Energetic efficiency of infant formulae: a review

Breast-fed and formula-fed infants differ in terms of nutrient intake, growth, and metabolic and endocrine responses. The energetic efficiency, i.e. the weight or length gain per 100 kcal of energy intake, of breast-fed infants is about 11% higher than the energetic efficiency of formula-fed infants. Only limited data is available on the influence of formula composition on the energetic efficiency of infant formulae. We conducted a review of controlled trials to identify the impact of the macronutrient composition of infant formulae on energetic efficiency. An electronic literature search was conducted in February 2014. Intervention trials that investigated the effect of an infant formula with a modified macronutrient composition and reported the weight, length, and nutritional intake of apparently healthy, term, fully formula-fed infants with a normal weight were included. Thirteen trials met the inclusion criteria. The results showed no effect of the total content of energy, carbohydrate, protein, or fat on energetic efficiency. In contrast, small increasing effects of higher glycemic carbohydrates on energetic efficiency were identified. Improved fat absorption via the use of palmitic acid at the sn-2 ester position of triacylglycerol increased the energetic efficiency by 11%. The quality of formula protein, specifically an increased whey-to-casein ratio, an increased α-lactalbumin content, or a higher tryptophan content increased the energetic efficiency by about 13%. We conclude that fat absorption and protein quality have the potential to modulate energetic efficiency and may contribute to the observed differences in growth and metabolism between breast-fed and formula-fed infants.</jats:p

Phospholipid Species in Newborn and 4 Month Old Infants after Consumption of Different Formulas or Breast Milk

INTRODUCTION:Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important long-chain polyunsaturated fatty acids for neuronal and cognitive development and are ingredients of infant formulae that are recommended but there is no evidence based minimal supplementation level available. The aim of this analysis was to investigate the effect of supplemented AA and DHA on phospholipid metabolism. METHODS:Plasma samples of a randomized, double-blind infant feeding trial were used for the analyses of phospholipid species by flow-injection mass spectrometry. Healthy term infants consumed isoenergetic formulae (intervention formula with equal amounts of AA and DHA-IF, control formula without additional AA and DHA-CF) from the first month of life until the age of 120 days. A group of breast milk (BM) -fed infants was followed as a reference. RESULTS:The plasma profile detected in newborns was different from 4 month old infants, irrespective of study group. Most relevant changes were seen in higher level of LPC16:1, LPC20:4, PC32:1, PC34:1 and PC36:4 and lower level of LPC18:0, LPC18:2, PC32:2, PC36:2 and several ether-linked phosphatidylcholines in newborns. The sum of all AA and DHA species at 4 month old infants in the CF group showed level of 40% (AA) and 51% (DHA) of newborns. The supplemented amount of DHA resulted in phospholipid level comparable to BM infants, but AA phospholipids were lower than in BM infants. Interestingly, relative contribution of DHA was higher in ether-linked phosphatidylcholines in CF fed infants, but IF and BM fed infants showed higher overall ether-linked phosphatidylcholines levels. CONCLUSION:In conclusion, we have shown that infant plasma phospholipid profile changes remarkably from newborn over time and is dependent on the dietary fatty acid composition. A supplementation of an infant formula with AA and DHA resulted in increased related phospholipid species

Effects of a Follow-On Formula Containing Isomaltulose (Palatinose) on Metabolic Response, Acceptance, Tolerance and Safety in Infants: A Randomized-Controlled Trial

UNLABELLED:Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50) were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™)/100mL) or an isocaloric conventional formula (CF) providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60 min after start of feeding (primary outcome) was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60 min after start of feeding was 122(105,140) mg/dL in IF (median, interquartile range) and 111(100,123) in CF (p = 0.01). Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0) vs. CF:56.8(37.5, 129),p = 0.43). Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045), protein (R = 0.42,p = 0.006) and fat (R = 0.40,p = 0.01) but not with carbohydrate intake (R = 0.22,p = 0.16). Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60 min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants. TRIAL REGISTRATION:ClinicalTrials.gov NCT01627015

Association of infant formula composition and anthropometry at 4 years: Follow-up of a randomized controlled trial (BeMIM study)

The relationships between nutrition, metabolic response, early growth and later body weight have been investigated in human studies. The aim of this follow-up study was to assess the long-term effect of infant feeding on growth and to study whether the infant metabolome at the age of 4 months might predict anthropometry at 4 years of age. The Belgrade-Munich infant milk trial (BeMIM) was a randomized controlled trial in which healthy term infants received either a protein-reduced infant formula (1.89 g protein/100 kcal) containing alpha-lactalbumin enriched whey and long-chain polyunsaturated fatty acids (LC-PUFA), or a standard formula (2.2 g protein/100 kcal) without LC-PUFA, focusing on safety and suitability. Non-randomized breastfed infants were used as a reference group. Of the 259 infants that completed the BeMIM study at the age of 4 months (anthropometry assessment and blood sampling), 187 children participated in a follow-up visit at 4 years of age. Anthropometry including weight, standing height, head circumference, and percent body fat was determined using skinfolds (triceps, subscapular) and bioelectrical impedance analysis. Plasma metabolite concentration, collected in samples at the age of 4 months, was measured using flow-injection tandem mass spectrometry. A linear regression model was applied to estimate the associations between each metabolite and growth with metabolites as an independent variable. At 4 years of age, there were no significant group differences in anthropometry and body composition between formula groups. Six metabolites (Asn, Lys, Met, Phe, Trp, Tyr) measured at 4 months of age were significantly associated with changes in weight-for-age z-score between 1 to 4 months of age and BMI-for-age z-score (Tyr only), after adjustment for feeding group. No correlation was found between measured metabolites and long-term growth (up to 4 years of age). No long-term effects of early growth patterns were shown on anthropometry at 4 years of age. The composition of infant formula influences the metabolic profile and early growth, while long-term programming effects were not observed in this study

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial

Objective: A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. Methods: In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. Results: A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin;per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. Conclusions: All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life

Early-Life Metabolic and Hormonal Markers in Blood and Growth until Age 2 Years:Results from a Randomized Controlled Trial in Healthy Infants Fed a Modified Low-Protein Infant Formula

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age

Infant Feeding Choices during the First Post-Natal Months and Anthropometry at Age Seven Years: Follow-Up of a Randomized Clinical Trial

The Belgrade&ndash;Munich Infant Milk Trial (BeMIM) randomized healthy term infants into either a protein-reduced intervention infant formula (IF) group, with an &alpha;-lactalbumin-enriched whey and long-chain polyunsaturated fatty acids, or a control infant formula (CF) group. A non-randomized breastfed group (BF) was studied for reference. We assessed the long-term effects of these infant feeding choices on growth measures until the age of seven years. Weight, standing height, head circumference, and percent body fat (using skinfolds and bioelectrical impedance) were determined with standardized methods. A total of 161 children out of the 256 completers of the initial study (63%) participated in the seven-year follow-up. Children in the three study groups did not differ in their anthropometric measures, including body mass index (IF 16.1 &plusmn; 2.6, CF: 15.6 &plusmn; 1.7, BF: 15.6 &plusmn; 2.5 kg/m2, mean &plusmn; SD). IGF-1 serum concentrations determined at the age of 4 months contributed to explaining the variances in weight (p = 0.001), height (p = 0.001) and BMI (p = 0.035) z-scores at the age of seven years, whereas insulin levels at four months did not. Different feeding choices during the first four months of life leading to higher energy efficiency and increased growth with IF did not affect later growth outcomes at an early school age. Diet-induced modulation of IGF-1 in the first months of life may have lasting programming effects on later growth

Phospholipid Species in Newborn and 4 Month Old Infants after Consumption of Different Formulas or Breast Milk

<div><p>Introduction</p><p>Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important long-chain polyunsaturated fatty acids for neuronal and cognitive development and are ingredients of infant formulae that are recommended but there is no evidence based minimal supplementation level available. The aim of this analysis was to investigate the effect of supplemented AA and DHA on phospholipid metabolism.</p><p>Methods</p><p>Plasma samples of a randomized, double-blind infant feeding trial were used for the analyses of phospholipid species by flow-injection mass spectrometry. Healthy term infants consumed isoenergetic formulae (intervention formula with equal amounts of AA and DHA—IF, control formula without additional AA and DHA—CF) from the first month of life until the age of 120 days. A group of breast milk (BM) -fed infants was followed as a reference.</p><p>Results</p><p>The plasma profile detected in newborns was different from 4 month old infants, irrespective of study group. Most relevant changes were seen in higher level of LPC16:1, LPC20:4, PC32:1, PC34:1 and PC36:4 and lower level of LPC18:0, LPC18:2, PC32:2, PC36:2 and several ether-linked phosphatidylcholines in newborns. The sum of all AA and DHA species at 4 month old infants in the CF group showed level of 40% (AA) and 51% (DHA) of newborns. The supplemented amount of DHA resulted in phospholipid level comparable to BM infants, but AA phospholipids were lower than in BM infants. Interestingly, relative contribution of DHA was higher in ether-linked phosphatidylcholines in CF fed infants, but IF and BM fed infants showed higher overall ether-linked phosphatidylcholines levels.</p><p>Conclusion</p><p>In conclusion, we have shown that infant plasma phospholipid profile changes remarkably from newborn over time and is dependent on the dietary fatty acid composition. A supplementation of an infant formula with AA and DHA resulted in increased related phospholipid species.</p></div