of formula onweight gain up to 36 months. A discrete event simulation estimated the corresponding impact on adult BMI, the incidence of obesity-related diseasesand consequent lifetime changes in health care resources use, health related quality of life (HRQoL), and productivity. <h3>Results</h3> Low protein infant formula reduced weight gain at 36 months by 0.31 kg (from 16.04 kg with standard formula to 15.74 kg with low protein formula). The simulation estimates the corresponding changes in the following outcomes over infants’ lifetimes: a BMI; incidence of diabetes, stroke, CHD; health care costs, HRQoL and productivity. <h3>Conclusions</h3> The use of low protein formula for infants of overweight orobese mothers not only reduces infant weight gain, but also generates lifetime improvements in quality of life, health cost savings and improvements in productivity.

Low‐Protein Formula Slows Weight Gain in Infants of Overweight Mothers

ABSTRACTObjectives:Infant formulas provide more protein than breast milk. High protein intakes, as well as maternal obesity, are risk factors for later obesity. The present study tested whether a formula with lower protein content slows weight gain of infants of overweight mothers (body mass index [BMI] > 25 kg/m2).Methods:In a randomized double-blind study infants of overweight mothers received from 3 months an experimental (EXPL) formula with 1.65 g of protein/100 kcal (62.8 kcal/100 mL) and containing probiotics, or a control (CTRL) formula with 2.7 g of protein/100 kcal (65.6 kcal/100 mL). Breast-fed infants were studied concurrently. Primary assessment was between 3 and 6 months, although formulas were fed until 12 months. Biomarkers of protein metabolism (blood urea nitrogen, insulin growth factor-1, insulinogenic amino acids) were measured.Results:Infants fed the low-protein EXPL formula gained less weight between 3 and 6 months (−1.77 g/day, P = 0.024) than infants fed the CTRL formula. In the subgroup of infants of mothers with BMI > 30 kg/m2 the difference was −4.21 g/day (P = 0.017). Weight (P = 0.011) and BMI (P = 0.027) of EXPL infants remained lower than that of CTRL infants until 2 years but were similar to that of breast-fed infants. Blood urea nitrogen, insulin growth factor-1, and insulinogenic amino acids at 6 months were significantly lower in EXPL compared with CTRL.Conclusions:A low-protein formula with probiotics slowed weight gain between 3 and 6 months in infants of overweight mothers. Weight gain and biomarkers were more like those of breast-fed infants.

Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial

Observational studies have indicated that differences in the composition of human milk and infant formula yield benefits in cognitive development and early growth for breastfed infants. The objective was to test the hypothesis that feeding an infant formula with reduced energy and protein densities and supplemented with bovine milk fat globule membrane (MFGM) reduces differences in cognitive development and early growth between formula-fed and breastfed infants. In a prospective, double-blind, randomized controlled trial, 160 infants <2 mo of age were randomly assigned to be fed an MFGM-supplemented, low-energy, low-protein experimental formula (EF) or a standard formula (SF) until 6 mo of age. The energy and protein contents of the EF and SF were 60 and 66 kcal/100 mL and 1.20 and 1.27 g/100 mL, respectively. A breastfed reference (BFR) group consisted of 80 infants. At 12 mo of age, the cognitive score (mean ± SD) on testing with the Bayley Scales of Infant and Toddler Development, Third Edition, was significantly higher in the EF group than in the SF group (105.8 ± 9.2 compared with 101.8 ± 8.0; P = 0.008) but was not significantly different from that in the BFR group (106.4 ± 9.5; P = 0.73). The EF group ingested larger volumes of formula than did the SF group (864 ± 174 compared with 797 ± 165 mL/d; P = 0.022), fully compensating for the lower energy density. No significant differences in linear growth, weight gain, body mass index, percentage body fat, or head circumference were found between the EF and SF groups. MFGM supplementation to infant formula narrows the gap in cognitive development between breastfed and formula-fed infants. Between 2 and 6 mo of age, formula-fed term infants have the capacity to upregulate their ingested volumes when the energy density of formula is reduced from 66 to 60 kcal/100 mL.

Impact of breast-feeding and high- and low-protein formula on the metabolism and growth of infants from overweight and obese mothers

The combination of maternal obesity in early pregnancy and high protein intake in infant formula feeding might predispose to obesity risk in later life. This study assesses the impact of breast- or formula-feeding (differing in protein content by 1.65 or 2.7 g/100 kcal) on the metabolism of term infants from overweight and obese mothers. From birth to 3 mo of age, infants received exclusively either breast- or starter formula-feeding and until 6 mo, exclusively either a formula designed for this study or breast-feeding. From 6 to 12 mo, infants received complementary weaning food. Metabonomics was conducted on the infants' urine and stool samples collected at the age of 3, 6, and 12 mo. Infant formula-feeding resulted in higher protein-derived short-chain fatty acids and amino acids in stools. Urine metabonomics revealed a relationship between bacterial processing of dietary proteins and host protein metabolism stimulated with increasing protein content in the formula. Moreover, formula-fed infants were metabolically different from breast-fed infants, at the level of lipid and energy metabolism (carnitines, ketone bodies, and Krebs cycle). Noninvasive urine and stool metabolic monitoring of responses to early nutrition provides relevant readouts to assess nutritional requirements for infants' growth.

Increased protein intake augments kidney volume and function in healthy infants

Protein intake has been directly associated with kidney growth and function in animal and human observational studies. Protein supply can vary widely during the first months of life, thus promoting different kidney growth patterns and possibly affecting kidney and cardiovascular health in the long term. To explore this further, we examined 601 healthy 6-month-old formula-fed infants who had been randomly assigned within the first 8 weeks of life to a 1-year program of formula with low-protein (LP) or high-protein (HP) contents and compared them with 204 breastfed (BF) infants. At 6 months, infants receiving the HP formula had significantly higher kidney volume (determined by ultrasonography) and ratios of kidney volume to body length and kidney volume to body surface area than did infants receiving the LP formula. BF infants did not differ from those receiving the LP formula in any of these parameters. Infants receiving the HP formula had significantly higher serum urea and urea to creatinine ratios than did LP formula and BF infants. Hence, in this European multicenter clinical trial, we found that a higher protein content of the infant formula increases kidney size at 6 months of life, whereas a lower protein supply achieves kidney size indistinguishable from that of healthy BF infants. The potential long-term effects of a higher early protein intake on long-term kidney function needs to be determined.

Critical appraisal of the management of severe malnutrition: 2. Dietary management

In the dietary management of severe acute malnutrition in children, there is evidence to support the WHO Manual's protocol of cautious feeding of a low energy and protein formula with small frequent feeds in the initial phase of treatment, particularly in kwashiorkor. However, this initial milk diet (WHO F-75) might benefit from increasing the sulphur amino acid, phosphorus and potassium content and reducing the lactose content, but further studies are needed. Careful tube-feeding results in faster initial recovery and weight gain, but has a significant risk of aspiration in poorly supervised settings. Ready-to-use therapeutic food is an important recent advance in the dietary management of malnutrition in ambulatory settings, allowing more effective prevention programmes and earlier discharge from hospital where community follow-up is available. It should be included in future protocols. There is very good evidence on the use of micronutrients such as zinc, and preliminary evidence suggests that smaller doses of daily vitamin A are preferable to a single large dose on admission for severe malnutrition.

Influence of Protein Source, Type, and Concentration, and Product Form on the Protein Quality of Commercial Enteral Formulas

ABSTRACT: The total, protein, and nonprotein nitrogen, 3 amino acids (lysine, histidine, and tyrosine), available lysine, and in vitro protein digestibility in enteral formulas were determined. Available lysine and protein digestibility were lower in the liquid formulas tested than in the powdered formulas. The protein quality of the formula made from soy protein isolate (soy) was lower than that of the formulas made from casein, and the protein quality of a low‐protein formula was lower than that of the standard formulas. There was a statistically significant correlation between the available lysine content and protein digestibility in the polymeric formulas. New methods are required for assessing the protein quality of formulas containing hydrolyzed proteins.

Continuous Renal Replacement Therapy in the Initial Management of Neonatal Hyperammonemia Due to Urea Cycle Defects

After completing this article, readers should be able to: 1. Describe the metabolic acidosis that may be seen in urea cycle defects. 2. Delineate the most important factor in determining neurologic outcome in urea cycle defects. 3. Explain the factors that affect the blood ammonia concentration in continuous renal replacement therapy (CRRT). 4. Delineate the most difficult issue in pursuing CRRT in neonates. 5. Describe the morbidities associated with CRRT. MP was born at 39 weeks' estimated gestational age by vaginal delivery to a 35-year-old gravida 3 para 2 woman who had an uncomplicated pregnancy. The 3- and 6-year-old female siblings of the patient were healthy. Apgar scores were 8 at 1 minute and 9 at 5 minutes. The newborn was discharged to home after a 2-day stay in the well baby nursery during which time she appeared to be alert and was breastfeeding appropriately. She presented to the emergency department less than 1 day later after her parents noted increasing lethargy and very poor feeding at home. She was admitted to the neonatal intensive care unit (NICU). Results of a complete blood count with differential count and C-reactive protein evaluation were unremarkable, but the patient progressed to worsening lethargy, respiratory failure, and abdominal distension requiring intubation within hours of admission. The anterior fontanelle was soft on admission physical examination. Further testing revealed a base deficit of 6.1 on arterial blood gas, serum ammonia level of 810 mcmol/L (1,134 mcg/dL), serum lactate level of 5.6 mmol/L (5.6 mEq/L), and serum pyruvate level of 0.06 mmol/L. Results of liver function tests were abnormal, and the infant had a prothrombin time of 35.9 seconds, a partial thromboplastin time of 54.3 seconds, and a fibrinogen concentration of 1.75 g/L (175 mg/dL). Genetic and nephrology consultations were requested immediately. Additional metabolic studies were obtained, including measurement of plasma amino …

Serial measurements of GFR in infants using the continuous iothalamate infusion technique

We undertook a preliminary study to determine if a clinical trial was feasible that would compare the effect of a low protein vs a control formula on GFR and growth in infants with congenital renal insufficiency (CIo < 55 ml/min/1.73 m2). In this report from the Infant Diet Protein Study, we describe validation of a method using the plasma clearance of iothalamate (CIo) as an estimate of glomerular filtration rate (GFR) and results of the preliminary study relating to renal function. The plasma CIo method was validated as an accurate estimate of GFR by showing it to be the same as the plasma clearance of inulin (CIn). In the preliminary study infants who qualified for the study were randomly assigned to a low protein or control formula and were followed from 8 to 18 months of age. CIo was measured at 8, 14 and 18 months of age in 21 of the infants and at 8 and 18 months of age in all twenty four infants that entered the study. Average absolute GFR in the 24 infants increased in the 10 month period from 5.3 +/- 2.7 to 7.6 +/- 4.5 ml/min. The percent increase in GFR was no different in infants whose GFR at 8 months of age was severely reduced from those whose GFR was only moderately reduced. When adjusted for age and body size, GFR did not change. Change in mean CIo or serum creatinine (SCr) from 8 to 18 months of age between the infants in each diet groups was not different. We conclude that a clinical trial enrolling more infants and extending the study period is necessary to evaluate dietary protein effect.

Antibody Responses to Parenteral and Oral Vaccines Are Impaired by Conventional and Low Protein Formulas as Compared to Breast‐feeding

The vaccine response to poliovirus, diphtheria and tetanus toxoids in relation to protein intake was studied in infants, either breast-fed or given low (1.1 g/100 ml) or conventional (1.5 g/100 ml) protein formula. Serum, saliva and faeces antibodies were measured by the enzyme-linked immunosorbent assay. Neutralizing poliovirus antibodies were determined. The serum, saliva and faeces antibody responses in the two formula-fed groups of infants did not differ significantly, but for the low protein formula group which had significantly higher serum neutralizing titres to poliovirus after the second vaccine dose than the conventional formula group. However, the breast-fed group had significantly higher antibody levels than the two formula-fed groups together: serum IgG to diphtheria toxoid (p less than 0.01) and serum neutralization of poliovirus (p less than 0.001) at 21-40 months of age, saliva secretory IgA to tetanus (p less than 0.01), diphtheria toxoid (p less than 0.01) and poliovirus (p less than 0.05), as well as faecal IgM to tetanus toxoid (p less than 0.05) and poliovirus (p less than 0.01 and p less than 0.05) at 3 and 4 months of age. Breast-fed infants thus showed better serum and secretory responses to peroral and parenteral vaccines than the formula-fed, whether with a conventional or low protein content.

Late metabolic acidosis and poor weight gain in moderately pre-term babies fed with a casein-predominant formula: a continuing need for caution

When our neonatal unit opened in 1984 our formula feeding policy for moderately preterm babies was for casein-predominant rather than "humanized" whey-predominant milk formulae to be given. However, an early cluster of cases of late persistent metabolic acidosis prompted an investigation into the acid-base status and weight gain in preterm infants. This study of 70 healthy, moderately preterm (32-35 weeks) Chinese babies has convincingly shown that a casein-predominant low protein formula is associated with significant metabolic acidosis, persisting sometimes for as long as 8 weeks, and poor weight gain when compared with infants fed on either a humanized or a special low-birthweight formula. This is an important message for the many neonatal units in developing countries where the cost of humanized formulae might initially seem prohibitive, encouraging instead casein-predominant formulae when breast milk is not available. Any additional expense incurred in using humanized formulae will be compensated for by the shortened time spent in hospital.

87 FORMULA WITH REDUCED PROTEIN CONTENT IN TERM INFANTS DURING WEANING: RESPONSES ON GROWTH AND NITROGEN METABOLISM

20 healthy term infants between 4 and 6 months of age were randomly assigned to either a low protein formula (LP) containing 1.3 g protein/dl or a high protein formula (HP) containing 1.8 g/dl. Both were isocaloric (72 kcal/dl) and had a whey-casein ratio of 50:50. 10 control infants were breast-fed (BF). The mean protein intakes were: 1.9, 2.6 and 1.3 g/kg/d respectively. The mean concentrations of serum urea were 2.8 (LP), 4.1 (HP) and 2.2 mmol/l (BF) at 6 months (HP vs BP p<0.001). The urine excretion of nitrogen were similar in the BE and LP groups, being 75 and 81 mg/kg/d. In the HP-group nitrogen excretion was markedly higher, 138 mg/kg/d. Plasma concentrations of albumin, prealbumin and transferrin were normal and similar among the groups. The concentrations of methionine, threonine, leucine, isoleucine, valine, tyrosine and phenylalanine were significantly elevated in the infants in the HP-group when compared to the BF-group. Weight gain was significantly higher in the HP-group 22.8±1.7 g/kg/week when compared to the LP- and BF-groups, 19.9±3.9 and 18.0±4.3 (p<0.01) respectively. These data indicate that a decreased protein intake from a whey adapted formula during weaning results in many indices of protein metabolism and growth more similar to those found in breast-fed infants than when conventional high protein formulas are used.

Effects of Perinatal Malnutrition on Lipid Composition of Neural Tissues from Rhesus Monkeys

The effects of two forms of early deprivation on the compo sition of neural tissues were assessed. Female rhesus monkeys (Macaca mulatta) were fed a low protein diet prior to conception or from gesta- tional day 50 until the infants were delivered by Caesarean section at gestational day 160; the infant monkeys were then fed a low protein formula until day 195, 5 weeks after birth. In another group of pregnant rhesus monkeys, the bridging vessels between the two discs of the bipartite placenta were ligated at gestational day 90, thereby reducing the func tional placental mass; the infants were delivered at gestational day 155 and also fed a low protein diet until day 195. Control mothers and their infants were fed nutritionally adequate diets throughout. At gestational day 195 the infant body and total weights were significantly lower in nine monkeys of the protein deprivation and six from the placental ligation groups than in nine controls. The most marked reduction in weight was in the brain which here included the corpus collosum, corpus striatum, and external capsule. Significant weight reductions were also found in the cerebellum of both deprived groups and the cerebrum of the protein de ficient group. The concentrations of cerebrosides and sulfatides were 20 to 40 times greater in the pons than in cortical gray matter, reflecting their presence specifically in myelin. Their concentrations in tissue were not affected by the experimental conditions, but total content was signifi cantly reduced in the stem of both deprived groups. The concentra tions of five different classes of phospholipids were lower in the sciatic nerves of protein-deprived monkeys than in controls. J. Nutr. 107; 2228-2235, 1977.

19. Studies of sulfur amino acids in the immature human: Is cyst(e)ine essential?

Cystathionase activity was not measurable in the liver or brain of 24 human fetuses and 4 prematures. Methionie-activating enzyme and cystathionine systhase were present. None of these enzymes of transsulfuration was present in the placenta. Thus cyst(e)ine may be an essential amino acid in the immature human until sometime after birth. A single full term infant who died at 7 hr had 7% of normal cystathionase activity in the liver. Amino acid analyes of simultaneously obtained maternal and fetal blood, amniotic fluid, placenta, fetal liver, and fetal brain were performed. No consistent trends were noted during the period studied. However, the fetal-maternal ratio of all plasma amino acid concentrations at time of abortion was high (as at term). The highest ratio, by far, was that of custine. In some cases, cystine was not measurable in the blood of the mother. Furthermore, in contrast to the mature human, cystathionine, the substrate for cystathonase, was higher in fetal liver than in fetal brain. In spite of this accumulation of cystathionine in fetal liver, there was none measurable in fetal or maternal blood nor in amniotic fluid. These studies suggest that the human fetus is entirely dependent on a maternal source of cyst(e)ine and that prematures and perhaps evn full term newly born infants are dependent upon dietary sourches of cyst(e)ine. Human milk is a high cyst(e)ine, low protein formula, whereas cow's milk is a low cyst(e)ine, high protein formula. Thus, these studies suggest that premature infants fed a high protein cow's milk formula retain more nitrogen and grow faster than infants fed cow's milk formula containing lower amounts of protein, closer to that found in human milk, because the amount of cyst(e)ine, rather than total nitrogen, may be a limiting factor for protein synthesis. Theses results may also afford an enzymatic explanation for the transient hypermethioninemia seen in infants on high protein diets.

Nutritional Studies on Hysterectomy-obtained SPF Baby Pigs Fed Infant Formula Products

Three liquid formula products used for feeding human infants were fed to hysterectomy-obtained SPF (specific pathogen free) pigs from birth to 4 weeks of age to determine whether baby pigs could be raised with these low protein formulas and whether any differences in growth could be attributed to differences in formula composition. The baby pigs grew well but at a somewhat slower rate than those fed a simulated sow's milk formula. The lower weight gains, poorer caloric efficiencies and higher carcass fat levels observed with the infant formula products were related mainly to the low protein levels of the infant formulas. The lowest weight gain was noted with the infant formula which also contained levels of calcium and phosphorus below the requirements of the pig. Femur weights and ash content were also low in pigs fed this formula. Low hemoglobin levels in one group of pigs were apparently related to the low copper level of the formula fed. Some of the other differences in organ weights and composition may also be related to nutritional factors in these diets. The results indicate that the newborn baby pig may be a useful experimental animal for studying human infant formula products and for determining the effects of limiting levels of specific nutritional factors in the diet.

Effects of protein level and type of heat treatment of milk formulas on growth and maturation of infants

Four formulas designed to provide two levels of protein density and sterilized by two different methods (autoclaved and flash sterilized) were assigned to four groups of 27 infants for consumption from birth to 16 weeks of life. In the flash sterilized formulas, corn oil replaced butter fat. The weight gain and anthropometric performance were not significantly different among the various groups. The cholesterol levels in infants receiving formulas with butter fat (autoclaved) were higher than those receiving formulas with corn oil (flash sterilized). Blood urea nitrogen was higher in the infants consuming high-protein formulas. Infants receiving high-protein formulas consumed more calories. The caloric and protein efficiency ratios of low-protein formulas were significantly higher than those of the high-protein formulas, as were the ratios of the low-protein flash sterilized milks in comparison with the low-protein autoclaved ones. This latter difference could be evidence of protein injury resulting from autoclaving in the lower protein formulas.