Assessing the impact of obesity interventions in the early years: a systematic review of UK-based studies.

OBJECTIVES: Childhood obesity rates in the UK are high. The early years of childhood are critical for establishing healthy behaviours and offer interventional opportunities. We aimed to identify studies evaluating the impact of UK-based obesity interventions in early childhood. DESIGN: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Nine databases were searched in March 2023. ELIGIBILITY CRITERIA: We included UK-based obesity intervention studies delivered to children aged 6 months to 5 years that had diet and/or physical activity components and reported anthropometric outcomes. The primary outcome of interest was z-score Body Mass Index (zBMI) change (within and between subjects). Studies evaluating the effects of breastfeeding interventions were not included as obesity prevention interventions, given that best-practice formula feeding is also likely to encourage healthy growth. The publication date for studies was limited to the previous 12 years (2011-23), as earlier reviews found few evaluations of interventions in the UK. DATA EXTRACTION AND SYNTHESIS: The reviewers worked independently using standardised approach to search, screen and code the included studies. Risk of bias was assessed using Cochrane tools (ROB 2 or ROBINS-I). RESULTS: Six trials (five studies) were identified, including two randomised controlled trials (RCT), one cluster randomised trial (CRT), two feasibility CRTs and one impact assessment. The total number of participants was 566. Three trials focused on disadvantaged families and two included high-risk children categorised as having overweight or obesity. Compared with baseline, five interventions reported reductions in zBMI, three of which were statistically significant (p<0.05). Compared with control, five interventions showed zBMI reductions, one of which was significant. Only two trials were followed up beyond 12 months. All studies were found to have a high risk of bias. Meta-analysis was not possible due to the heterogeneity of studies. CONCLUSION: UK evidence was limited but some interventions showed promising results in promoting healthy growth. As part of a programme of policies, interventions in the early years may have an important role in reducing the risk of childhood obesity. PROSPERO REGISTRATION NUMBER: CRD42021290676.

Infant feeding practices and risk of preschool obesity in AlAin, UAE: A cross-sectional study.

Early childhood obesity is serious public health problem, and poses a risk of obesity in later life. The study aimed to investigate whether infant feeding affects risk of overweight and obesity in preschool children in the United Arab Emirates (UAE). A cross-sectional study was carried out. Data was collected in a kindergarten in Al Ain, UAE. One hundred and fifty parents and preschool children aged 2 to 6 years participated in the study. Univariate and multivariate linear regression were used to investigate associations. A longer duration of breastfeeding and later introduction of complementary foods were associated with a lower BMI z-score in preschool children. Each month of any breastfeeding was associated with a lower BMI z-score in the unadjusted model (ß = -0.03; 95% CI -0.05, -0.01; p = 0.01), and each month increase in the age of introducing complementary foods was associated with a lower BMI z-score in the unadjusted model (ß = -0.43; 95% CI: -0.60 to-0.027; p<0.001). These associations remained after adjustment for potential confounding factors (age, sex, maternal BMI, maternal education level, mother's age, social class, father's BMI) for duration of breastfeedinig (ß = -0.02; 95% CI: -0.05 to 0.00; p<0.001) and age of complementary feeding (ß = -0.39; 95% CI: -0.57 to-0.21; p<0.001). Poor infant feeding practices (shorter duration of breastfeedinig and early introduction of complementary foods) were found to be associated with higher BMI in preschool children. Promoting appropriate proper infant feeding practices in line with recommendations could be one strategy to help prevent childhood obesity in the UAE.

Does human milk composition predict later risk of obesity? A systematic review.

BACKGROUND: Possible mechanisms behind the association of breastfeeding with a lower risk of later obesity are unknown but one possibility is the unique composition of human milk. Here, we systematically reviewed the evidence linking breast-milk macronutrient and hormonal composition with later obesity. METHODS: We searched 7 databases for studies that included infants predominantly breast-fed for the first 3 months and which analysed associations between a measure of breast-milk composition and later (> 6 months) measures of obesity or body composition. RESULTS: 47 publications were identified for full-text screening, of which 10 were eligible and only 3 found significant associations. Higher leptin concentration in breast milk at age 1 month was associated with lower infant BMI at 12, 18 and 24 months of age (1 study). Higher breast-milk adiponectin concentration at 6 weeks and 4 months were associated with adiposity at age 12 and 24 months (1 study). In 1 study, breast-milk carbohydrate content was positively associated, and fat content negatively associated, with adiposity at age 12 months. No significant associations were found between other hormones or macronutrients in human milk and later risk of obesity or body composition. CONCLUSIONS: The evidence linking breast-milk composition with later obesity was inconsistent and confined to single, individual studies. Our review highlights the methodological limitations of previous studies and the need for further research in this area.

Weight Gain in Early Infancy Impacts Appetite Regulation in the First Year of Life. A Prospective Study of Infants Living in Cyprus.

BACKGROUND: Eating behavior is associated with weight gain in infancy and childhood. Few studies found a bidirectional association between weight gain and eating behavior development in childhood, but there is little data on the association in early infancy, a period critical for the programming of obesity risk. OBJECTIVE: We investigated the bidirectional association between appetite traits and weight gain during the first year of life. METHODS: Participants were part of a cohort of 432 infants born in Cyprus. Appetite traits were measured using the Baby Eating Behavior Questionnaire or the Child Eating Behavior Questionnaire at age 2 to 4 wk, 6 mo, and 12 mo. Weight and length were collected at birth, 4 wk, 6 mo, and 12 mo. Multivariable linear regression was used to analyze associations between appetite traits at 2 to 4 wk and 6 mo and weight for age z-score change (WFAZC) between 4 wk and 6 mo and 6 and 12 mo. Associations were also analyzed in the opposite direction, between WFAZC from birth to 4 wk, 4 wk to 6 mo, and 6 mo to 12 mo and appetite traits at 4 wk, 6 mo, and 12 mo. RESULTS: Satiety responsiveness (SR) at 2 to 4 wk was associated with lower WFAZC from 4 wk to 6 mo (ß: -0.17; 95% CI: -0.30, -0.04) and SR at age 6 mo was associated with lower WFAZC from 6 to 12 mo (ß: -0.09; 95% CI: -0.17, -0.02). WFAZC from 4 wk to 6 mo was associated with higher enjoyment of food at 12 mo (ß: 0.11; 95% CI: 0.01, 0.20), higher food responsiveness at 12 mo (ß: 0.17; 95% CI: 0.04, 0.30), and lower SR at both 6 mo (ß: -0.11; 95% CI: -0.21, -0.01) and 12 mo (ß: -0.14; 95% CI: -0.24, -0.03). CONCLUSIONS: We found a bidirectional association between weight gain and appetite traits in infancy, suggesting that the effect of postnatal weight gain on obesity development is partly mediated by programming of appetite traits.

Complications and outcomes of gastrostomy versus nasogastric tube feeding in paediatric allogeneic bone marrow transplant: A prospective cohort study.

BACKGROUND & AIMS: The intensive conditioning regimens administered during bone marrow transplant (BMT) frequently cause mucositis, gastrointestinal toxicity and reduced oral intake. Children are consequently at risk of malnutrition. First-line nutrition support is recommended as enteral nutrition (EN). Nasogastric tube (NGT) is the mainstay for administration. Gastrostomies provide an alternative, but there is limited evidence of their efficacy and safety in paediatric BMT. This study aimed to compare enteral tube complications and nutritional and clinical outcomes between children with a gastrostomy versus NGT throughout BMT. METHODS: A prospective cohort study was conducted at a single centre in the United Kingdom. During pre-admission consultations families were offered choice of a prophylactic gastrostomy or NGT. Children undergoing allogeneic BMT were recruited from April 2021 to April 2022. Data compared between children with either tube included: tube complications, change in weight, body mass index and mid-upper-arm circumference, calorie, protein and fluid intake, timing and use of EN and parenteral nutrition, survival, graft-versus-host disease and length of admission. Following BMT, data were collected weekly for the first six weeks from electronic records, monthly thereafter from 3-day averaged food diaries and clinic assessments, until six months post-BMT. RESULTS: Nineteen children with NGT were compared to 24 with a gastrostomy. Of gastrostomy complications, 94.2% (129/137) were minor, mechanical issues being most common (80/137). Dislodgement comprised 80.2% (109/136) of NGT complications. No significant differences were seen between tubes on nutritional, anthropometric and clinical outcomes. CONCLUSIONS: Gastrostomies were popular with families, relatively safe, associated with mostly minor complications and similarly effective as NGTs in supporting children's nutritional intake and status. Where an NGT may not be tolerated, a prophylactic gastrostomy could be considered. Placement of either tube requires balancing their risks, benefits, the child's nutritional status, conditioning, expected duration of EN and family preferences.

Quantity and Source of Protein during Complementary Feeding and Infant Growth: Evidence from a Population Facing Double Burden of Malnutrition.

BACKGROUND: While high protein intake during infancy may increase obesity risk, low qualities and quantities of protein contribute to undernutrition. This study aimed to investigate the impact of the amount and source of protein on infant growth during complementary feeding (CF) in a country where under- and overnutrition co-exist as the so-called the double burden of malnutrition. METHODS: A multicenter, prospective cohort was conducted. Healthy term infants were enrolled with dietary and anthropometric assessments at 6, 9 and 12 months (M). Blood samples were collected at 12M for IGF-1, IGFBP-3 and insulin analyses. RESULTS: A total of 145 infants were enrolled (49.7% female). Animal source foods (ASFs) were the main protein source and showed a positive, dose-response relationship with weight-for-age, weight-for-length and BMI z-scores after adjusting for potential confounders. However, dairy protein had a greater impact on those parameters than non-dairy ASFs, while plant-based protein had no effect. These findings were supported by higher levels of IGF-1, IGFBP-3 and insulin following a higher intake of dairy protein. None of the protein sources were associated with linear growth. CONCLUSIONS: This study showed the distinctive impact of different protein sources during CF on infant growth. A high intake of dairy protein, mainly from infant formula, had a greater impact on weight gain and growth-related hormones.

Research Priorities for Pediatric Intensive Care Nutrition Within the United Kingdom: A National Institute of Health Research James Lind Alliance Priority Setting Partnership.

OBJECTIVES: To determine research priorities in PICU nutrition, which represent the shared priorities of patients, parents, carers, and PICU healthcare professionals within the United Kingdom. DESIGN: A national multiphase priority setting methodology in partnership with the James Lind Alliance delivered over 16 months (June 2020-September 2021). Part 1: a national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. Part 2: summarizing and evidence-checking the submitted uncertainties. Part 3: interim prioritization survey. Part 4: consensus workshop. SETTING: PICU. PARTICIPANTS: Patients, parents, and carers of patients who had been admitted to PICU, and PICU healthcare professionals involved in the treatment of these patients within the United Kingdom. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. In the first survey, 165 topic ideas were suggested (12% by parents/carers and 88% by PICU healthcare professionals). These were categorized into 57 summary questions. The existing evidence was searched to ensure that the proposed summary questions had not already been answered. Forty were judged to be true uncertainties following a systematic literature review. These 40 uncertainties were grouped into eight themes for the second interim survey, which asked respondents to prioritize their top research questions. One hundred and forty participants contributed to this second interim survey. A final shortlist of 25 questions was derived, with the top 18 questions taken to a multistakeholder workshop where a consensus was reached on the top 10 priorities. CONCLUSIONS: This research identified important research gaps in the management of patients in PICU. Areas that need to be addressed as a priority include energy requirements in ventilated neonates, nutritional supplementation of probiotics to manage and prevent sepsis, the impact of postintensive care syndrome on nutrition and growth, and when to commence parenteral (IV) nutrition. The challenge now is to refine and deliver answers to these research priorities.

Nutritional support practices and opinions toward gastrostomy use in pediatric bone marrow transplant centers: A national survey.

OBJECTIVE: Previous surveys have shown deviations in nutritional practices from international guidelines during bone marrow transplant (BMT). Guidelines recommend enteral nutrition first-line and nasogastric tubes are the mainstay for its provision. Gastrostomies provide an alternative, yet their use is less common. This national survey investigated nutrition support practices in pediatric allogeneic BMT centers and compared clinicians' opinions on gastrostomy use. The aim of this study was to identify the national picture of nutritional support practices across pediatric allogeneic BMT centers, including use and opinions of dietitians, clinical nurse specialists, and physicians, toward gastrostomy feeding. METHODS: An online survey was administered to 12 centers. The lead dietitian answered questions regarding nutritional counseling, screening, assessment, and interventions. Questions regarding current use, perceived advantages, and problems of gastrostomies were answered by the dietitian, lead clinical nurse specialist, and physician. RESULTS: A 100% response rate was achieved from 12 centers (N = 36 clinicians). Nutritional counseling was provided in 92% of centers before and routinely throughout admission, 83% screened on and regularly throughout admission, 83% assessed nutritional status before transplant, and 92% used enteral nutrition first-line. Forty-two percent of the centers used gastrostomies. In those not using gastrostomies, 76% of clinicians felt some children should be offered a gastrostomy. Clinicians perceived less displacements (78%) and cosmetic appearance (69%) as the most common advantages of gastrostomies over nasogastric tubes. Risks associated with surgery (92%) and tube/stoma complications (58%) were the most common perceived problems. CONCLUSIONS: A similar approach was shown on many aspects of nutritional support. Gastrostomy use divided opinion with differences in use and perceived advantages, but agreement on potential complications. Despite their risks, clinicians wanted to use gastrostomies more. Placement requires careful consideration of the risks, benefits, and family preferences.

Systematic review of gastrostomy complications and outcomes in pediatric cancer and bone marrow transplant.

BACKGROUND: Nutrition support is essential in children with cancer, including those undergoing bone marrow transplant (BMT), to reduce the risk of malnutrition and associated deleterious outcomes. Enteral nutrition is more commonly provided via nasogastric than gastrostomy tubes because of safety concerns with the latter in immunocompromised children. This systematic review investigated the incidence and type of complications and outcomes in pediatric cancer patients fed by gastrostomy. METHODS: Databases were searched for randomized and observational studies investigating the use of any gastrostomy device in children aged <18 years with any cancer diagnosis, including those undergoing BMT. Five cohort and 11 case series studies were included. Owing to clinical heterogeneity, meta-analyses were not performed. RESULTS: Quality of evidence varied, with five studies judged at serious risk of bias and poor quality; however, the remaining 11 were considered to range from moderate to good quality. Across studies, 54.6% of children developed one or more complications, of which 76.6% were classified as minor, 23.4% major. The most frequent complications included inflammation (52% of episodes), infection (42.1%), leakage (22.3%), and granuloma (21%). Evidence regarding infection rates in cancer/BMT patients compared with other disease states was inconclusive. Gastrostomy feeding was associated with improvement or stabilization of nutrition status in 77%-92.7% of children. CONCLUSION: Gastrostomy feeding in this population is relatively safe and effective in stabilizing or improving nutrition status throughout treatment. Complications are frequent but mostly minor. Placement requires careful consideration of the complications, benefits, nutrition risk and status at diagnosis, and quality of life.

Comparison of 24-Hour Recall and 3-Day Food Records during the Complementary Feeding Period in Thai Infants and Evaluation of Plasma Amino Acids as Markers of Protein Intake.

BACKGROUND: An accurate and reliable measurement of nutrient intake is the first and foremost step in order to optimise infant nutrition and evaluate its impact on health outcomes. However, research on the validity of dietary assessment tools used during the weaning period is limited, especially in lower-middle income countries. The primary aim of this study was to evaluate relative validity of a 24-h recall method (24-HR) using a 3-day food record (3-DFR). A secondary aim was to investigate association between protein intake from 3-DFR and plasma amino acids as a potential protein biomarker. Methods A multicentre, prospective cohort study was conducted in Chiang Mai, Thailand from June 2018 to May 2019. Food consumption data were collected in healthy infants using 24-HR and 3-DFR at 9 and 12 months of age. Blood samples were obtained at 12 months (M). Plasma amino acids were analysed using high performance liquid chromatography. Results Of 145 infants, 49% were female. At group level, paired t-tests/Wilcoxon signed rank tests did not show significant differences between average nutrient intakes from the 2 dietary assessment methods, except for vitamin A and vitamin C. Weighted kappa (Kw) was acceptable for all nutrients, except for vitamin A intake at 9 M (Kw = 0.15). The Bland-Altman analyses were unbiased for most nutrients with variable limits of agreement. At individual level, correlation coefficients (r) ranged from acceptable to excellent (r = 0.37-0.87) while cross-classifications showed acceptable outcomes, except for vitamin A. Multivariate analyses showed significant associations between protein intake at 12 M from the 3-DFR and plasma concentrations of branched-chain amino acids (BCAA) and essential amino acids (EAA), even after adjusting for gender, milk feeding type and energy intake. Conclusions For infants aged 9-12 M, a 24-HR can be used as a more practical alternative to a 3-DFR for most nutrients although caution is required for some micronutrients, especially vitamin A. A repeated interview might further improve the accuracy. Furthermore, protein intake, particularly animal-based protein, significantly predicted plasma BCAA and EAA concentrations regardless of gender, type of milk feeding and energy consumption.

The Impact of Dietary Protein in Complementary Foods on Infant Growth and Body Composition in a Population Facing the Double Burden of Malnutrition: Protocol for a Multicenter, Prospective Cohort Study.

BACKGROUND: Protein is an essential macronutrient with an important role during complementary feeding. Low protein intake contributes to undernutrition while high intake, especially from animal sources, may increase obesity risk. However, the influences of different protein sources (dairy, meat, and plants) on growth, and underlying mechanisms for these effects, are poorly understood. Animal-sourced foods provide both high-quality protein and iron and are recommended to improve iron status. However, it is unclear whether current dietary recommendations are adequate to support healthy growth and optimize iron status. These issues are of particular concern in countries facing the double burden of malnutrition, the coexistence of all forms of malnutrition. More evidence is needed to develop appropriate recommendations for these countries. OBJECTIVE: This study will investigate associations between protein intake during complementary feeding and growth, body composition, and iron status of infants in Thailand, a country facing the double burden of malnutrition. The study will also explore how different protein sources influence growth via the growth hormone-insulin-like growth factor I (IGF-1) axis and plasma amino acids. METHODS: A multicenter cohort study will be conducted in Chiang Mai, Thailand, in 150 healthy term infants aged 4-6 months with birth weight ≥2500 g. Demographic data, dietary intake, and anthropometry will be collected at 6, 9, and 12 months. Dietary intake will be assessed using 24-hour dietary recalls, 3-day food records, and food frequency questionnaires. Blood samples for iron status, growth hormone, IGF-1, insulin-like growth factor-binding protein III (IGFBP-3), and plasma amino acids and urine samples for body composition analysis using stable isotope dilution will be obtained at 12 months. RESULTS: The recruitment of study participants and data collection was undertaken from June 2018 to May 2019. Data and laboratory analyses are ongoing and are expected to be completed by December 2020. A total of 150 participants were enrolled, and 146 completed the study. We hypothesized that protein intake from animal-sourced foods in recommended quantities could support normal weight and length gain and lower the risk of undernutrition associated with similar amounts of plant-based protein. However, higher protein intake, especially from milk protein, may be linked to increased body fat via plasma amino acids and the growth hormone-IGF axis. CONCLUSIONS: The results of this study will provide data on current complementary feeding practices, focusing on protein and iron intake in Thai infants. This information, combined with data on associations with infant growth and iron status, will help inform complementary feeding recommendations for this population and may be found relevant to other settings experiencing the double burden of malnutrition. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18112.

Complementary feeding: Attitudes, knowledge and practices of urban families in northern Thailand.

AIM: Urban families in middle-income countries are currently facing cultural and lifestyle transition. Changing from an agricultural to an industrial society may affect family roles and child-care practices. The present study aims to reveal family attitudes, knowledge and practices focusing on complementary feeding (CF). METHODS: A cross-sectional study was conducted in three Child Health Clinics in Chiang Mai, Thailand. Self-administered questionnaires were given to families caring for healthy infants and children less than 18 months of age during October to November 2016. RESULTS: One-hundred and eight respondents completed questionnaires. The study found different attitudes and knowledge gaps between the respondents who were mothers and other family members ('others'). The 'others' were less likely to value CF as a crucial factor promoting child growth and development. Moreover, they had misperceptions about the benefits of animal-based protein and were less confident in their ability to feed the child properly. Most families reported timely introduction of complementary food, using proper milk products and encouraging age-appropriate feeding methods. However, there were undesirable practices including delaying introduction of animal-based protein, inadequate food diversity, the use of seasoning, feeding premasticated food and offering food as a reward. CONCLUSIONS: These findings suggest that nutritional education should be extended to all caregivers involved in CF to improve the adherence to feeding recommendations.

Prevention of overweight and obesity in early life.

Childhood obesity is a serious challenge for public health. The problem begins early with most excess childhood weight gained before starting school. In 2016, the WHO estimated that 41 million children under 5 were overweight or obese. Once established, obesity is difficult to reverse, likely to persist into adult life and is associated with increased risk of CVD, type 2 diabetes and certain cancers. Preventing obesity is therefore of high importance. However, its development is multi-factorial and prevention is a complex challenge. Modifiable lifestyle behaviours such as diet and physical activity are the most well-known determinants of obesity. More recently, early-life factors have emerged as key influencers of obesity in childhood. Understanding risk factors and how they interact is important to inform interventions that aim to prevent obesity in early childhood. Available evidence supports multi-component interventions as effective in obesity prevention. However, relatively few interventions are available in the UK and only one, TrimTots, has been evaluated in randomised controlled trials and shown to be effective at reducing obesity risk in preschool children (age 1-5 years). BMI was lower in children immediately after completing TrimTots compared with waiting list controls and this effect was sustained at long-term follow-up, 2 years after completion. Developing and evaluating complex interventions for obesity prevention is a challenge for clinicians and researchers. In addition, parents encounter barriers engaging with interventions. This review considers early-life risk factors for obesity, highlights evidence for preventative interventions and discusses barriers and facilitators to their success.

Docosahexaenoic acid supplementation, vascular function and risk factors for cardiovascular disease: a randomized controlled trial in young adults.

BACKGROUND: A high consumption of omega-3 long-chain polyunsaturated fatty acids, and particularly docosahexaenoic acid (DHA), has been suggested to reduce the risk of cardiovascular disease (CVD). However, while DHA supplementation may have benefits for secondary prevention, few studies have investigated the role of DHA in the primary prevention of CVD. Here, we tested the hypothesis that DHA supplementation improves endothelial function and risk factors for CVD. METHODS AND RESULTS: Healthy volunteers (n=328), aged 18 to 37 years, were randomly assigned to 1.6 g DHA/day (from a microalgae source) together with 2.4 g/day carrier oil (index group) or to 4.0 g/day olive oil (control) (both given in eight 500-mg capsules/day for 16 weeks). Flow-mediated endothelium-dependent vasodilation (FMD) of the brachial artery (primary outcome) was measured before and after the intervention (n=268) using high-resolution vascular ultrasound. FMD was the same in both groups at randomization (mean, SD; 0.27, 0.1 mm), but postintervention was higher in the control group (0.29, 0.1 mm) compared with the DHA-supplemented group (0.26, 0.1 mm; mean difference -0.03 mm; 95% CI -0.005 to -0.06 mm; P=0.02). Of other outcomes, only triglyceride (mean difference -28%, 95% CI -40% to -15%; P<0.0001) and very low-density lipoprotein concentrations were significant lower in DHA-supplemented individuals compared with controls. CONCLUSIONS: DHA supplementation did not improve endothelial function in healthy, young adults. Nevertheless, lower triglyceride concentrations with DHA supplementation was consistent with previous reports and could have benefits for the prevention of CVD.

Effect of specific ART drugs on lipid changes and the need for lipid management in children with HIV.

BACKGROUND: We investigated the effects of individual antiretrovirals on lipids in HIV-infected children and the proportion potentially eligible for dietary or pharmacologic intervention. METHODS: St Mary's and Great Ormond Street Hospital's, London, United Kingdom, patients between 1995 and 2007 were included. Associations between lipids (millimoles per liter) and specific antiretroviral therapy were assessed using mixed-effects models adjusted for confounders. Children eligible for lipid-lowering management were assessed according to American Academy of Pediatric criteria [low-density lipoprotein (LDL) > 190 mg/dL or 4.9 mmol/L for children with no known cardiovascular disease risk factors or LDL > 160 mg/dL or 4.1 mmol/L for children with 2 or more cardiovascular disease risk factors]. RESULTS: Four hundred forty-nine children had median 4.5-year follow-up. On average, antiretroviral therapy-naive children had normal lipids except for low high-density lipoprotein cholesterol (HDL) (median 0.8). All cholesterol subsets were elevated for the 4 drugs assessed. Protease inhibitors had greater rises in total cholesterol with the maximal non-HDL rise for lopinavir/ritonavir at 4+ years of exposure, 0.8 (0.57-1.03). The nonnucleoside reverse transcriptase inhibitors also raised non-HDL, but this was associated with additional clinically significant increases in HDL. Nevirapine raised non-HDL by 0.38 (0.09-0.31) at 2-3 years and HDL by 0.34 (0.28-0.41). Efavirenz raised non-HDL by 0.2 (0.09-0.31) and HDL by 0.12 (0.08-0.17) at 1 year. Ten percent had LDL above the 95th percentile, but only 3 met the 4.9 cutoff for pharmacologic intervention. CONCLUSIONS: Intervention strategies (dietary and exercise advice, treatment switching, and pharmacotherapy) are required for persistent hyperlipidemia and should be assessed in randomized control trials.

Nutrition in infancy and long-term risk of obesity: evidence from 2 randomized controlled trials.

BACKGROUND: Growth acceleration as a consequence of relative overnutrition in infancy has been suggested to increase the risk of later obesity. However, few studies have investigated this association by using an experimental study design. OBJECTIVE: We investigated the effect of early growth promotion on later body composition in 2 studies of infants born small for gestational age (weight <10th percentile in study 1 and <20th percentile in study 2). DESIGN: We reviewed a subset of children (n = 153 of 299 in study 1 and 90 of 246 in study 2) randomly assigned at birth to receive either a control formula or a nutrient-enriched formula (which contained 28-43% more protein and 6-12% more energy than the control formula) at 5-8 y of age. Fat mass was measured by using bioelectric impedance analysis in study 1 and deuterium dilution in study 2. RESULTS: Fat mass was lower in children assigned to receive the control formula than in children assigned to receive the nutrient-enriched formula in both trials [mean (95% CI) difference for fat mass after adjustment for sex: study 1: -38% (-67%, -10%), P = 0.009; study 2: -18% (-36%, -0.3%), P = 0.04]. In nonrandomized analyses, faster weight gain in infancy was associated with greater fat mass in childhood. CONCLUSIONS: In 2 prospective randomized trials, we showed that a nutrient-enriched diet in infancy increased fat mass later in childhood. These experimental data support a causal link between faster early weight gain and a later risk of obesity, have important implications for the management of infants born small for gestational age, and suggest that the primary prevention of obesity could begin in infancy.

The effect of intrauterine growth on verbal IQ scores in childhood: a study of monozygotic twins.

OBJECTIVE: Given the adverse neurobiological effects of suboptimal nutrition on the developing brain, it is of social and medical importance to determine if the global prevalence of poor intrauterine growth causes lasting cognitive deficits. We examined whether suboptimal intrauterine growth relates to impaired cognitive outcome by comparing birth weight and cognition in monozygotic twins and considered whether children within-pair differences in birth weight were related to within-pair differences in IQ scores. METHODS: A total of 71 monozygotic twin pairs (aged 7 years 11 months to 17 years 3 months) participated. The Wechsler Intelligence Scale for Children, Third Edition, was administered, and verbal IQ (VIQ) and performance IQ (PIQ) scores were calculated. Regression was used to relate within-pair differences in birth weight to within-pair differences in IQ scores. RESULTS: VIQ but not PIQ score was affected by prenatal growth restriction. The results suggest that the mean advantage for heavier twins relative to their lighter co-twins can be as much as half an SD in VIQ points. In pairs with minimal discordance, heavier twins had lower VIQ scores than their lighter co-twins. CONCLUSIONS: Our study results suggest that lower birth weight in monozygotic twins can also have a negative long-term impact on cognition both in infants who are small at birth and also those with birth weights across the spectrum. Studying monozygotic twins enabled us to examine the effect of reduced intrauterine growth on cognition independently of confounding factors, including parental IQ and education and infant gender, age, genetic characteristics, and gestation.

Prevention of obesity in preschool children.

Obesity is a serious problem that affects children from diverse ethnic backgrounds in both industrialised and developing countries. Worldwide, an estimated twenty-two million children <5 years of age were overweight in 2007. In the UK if current trends continue an estimated one-quarter of all children <16 years of age will be obese by 2050. Recent evidence suggests that most obesity is established during the preschool years, and because one in five obese 4 year olds will become obese adults this situation has major implications for public health. The causes of obesity in preschool children are complex and multifactorial. Although 30-50% of the predisposition towards obesity in preschool children can be explained by genetic factors, environmental influences also play a crucial role. The preschool period in particular is a pivotal time during which long-term dietary and physical activity habits are established, with potential lifelong effects on health. However, research in this age-group is limited. Previous studies have aimed to improve diet, increase physical activity and achieve behavioural change. However, few of these studies have been successful and there is an urgent need, therefore, for the development of evidence-based interventions aimed at the prevention of preschool obesity.

Early nutrition and long-term health: a practical approach.

Nutrition in early life, a critical period for human development, can have long-term effects on health in adulthood. Supporting evidence comes from epidemiological studies, animal models and experimental interventions in human subjects. The mechanism is proposed to operate through nutritional influences on growth. Substantial evidence now supports the hypothesis that 'accelerated' or too fast infant growth increases the propensity to the major components of the metabolic syndrome (glucose intolerance, obesity, raised blood pressure and dyslipidaemia), the clustering of risk factors that predispose to cardiovascular morbidity and mortality. The association between infant growth and these risk factors is strong, consistent, shows a dose-response effect and is biologically plausible. Moreover, experimental data from prospective randomised controlled trials strongly support a causal link between infant growth and later risk factors for atherosclerosis. Evidence that infant growth affects the development of atherosclerosis therefore suggests that the primary prevention of CVD should begin from as early as the first few months of life. The present review considers this evidence, the underlying mechanisms involved and its implications for public health.

Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial.

BACKGROUND: Dietary nucleotides are nonprotein nitrogenous compounds that are thought to be important for growth, repair, and differentiation of the gastrointestinal tract. A higher nucleotide intake may also have favorable effects on the fecal microbial composition and incidence of diarrhea in infancy. However, few studies have tested this hypothesis with an experimental study design. OBJECTIVE: We tested the hypothesis that nucleotide supplementation of infant formula has beneficial effects on fecal bacteriology. DESIGN: Oligonucleotide probes were used to measure bacterial genus-specific 16S ribosomal RNA in stools of a subset of infants (mean age: 20.4 wk) who were randomly assigned to nucleotide-supplemented (31 mg/L; n = 35) or control formula (n = 37) from birth until age 20 wk or were breastfed (reference group; n = 44). The microbial pattern was assessed as the ratio of Bacteroides-Porphyromonas-Prevotella group (BPP) to Bifidobacterium species. RESULTS: The ratio of BPP to Bifidobacterium spp. rRNA in infants randomly assigned to the nucleotide-supplemented formula was lower than in infants receiving the control formula (mean difference: -118%; 95% CI: -203%, -34%; P = 0.007), but it did not differ in infants who were breastfed. The difference between randomized formula-fed groups was independent of potential confounding factors (P = 0.003). CONCLUSIONS: Our data support the hypothesis that nucleotide supplementation improves the composition of the gut microbiota in formula-fed infants. Because this effect could contribute to previously described benefits of nucleotide supplementation for gastrointestinal tract and immune function, these findings have important implications for optimizing the diet of formula-fed infants.