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Purpose: The objective of this secondary analysis is to describe the types of commercial complementary foods (CCF) consumed by infants and young children enrolled in the European Childhood Obesity Project (CHOP), to describe the contribution of CCF to dietary energy intakes and to determine factors associated with CCF use over the first 2 years of life., Methods: The CHOP trial is a multicenter intervention trial in Germany, Belgium, Italy, Poland and Spain that tested the effect of varying levels of protein in infant formula on the risk for childhood obesity. Infants were recruited from October 2002 to June 2004. Dietary data on CCF use for this secondary analysis were taken from weighted, 3-day dietary records from 1088 infants at 9 time points over the first 2 years of life., Results: Reported energy intakes from CCF during infancy (4-9 months) was significantly higher (p ≤ 0.002) amongst formula-fed children compared to breastfed children. Sweetened CCF intakes were significantly higher (p ≤ 0.009) amongst formula-fed infants. Female infants were fed significantly less CCF and infant age was strongly associated with daily CCF intakes, peaking at 9 months of age. Infants from families with middle- and high-level of education were fed significantly less quantities of CCF compared to infants with parents with lower education. Sweetened CCF were very common in Spain, Italy and Poland, with over 95% of infants and children fed CCF at 9 and 12 months of age consuming at least one sweetened CCF. At 24 months of age, 68% of the CHOP cohort were still fed CCF., Conclusions: CCF comprised a substantial part of the diets of this cohort of European infants and young children. The proportion of infants being fed sweetened CCF is concerning. More studies on the quality of commercial complementary foods in Europe are warranted, including market surveys on the saturation of the Western European market with sweetened CCF products.

Breastfeeding is associated with a reduced later obesity risk, relative to feeding convention infant formula. Breastfeeding induces less weight gain during the first two years of life, which predicts less obesity up to adulthood. We tested the hypothesis that a high infant protein supply promotes weight gain and obesity risk, mediated by increased plasma amino acids and growth factors, insulin and insulin like growth factor 1 (IGF-1). A large multi-centre double blind trial randomized formula-fed infants to conventional bottle milk with a high protein content, or an intervention formula with a reduced protein content more similar to levels provided with human milk. Protein-reduced formula normalized weight, body mass index and body fatness up to 6 years, relative to a breastfed reference group, and reduced the adjusted odds for obesity 2.6-fold. Available data indicate potential underlying mechanisms. We conclude that infant feeding has very marked long-term programming effects on later BMI, obesity and adiposity, with major public health implications. Breastfeeding lowers the risk for later obesity and adiposity. This provides additional motivation for proactively and enthusiastically promoting, protecting and supporting breastfeeding. A high milk protein intake in infancy increases the long-term risk for obesity and adiposity. Infants not or not fully breastfed should receive infant formula delivering protein in amounts more similar to human milk contents, with high protein quality. Other sources of very high infant protein intakes, particular drinking unmodified cows' milk, should be avoided in infancy., (Copyright © 2019. Published by Elsevier Inc.)

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

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., Competing Interests: All authors have made substantial contributions to the conception and design of the study, or acquisition of data, or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content. Each author has seen and approved the contents of the submitted manuscript. This study was financially supported in part by HiPP & Co. Vertrieb KG who supplied the respective formulae during the main study and provided support in the form of salaries for authors (BK, MF, HD, VG). MF carried out analyses while she was employed at the Dr. von Hauner Children’s Hospital Munich, Div. of Metabolic and Nutritional Medicine. She is now an employee at HiPP GmbH & Co Vertrieb KG. BT is an employee of HiPP & Co. Vertrieb KG and received salaries for data collection. These employments do not alter the adherence to PLOS ONE policies on sharing data and materials. The specific roles of these authors are articulated in the ‘author contributions’ section.

Objective: The objective of this study was to investigate the effect of lower protein (LP) versus higher protein (HP) content in infant formula on body composition from 3 months to 6 years., Methods: In a multicenter, double-blind European trial, healthy infants (N = 1,090) were randomly assigned to different protein content formulas (upper [HP] and lower [LP] limits of the European Union regulations in 2001) during the first year; breastfed infants (N = 588) were recruited for reference values. Weight, height, and triceps and subscapular skinfold (SF) thickness were measured repeatedly (N = 650 at 6 years), and body composition was estimated (Slaughter). The 99th percentile of fat mass index reference data were used to assess excess body fat at 6 years., Results: At 2 and 6 years, the study observed greater sum of SFs (Δ 2 years: 0.5 mm, P = 0.026, Δ 6 years: 0.6 mm, P = 0.045), fat mass index (Δ 2 years: 0.12 kg/m², P = 0.008, Δ 6 years: 0.15 kg/m², P = 0.011), and fat-free mass index (Δ 2 years: 0.17 kg/m², P = 0.003, Δ 6 years: 0.18 kg/m², P = 0.010) in the HP group compared with the LP group. At 6 years, the HP group had a twofold higher risk than the LP group for excess body fat (adjusted odds ratio: 2.13, P = 0.019)., Conclusions: Infant formula with HP levels induced greater fat mass in children from 2 to 6 years. Lowering the protein content of infant formula may result in a healthier body composition in early childhood., (© 2018 The Obesity Society.)

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.)

Purpose: Insulin-like growth factor-I (IGF-I) is related to growth and its secretion is modified by protein intake in early infancy. We examined the relationship of dietary protein and circulating amino acids on plasma IGF-I levels and early growth., Methods: Healthy formula-fed infants (n = 213) were randomly assigned to receive either a protein-reduced infant formula with alpha-lactalbumin-enriched whey and free tryptophan and phenylalanine (IF) or an isocaloric standard formula without free amino acids (CF) for the first 120 days of life. A group of breastfed (BF) infants was studied as a non-randomized reference cohort. Biochemical variables were measured shortly after birth (subpopulation) and at an age of 120 days. A path analysis was used to explore the relationship between IGF-I, insulin and amino acids. Results are derived from secondary analyses of a randomized controlled trial., Results: Plasma concentrations of IGF-I at 120 days were significantly higher in IF than in CF infants [58.5 (15.0) vs. 53.7 (9.95) ng/mL; p = 0.020]. BF infants showed lower IGF-I concentrations of 41.6 (10.7) ng/mL. All amino acids but Thr and Cit had a more marked effect on insulin than on IGF-I level. Considering weight, sex and feeding group, Trp explained an equal percentage of variance of IGF-I and insulin (total R 2 12.5 % of IGF-I and 12.3 % of insulin), while branched-chain AA explained an up to twofold higher variance of insulin than IGF-I. Compared to CF, IF explained 18.9 % of the IGF-I level (p = 0.03), while for insulin no direct effect was detectable., Conclusion: Higher IGF-I concentrations and growth velocities in infants receiving protein-reduced IF indicate that the protein concentration of an infant formula alone does not control IGF-I levels and growth. Other components (e.g., selected amino acids) of infant formulae might control directly or indirectly via insulin influence IGF-I.

Background/aims: Dietary factors can modify calciuria. We aim to investigate urinary calcium excretion in healthy infants according to their protein., Methods: Secondary data analysis from a randomized clinical trial where healthy term infants were randomized after birth to a higher (HP) or lower (LP) protein content formula that was consumed until age 1 year. A non-randomized group of breastfed (BF) infants was used for reference. Anthropometry, dietary intakes and calciuria (calcium/creatinine ratios) from spot urine samples were assessed at ages 3 and 6 months. At 6 months, the kidney volumes were assessed using ultrasonography, and the serum urea and creatinine levels were determined., Results: BF infants showed the highest calciuria levels, followed by the HP and the LP groups (p < 0.001 for all comparisons). Either protein intakes or formula types modulated the calciuria in linear regression models adjusted for other influencing dietary factors. The usual cut-off values classified 37.8% (BF), 16.8% (HP) and 4.9% (LP) of the infants as hypercalciuric., Conclusions: Feeding types during the first months of life affect calciuria, with BF infants presenting the highest levels. We propose new cut-off values, based on feeding types, to prevent the overestimation in hypercalciuria diagnoses among BF infants., (© 2017 S. Karger AG, Basel.)

Background and Aims: The double-blind randomized European Childhood Obesity Project (CHOP) demonstrated that reduced protein content in infant formula leads to a lower body mass index (BMI) up to six years of age. Here we aimed at assessing pre-peritoneal fat, a marker of visceral fat, in children participating in the CHOP trial., Methods and Results: Healthy term formula-fed infants in five European countries were randomized either to higher (n = 550) or lower (n = 540) protein formulas in the first year of life. Infants who were exclusively breastfed for at least three months (n = 588) were enrolled as an observational (non randomized) group. At age 5 years, subcutaneous fat (SC) and pre-peritoneal fat (PP) were measured by ultrasound in a subgroup of 275 children. The PP fat layer was thicker in the higher compared to the lower protein group (adjusted estimated difference: 0.058 cm, 95%CI 0.002; 0.115; p = 0.043), while SC fat was not different. Girls showed a thicker SC fat layer than boys., Conclusions: Higher protein intake in formula-fed infants appears to enhance pre-peritoneal fat tissue accumulation at the age of 5 years, but not of subcutaneous fat, which may trigger adverse metabolic and health consequences., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. 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.

Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar - but not equal - metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy., (Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Introduction: Higher protein intake during the first year of life is associated with increased weight gain velocity and body mass index (BMI). However, the relationship of protein intake and weight gain velocity with body composition is unclear., Objective: To assess if the increases in weight gain velocity and BMI induced by protein intake early in life are related to an increase in fat or fat-free mass., Materials and Methods: In all, 41 infants randomized at birth to a higher or lower protein content formula (HP=17 and LP=24, respectively) and 25 breastfed infants were included. Anthropometric measures were assessed at baseline, 6, 12 and 24 months, and fat-free mass (FFM) and fat mass (FM) were assessed by isotope dilution at 6 months., Results: Weight gain velocity (g per month) during the first 6 months of life was significantly higher among HP infants (807.8 (±93.8) vs 724.2 (±110.0) (P=0.015)). Weight gain velocity strongly correlated with FM z-score (r=0.564, P<0.001) but showed no association with FFM z-scores. FFM showed no association with BMI. Nevertheless, FM strongly correlated with BMI at 6, 12 and 24 months (r=0.475, P<0.001; r=0.332, P=0.007 and r=0.247, P=0.051, respectively). FFM and FM z-scores did not differ significantly between HP and LP infants (0.32±1.75 vs -0.31±1.17 and 0.54±2.81 vs -0.02±1.65, respectively)., Conclusion: Our findings support the hypothesis that higher protein intakes early in life are associated with faster weight gain and in turn to higher adiposity. This mechanism could be a determinant factor for later obesity risk.

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.

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.

Objectives: The aim of this study was to describe developed methods for repeated longitudinal assessment of feeding habits and nutrient intakes of children in a multicenter trial in different European countries and to assess feasibility., Patients and Methods: Nutrient intake and dietary habits of formula-fed and breast-fed infants were assessed in 5 European countries (Belgium, Germany, Italy, Poland, and Spain). Prospective age-adapted 3-day weighed food records were used from birth to 2 years of age (1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 18, and 24 months). Standard operating procedures were developed to check each day's food record for quality. Dietitians were trained by using standardized food records. Data entry and nutrient analyses were performed with a dedicated software developed for this project., Results: Of 1368 study participants, at least one 3-day food record was available; of 25,367 1-day food records, data on quality could be evaluated. Overall, between 81% and 97% (depending on the country) of the food records had been completed with high accuracy. The implementation of solid foods and regular family foods decreased the recording quality significantly during the 2-year time course (P < 0.001). The standardized training shows coefficients of variation up to a maximum of about 41%, indicating differences in data entry., Conclusions: The experiences gathered indicate that collecting dietary and behavioral data in a large number of infants from different cultures is a challenging but feasible task in which permanent supervision and training is vital. However, we conclude that the established methodology is suitable to obtain valuable results on current infant nutrition practice in Europe.

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.)

Metabolic factors acting during limited and sensitive time periods of pre- and postnatal development can induce lasting effects on health and disease risk in later life up to old age, including later obesity risk, which is referred to as early metabolic programming of long-term health. Three meta-analyses of observational studies found that obesity risk at school age was reduced with early breastfeeding compared to formula feeding. We assumed 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 to usual infant formulas (the "early protein hypothesis"). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial enrolling 1,678 infants in five countries (Belgium, Germany, Italy, Poland, Spain). We have randomized healthy infants 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 years indicates that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the current WHO 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. The results obtained should stimulate the review of recommendations and policies for infant formula composition.

Objectives: Little is known about the practice of introducing complementary feeding across Europe. We aim at describing times of solid introduction in healthy infants in 5 European countries., Materials and Methods: Between October 2002 and June 2004, 1678 healthy term infants were either breast-fed (BF) for at least 4 months (n = 588) or study formula-fed (FF) (n = 1090) with different protein contents. Three-day-weighed food protocols were obtained at ages 1, 2, 3, 4, 5, 6, 7, 8, 9, and 12 completed months., Results: Solids were introduced earlier in FF infants (median 19 weeks, interquartile range 17-21) than BF infants (median 21 weeks, interquartile range 19-24). Some 37.2% of FF infants and 17.2% of BF infants received solid foods at 4 completed months, which is earlier than recommended in Europe. Solids had been introduced at 7 completed months in 99.3% of FF infants and 97.7% of BF infants, respectively. Belgium had the highest percentage of solids feeding in FF infants at 3 (15.8%) and 4 (55.6%) completed months, and in BF infants at 4 (43%) and 5 (84.8%) completed months. Multiple regression showed low maternal age, low education level, and maternal smoking to predictors an early introduction of solids at 3 and 4 completed months., Conclusions: Complementary feeding is introduced earlier than recommended in a sizeable number of infants, particularly among FF infants. Country- and population-specific approaches to adequately inform parents should be explored.

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.