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Background & aim: High protein intake in early life is associated with an increased risk of childhood obesity. Feeding a modified lower-protein (mLP) infant formula (1.7 g protein/100 kcal) until the age of 6 months is safe and supports adequate growth. The aim of the present study is to assess longer-term anthropometry with BMI at 1 and 2 years as primary outcome parameter and body composition in children fed mLP formula. Methods: Healthy term-born infants received mLP or control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double-blinded RCT. A breast-fed (BF) group served as a reference. Anthropometry data were obtained at 1 and 2 years of age. At the age of 2 years, body composition was measured with air-displacement plethysmography. Groups were compared using linear mixed model analysis. Results: At 1 and 2 years of age, anthropometry, including BMI, and body composition did not differ between the formula groups (n = 74 mLP; n = 69 CTRL). Compared to the BF group (n = 51), both formula-fed groups had higher z scores for weight for age, length for age, waist circumference for age, and mid-upper arm circumference for age at 1 year of age, but not at 2 years of age (except for z score of weight for age in the mLP group). In comparison to the BF group, only the mLP group had higher fat mass, fat-free mass, and fat mass index. However, % body fat did not differ between feeding groups. Conclusions: In this follow-up study, no significant differences in anthropometry or body composition were observed until 2 years of age between infants fed mLP and CTRL formula, despite the significantly lower protein intake in the mLP group during the intervention period. The observed differences in growth and body composition between the mLP group and the BF reference group makes it necessary to execute new trials evaluating infant formulas with improved protein quality together with further re-ductions in protein content. Clinical Trial Registry: This trial was registered in the Dutch Trial Register (Study ID number NTR4829, trial number NL4677). https://www.trialregister.nl/trial/4677. (c) 2021 Published by Elsevier Ltd.

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 &lt, 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p &lt, 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p &lt, 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.

Objective: Glucocorticoids (GCs) in breastmilk have previously been associated with infant body growth and body composition. However, the diurnal rhythm of breastmilk GCs was not taken into account, and we therefore aimed to assess the associations between breastmilk GC rhythmicity at 1 month and growth and body composition at 3 months in infants. Methods: At 1 month postpartum, breastmilk GCs were collected over a 24-h period and analyzed by LC-MS/MS. Body composition was measured using air-displacement plethysmography at 3 months. Length and weight were collected at 1, 2, and 3 months. Results: In total, 42 healthy mother&ndash, infant pairs were included. No associations were found between breastmilk GC rhythmicity (area-under-the-curve increase and ground, maximum, and delta) and infant growth trajectories or body composition (fat and fat free mass index, fat%) at 3 months. Conclusions: This study did not find an association between breastmilk GC rhythmicity at 1 month and infant&rsquo, s growth or body composition at 3 months. Therefore, this study suggests that previous observations linking breastmilk cortisol to changes in infant weight might be flawed by the lack of serial cortisol measurements and detailed information on body composition.

Background: EarlyNutrition (www.project-earlynutrition.eu) is an international research consortium investigating the effects of early nutrition on metabolic programming. Objective: To summarize current evidence and standards, recommendations, guidelines, and regulations on nutrition or supplements in lactating women with emphasis placed on long-term health effects in offspring, including cardiovascular disease, hypertension, overweight/obesity, metabolic syndrome, diabetes, or glucose intolerance. Methods: Medline, Embase, selected databases and websites were searched for documents published between 2010 and 2015. Results: Thirteen documents met the inclusion criteria. Effects of maternal long-chain polyunsaturated fatty acid (LC-PUFA) supplementation on overweight/obesity or hypertension in offspring were assessed in 10 studies. One study described the effect of maternal vitamin D supplementation on overweight/obesity, and the remaining 2 studies assessed the effects of maternal probiotic/synbiotic supplementation during lactation on overweight/obesity or metabolic syndrome in their infants. Forty-one documents contained dietary recommendations on various macro- and micronutrients for lactating women, but without consideration of our long-term health outcomes in infants. Conclusion: Literature on nutrition of lactating women and its effect on their infants' later health with respect to metabolic programming outcomes appeared to be scarce, and focused mostly on supplementation of LC-PUFA's. No recent guidelines or recommendations were available, highlighting the significant research gaps regarding this topic.

Background: Children with intestinal failure (IF) are at risk of growth failure, but little information about body composition is available. Our aim was to assess body composition using air displacement plethysmography (ADP) and relate it to clinical and growth parameters. Methods: In this prospective descriptive observational 2-center cohort study, children aged 2–18 years receiving home parenteral nutrition (PN) for ≥6 months underwent ADP measurement. Fat mass index (FMI) and fat-free mass index (FFMI) standard deviation scores (SDSs) were calculated to normalize for small body size. Results: Twenty-one out of 22 children, median age 7.4 years, underwent successful ADP measurement after a median PN duration of 5.5 years. They were significantly lighter (median weight for age SDS −0.71, P = 0.004) and shorter (median height for age SDS −1.55, P < 0.001) than the normal population mean; 52% were growing below target height range. They had low FFMI (median SDS −1.53, P < 0.001) and high FMI (median SDS 0.80, P = 0.002). Weight for height and body mass index (BMI) were significantly associated with FFMI and BMI with FMI, but children with the same weight and height showed different body composition. In 13 patients with 1-year follow-up, growth and body composition did not change significantly. Conclusion: Children with IF receiving long-term PN show lower FFM and higher FM than healthy children. Additionally, children with similar routine growth parameters showed different body composition. Further studies should evaluate the effect of a patient-tailored approach including physical activity and nutrition advice based on body composition.

Background Protein intake may influence important health outcomes in later life. Objective The objective of this study was to investigate current evidence on the effects of infant formulas and follow-on formulas with different protein concentrations on infants' and children's growth, body composition, and later risk of overweight and obesity. Methods In this systematic review, we searched electronic databases (including MEDLINE, Embase, and the Cochrane Library) up until November 2014 for randomized controlled trials (RCTs). Eligible studies had to include children aged 0-3 y who represented the general population and were fed cow milk-based infant formulas with variations in protein concentration. Control groups received lower-protein cow milk-based formulas (as defined by the authors). The primary outcomes were growth, overweight, obesity, and adiposity. Various time points for outcomes assessment were accepted for inclusion. If possible, a meta-analysis was performed. Results Twelve RCTs met our inclusion criteria. Different formula protein concentrations did not affect linear growth other than a transient effect on mean length at 3 mo observed in a meta-analysis of 4 studies (mean difference, - 0.27 cm; 95% CI: -0.52, -0.02). Lower mean weight and weight z scores obtained from the infants fed lower-protein formulas were observed only from 6 to 12 mo of age. Data from one large RCT showed that consumption of a lower-protein infant formula may reduce body mass index at 12 mo of age and later (12 mo, 24 mo, and 6y) and the risk of obesity at 6 y. Effects on body composition remained unclear. Conclusions The current evidence is insufficient for assessing the effects of reducing the protein concentration in infant formulas on long-term outcomes, but, if confirmed, this could be a promising intervention for reducing the risk of overweight and obesity in children. In view of the limited available evidence, more studies replicating effects on long-term health outcomes are needed.

Background. EarlyNutrition (www.project-earlynutrition.eu) is an international research project investigating the effects of early nutrition on metabolic programming.Objective. To summarize, by performing a systematic review, current standards, recommendations, guidelines, and regulations (hereafter, referred to as documents) on the nutrition of children up to three years of age. Special emphasis was placed on long-term effects of early nutrition, such as the risk of cardiovascular disease, hypertension, overweight, obesity, metabolic syndrome, diabetes, or glucose intolerance.Methods. MEDLINE, selected databases, and websites were searched for documents published between 2008 and January 2013.Results. Forty two documents met the inclusion criteria. The strongest and most consistent evidence for a protective, long-term effect was documented for breastfeeding. Also, limiting the intake of sodium and rapidly absorbed carbohydrates, use of a specific meal pattern, reducing the consumption of saturated fatty acids by replacing them with polyunsaturated fatty acids, and lowering the intake of trans fatty acids, seems beneficial. Many documents did not evaluate long-term outcomes of interest to us, or reported insufficient or imprecise data. Inconsistency in recommendations for some outcomes and research gaps were identified.Conclusions. Our findings may serve as a helpful tool in planning further research, preventive actions against important diet-related diseases, and guidelines improvement.

Background: The incidence of necrotizing enterocolitis (NEC) and possibly also of sepsis is lower in preterm infants fed their own mother’s milk (hereafter ‘mother’s milk’) compared with formula-fed infants. It is unclear whether this is caused by the protective properties of breast milk or by the absence of cow’s milk. Especially in early life, mother’s milk is often unavailable to preterm infants, while minimal enteral nutrition is initiated immediately. Objectives: To determine whether there is an association between intake of mother’s milk during the first days of life and the combined outcome of sepsis, NEC and death over a prolonged period. Methods: Retrospective study in infants with a birth weight Results: In total, 349 infants were included. Intake of mother’s milk during the first 5 days of life was associated with a lower incidence of NEC, sepsis and/or death during the first 60 days of life (hazard ratio (HR) in the category 0.01–50% intake of mother’s milk: 0.49, 95% confidence interval (CI) 0.28, 0.87; HR in the category 50.01–100% intake of mother’s milk: 0.50, 95% CI 0.31, 0.83, both compared to no mother’s milk). During days 6–10, the protective effect was only present if >50% of the total intake was mother’s milk (HR = 0.37, 95% CI 0.22, 0.65). Conclusion: The type of enteral nutrition during the first 10 days of life is associated with the risk of NEC, sepsis and/or death during the first 60 days of life.