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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.

Background: Universal varicella vaccination (UVV) for children introduced in Germany in 2004 resulted in a significant overall decline of varicella-related hospitalizations (VRHs). We investigated the incidence of specific types of varicella-related complications (VRCs) in hospitalized children and the impact of UVV on VRCs during the first 7 years of UVV. Methods: Children < 17 years of age hospitalized with an ICD-10-based (International Classification of Diseases, 10th Revision) discharge diagnosis of varicella were identified as VRH in pediatric hospitals in Bavaria by annual standardized data queries of the hospital databases (2005–2011). For each VRH, the hospitals reported basic demographic data, duration of hospital stay, all diagnostic and procedural codes, and outcome. VRCs were reported overall, per year, and by immune status. Complication rates were calculated as mean number per complication category per hospital and per year; VRC trends over time were assessed by linear regression. Results: Between 78% (2005) and 61% (2011) of Bavarian hospitals participated and reported a total of 1263 VRHs. Specific VRCs were reported in 954 (76%) children. Complication rates per hospital and year decreased from 6.7 [95% confidence interval (CI): 5.1–8.3] in 2005 to 1.5 (95% CI: 0.8–2.3) in 2011, with the strongest reduction of 90% in children < 5 years of age from 5.3 (95% CI: 4.0–6.6) in 2005 to 0.5 (95% CI: 0.1–0.9) in 2011. Significant decreases were observed for children with upper respiratory tract (URT, by 97%), lower respiratory tract (LRT, by 90%), skin (by 81%), gastrointestinal (by 78%), and neurologic (by 65%) VRCs. Forty-eight children with VRCs were immunocompromised; their annual rate decreased by 87%. Discussion: Corresponding to increasing varicella vaccination coverage in the population, the incidence of VRC decreased by 77% from 2005 to 2011, with the most substantial decrease in the target group for UVV. Conclusion: Within 7 years, UVV in Germany led to a decrease of about 77% of all types of VRCs, with the highest reductions observed for VRCs of the respiratory tract.

Fetal and early life represent a period of developmental plasticity during which metabolic pathways are modified by environmental and nutritional cues. Little is known on the pathways underlying this multifactorial complex. We explored whether 6 months old breast-fed infants could be clustered into metabolically similar groups and that those metabotypes could be used to predict later obesity risk. Plasma samples were obtained from 183 breast-fed infants aged 6 months participating in the European multicenter Childhood Obesity Project study. We measured amino acids along with polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins). We determined the metabotypes using a Bayesian agglomerative clustering method and investigated the properties of these clusters with respect to clinical, programming, and metabolic factors up to 6 years of age. We identified 20 metabolite clusters comprising 1 to 39 children. Phosphatidylcholines predominantly influenced the clustering process. In the largest clusters (n = 14), large differences existed for birth length (unadjusted P< 0.0001) and length and weight at 6 months (unadjusted P< 0.0001 and P= 0.012, respectively). Infants tended to cluster together by country (unadjusted P< 0.001). The body mass index (BMI) zscore at 6 years of age tended to differ (unadjusted P= 0.07). Our exploratory study provided evidence that breast-fed infants are not metabolically homogeneous and that variation in metabolic profiles among infants may provide insight into later development and health. This work highlights the potential of metabotypes for identifying inter-individual differences that may form the basis for developing personalized early preventive strategies.

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AbstractBackground:Early adiponectin and leptin in children correlate with those measured at a later age. Prenatal and early life factors may influence the pattern of leptin and adiponectin longitudinal changes. We aimed to identify subgroups of children with distinct trajectories of leptin and adiponectin over the first eight years of life, and to explore determinants predisposing an individual to be included in a specific trajectory class.Methods:The analysis was based on data obtained from the EU Childhood Obesity Project (CHOP) cohort. The current study involved 459 children with adiponectin and leptin measured at 6 months, 5½ and 8 years of age.Results:Three groups of leptin trajectories were identified: low-decreasing, medium-stable, and high-increasing, and two trajectory groups for adiponectin: lower and higher. The risk to be classified in the high-increasing group was higher than in the low-decreasing group for female gender (OR 10.67; 95% CI 4.94–23.05; p< 0.001); formula feeding (OR 3.34; 95% CI 1.11–10.09; p< 0.05); maternal overweight (OR 4.43; 95% CI 2.20–8.94; p< 0.001); and smoking in pregnancy (OR 4.14; 95% CI 2.07–8.29; p< 0.001). No predictors for being in the higher vs. lower adiponectin group were discovered.Conclusions:Mothers' smoking during pregnancy, maternal overweight, and formula feeding distinguished different courses of leptin trajectories; but the effect may be associated with changes in adiposity.

Background:Protein intake may modulate cardiac structure and function in pathological conditions, but there is a lack of knowledge on potential effects in healthy infants.Methods:Secondary analysis of an ongoing randomized clinical trial comparing two groups of infants receiving a higher (HP) or lower (LP) protein content formula in the first year of life, and compared with an observational group of breastfed (BF) infants. Growth and dietary intake were assessed periodically from birth to 2 y. Insulin-like growth factor 1 (IGF-1) axis parameters were analyzed at 6 mo in a blood sample. At 2 y, cardiac mass and function were assessed by echocardiography.Results:HP infants (n = 50) showed a higher BMI z-score at 2 y compared with LP (n = 47) or BF (n = 44). Cardiac function parameters were increased in the HP group compared with the LP and were directly related to the protein intake during the first 6 mo of life. Moreover, there was an increase in free IGF-1 in the HP group at 6 mo.Conclusion:A moderate increase in protein supply during the first year of life is associated with higher cardiac function parameters at 2 y. IGF-1 axis modifications may, at least in part, underlie these effects.

This article will summarize recent progress in research in the area of complementary feeding as it relates to childhood obesity. Newly emerged findings demonstrate how research on contributing factors has shifted. Examining nutrient and caloric intakes alone has failed to answer the critical question, ‘Why are some children obese, whereas others are not’ Recent research explores parental attitudes, beliefs and parental feeding styles as contributing factors.

Background:Animal models have shown that insulin-like growth factor I (IGF-I) may mediate protein-induced kidney growth. Our aim was to analyze the effect of IGF-I on protein-induced kidney growth in healthy infants.Methods:This is a secondary analysis of a randomized trial that compared growth of infants fed with a higher-protein (HP) (n = 169) vs. lower-protein (LP) (n = 182) formula (in the first year of life). Outcome measures were anthropometric parameters, kidney volume (cm3), and total and free IGF-I (ng/ml).Results:The highest levels of total and free IGF-I were found in the HP group. Both parameters correlated significantly with BMI z-score (r = 0.229, P < 0.001 and r = 0.223, P < 0.001, respectively), kidney volume (r = 0.115, P = 0.006 and r = 0.208, P < 0.001, respectively), and kidney volume/body length (r = 0.109, P = 0.010 and r = 0.194, P < 0.001, respectively) at 6 mo. Linear regression analyses showed a significant effect of free IGF-I on kidney volume in models, including significant effects of HP formula and anthropometry. The structural equation model revealed a significant direct effect of the HP formula on kidney volume and an indirect effect mediated by free IGF-I.Conclusion:This study suggests that IGF-I partly mediates protein-induced kidney growth in healthy infants. IGF-I could be involved in a pathway for the programming of the renal system.

Obesity is a multifaceted public health problem, which should be addressed with an all-encompassing approach. Recent research has asked questions that link specific infant nutritional risks to childhood obesity. This article brings recent research in the area of complimentary feeding practices to light and summarizes the research on its consequent impact on obesity risk.

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.

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.

The true burden of varicella complications in Germany is not known. We investigated the incidence and pattern of varicella complications in children and adolescents using 3 independent surveillance sources.

Living close to major roads or highways has been suggested to almost double the risk of dying from cardiopulmonary causes. We assessed whether long-term exposure to air pollution originating from motorized traffic and industrial sources is associated with total and cause-specific mortality in a cohort of women living in North Rhine-Westphalia, Germany.

In Germany, Haemophilus influenzaetype b (Hib), polio and hepatitis B (HBV) vaccines have been combined with diphtheria, tetanus and acellular pertussis vaccines. We examined whether the use of combination vaccines has improved the timing of these vaccinations.

Recently an increase in the number of invasive Haemophilus influenzaetype b (Hib) cases was observed in the United Kingdom, which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis (DTaP) Hib vaccines. A study in Germany based on approximately 2 years of follow-up, estimated vaccine effectiveness (VE) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high.

IgG antibody values against measles, mumps, rubella and varicella-zoster virus in 71 full term and 101 preterm infants and their 152 mothers and the decay of maternally acquired antibodies during infancy were studied. Both magnitude of transplacental antibody passage and cord blood antibody values correlated with gestational age. After 6 months preterm infants born before 32 weeks of gestation had lost maternal antibodies.