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Background & Aims: Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages., Methods: We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile., Results: The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively)., Conclusion: A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population., Competing Interests: Conflict of interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: it has previously been described that dietary patterns established early in life tracked to late childhood. The aim of the present work was to analyse the association of dietary patterns that tracked from 2 to 8y with cardiometabolic markers at 8y of age., Methods: The 3 identified patterns at 2y (that previous analyses showed to track to age 8y) were: "Core DP ", loaded for vegetables, fruits, fish, olive oil, etc.; "F&S DP ", loaded by poor-quality fats and sugars; and "Protein DP ", mainly loaded by animal protein sources. Cardiometabolic markers at 8y were systolic blood pressure (SBP), insulin resistance (HOMA-IR), and triglycerides, and BMI z-score. To examine whether the association of diet with the outcomes was the result of a direct effect of diet at either two or 8y, or synergy between them, we used structural equation models., Results: the associations between the patterns and the health outcomes were: Core DP was inversely associated with SBP and HOMA-IR; Protein DP was directly associated with HOMA-IR and SBP; and adherence to F&S DP was directly associated with triglycerides and SBP. The associations between the patterns and the health outcomes were independent of BMI and were the result of a direct effect of diet at 2y, an indirect effect of diet at 2y through diet at 8y or a combination between both pathways., Conclusion: dietary patterns acquired in early life, persisting to later childhood, were associated with cardiometabolic markers at school age independently of BMI., Competing Interests: Conflicts of interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bone mineralization can be influenced by genetic factors, hormonal status, nutrition, physical activity and body composition. The association of higher calcium (Ca) intake or Ca supplementation with better bone mineral density (BMD) remains controversial. Furthermore, it has been speculated that maintaining long-term adequate Ca intake rather than having a brief supplementation period is more effective. The aim of the study was to prospectively analyse the influence of adequate Ca intake on BMD at 7 years of age in European children., Methods: Data from the Childhood Obesity Project were analysed in a prospective longitudinal cohort trial. Dietary intake was recorded using 3-day food records at 4, 5 and 6 years of age. The probability of adequate intake (PA) of Ca was calculated following the American Institute of Medicine guidelines for individual assessments, with FAO, WHO and United Nations University joint expert consultation dietary recommendations. Children were categorised as having high Ca PA (PA >95%) or not (PA <95%). At 7 years, whole body (WB) and lumbar spine (LS) BMD were measured in the Spanish subsample by dual-energy x-ray absorptiometry. Internal BMD z-scores were calculated; BMD below -1 z-score were considered to indicate osteopenia, and BMD z-scores below -2, "low bone mineral density for age"., Results: BMD was measured in 179 children. Ca intake at 6 years was positively correlated with LS BMD at 7 years (R = 0.205, p = 0.030). A Ca increase of 100 mg/day explained 19.4% (p = 0.011) of the LS BMD z-score variation, modifying it by 0.089 (0.021, 0.157) units. Children with Ca PA >95% at 5 and 6 or from 4 to 6 years of age showed higher BMD z-scores at the LS and WB levels than children with Ca PA <95% (p < 0.001 and p < 0.05 for LS and WB BMD, respectively). Ca PA >95% maintained over 2 years explained 26.3% of the LS BMD z-score variation (p < 0.001), increasing it by 0.669 (0.202, 1.137). PA >95% maintained over 3 years explained 24.9% of the LS BMD z-score variation, increasing it by 0.773 (0.282, 1.264). The effects of Ca adequacy on WB BMD were similar. Children with PA >95% over 2 years had an Odds ratio of 13.84 and 12 for osteopenia at the LS and WB levels, respectively (p = 0.001)., Conclusions: Long periods of adequate Ca intake in childhood increase BMD and reduce osteopenia risk. The Childhood Obesity Project clinical trial (CHOP) was registered at clinicaltrials.gov as NCT00338689., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Misreporting is a major source of reporting bias in nutritional surveys. It can affect the analysis of associations between diet and disease. Although various methods have been proposed to identify misreporting, their application to infants and young children is difficult. We identify misreporting of energy intake in infants and young children and propose a simplified approach., Methods: 1199 children were enrolled in the Childhood Obesity Programme (CHOP) based in 5 European countries (Belgium, Germany, Italy, Poland and Spain) with repeated measurements of 3-day weighed food protocol and anthropometric indices at 10 time points between ages 1-96 months. Individual cut-offs for the ratio of reported energy intake and estimated energy requirement were calculated to identify misreporters. Misreporting was studied according to age, gender, BMI z-scores and country., Results: We identified a higher proportion of over-reporters (18.9%) as compared to under-reporters (10.6%). The proportion of over-reporting was higher among infants while under-reporting was more prevalent in school-aged children. Under-reporting was higher in boys (12.0%) and in obese/over-weight children (36.3%). Mean values for upper and lower cut-offs for the ratio of reported energy intake and estimated energy requirement in children ≤12 months were 0.80 and 1.20, and 0.75 and 1.25 for children >12 months, respectively. Using these fixed (mean) values, 90.4% (kappa statistic: 0.78) of all misreporters could be identified., Conclusions: Despite intensive measures to obtain habitual intake of children, an essential proportion of nutritional reports were found to be implausible. Both over- and under-reporting should be carefully analysed, even in studies on infants. Fixed cut-offs can be applied to identify misreporting if no individual variation in energy intake can be calculated., Clinical Trial Registry: This trial was registered at https://clinicaltrials.gov/show/NCT00338689., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Dietary habits established in infancy may persist into adulthood and determine long-term health., Objectives: The aims of this work were to describe dietary patterns, predictors of adherence to them, and their tracking from ages 1 to 8 y in European children., Methods: Three-day food diaries were prospectively collected at ages 1, 2, 3, 4, 5, 6 and 8 y. Foods were allocated to 1 of 29 food groups, which were included in exploratory factor analyses at each children's age. The tracking of patterns through childhood was assessed by an estimated general equation model., Results: At age 1 y (n = 633), 2 patterns were identified. One was labeled "core foods" (CORE), since it was positively loaded for vegetables, fish, olive oil, and white and red meat, and negatively loaded for ready-to-eat infant products, sugar, and confectioneries. The other was positively loaded for saturated spreads, sugar, fruit juices, and confectioneries, and negatively loaded for olive oil, fish, and cow milk; this was labeled as the "poor-quality fats and added sugars" (F&S) pattern. From ages 2 to 8 y, 3 patterns were repeatedly identified: CORE, F&S, and a "high protein sources" (PROT) pattern that was positively loaded for milk, flavored milks, fish, eggs, white and processed meat, chips, and olive oil, and negatively loaded for fresh fruits at almost all time points. Of those children in the highest quartiles of the CORE, F&S, and PROT patterns at 2 y, 45%, 72%, and 36%, respectively, remained in the highest quartile at 8 y [OR = 2.01 (1.08, 3.8), OR = 3.6 (1.5, 8.4) and OR = 0.80 (0.4,1.6), respectively; P = 0.510]., Conclusions: Dietary patterns are established between 1 and 2 y of age and track into mid-childhood. A dietary pattern characterized by added sugars, unhealthy fats, and poor consumption of fish and olive oil was the most stable throughout childhood. Further analyses will reveal whether those dietary patterns are associated with metabolic disease risk.

Background: In European countries, suboptimal intake has been reported for several micronutrients (as calcium, iron, zinc, vitamin B12, D and folate) in both adulthood and childhood. No studies to date have prospectively compiled nutrient intake from healthy children in different European countries using the same methodology., Aim: To describe the adequacy of micronutrient intake during the first eight years of life in children from 5 European countries., Methods: Prospective observational trial analyzing data from the EU Childhood Obesity Project. Infants were enrolled within the first two months of life and were followed regularly to age 8 years. Dietary intake was collected periodically with 3-day food records. Nutrient intake adequacy was estimated for calcium, phosphorus, iron, zinc, magnesium, iodine, folate and vitamins B12, A and D, following the American Institute of Medicine (IOM) guidelines at group (prevalence of adequacy >80%) and individual (high probability of adequate intake >80% of the children) level; the assessment was based on the Estimated Average Requirements of nutrients of the FAO, WHO and United Nations University (FAO/WHO/UNU) or the IOM if FAO/WHO/UNU data were not available., Results: Intake data were available for a decreasing number of children, from 904 at 3 months to 396 at 8 years. Iron, iodine, folate and vitamin D were inadequately consumed when assessing adequacy at group level; at individual-level less than 80% of the children showed high probability of adequate intake for iron, iodine, folate and zinc at all ages, and calcium from 12 months onwards., Conclusions: Accurate dietary intake and adequacy assessment methodology in this prospective cohort of European children found iron, calcium, vitamin D, folate, iodine and zinc to be inadequately consumed in childhood, as described previously by epidemiologic studies. Further studies are needed to elucidate health consequences of these deficiencies. CHOP trial was registered at clinicaltrials.gov as NCT00338689., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Growth patterns of breastfed and formula-fed infants may differ, with formula-fed infants growing more rapidly than breastfed infants into childhood and adulthood. Objective: Our objectives were to identify growth patterns and investigate early nutritional programming potential on growth patterns at 6 y and on body composition at 20 y. Design: The West Australian Pregnancy Cohort (Raine) Study and 3 European cohort studies (European Childhood Obesity Trial, Norwegian Human Milk Study, and Prevention of Coeliac Disease) that collaborate in the European Union-funded Early Nutrition project combined, harmonized, and pooled data on full breastfeeding, anthropometry, and body composition. Latent growth mixture modeling was applied to identify growth patterns among the 6708 individual growth trajectories. The association of full breastfeeding for <3 mo compared with ≥3 mo with the identified trajectory classes was assessed by logistic regression. Differences in body composition at 20 y among the identified trajectory classes were tested by analysis of variance. Results: Three body mass index (BMI; in kg/m 2 ) trajectory patterns were identified and labeled as follows-class 1: persistent, accelerating, rapid growth (5%); class 2: early, nonpersistent, rapid growth (40%); and class 3: normative growth (55%). A shorter duration of full breastfeeding for <3 mo was associated with being in rapid-growth class 1 (OR: 2.66; 95% CI: 1.48, 4.79) and class 2 (OR: 1.96; 95% CI: 1.51, 2.55) rather than the normative-growth class 3 after adjustment for covariates. Both rapid-growth classes showed significant associations with body composition at 20 y ( P < 0.0001). Conclusions: Full breastfeeding for <3 mo compared with ≥3 mo may be associated with rapid growth in early childhood and body composition in young adulthood. Rapid-growth patterns in early childhood could be a mediating link between infant feeding and long-term obesity risk., (© 2017 American Society for Nutrition.)

Background & Aims: Previous studies reported a wide range of estimated malnutrition prevalence (6-30%) in paediatric inpatients based on various anthropometric criteria. We performed anthropometry in hospitalised children and assessed the relationship between malnutrition and length of hospital stay (LOS) and complication rates., Methods: In a prospective multi-centre European study, 2567 patients aged 1 month to 18 years were assessed in 14 centres in 12 countries by standardised anthropometry within the first 24 h after admission. Body mass index (BMI) and height/length <-2 standard deviation scores (SDS, WHO reference) were related to LOS (primary outcome), frequency of gastrointestinal (diarrhoea and vomiting) and infectious complications (antibiotic use), weight change during stay (secondary outcomes) and quality of life., Results: A BMI <-2 SDS was present in 7.0% of the patients at hospital admission (range 4.0-9.3% across countries) with a higher prevalence in infants (10.8%) and toddlers aged 1-2 years (8.3%). A BMI <-2 to ≥-3 SDS (moderate malnutrition) and a BMI <-3 SDS (severe malnutrition) was associated with a 1.3 (CI95: 1.01, 1.55) and 1.6 (CI95: 1.27, 2.10) days longer LOS, respectively (p = 0.04 and p < 0.001). Reduced BMI <-2 SDS was also associated to lower quality of life, and more frequent occurrence of diarrhoea (22% vs 12%, p < 0.001) and vomiting (26% vs 14%, p < 0.001)., Conclusion: Disease associated malnutrition in hospitalised children in Europe is common and is associated with significantly prolonged LOS and increased complications, with possible major cost implications, and reduced quality of life. This study was registered at clinicaltrials.gov as NCT01132742., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Protein source, macronutrient composition and content of long chain-polyunsaturated fatty acids (LC-PUFA) of infant formulae may influence infant growth. We aimed to assess the effect of a modified infant formula on growth., Methods: In a randomized, double-blind trial, 213 healthy term infants consumed isoenergetic study formulae (intervention formula - IF, control formula - CF) from the first month of life until the age of 120 days. IF (1.89 g protein/100 kcal) contained α-lactalbumin (ALAB) and LC-PUFA, while CF (2.30 g protein/100 kcal) provided standard whey and no LC-PUFA. Anthropometry and dietary intake were regularly assessed. A venous blood sample was obtained on day 120., Results: Both formulae were well-accepted without significant differences in health related observations. Weight gain was not statistically different between formula groups (IF: 30.2 ± 6.3 vs. CF: 28.3 ± 6.5 g/day, mean ± SD, P = 0.06). Length gain was higher in IF (0.11 ± 0.02 vs. 0.10 ± 0.02 cm/day, P = 0.02). Energy intake from formula was higher in CF at 90 and 120 days (IF: 509 ± 117 and 528 ± 123 vs. CF: 569 ± 152 and 617 ± 169 kcal/day, P < 0.01). Protein intake in CF was significantly higher at each assessment. Growth per energy intake was higher in IF compared to CF for weight (6.45 ± 2.01 vs. 5.67 ± 2.21 g/100 kcal, P = 0.02) and length (0.23 ± 0.08 vs. 0.20 ± 0.08 mm/100 kcal, P = 0.04)., Conclusions: The modified infant formula with reduced protein content with added ALAB and LC-PUFA, meets infant requirements of protein for adequate growth. The increased energetic efficiency of the new infant formula might result from improved protein composition by added ALAB. Apparently minor differences in composition can markedly affect energetic efficiency for growth. The study was registered at ClinicalTrials.gov (NCT01094080)., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early nutrition is recognized as a target for the effective prevention of childhood obesity. Protein intake was associated with more rapid weight gain during infancy-a known risk factor for later obesity., Objective: We tested whether the reduction of protein in infant formula reduces body mass index (BMI; in kg/m(2)) and the prevalence of obesity at 6 y of age., Design: The Childhood Obesity Project was conducted as a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants born between October 2002 and July 2004. Formula-fed infants (n = 1090) were randomly assigned to receive higher protein (HP)- or lower protein (LP)-content formula (within recommended amounts) in the first year of life; breastfed infants (n = 588) were enrolled as an observational reference group. We measured the weight and height of 448 (41%) formula-fed children at 6 y of age. BMI was the primary outcome., Results: HP children had a significantly higher BMI (by 0.51; 95% CI: 0.13, 0.90; P = 0.009) at 6 y of age. The risk of becoming obese in the HP group was 2.43 (95% CI: 1.12, 5.27; P = 0.024) times that in the LP group. There was a tendency for a higher weight in HP children (0.67 kg; 95% CI: -0.04, 1.39 kg; P = 0.064) but no difference in height between the intervention groups. Anthropometric measurements were similar in the LP and breastfed groups., Conclusions: Infant formula with a lower protein content reduces BMI and obesity risk at school age. Avoidance of infant foods that provide excessive protein intakes could contribute to a reduction in childhood obesity. This trial was registered at clinicaltrials.gov as NCT00338689.

Objective: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied., Design: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6 g/100 mL) or higher (HP: 2.05 and 3.2 g/100 mL) protein contents for the first 12 months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6 months were regressed on determined SNPs and feeding groups in 501 infants., Results: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3 ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3 ng/mL and ~1.3 and decreased in BF infants by ~0.6 ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450 ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing., Conclusions: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Protein intake in early infancy has been suggested to be an important risk factor for later obesity, but information on potential mechanisms is very limited., Objective: This study examined the influence of protein intake in infancy on serum amino acids, insulin, and the insulin-like growth factor I (IGF-I) axis and its possible relation to growth in the first 2 y of life., Design: In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow-milk-based infant and follow-on formulas with lower protein (LP; 1.77 and 2.2 g protein/100 kcal) or higher protein (HP; 2.9 and 4.4 g protein/100 kcal) contents for the first year. Biochemical variables were measured at age 6 mo in 339 infants receiving LP formula and 333 infants receiving HP formula and in 237 breastfed infants., Results: Essential amino acids, especially branched-chain amino acids, IGF-I, and urinary C-peptide:creatinine ratio, were significantly (P < 0.001) higher in the HP group than in the LP group, whereas IGF-binding protein (IGF-BP) 2 was lower and IGF-BP3 did not differ significantly. The median IGF-I total serum concentration was 48.4 ng/mL (25th, 75th percentile: 27.2, 81.8 ng/mL) in the HP group and 34.7 ng/mL (17.7, 57.5 ng/mL) in the LP group; the urine C-peptide:creatinine ratios were 140.6 ng/mg (80.0, 203.8 ng/mg) and 107.3 ng/mg (65.2, 194.7 ng/mg), respectively. Most essential amino acids, IGF-I, C-peptide, and urea increased significantly in both the LP and HP groups compared with the breastfed group. Total IGF-I was significantly associated with growth until 6 mo but not thereafter., Conclusions: HP intake stimulates the IGF-I axis and insulin release in infancy. IGF-I enhances growth during the first 6 mo of life. This trial was registered at clinicaltrials.gov as NCT00338689.

Background: Early introduction of solid food has been suspected to induce excessive infant energy intake and weight gain., Objective: The objective of this study was to test whether introduction of solid foods influences energy intake or growth., Design: Healthy, formula-fed infants who were recruited in 5 European countries were eligible for study participation. Anthropometric measurements were taken at recruitment and at 3, 6, 12, and 24 mo. Time of introduction of solid foods and energy intake were determined by questionnaires and 3-d weighed food records at monthly intervals. Age at introduction of solid food was categorized into 4 groups: ≤ 13 wk, 14-17 wk, 18-21 wk, and ≥ 22 wk., Results: Of 1090 recruited infants, 830 (76%) had data available for age at first introduction of solid food, and 671 (61%) completed the study until 24 mo of age. The median age at introduction of solid food was 19 wk. The time of introduction of solid foods was associated with country, sex, birth weight, parental education and marital status, and maternal smoking. Energy intake was higher in the first 8 mo of life in children with solid-food intake. Solid-food introduction did not predict anthropometric measures at 24 mo. Growth trajectories differed significantly: children with solid-food introduction in the first 12 wk experienced early catch-up growth, whereas those introduced to solid food at >22 wk of age grew more slowly and stayed on lower trajectories., Conclusions: Solid foods do not simply replace infant formula but increase energy intake. Time of introduction of solid food has little influence on infant growth. This trial was registered at clinicaltrials.gov as NCT00338689.

Background: Nutritional factors during a sensitive period can influence child development in a sex-related manner., Objective: Our aim was to investigate whether sex modulates the responses of relevant biochemical parameters and growth to different protein intakes early in life., Design: In a randomized controlled trial, formula-fed infants were assigned to receive formula with higher protein (HP) or lower protein (LP) content. The main outcome measures were insulin-like growth factor (IGF)-1 axis parameters, weight, length, BMI, leptin, and C-peptide/creatinine ratio at 6 mo of age. Dietary intake during the first 6 mo of life was also assessed., Results: The IGF-1 axis response to HP feeding was modulated by sex. Total and free IGF-1 and IGF binding protein 3 concentrations were higher in girls than in boys. Compared with the LP diet, the HP diet was associated with higher IGF-1 and lower IGF binding protein 2 secretion. The response to this HP content formula tended to be stronger in girls than in boys. The HP diet was associated with a higher C-peptide/creatinine ratio. The leptin concentration was higher in girls than in boys and was correlated to the IGF-1 axis parameters. No interaction between sex and nutritional intervention was shown on growth., Conclusions: Our findings show that the endocrine response to a high protein diet early in life may be modulated by sex. The IGF-1 axis of female infants shows a stronger response to the nutritional intervention than does that of male infants, but there is no enhanced effect on growth. This trial was registered at clinicaltrials.gov as NCT00338689.

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.

Background: Intake of energy providing liquids (EPL) other than breast milk or formula to infants is discouraged because it may displace milk intake. Data on actual practice is lacking., Aim: To describe the current practice of EPL supply to infants in five European countries., Method: Breastfed (BF) infants and infants fed using two formulae (FF) with different protein content were recruited from October 2002 to June 2004. Three-day weighed food protocols of 1368 infants were obtained monthly at the ages of 1 to 9 and again at 12 completed months., Results: At the age of 4 months, 13% of BF and 43% of FF infants received EPL. FF infants started EPL earlier (median 17 weeks) than BF infants (median 30 weeks). EPL intake was associated with a lower intake of formula milk and solids (kcal/d) in the first year of life. Multiple regression analysis showed significant differences in EPL introduction between the individual countries., Conclusion: In contrast to recommendations, EPL is frequently given during the first months of life to breastfed and particularly to formula fed infants. Infants given EPL showed lower intakes of infant formula and solids. Caregivers should receive better counselling on appropriate infant feeding., (Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Protein intake during infancy was associated with rapid early weight gain and later obesity in observational studies., Objective: The objective was to test the hypothesis that higher protein intake in infancy leads to more rapid length and weight gain in the first 2 y of life., Design: In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow milk-based infant and follow-on formula with lower (1.77 and 2.2 g protein/100 kcal, respectively) or higher (2.9 and 4.4 g protein/100 kcal, respectively) protein contents for the first year. For comparison, 619 exclusively breastfed children were also followed. Weight, length, weight-for-length, and BMI were determined at inclusion and at 3, 6, 12, and 24 mo of age. The primary endpoints were length and weight at 24 mo of age, expressed as length and weight-for-length z scores based on the 2006 World Health Organization growth standards., Results: Six hundred thirty-six children in the lower (n = 313) and higher (n = 323) protein formula groups and 298 children in the breastfed group were followed until 24 mo. Length was not different between randomized groups at any time. At 24 mo, the weight-for-length z score of infants in the lower protein formula group was 0.20 (0.06, 0.34) lower than that of the higher protein group and did not differ from that of the breastfed reference group., Conclusions: A higher protein content of infant formula is associated with higher weight in the first 2 y of life but has no effect on length. Lower protein intake in infancy might diminish the later risk of overweight and obesity. This trial was registered at clinicaltrials.gov as NCT00338689.

Since the concept of lasting programming effects on disease risk in human adults by the action of hormones, metabolites, and neurotransmitters during sensitive periods of early development was proposed >3 decades ago, ample supporting evidence has evolved from epidemiologic and experimental studies and clinical trials. For example, numerous studies have reported programming effects of infant feeding choices on later obesity. Three meta-analyses of observational studies found that obesity risk at school age was reduced by 15-25% with early breastfeeding compared with formula feeding. We proposed that breastfeeding protects against later obesity by reducing the occurrence of high weight gain in infancy and that one causative factor is the lower protein content of human milk compared with most infant formula (the early protein hypothesis). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial that includes >1000 infants in 5 countries (Belgium, Germany, Italy, Poland, and Spain). We randomly assigned healthy infants who were born at term to receive for the first year infant formula and follow-on formula with higher or lower protein contents, respectively. The follow-up data obtained at age 2 y indicate that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the new World Health Organization growth standard, which may furnish a significant long-term protection against later obesity. We conclude that infant feeding practice has a high potential for long-term health effects, and the results obtained should stimulate the review of recommendations and policies for infant formula composition.