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1.
Effect of an infant formula containing sn-2 palmitate on fecal microbiota and metabolome profiles of healthy term infants: a randomized, double-blind, parallel, controlled study.
Guo, D, Li, F, Zhao, J, Zhang, H, Liu, B, Pan, J, Zhang, W, Chen, W, Xu, Y, Jiang, S, et al
Food & function. 2022;(4):2003-2018
Abstract
Different infant diets have strong effects on child development and may engender variations in fecal microbiota and metabolites. The objective of this study was to evaluate the effect of an infant formula containing sn-2 palmitate on fecal microbiota and metabolites in healthy term infants. The study involved three groups as indicated below. Investigational: the group fed a formula containing high sn-2 palmitate for 16 weeks. Control: the group fed a formula using a regular vegetable oil for 16 weeks. Breastfed: the group fed breast milk for 16 weeks. Fecal samples were collected at 8 weeks (n = 35, 37, and 35, respectively) and 16 weeks (n = 30, 32, and 30, respectively) for the control, investigational, and breastfed infants. Microbiota data were obtained using 16S rRNA sequencing. Short-chain fatty acid (SCFA) analysis was performed using GC-MS, and untargeted metabolomics was conducted using LC-MS. The effect of the formula containing sn-2 palmitate was different from that of the control formula on microbiota and metabolites. Sn-2 palmitate promoted the proliferation of Bifidobacterium and reduced the abundance of Escherichia-Shigella at 8 weeks. Furthermore, it increased α-diversity and enhanced acetate content in feces at both 8 and 16 weeks. In the investigational group infants, the abundance of DL-tryptophan, indole-3-acrylic acid, acetyl-β-methylcholine, L-methionine, and 2-hydroxyvaleric acid significantly increased at 8 weeks, while a notable increase in the abundance of 3-phenyllactic acid, palmitic acid, L-phenylalanine, and leucylproline was observed at 16 weeks. In addition, compared with that of the control infants, the intestinal microbiota and metabolites of sn-2 palmitate-supplemented infants were more similar to those of the breastfed infants. The study hopes to provide a scientific basis for the development of functional infant formulas in the future.
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2.
Serum cytokine patterns are modulated in infants fed formula with probiotics or milk fat globule membranes: A randomized controlled trial.
Li, X, Peng, Y, Li, Z, Christensen, B, Heckmann, AB, Lagerqvist, C, Stenlund, H, Lönnerdal, B, Hernell, O, West, CE
PloS one. 2021;(5):e0251293
Abstract
BACKGROUND Proteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants. OBJECTIVE To compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants. DESIGN FF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively. RESULTS Compared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups. CONCLUSIONS Contrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.
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3.
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.
Kouwenhoven, SMP, Fleddermann, M, Finken, MJJ, Twisk, JWR, van der Beek, EM, Abrahamse-Berkeveld, M, van de Heijning, BJM, van Harskamp, D, van Goudoever, JB, Koletzko, BV
Nutrients. 2021;(4)
Abstract
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.
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4.
Efficacy of Soy-Based Formulas in Alleviating Gastrointestinal Symptoms in Infants With Milk-Based Formula Intolerance: A Randomized Clinical Trial.
Lasekan, JB, Baggs, GE
Clinical pediatrics. 2021;(3):184-192
Abstract
A randomized, blinded pilot clinical study was conducted to assess gastrointestinal (GI) tolerance in healthy, full-term infants (2-9 weeks old), whose pediatricians recommended a formula change due to perceived cow's milk formula intolerance. Infants were randomized and exclusively fed either a commercial control soy formula (SF; n = 22), an experimental partially hydrolyzed SF (10% hydrolyzed, n = 23), or a 5% hydrolyzed SF (n = 26) for 2 weeks. Age-matched reference cohorts (n = 72) with no GI intolerance on milk-based formula were assessed in parallel. Results indicated that all SF-fed groups contributed to reduction (P < .05) in common GI tolerance symptoms to levels not different from the non-symptomatic reference cohort at study end. The control SF group had more reduced fussiness, gas, and crying and higher formed stools versus hydrolyzed SF groups. In conclusion, the study suggests that SFs reduced GI intolerance symptoms in otherwise healthy infants with poor tolerance on milk-based formulas.
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5.
Effects of Early Weight Gain Velocity, Diet Quality, and Snack Food Access on Toddler Weight Status at 1.5 Years: Follow-Up of a Randomized Controlled Infant Formula Trial.
Mennella, JA, Smethers, AD, Decker, JE, Delahanty, MT, Stallings, VA, Trabulsi, JC
Nutrients. 2021;(11)
Abstract
This study followed children who participated in a feeding trial in which the type of randomized infant formula fed from 2 weeks significantly affected weight gain velocity during the first 4 months and weight-for-length Z (WLZ) scores up to 11.5 months. We focused on measures of anthropometry, dietary intakes, and parenting related to the provision of snack foods that were collected at the end of the trial (1 year) and the 1.5 years follow-up visit. We not only describe what toddlers are eating, but we also determined the independent and/or interactive effects of randomized formula group, early weight gain velocity, the nutrient content of the post-formula diet, and maternal snack food practices, on toddlers' weight status. Diet quality underwent drastic changes during this 6-month period. As infant formula disappeared from the diet, fruit and 100% fruit juice intake increased slightly, while intake of "What We Eat in America" food categories sweetened beverages and snacks and sweets more than doubled. Added sugars accounted for 5% of energy needs at 1 year and 9% at 1.5 years. Generalized linear mixed models revealed that, independent of the randomized formula group, greater velocities of weight gain during early infancy and lower access to snacks as toddlers predicted higher WLZ and a greater proportion of toddlers with overweight at 1.5 years. Energy and added sugar intake had no significant effects. These findings add to the growing body of evidence that unhealthy dietary habits are formed even before formula weaning and that, along with improving early diet, transient rapid weight gain and parental feeding practices are modifiable determinants that may reduce risks for obesity.
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6.
A randomized controlled trial of different young child formulas on upper respiratory and gastrointestinal tract infections in Chinese toddlers.
Leung, TF, Ulfman, LH, Chong, MKC, Hon, KL, Khouw, IMSL, Chan, PKS, Delsing, DJ, Kortman, GAM, Bovee-Oudenhoven, IMJ
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2020;(7):745-754
Abstract
BACKGROUND Bioactive proteins and human milk oligosaccharides (HMOs), important ingredients in breast milk, that protect against infections are lacking in young child formula (YCF). This study investigated the effects of new YCFs on respiratory and gastrointestinal infections in toddlers. METHODS Four hundred and sixty one healthy Chinese children aged 1-2.5 years were recruited in this randomized, controlled, double-blind, parallel-group clinical trial of different YCFs. They were randomly assigned to either standard milk formula (YCF-Ref) or one of three new YCFs containing bioactive proteins and/or the HMO 2'-fucosyllactose (2'-FL) and/or milk fat for six months. Primary outcomes were incidence of upper respiratory tract infection (URTI) and duration of gastrointestinal tract infections (GITI). RESULTS There were no significant between-group differences in primary outcomes. For secondary outcomes, subjects receiving 2'-FL-supplemented YCF had longer URTI. Subjects receiving YCF supplemented with milk fat and intact bioactive proteins, and 2'-FL at levels found in breast milk, had more GITI episodes and shorter time to first GITI but similar effects on URTI duration than YCF-Ref recipients. No effects on URTI and GITI were observed in toddlers receiving YCF with bioactive proteins at lower levels than breast milk. Occurrence of adverse events and anthropometry were similar in all groups. CONCLUSIONS All three YCFs supplemented with different combinations of intact bioactive proteins, 2'-FL, and milk fat are safe in toddlers. No difference is detected among YCFs on URTI incidence and GITI duration. Further studies are needed to verify these findings especially in infants who may benefit most from the immune-boosting effects of bioactive proteins and HMOs.
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7.
The Effects of an Infant Formula Enriched with Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids and Synbiotics on Child Behavior up to 2.5 Years Old: The COGNIS Study.
Nieto-Ruiz, A, Diéguez, E, Sepúlveda-Valbuena, N, Herrmann, F, Cerdó, T, López-Torrecillas, F, De-Castellar, R, Jiménez, J, Pérez-García, M, Miranda, MT, et al
Nutrients. 2020;(12)
Abstract
Although early life nutrition influences brain development and mental health, the long-term effects of supplemented infant formula on children´s behavior remain unclear. We analyzed the effects of a bioactive nutrients-enriched-infant formula on children's behavior up to 2.5 years, compared to a standard infant formula or breastfeeding. Current analysis involved 70 children who were fed a standard infant formula (SF, n = 29) or a bioactive compounds enriched-infant formula (EF, n = 41), during their first 18 months of life, and 33 breastfed (BF) children (reference group) participating in the COGNIS study. Behavioral problems were evaluated using the Child Behavior Checklist at 18 months and 2.5 years. Different statistical analyses were performed using SPSS. EF children aged 2.5 years presented fewer pathological affective problems than SF children. Besides, SF children were classified more frequently as bordering on internalizing problems than BF children. Rates of externalizing problems were increased in SF infants compared to EF and BF infants. Higher maternal IQ was found to have beneficial effects on internalizing and total problem rate in their offspring at 18 months of life; finally, higher maternal educational level was related with fewer ADHD problems in children at 18 months, as well as internalizing, externalizing, total and anxiety problems in children aged 2.5 years. Our analysis suggests that enriched infant formula fed infants seem to show fewer behavioral problems up to 2.5 years compared to a standard infant formula-fed infants. In addition to type of early feeding, maternal IQ and educational level seem to play a key role on children behavioral development.
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8.
Impact of infant protein supply and other early life factors on plasma metabolome at 5.5 and 8 years of age: a randomized trial.
Kirchberg, FF, Hellmuth, C, Totzauer, M, Uhl, O, Closa-Monasterolo, R, Escribano, J, Gruszfeld, D, Gradowska, K, Verduci, E, Mariani, B, et al
International journal of obesity (2005). 2020;(1):69-81
Abstract
OBJECTIVES A high dairy protein intake in infancy, maternal pre-pregnancy BMI, and delivery mode are documented early programming factors that modulate the later risk of obesity and other health outcomes, but the mechanisms of action are not understood. METHODS The Childhood Obesity Project is a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants. Participating infants were either breastfed (BF) or randomized to receive higher (HP) or lower protein (LP) content formula in the first year of life. At the ages 5.5 years (n = 276) and 8 years (n = 232), we determined plasma metabolites by liquid chromatography tandem-mass-spectrometry of which 226 and 185 passed quality control at 5.5 years and 8 years, respectively. We assessed the effects of infant feeding, maternal pre-pregnancy BMI, smoking in pregnancy, delivery mode, parity, birth weight and length, and weight gain (0-24 months) on the metabolome at 5.5 and 8 years. RESULTS At 5.5 years, plasma alpha-ketoglutarate and the acylcarnitine/BCAA ratios tended to be higher in the HP than in the LP group, but no metabolite reached statistical significance (Pbonferroni>0.09). There were no group differences at 8 years. Quantification of the impact of early programming factors revealed that the intervention group explained 0.6% of metabolome variance at both time points. Except for country of residence that explained 16% and 12% at 5.5 years and 8 years, respectively, none of the other factors explained considerably more variance than expected by chance. CONCLUSIONS Plasma metabolome was largely unaffected by feeding choice and other early programming factors and we could not prove the existence of a long term programming effect of the plasma metabolome.
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9.
A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial.
Kouwenhoven, SMP, Antl, N, Finken, MJJ, Twisk, JWR, van der Beek, EM, Abrahamse-Berkeveld, M, van de Heijning, BJM, Schierbeek, H, Holdt, LM, van Goudoever, JB, et al
The American journal of clinical nutrition. 2020;(5):962-974
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Abstract
BACKGROUND A high protein intake in early life is associated with a risk of obesity later in life. The essential amino acid requirements of formula-fed infants have been reassessed recently, enabling a reduction in total protein content and thus in protein intake. OBJECTIVES We aimed to assess the safety of an infant formula with a modified amino acid profile and a modified low-protein (mLP) content in healthy term-born infants. Outcomes were compared with a specifically designed control (CTRL) infant formula. METHODS In this double-blind, randomized controlled equivalence trial, infants received either mLP (1.7 g protein/100 kcal; n = 90) or CTRL formula (2.1 g protein/100 kcal; n = 88) from enrollment (age ≤ 45 d) to 6 mo of age. A breastfed group served as a reference (n = 67). Anthropometry and body composition were determined at baseline, 17 wk (including safety blood parameters), and 6 mo of age. The primary outcome was daily weight gain from enrollment up until the age of 17 wk (at an equivalence margin of ±3.0 g/d). RESULTS Weight gain from baseline (mean ± SD age: 31 ± 9 d) up to the age of 17 wk was equivalent between the mLP and CTRL formula groups (27.9 and 28.8 g/d, respectively; difference: -0.86 g/d; 90% CI: -2.36, 0.63 g/d). No differences in other growth parameters, body composition, or in adverse events were observed. Urea was significantly lower in the mLP formula group than in the CTRL formula group (-0.74 mmol/L; 95% CI: -0.97, -0.51 mmol/L; P < 0.001). Growth rates, fat mass, fat-free mass, and several essential amino acids were significantly higher in both formula groups than in the breastfed reference group. CONCLUSIONS Feeding an infant formula with a modified amino acid profile and a lower protein content from an average age of 1 mo until the age of 6 mo is safe and supports an adequate growth, similar to that of infants consuming CTRL formula. This trial was registered at www.trialregister.nl as Trial NL4677.
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10.
Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age: A Randomized Controlled Trial.
Björmsjö, M, Hernell, O, Lönnerdal, B, Berglund, SK
Nutrients. 2020;(1)
Abstract
Many infant formulas are fortified with iron at 8-14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf-) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 µg/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.