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Objectives: There's paucity of longitudinal studies assessing the role of adolescent growth on adult body composition in developing countries. The aims of this study were to assess the association between adolescent change in height, weight and BMI and early adult height, weight, body fat and lean mass. Methods: Magnitude, timing and intensity of height, weight and BMI growth were modelled for participants from the Birth to Thirty (Bt30) cohort (7–23 years). Early adult height, weight, BMI and DXA-derived body composition were obtained 1881 black participants (21–24 years). Linear regression analyses were used to assess associations. Results: Adolescents with an earlier onset of puberty were heavier in childhood and had an earlier timing and faster weight gain velocity in late adolescence. The intensity of adolescent weight gain was positively associated with adult BMI and fat mass index (FMI) in females. Early timing of adolescent BMI gain was associated with increased weight and BMI in adult females and FMI in adult males. Achieving peak weight velocity around age at peak height velocity was associated with lower BMI and fat mass in both sexes. Conclusion: This study confirms the adverse consequences of excessive weight gain prior to puberty, which is associated with an earlier and faster resurgence in weight gain velocity in early adulthood. Factors that contribute to an asynchronous timing of ages of peak weight and peak height velocities may accentuate the risk of adult obesity. [ABSTRACT FROM AUTHOR]

Purpose: We quantified levels of ultra-processed food (UPF) consumption and investigated consumption patterns in a representative sample of UK adolescents. Methods: We used data from 4-day food diaries from adolescents in the UK National Diet and Nutrition Survey (NDNS) (2008/09–2018/19). UPF were identified using the NOVA classification. We estimated the percentage of Total Energy Intake (%TEI) and the absolute weight (grams). Linear regression models quantified differences in UPF consumption across survey years and its association with participant's individual characteristics. This was an analysis of the repeated cross-sectional data from the UK NDNS Rolling Programme waves 1–11 (2008/09–2018/19). A total of 2991 adolescents (11–18y) with complete information on dietary intake were included. Results: Mean UPF consumption was 861 (SD 442) g/d and this accounted for 65.9% (SD 13.4%) of TEI. Between 2008 and 2019, mean UPF consumption decreased from 996 to 776 g/d [ – 211 (95%CI – 302; – 120)] and from 67.7% to 62.8% of TEI [ – 4.8% (95%CI – 8.1; – 1.5)]. Higher %TEI was consumed by adolescents with lower socioeconomic status; white ethnicity and living in England North. A higher weight of UPF consumption (g/d) was associated with being male, white, age 18y, having parents with routine or manual occupation, living in England North, and living with obesity. Conclusion: Average energy intake from UPF has decreased over a decade in UK adolescents. We observed a social and regional patterning of UPF consumption, with higher consumption among adolescents from lower socioeconomic backgrounds, from a white ethnicity and living in England North. Our findings suggest inequalities associated with UPF intake and factors that might lie beyond individual choice. [ABSTRACT FROM AUTHOR]

In utero exposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet (HFD) in offspring of obese mothers that precedes the development of obesity. Through small RNA sequencing, we identified programmed overexpression of hypothalamic miR-505-5p that is established in the fetus, lasts to adulthood and is maintained in hypothalamic neural progenitor cells cultured in vitro. Metabolic hormones and long-chain fatty acids associated with obesity increase miR-505-5p expression in hypothalamic neurons in vitro. We demonstrate that targets of miR-505-5p are enriched in fatty acid metabolism pathways and overexpression of miR-505-5p decreased neuronal fatty acid metabolism in vitro. miR-505-5p targets are associated with increased BMI in human genetic studies. Intra-cerebroventricular injection of miR-505-5p in wild-type mice increased HFD intake, mimicking the phenotype observed in offspring exposed to maternal obesity. Conversely, maternal exercise intervention in an obese mouse pregnancy rescued the programmed increase of hypothalamic miR-505-5p in offspring of obese dams and reduced HFD intake to control offspring levels. This study identifies a novel mechanism by which maternal obesity programs obesity in offspring via increased intake of high-fat foods. Perinatal exposure to maternal obesity increases the risk of developing obesity in offspring as they grow up. This study identifies an underlying mechanism of this phenomenon - showing that maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring, which in turn regulates fatty acid sensing and promotes consumption of fatty food. [ABSTRACT FROM AUTHOR]

Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized. Among 1,349 proteins tested for causal association with ANM using MR, we identified 19 causal proteins among which 7 proteins (CPNE1, TYMP, DNER, ADAMTS13, LCT, ARL and PLXNA1) colocalized. Follow-up pathway and gene enrichment analyses demonstrated links between AAM-related proteins and obesity and diabetes, and between AAM and ANM-related proteins and various types of cancer. In conclusion, we identified proteomic signatures of reproductive ageing in women, highlighting biological processes at both ends of the reproductive lifespan. Mendelian randomization and colocalization analyses identified 13 circulating proteins causally associated with age at menarche and 7 proteins associated with age at natural menopause, highlighting the proteomic signatures encompassing both ends of women's reproductive lifespans. [ABSTRACT FROM AUTHOR]

Context: Vitamin D has been variably implicated in risk of developing type 1 diabetes based on cohorts of at-risk individuals. Emergent type 1 diabetes in childhood is putatively preceded by altered growth. Objective: We explored whether polymorphisms in vitamin D metabolism genes modify risk of type 1 diabetes via effects on growth in a prospective, population-based cohort of infants. Methods: The Cambridge Baby Growth Study enrolled newborns from Cambridgeshire, UK, for follow-up in infancy. In 612 infants, we genotyped single nucleotide polymorphisms in vitamin D metabolism genes that relate with type 1 diabetes: rs10741657 and rs12794714 in CYP2R1, rs12785878 in DHCR7, and rs10877012 in CYP27B1. Multivariate linear regression analyses tested associations between genotypes and anthropometric indices (weight, length, and skinfold thickness) or growth-related hormones (C-peptide, IGF-1, and leptin) in infancy. Results: Birth weight showed borderline associations with the diabetes risk-increasing alleles in CYP2R1, rs10741657 (ß = -.11, P = .02) and rs12794714 (ß = -.09, P = .04). The risk-increasing allele rs12794714 was also associated with higher IGF-1 levels at age 24 months (ß = .30, P = .01). At age 3 months, the risk-increasing allele rs12785878 in DHCR7, known to negatively associate with 25-hydroxyvitamin D levels, showed a positive association with leptin levels (ß = .23, P = .009), which was pronounced in girls (P = .004) vs boys (P = .7). Conclusion: The vitamin D metabolism genes DHCR7 and CYP2R1 might influence infancy leptin and IGF-1 levels respectively. These findings open the possibility for a developmental role of vitamin D that is mediated by growth-related hormones with implications for the onset of type 1 diabetes autoimmunity. [ABSTRACT FROM AUTHOR]

Background Early puberty timing is associated with adverse health outcomes. We aimed to examine prospective associations between objectively measured physical activity and puberty timing in boys and girls. Methods In the UK Millennium Cohort Study, physical activity volume and intensities at 7 years were measured using accelerometers. Status of several pubertal traits and age at menarche were reported at 11, 14 and 17 years. Age at menarche in girls was categorized into tertiles. Other puberty traits were categorized into earlier or later than the median ages calculated from probit models, separately in boys and girls. Multivariable regression models, with adjustment for maternal and child characteristics including body mass index (BMI) at age 7 years as potential confounders, were performed to test the associations of total daily activity counts and fractions of activity counts across intensities (in compositional models) with puberty timing, separately in boys (n =  2531) and girls (n =  3079). Results Higher total daily activity counts were associated with lower risks for earlier (vs later) growth spurt, body hair growth, skin changes and menarche in girls, and more weakly with lower risks for earlier skin changes and voice breaking in boys (odds ratios = 0.80–0.87 per 100 000 counts/day). These associations persisted on additional adjustment for BMI at 11 years as a potential mediator. No association with puberty timing was seen for any physical activity intensity (light, moderate or vigorous). Conclusions More physical activity regardless of intensity may contribute to the avoidance of earlier puberty timing, independently of BMI, particularly in girls. [ABSTRACT FROM AUTHOR]

Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children's Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9–17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0–3 months, 3–24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs. [ABSTRACT FROM AUTHOR]

Growth patterns of breastfed infants show substantial inter-individual differences, partly influenced by breast milk (BM) nutritional composition. However, BM nutritional composition does not accurately indicate BM nutrient intakes. This study aimed to examine the associations between both BM intake volumes and macronutrient intakes with infant growth. Mother–infant dyads (n 94) were recruited into the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) from a single maternity hospital at birth; all infants received exclusive breast-feeding (EBF) for at least 6 weeks. Infant weight, length and skinfolds thicknesses (adiposity) were repeatedly measured from birth to 12 months. Post-feed BM samples were collected at 6 weeks to measure TAG (fat), lactose (carbohydrate) (both by 1H-NMR) and protein concentrations (Dumas method). BM intake volume was estimated from seventy infants between 4 and 6 weeks using dose-to-the-mother deuterium oxide (2H2O) turnover. In the full cohort and among sixty infants who received EBF for 3+ months, higher BM intake at 6 weeks was associated with initial faster growth between 0 and 6 weeks (β + se 3·58 + 0·47 for weight and 4·53 + 0·6 for adiposity gains, both P < 0·0001) but subsequent slower growth between 3 and 12 months (β + se − 2·27 + 0·7 for weight and −2·65 + 0·69 for adiposity gains, both P < 0·005). BM carbohydrate and protein intakes at 4–6 weeks were positively associated with early (0–6 weeks) but tended to be negatively related with later (3–12 months) adiposity gains, while BM fat intake showed no association, suggesting that carbohydrate and protein intakes may have more functional relevance to later infant growth and adiposity. [ABSTRACT FROM AUTHOR]

Butyrate in human milk (HM) has been suggested to reduce excessive weight and adipo-sity gains during infancy. However, HM butyrate's origins, determinants, and its influencing mechanism on weight gain are not completely understood. These were studied in the prospective longitudinal Cambridge Baby Growth and Breastfeeding Study (CBGS-BF), in which infants (n = 59) were exclusively breastfed for at least 6 weeks. Infant growth (birth, 2 weeks, 6 weeks, 3 months, 6 months, and 12 months) and HM butyrate concentrations (2 weeks, 6 weeks, 3 months, and 6 months) were measured. At age 6 weeks, HM intake volume was measured by deuterium-labelled water technique and HM microbiota by 16S sequencing. Cross-sectionally at 6 weeks, HM butyrate was associated with HM microbiota composition (p = 0.036) although no association with the abundance of typical butyrate producers was detected. In longitudinal analyses across all time points, HM butyrate concentrations were overall negatively associated with infant weight and adiposity, and associations were stronger at younger infant ages. HM butyrate concentration was also inversely correlated with HM intake volume, supporting a possible mechanism whereby butyrate might reduce infant growth via appetite regulation and modulation of HM intake. [ABSTRACT FROM AUTHOR]

Background Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers. Methods In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3–6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child's sex, gestational age, age at follow-up, and other maternal factors. Results Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, β (95% CI): −1.31 mmHg (−2.57, −0.06); DBP: −0.79 mmHg (−1.74, 0.15)] and body fat percentage [SBP: −1.46 mmHg (−2.73, −0.19); DBP: −0.80 mmHg (−1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (−1.29, 1.83)]; DBP: −0.14 mmHg (−1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk. Conclusions At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life. [ABSTRACT FROM AUTHOR]

Objective: While several studies have shown that milk formula feeding is associated with faster infant weight gain compared with exclusively breast feeding (EBF), we explored the possible reverse association that infant weight gain influences the duration of EBF.Design: Prospective birth cohort study (Cambridge Baby Growth Breastfeeding Study) born 2015-2018.Setting: Cambridge, UK.Participants: Full-term, singleton, normal birthweight infants who received EBF for 2-5 completed weeks (n=54), 6-11 weeks (n=14) or 12 or more weeks (n=80).Intervention: Weight gain from birth to 2 and 6 weeks.Main Outcome and Measure: Duration of EBF.Results: Faster infant weight gain during EBF predicted longer duration of EBF. Among all 148 infants, each +1 unit gain in weight SD score (SDS) between birth and 2 weeks (while all infants received EBF) reduced the likelihood of stopping EBF between 2 and 5 weeks by ~70% (OR 0.32; 95% CI 0.12 to 0.77; adjusted for sex, gestational age at birth, birth weight and mother's age, prepregnancy BMI and education). Similarly, among infants EBF for 6 or more weeks (n=94), each +1 unit gain in weight SDS between birth and 6 weeks reduced the likelihood of stopping EBF between 6 and 11 weeks by ~80% (OR 0.18; 95% CI 0.05 to 0.63).Conclusions: Slower early infant weight gain was consistently associated with subsequent earlier discontinuation of EBF. We conjecture that broader recognition of the wide range of normal infant growth might encourage parents to not stop EBF earlier than they intended. [ABSTRACT FROM AUTHOR]

Objectives: Considering the importance of the early life period, in conjunction with the increasing prevalence of adiposity and insufficient physical activity already evident in early childhood, this study aimed to determine associations between abdominal adiposity, body size, and objectively measured physical activity in infancy. Methods: Infants (n = 138, aged 3–24 months) from Soweto, South Africa were recruited to this cross-sectional study. Visceral (VAT) and subcutaneous abdominal fat (SAT) were measured using ultrasound. Physical activity was assessed using accelerometry and analysed at the hourly level. Multilevel linear regression analyses were run with body composition exposures adjusted for age, sex, and length; models with VAT and SAT were also adjusted for total abdominal fat. Results: Mean (SD) age was 11.8 (7.6) months; 86% were normal weight, 7% were underweight and 7% overweight. In linear models, no body composition variable was significantly associated with physical activity. Physical activity was higher with each increasing length tertile (ANOVA p < 0.01); with a mean(95%CI) 29(60–60)mg in the lowest tertile, 39(71–71)mg in the middle tertile, and 50(81–82)mg in the highest tertile. Infants with normal weight had higher mean(95%CI) physical activity (40(70–80)mg) than underweight (34(73–85)mg, p = 0.01) or overweight infants (31(63–78)mg, ANOVA p < 0.01). When also adjusting for total abdominal fat, infants in the lowest SAT tertile had higher physical activity than those in the middle or highest SAT tertiles (p < 0.01). Conclusions: These findings lend support for higher physical activity as a marker of healthy growth in the first two years of life. [ABSTRACT FROM AUTHOR]

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes. Author summary: Food and drink consumption is one of the most important factors influencing human health and wellbeing. The role of diet in human physiology and disease has been widely studied, but challenges in accurately assessing long term diet result in contradicting findings. Mendelian randomization is a statistical technique that uses genetic variants associated with modifiable exposures to estimate the causal effect of an exposure to a health outcome and could be extremely useful in the context of diet-health relationships. In our study, we initially identified genetic variants associated to 29 measures of food and drink consumption. We then show that genetic variants associated with food and drink consumption are subject to reverse causation and confounding. We have thus developed a statistical genetics method to identify genetic variants directly associated with food and drink consumption. By using these genetic variants (and their corresponding direct effects) in Mendelian randomization analyses we provided consistent evidence of causal associations of food and drink consumption with obesity, blood lipid status, and several other risk factors and health outcomes. [ABSTRACT FROM AUTHOR]

It was previously observed that maternal iron supplementation in pregnancy was associated with increased offspring size and adiposity at birth, possibly mediated through increased risk of gestational diabetes. In this study we investigated potential long-term associations of maternal iron supplementation in pregnancy with offspring growth in infancy, and growth and cardiometabolic risk factors in mid-childhood to seek evidence of nutritional programming. Using a nested case-control format, markers of growth and adiposity were measured at 3, 12 and 24 months of age in 341 infants from the Cambridge Baby Growth Study whose mothers supplemented with iron in pregnancy and 222 infants whose mothers did not. Measures of growth, glucose tolerance (using a 30 minute 1.75 g glucose/kg body weight oral glucose tolerance test), insulin sensitivity (HOMA IR) and blood pressure were collected in 122 and 79 of these children, respectively, at around 9.5 years of age. In infancy adiposity-promoting associations with maternal iron supplementation in pregnancy were evident at 3 months of age (e.g. mean difference in skinfold thickness: β = +0.15 mm, p = 0.02, in n = 341 whose mothers supplemented versus 222 that did not; waist circumference: β = +0.7 cm, p = 0.04, in n = 159 and 78, respectively) but differences lessened after this time (e.g. 3–12 month change in mean difference in skinfold thickness: β = -0.2 mm, p = 0.03, in n = 272 and 178, respectively). At ~9.5 years of age children whose mothers supplemented with iron in pregnancy had lower mean arterial blood pressures (β = -1.0 mmHg, p = 0.03, in n = 119 and 78, respectively). There were no apparent differences in markers of growth or other cardiometabolic factors. These results suggest that most of the associations of maternal iron supplementation in pregnancy on growth and adiposity evident at birth disappear during infancy, but there may be some evidence of long-term nutritional programming of blood pressure in mid-childhood. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that fetal sex may be able to modify maternal metabolism and physiology during pregnancy. Recently pregnant women carrying a male fetus were reported to be more insulin sensitive than those carrying females, although related evidence is inconsistent. Methods: In this study we administered a 75 g oral glucose tolerance test at around week 28 of pregnancy in 813 pregnant women from a contemporary birth cohort (the Cambridge Baby Growth Study), derived surrogate indices of insulin secretion and sensitivity, and related them to the fetal sex. Results: Carrying a male fetus was associated with lower fasting glucose (difference in mean concentrations ≈ 0.1 mmol/L; β′ = 0.063; p = 0.02) and insulin (≈ 1.1 pmol/L; β′ = 0.075; p = 0.01) concentrations but not with post-load glucose or insulin concentrations. Male fetal sex was also associated with lower HOMA IR (≈ 1.08 units; β′ = 0.071; p = 0.02) and higher QUICKI (≈ 1.06 units; β′ = 0.080; p = 0.007) values suggesting increased basal insulin sensitivity. There were no differences in indices of insulin secretion, except for the insulin disposition index which was higher in women carrying a male fetus (≈ 1.15 units; β′ = 0.090; p = 0.007). Birth weights were higher in male offspring. Conclusions: Women carrying a male fetus were relatively more insulin sensitive in the fasting state and secreted more insulin relative to this degree of insulin sensitivity. These results are consistent with the idea that the fetal sex may be able to modify the maternal glucose-insulin axis. Highlights: Pregnant women carrying a male fetus were more insulin sensitive than those carrying a female at around week 28 of pregnancy in a contemporary birth cohort. They also appeared to secrete more insulin relative to their degree of insulin sensitivity. The differences in glucose and insulin concentrations were evident in the basal state but disappeared after the consumption of a glucose load. Fetal sex appears to be able to influence maternal glucose and insulin concentrations in pregnancy. [ABSTRACT FROM AUTHOR]

Summary: Background and Objectives: Early life is a critical window for adiposity programming. Metabolic‐profile in early life may reflect this programming and correlate with later life adiposity. We investigated if metabolic‐profile at 3 months of age is predictive for body composition at 2 years and if there are differences between boys and girls and between infant feeding types. Methods: In 318 healthy term‐born infants, we determined body composition with skinfold measurements and abdominal ultrasound at 3 months and 2 years of age. High‐throughput‐metabolic‐profiling was performed on 3‐month‐blood‐samples. Using random‐forest‐machine‐learning‐models, we studied if the metabolic‐profile at 3 months can predict body composition outcomes at 2 years of age. Results: Plasma metabolite‐profile at 3 months was found to predict body composition at 2 years, based on truncal: peripheral‐fat‐skinfold‐ratio (T:P‐ratio), with a predictive value of 75.8%, sensitivity of 100% and specificity of 50%. Predictive value was higher in boys (Q2 = 0.322) than girls (Q2 = 0.117). Of the 15 metabolite variables most strongly associated with T:P‐ratio, 11 were also associated with visceral fat at 2 years of age. Conclusion: Several plasma metabolites (LysoPC(22:2), dimethylarginine and others) at 3 months associate with body composition outcome at 2 years. These results highlight the importance of the first months of life for adiposity programming. [ABSTRACT FROM AUTHOR]

Purpose: Early puberty is associated with adverse health outcomes. To identify potential modifiable factors for puberty timing, we examined the associations of prepubertal childhood macronutrient intakes with puberty timing in boys and girls. Methods: In the Avon Longitudinal Study of Parents and Children, macronutrient intakes at age 6 years were predicted using random intercepts linear regression models of dietary data at 3, 4, 7 (assessed by food frequency questionnaires) and 7.5 years (by 3-day food diaries). Timings of puberty onset (Tanner stage 2 genital or breast (B2) development) and puberty completion (voice breaking (VB) or menarche) were calculated from annual parental and child reports at 8–17 years. Age at peak height velocity (PHV) was derived from repeated height measurements at 5–20 years. Linear regression models were fit to estimate the associations of total energy (TEI) and macronutrient intakes (carbohydrate, fat, protein) with puberty timing traits, adjusting for maternal and infant characteristics. Results: Among 3811 boys, higher TEI, but no macronutrient, was associated with earlier VB. Among 3919 girls, higher TEI was associated with earlier ages at B2, PHV, and menarche. Higher protein intake but not carbohydrate or fat intake (in energy partition models) and substitution of dietary protein for carbohydrate (in nutrient density and residual models) was associated with earlier B2, PHV, and menarche in girls. Findings were not attenuated on additional adjustment for body fat percentage during adolescence. Conclusions: These findings suggest habitual total energy intakes in children, and protein intakes in girls, as potential modifiable determinants of puberty timing. [ABSTRACT FROM AUTHOR]

Summary: Background: Anthropometry‐based equations are commonly used to estimate infant body composition. However, existing equations were designed for newborns or adolescents. We aimed to (a) derive new prediction equations in infancy against air‐displacement plethysmography (ADP‐PEA Pod) as the criterion, (b) validate the newly developed equations in an independent infant cohort and (c) compare them with published equations (Slaughter‐1988, Aris‐2013, Catalano‐1995). Methods: Cambridge Baby Growth Study (CBGS), UK, had anthropometry data at 6 weeks (N = 55) and 3 months (N = 64), including skinfold thicknesses (SFT) at four sites (triceps, subscapular, quadriceps and flank) and ADP‐derived total body fat mass (FM) and fat‐free mass (FFM). Prediction equations for FM and FFM were developed in CBGS using linear regression models and were validated in Sophia Pluto cohort, the Netherlands, (N = 571 and N = 447 aged 3 and 6 months, respectively) using Bland–Altman analyses to assess bias and 95% limits of agreement (LOA). Results: CBGS equations consisted of sex, age, weight, length and SFT from three sites and explained 65% of the variance in FM and 79% in FFM. In Sophia Pluto, these equations showed smaller mean bias than the three published equations in estimating FM: mean bias (LOA) 0.008 (−0.489, 0.505) kg at 3 months and 0.084 (−0.545, 0.713) kg at 6 months. Mean bias in estimating FFM was 0.099 (−0.394, 0.592) kg at 3 months and −0.021 (−0.663, 0.621) kg at 6 months. Conclusions: CBGS prediction equations for infant FM and FFM showed better validity in an independent cohort at ages 3 and 6 months than existing equations. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides (HMOs) are indigestible carbohydrates with prebiotic, pathogen decoy and immunomodulatory activities that are theorized to substantially impact infant health. The objective of this study was to monitor HMO concentrations over 1 year to develop a long-term longitudinal dataset. HMO concentrations in the breast milk of healthy lactating mothers of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) were measured at birth, 2 weeks, 6 weeks, 3 months, 6 months and 12 months postpartum. HMO quantification was conducted by high-performance anion-exchange chromatography with pulsed amperometric detection using a newly validated "dilute-and-shoot" method. This technique minimizes sample losses and expedites throughput, making it particularly suitable for the analysis of large sample sets. Varying patterns of individual HMO concentrations were observed with changes in lactation timepoint and maternal secretor status, with the most prominent temporal changes occurring during the first 3 months. These data provide valuable information for the development of human milk banks in view of targeted distribution of donor milk based on infant age. Maternal FUT2 genotype was determined based on identification at single-nucleotide polymorphism rs516246 and compared with the genotype expected based on phenotypic markers in the HMO profile. Surprisingly, two mothers genotyped as secretors produced milk that displayed very low levels of 2′-fucosylated moieties. This unexpected discrepancy between genotype and phenotype suggests that differential enzyme expression may cause substantial variation in HMO profiles between genotypically similar mothers, and current genotypic methods of secretor status determination may require validation with HMO markers from milk analysis. [ABSTRACT FROM AUTHOR]

Background: Despite early childhood weight gain being a key indicator of obesity risk, we do not have a good understanding of the different patterns that exist. Objectives: To identify and characterise distinct groups of children displaying similar early‐life weight trajectories. Methods: A growth mixture model captured heterogeneity in weight trajectories between 0 and 60 months in 1390 children in the Avon Longitudinal Study of Parents and Children. Differences between the classes in characteristics and body size/composition at 9 years were investigated. Results: The best model had five classes. The "Normal" (45%) and "Normal after initial catch‐down" (24%) classes were close to the 50th centile of a growth standard between 24 and 60 months. The "High‐decreasing" (21%) and "Stable‐high" (7%) classes peaked at the ~91st centile at 12‐18 months, but while the former declined to the ~75th centile and comprised constitutionally big children, the latter did not. The "Rapidly increasing" (3%) class gained weight from below the 50th centile at 4 months to above the 91st centile at 60 months. By 9 years, their mean body mass index (BMI) placed them at the 98th centile. This class was characterised by the highest maternal BMI; highest parity; highest levels of gestational hypertension and diabetes; and the lowest socio‐economic position. At 9 years, the "Rapidly increasing" class was estimated to have 68.2% (95% confidence interval [CI] 48.3, 88.1) more fat mass than the "Normal" class, but only 14.0% (95% CI 9.1, 18.9) more lean mass. Conclusions: Criteria used in growth monitoring practice are unlikely to consistently distinguish between the different patterns of weight gain reported here. [ABSTRACT FROM AUTHOR]

Objective: This study explored the link between HLA polymorphisms that predispose to type 1 diabetes and birth size, infancy growth, and/or circulating IGF-I in a general population-based birth cohort.Research Design and Methods: The Cambridge Baby Growth Study is a prospective observational birth cohort study that recruited 2,229 newborns for follow-up in infancy. Of these, 612 children had DNA available for genotyping single nucleotide polymorphisms in the HLA region that capture the highest risk of type 1 diabetes: rs17426593 for DR4, rs2187668 for DR3, and rs7454108 for DQ8. Multivariate linear regression models at critical ages (cross-sectional) and mixed-effects models (longitudinal) were performed under additive genetic effects to test for associations between HLA polymorphisms and infancy weight, length, skinfold thickness (indicator of adiposity), and concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3).Results: In longitudinal models, the minor allele of rs2187668 tagging DR3 was associated with faster linear growth (P = 0.007), which was more pronounced in boys (P = 3 × 10-7) than girls (P = 0.07), and was also associated with increasing IGF-I (P = 0.002) and IGFBP-3 (P = 0.003) concentrations in infancy. Cross-sectionally, the minor alleles of rs7454108 tagging DQ8 and rs17426593 tagging DR4 were associated with lower IGF-I concentrations at age 12 months (P = 0.003) and greater skinfold thickness at age 24 months (P = 0.003), respectively.Conclusions: The variable associations of DR4, DR3, and DQ8 alleles with growth measures and IGF-I levels in infants from the general population could explain the heterogeneous growth trajectories observed in genetically at-risk cohorts. These findings could suggest distinct mechanisms involving endocrine pathways related to the HLA-conferred type 1 diabetes risk. [ABSTRACT FROM AUTHOR]

Mosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that loss of function of two genes—CHEK2 and GIGYF1—reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3.04–11.81], p = 1.3 × 10−10). These same alleles are also associated with adverse metabolic health, including higher susceptibility to Type 2 Diabetes (OR = 6.10 [3.51–10.61], p = 1.8 × 10−12), 4 kg higher fat mass (p = 1.3 × 10−4), 2.32 nmol/L lower serum IGF1 levels (p = 1.5 × 10−4) and 4.5 kg lower handgrip strength (p = 4.7 × 10−7) consistent with proposed GIGYF1 enhancement of insulin and IGF-1 receptor signalling. These associations are mirrored by a common variant nearby associated with the expression of GIGYF1. Our observations highlight a potential direct connection between clonal mosaicism and metabolic health. Mosaic loss of chromosome Y (LOY) is a common form of clonal mosaicism in leukocytes. Here, the authors extend genetic association analyses to rare variation using exome-sequence data from 82,277 males, finding that loss-of-function alleles in GIGYF1 are associated with six-fold higher susceptibility to both LOY and Type 2 Diabetes. [ABSTRACT FROM AUTHOR]

Context: Adult height is highly heritable, yet no genetic predictor has demonstrated clinical utility compared to mid-parental height.Objective: To develop a polygenic risk score for adult height and evaluate its clinical utility.Design: A polygenic risk score was constructed based on meta-analysis of genomewide association studies and evaluated on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.Subjects: Participants included 442 599 genotyped White British individuals in the UK Biobank and 941 genotyped child-parent trios of European ancestry in the ALSPAC cohort.Interventions: None.Main Outcome Measures: Standing height was measured using stadiometer; Standing height 2 SDs below the sex-specific population average was considered as short stature.Results: Combined with sex, a polygenic risk score captured 71.1% of the total variance in adult height in the UK Biobank. In the ALSPAC cohort, the polygenic risk score was able to identify children who developed adulthood short stature with an area under the receiver operating characteristic curve (AUROC) of 0.84, which is close to that of mid-parental height. Combining this polygenic risk score with mid-parental height or only one of the child's parent's height could improve the AUROC to at most 0.90. The polygenic risk score could also substitute mid-parental height in age-specific Khamis-Roche height predictors and achieve an equally strong discriminative power in identifying children with a short stature in adulthood.Conclusions: A polygenic risk score could be considered as an alternative or adjunct to mid-parental height to improve screening for children at risk of developing short stature in adulthood in European ancestry populations. [ABSTRACT FROM AUTHOR]

Summary: Pharmacological options for management of obesity and type 2 diabetes mellitus (T2DM) in children are limited. We aimed to synthesize published randomized controlled trial (RCT) evidence on the efficacy of glucagon‐like peptide‐1 (GLP‐1) agonists in T2DM, pre‐diabetes, and obesity in children aged <18 years. Inclusion criteria were RCTs of any GLP‐1 agonist, solely or in conjunction with other drugs, for the treatment of obesity, pre‐diabetes, and/or T2DM in children aged <18 years old. Nine studies met the inclusion criteria (two for T2DM, one for pre‐diabetes, and six for obesity without diabetes). In total, 286 children were allocated to GLP‐1 agonist therapy. Compared with controls, GLP‐1 agonist therapy reduced HbA1c by −0.30% (95% confidence interval [CI] −0.57, −0.04) with a larger effect in children with (pre‐)diabetes (−0.72%; 95% CI −1.17, −0.28; three studies) than in children with obesity (−0.08%; 95% CI −0.13, −0.02; four studies). Conversely, GLP‐1 agonist therapy reduced body weight more in children with obesity (−2.74 kg; 95% CI −3.77, −1.70; six studies) than in children with T2DM (−0.97 kg; 95% CI −2.01, 0.08; two studies). Adverse effects included gastrointestinal symptoms and minor hypoglycemic episodes, but not severe hypoglycemia. GLP‐1 agonists are efficacious in treating children with obesity and/or T2DM. Effect sizes are comparable with those reported in adults. [ABSTRACT FROM AUTHOR]

Context: Delta like noncanonical notch ligand 1 (DLK1) is a paternally expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation and has roles in development and metabolism.Objective: We sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion, and (3) offspring size at birth.Patients, Design, and Setting: We measured third-trimester maternal serum DLK1 concentrations and examined their associations with parentally transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75-g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study.Results: Maternal DLK1 concentrations were associated with the paternally transmitted fetal DLK1 rs12147008 allele (P = 7.8 × 10-3) but not with maternal rs12147008 genotype (P = 0.4). Maternal DLK1 concentrations were positively associated with maternal prepregnancy body mass index (P = 3.5 × 10-6), and (after adjustment for maternal body mass index) with both maternal fasting insulin resistance (Homeostatic Model Assessment of Insulin Resistance: P = 0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index: P = 1.2 × 10-3; insulin disposition index: P = 0.049). Further positive associations were found with offspring weight (P = 0.02) and head circumference at birth (P = 0.04).Conclusion: These results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth. [ABSTRACT FROM AUTHOR]

Background: Studies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history. Methods: We administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16–90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults. Results: Autistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history. Limitations: Our sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships. Conclusions: Autistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep—and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep. [ABSTRACT FROM AUTHOR]

Objectives: The timing and magnitude of adolescent growth may be influenced by ethnicity and early life factors. We aimed to (a) characterize ethnic differences in the magnitude, timing, and intensity of adolescent growth in height, weight, and BMI; (b) assess the effect of early childhood growth on adolescent growth in black children. Methods: Data were from the Birth to Twenty Plus cohort (Bt20+) in Johannesburg, South Africa (n = 3273). Height, weight, and BMI were modeled with ethnic comparisons using the SuperImposition by Translation and Rotation for 2089 participants who had data from 7 to 23 years. Relative weight gain and relative linear growth between 0 and 24 months and 24 and 60 months were generated. Multiple regression analyses were used to assess associations between childhood and adolescent growth. Results: White children were 5 cm (SE: 0.7) taller than black children through adolescence. Black boys had a later timing of adolescent height (0.65 years ±0.12) than white boys, which in black girls was 0.24 years (0.11) earlier than in white girls. Black girls had faster BMI velocity than white girls. Among black children, birth weight and both relative weight gain 0 to 24 and relative linear growth between 3 and 24 months and 24 and 60 months were positively associated with the magnitude of adolescent growth and negatively associated with timing. Conclusion: Sex dimorphism in ethnic differences in timing of adolescent height growth may reflect some yet unexplained drivers for rapid weight gain and obesity in black females but not black males. Rapid weight gain in early life may contribute to faster adiposity accrual in adolescence. [ABSTRACT FROM AUTHOR]

Objective: We describe a new method for identifying and quantifying the magnitude and rate of short‐term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering. Materials and methods: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short‐term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics. Results: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated. Conclusions: This method identifies and quantifies short‐term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short‐term weight faltering relates to longer‐term outcomes. [ABSTRACT FROM AUTHOR]

Objective: Previously we observed that maternal multiple micronutrient supplementation in pregnancy was associated with increased offspring size at birth and adiposity, as well as with maternal gestational diabetes risk, in the Cambridge Baby Growth Study. In this study we therefore investigated whether folic acid supplementation specifically is associated with similar changes, to test the hypothesis that folic acid supplementation mediates such changes. Results: The majority of mothers who reported supplementing with folic acid in pregnancy (n = 776 in total, 526 of which took multiple micronutrient preparations) did so either from pre- (n = 139) or post-conception (n = 637) largely for all or just the first half of pregnancy. A minority of mothers (n = 198) reported not supplementing with folic acid. Folic acid supplementation in pregnancy was not associated with birth weight [β' = − 0.003, p = 0.9], height [β' = − 0.013, p = 0.6], head circumference [β' = 0.003, p = 0.09] or adiposity (ponderal index [β' = 0.020, p = 0.5], skinfolds thicknesses [β' = − 0.029 to + 0.008, p = 0.4–0.9]). Neither was it associated with the development of maternal gestational diabetes (risk ratio 1.2 [0.6‒2.2], p = 0.6). These results suggest that folic acid supplementation in pregnancy did not mediate the previously observed increases in offspring size at birth and adiposity, or the raised gestational diabetes risk, in response to supplementation with multiple micronutrients. [ABSTRACT FROM AUTHOR]

Low birthweight and reduced height gain during infancy (stunting) may arise at least in part from adverse early life environments that trigger epigenetic reprogramming that may favor survival. We examined differential DNA methylation patterns using targeted methyl sequencing of regions regulating gene activity in groups of rural Gambian infants: (a) low and high birthweight (DNA from cord blood (n = 16 and n = 20, respectively), from placental trophoblast tissue (n = 21 and n = 20, respectively), and DNA from peripheral blood collected from infants at 12 months of age (n = 23 and n = 17, respectively)), and, (b) the top 10% showing rapid postnatal length gain (high, n = 20) and the bottom 10% showing slow postnatal length gain (low, n = 20) based on z score change between birth and 12 months of age (LAZ) (DNA from peripheral blood collected from infants at 12 months of age). Using BiSeq analysis to identify significant methylation marks, for birthweight, four differentially methylated regions (DMRs) were identified in trophoblast DNA, compared to 68 DMRs in cord blood DNA, and 54 DMRs in 12‐month peripheral blood DNA. Twenty‐five DMRs were observed to be associated with high and low length for age (LAZ) at 12 months. With the exception of five loci (associated with two different genes), there was no overlap between these groups of methylation marks. Of the 194 CpG methylation marks contained within DMRs, 106 were located to defined gene regulatory elements (promoters, CTCF‐binding sites, transcription factor‐binding sites, and enhancers), 58 to gene bodies (introns or exons), and 30 to intergenic DNA. Distinct methylation patterns associated with birthweight between comparison groups were observed in DNA collected at birth (at the end of intrauterine growth window) compared to those established by 12 months (near the infancy/childhood growth transition). The longitudinal differences in methylation patterns may arise from methylation adjustments, changes in cellular composition of blood or both that continue during the critical postnatal growth period, and in response to early nutritional and infectious environmental exposures with impacts on growth and longer‐term health outcomes. [ABSTRACT FROM AUTHOR]

Background: Individuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of obesity was related to heterogeneity in cardiometabolic risk.Methods and Findings: We used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c). A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for <5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding.Conclusions: Given that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained. [ABSTRACT FROM AUTHOR]

Background: DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect(s) of aging it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline.Methods: AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed, and forced expiratory volume in one second [FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed.Results: AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n = 1,388-1,685). For example, a 1-year increase in AgeAccelPheno or AgeAccelGrim was associated with a 0.01 mL (95% confidence interval [CI]: 0.01, 0.02) or 0.03 mL (95% CI: 0.01, 0.05) lower mean FEV1 respectively. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p < .05). In a subset of NSHD participants (n = 482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance.Conclusions: We found little evidence to support associations between the first generation of DNAm-based biomarkers of aging and age-related physical or cognitive performance in midlife to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual's healthspan as proposed. [ABSTRACT FROM AUTHOR]

Background: Highly consistent positive associations are reported between infancy growth and later obesity risk. However, it is unclear whether infancy growth parameters beyond body weight add to the prediction of later obesity risk. Aim: To assess whether infancy length and skinfold thicknesses add to infancy weight in the prediction of childhood adiposity. Subjects and methods: This analysis included 254 children with available data on infant growth from birth to 24 months and childhood adiposity at age 6–11 years measured by DXA. Multilevel linear regression was used to examine the predictors of childhood percent body fat (%BF), with adjustment for sex and age at follow-up visit. Results: Birth weight and weight gain (modelled as changes in z-score) between 0–3 months and 3–24 months showed independent positive relationships with childhood %BF. The addition of gains in infant length and skinfolds between 0–3 months, but not 3–24 months, improved overall model prediction, from 18.7% to 20.7% of the variance in childhood %BF (likelihood ratio test, p < 0.0001), although their independent effect estimates were small (infant length gain: negative trend, partial R-square 0.6%, p = 0.2; skinfolds: positive trend, 1.3%, p = 0.09). Conclusion: Infancy length and skinfolds contribute significantly, but only modestly, to the prediction of childhood adiposity. [ABSTRACT FROM AUTHOR]

Background: Earlier age at menarche (AAM), a marker of puberty timing in females, has been associated with a higher likelihood of adolescent risk-taking behaviours and variably associated with educational attainment. Aim: To examine the association between AAM and educational attainment in the Pelotas, Brazil, 1982 Birth Cohort. Subjects and methods: AAM was categorised as Early (7–11 years), Average (12–13 years), or Late (14+ years). Primary outcome: years of education (age 30). Secondary outcomes: risk-taking behaviours, adult income and school grade failure. Results: In adjusted models, compared to Average AAM, Late AAM was associated with 0.64 fewer years of education (95% CI: −1.15, −0.13). Early AAM was associated with earlier age at first sexual intercourse (−0.25 years; 95% CI: −0.39, −0.12), whereas Late AAM was associated with 17% lower adult income (0.83; 95% CI: 0.71, 0.95) and 0.31 years older age at first alcohol consumption (95% CI: 0.10, 0.52). Conclusions: Our findings confirm the association between earlier puberty timing in females and a greater likelihood of risk-taking behaviours in this setting of recent secular changes towards earlier puberty. However, the association between Late AAM and lower education was surprising and may support a psychosocial rather than biological link between puberty timing and educational outcomes. [ABSTRACT FROM AUTHOR]

Background: Emerging studies have investigated the association between puberty timing, particularly age at menarche (AAM), and type 2 diabetes. However, whether this association is independent of adiposity is unclear. We aimed to systematically review published evidence on the association between puberty timing and type 2 diabetes (T2D) or impaired glucose tolerance (IGT), with and without adjustment for adiposity, and to estimate the potential contribution of puberty timing to the burden of T2D in the United Kingdom (UK).Methods and Findings: We searched PubMed, Medline, and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-variance-weighted random-effects meta-analysis was used to pool reported estimates, and meta-regression was used to explore sources of heterogeneity. Twenty-eight observational studies were identified. All assessed AAM in women (combined N = 1,228,306); only 1 study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was lower per year later AAM (relative risk [RR] = 0.91, 95% CI 0.89-0.93, p < 0.001, 11 estimates, n = 833,529, I2 = 85.4%) and higher for early versus later menarche (RR = 1.39, 95% CI 1.25-1.55, p < 0.001, 23 estimates, n = 1,185,444, I2 = 87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR = 0.97 per year, 95% CI 0.95-0.98, p < 0.001, 12 estimates, n = 852,268, I2 = 51.8%; early menarche: RR = 1.19, 95% CI 1.11-1.28, p < 0.001, 21 estimates, n = 890,583, I2 = 68.1%). Associations were stronger among white than Asian women, and in populations with earlier average AAM. The estimated population attributable risk of T2D in white UK women due to early menarche unadjusted and adjusted for adiposity was 12.6% (95% CI 11.0-14.3) and 5.1% (95% CI 3.6-6.7), respectively. Findings in this study are limited by residual and unmeasured confounding, and self-reported AAM.Conclusions: Earlier AAM is consistently associated with higher T2D/IGT risk, independent of adiposity. More importantly, this research has identified that a substantial proportion of T2D in women is related to early menarche, which would be expected to increase in light of global secular trends towards earlier puberty timing. These findings highlight the need to identify the underlying mechanisms linking early menarche to T2D/IGT risk. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This study aimed to explore the infancy growth trajectories of 'recent' and 'earlier' offspring of mothers with gestational diabetes mellitus (OGDM), each compared with the same control infants, and investigate whether 'recent' OGDM still exhibit a classical phenotype, with macrosomia and increased adiposity. Methods: Within a prospective observational birth cohort, 98 'earlier' OGDM born between 2001 and 2009 were identified using 75 g oral glucose tolerance testing at 28 weeks gestation, 122 recent OGDM born between 2011 and 2013 were recruited postnatally through antenatal diabetes clinics, and 876 normal birthweight infants of mothers with no history of diabetes were recruited across the full study period as the control group. All infants followed the same study protocol (measurements at birth, 3, 12 and 24 months, including weight, length and skinfold thickness indicating adiposity, and detailed demographic data). In all cases, GDM was defined using the International Association of Diabetes and Pregnancy Study Group criteria. Results: Earlier OGDM had higher birthweight SD scores (SDS) than control infants. Conversely, recent OGDM had similar birthweight- and length SDS to control infants (mean ± SD, 0.1 ± 1.0 and− 0.1 ± 0.9, respectively), but lower mean skinfold thickness SDS (−0.4 ± 0.6 vs 0.0 ± 0.9; p < 0.001). After birth, earlier OGDM showed reduced gains in weight and length between 3 and 12 months. In contrast, recent OGDM had increased weight and skinfold thickness gains until 3 months, followed by reduced gains in those variables from 3 to 12 months, compared with control infants. At 24 months, recent OGDM had lower adiposity than control infants (mean skinfold thickness SDS −0.3 ± 0.7 vs 0.0 ± 0.8; p < 0.001). At all time points recent OGDM had lower growth measurements than earlier OGDM. Conclusions/interpretation: Recent OGDM showed different growth trajectories to the earlier group, namely normalisation of birthweight and reduced adiposity at birth, followed by initial rapid weight gain but subsequent reduced adiposity postnatally. While avoidance of macrosomia at birth may be advantageous, the longer-term health implications of these changing growth trajectories are uncertain. [ABSTRACT FROM AUTHOR]

Aims: The incidence of gestational diabetes has been reported to have risen over the first decade of this century. Some studies have also found it to vary with seasons of the year. We investigated temporal and seasonal trends on gestational diabetes incidence in a single-centre cohort study from Cambridge, UK, and attempted to explain trends using associated risk factors. Methods: Using a cosinor model, we tested both temporal and seasonal trends in gestational diabetes incidence in 1074 women recruited to the Cambridge Baby Growth Study in 2001–2009 who underwent oral glucose tolerance tests around week 28 of pregnancy. Results: There was a temporal increase in gestational diabetes incidence over the course of recruitment to this study [0.014 (0.005, 0.022) proportional increase per year, p = 2.1 × 10−3], but no seasonal effect (p = 0.7). HOMA B [− 0.015 (− 0.025, − 0.005) per year, p = 3.0 × 10−3] and the insulin disposition index [− 0.036 (− 0.060, − 0.013) per year, p = 3.0 × 10−3], unlike HOMA S, showed negative temporal trends. Risk factor analyses showed a concomitant temporal slight increase in the index of multiple deprivation [0.191 (0.138, 0.257) units per year, p = 4.6 × 10−10]. This index was positively associated with HOMA B (p = 6.1 × 10−5) but not directly with gestational diabetes (p = 0.6), HOMA S (p = 0.2) or the insulin disposition index (p = 0.4). Conclusions: In this cohort, there were temporal, but not seasonal, increases in gestational diabetes incidence between the years 2001 and 2009, which appeared to be related more to reductions in insulin secretion than sensitivity. Possible mediators of this link include confounding factors related to deprivation. [ABSTRACT FROM AUTHOR]

Aim: To systematically appraise and summarise published evidence on the association between childhood physical activity (PA) and subsequent age at menarche (AAM).Methods: We searched PubMed (1990-2018) for studies that reported the relationship between childhood PA and AAM. We performed tabular synthesis of population-based studies and a random-effects meta-analysis of results of athlete/nonathlete studies.Results: One randomised controlled trial was identified, in which an intervention to prevent obesity reduced the likelihood of menarche during the two-year study period (relative risk: 0.75, 95% CI: 0.66-0.87; n = 422 girls). One of five prospective cohort studies (total n = 4492) reported a significant association between self-reported PA duration and subsequent menarche timing. Four of five historical cohort studies (total n = 89 470) reported significant associations between recalled premenarcheal PA and later AAM. Meta-analysis across 12 athlete/nonathlete studies showed that menarche occurred 1.13 years later (95% CI: 0.80-1.47) in athletes compared to nonathletes.Conclusion: These findings suggest that AAM is a behaviourally modifiable trait. However, the quality of reported population-based study evidence is low and estimation of the true relationship between childhood PA and AAM is likely confounded by concomitant changes in diet and lifestyle behaviours. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between dietary intake patterns from 1 to 4 years and BMI and body shape at age of 6 years. Methods: This longitudinal study was based on 3374 Brazilian children from the 2004 Pelotas Birth Cohort Study. We used previously described dietary patterns from 1 to 4 years as the main exposure. We defined body shape using scores for corpulence (a recently described body shape component measured by Photonic Scanner), and trunk and gynoid fat mass percentage from DXA. We run linear regression models to evaluate the associations between dietary patterns from 1 to 4 years and BMI and body shape at 6 years. Results: Several apparent associations between dietary patterns and BMI or body shape were explained by sociodemographic factors. High adherence to snacks (positive loadings to coffee, bread and cookies) at 4 years predicted lower BMI, but higher gynoid fat mass percentage at 6 years, while higher adherence to staple at 2 years (positive loadings to rice and beans) predicted higher trunk fat mass and lower gynoid fat mass. Finally, higher scores on milks at 1 year (positive loading to breast milk) predicted higher gynoid fat mass at 6 years. Conclusion: There were inconsistent associations between dietary patterns in infancy and early childhood and BMI and body shape at 6 years. In adjusted analyses, higher adherence to breast milk at 1 year and to snacks at 4 years appeared to be beneficial for body shape, associated with lower BMI, but higher peripheral fat. [ABSTRACT FROM AUTHOR]

Background: Presumed benefits of human milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient composition. However, data on breast milk composition and its relation with growth are sparse.Objective: We investigated whether short-chain fatty acids (SCFAs), known to be present in HM and linked to energy metabolism, are associated with infancy anthropometrics.Methods: In a prospective birth cohort, HM hindmilk samples were collected from 619 lactating mothers at 4-8 wk postnatally [median (IQR) age: 33.9 (31.3-36.5) y, body mass index (BMI) (kg/m2): 22.8 (20.9-25.2)]. Their offspring, born at 40.1 (39.1-41.0) wk gestation with weight 3.56 (3.22-3.87) kg and 51% male, were assessed with measurement of weight, length, and skinfold thickness at ages 3, 12, and 24 mo, and transformed to age- and sex-adjusted z scores. HM SCFAs were measured by 1H-nuclear magnetic resonance spectroscopy (NMR) and GC-MS. Multivariable linear regression models were conducted to analyze the relations between NMR HM SCFAs and infancy growth parameters with adjustment for potential confounders.Results: NMR peaks for HM butyrate, acetate, and formic acid, but not propionate, were detected. Butyrate peaks were 17.8% higher in HM from exclusively breastfeeding mothers than mixed-feeding mothers (P = 0.003). HM butyrate peak values were negatively associated with changes in infant weight (standardized B  = -0.10, P = 0.019) and BMI (B = -0.10, P = 0.018) between 3 and 12 mo, and negatively associated with BMI (B = -0.10, P = 0.018) and mean skinfold thickness (B = -0.10, P = 0.049) at age 12 mo. HM formic acid peak values showed a consistent negative association with infant BMI at all time points (B < = -0.10, P < = 0.014), whereas HM acetate was negatively associated with skinfold thickness at 3 mo (B = -0.10, P = 0.028) and 24 mo (B = -0.10, P = 0.036).Conclusions: These results suggest that HM SCFAs play a beneficial role in weight gain and adiposity during infancy. Further knowledge of HM SCFA function may inform future strategies to support healthy growth. [ABSTRACT FROM AUTHOR]

Background: A range of postnatal and maternal factors influences childhood obesity, but their relative importance remains unclear. This study aimed to assess the relative impact of postnatal rapid growth and maternal factors on early childhood growth trajectories.Subjects: Secondary longitudinal analysis of pooled data from the Melbourne Infant Feeding Activity and Nutrition Trial (InFANT) Program and the InFANT Extend Program (n = 977) was performed. Children's height and weight were collected at birth, 3, 9, 18, and 36/42 months. Body mass index-for-age and height-for-age z-scores (BAZ, HAZ) were computed using WHO growth standards. Mixed-effect polynomial regression models were fitted to examine BAZ and HAZ trajectories and their determinants.Results: Rapid growth from birth to 3 months, maternal country of birth, and pre-pregnancy BMI were each independently associated with BAZ from 3 to 42 months. Children with rapid growth, those whose mothers were Australian-born, and those whose mothers were overweight/obese pre-pregnancy had higher BAZ from 3 to 42 months. Children with rapid growth had an increase in HAZ growth, but their average HAZ from 3 to 42 months was smaller than children without rapid growth. Children of tall mothers (above average height) had higher HAZ than those of short mothers (below average height). Average HAZ from 3 to 42 months did not differ by maternal country of birth.Conclusion: Children who experienced rapid growth from birth to 3 months, whose mothers were Australian-born or whose mothers were overweight/obese pre-pregnancy demonstrated less favourable growth trajectories across early childhood, potentially predispose them for development of future obesity. [ABSTRACT FROM AUTHOR]

Published studies show an inconsistent association between age at menarche and the subsequent risk of developing gestational diabetes mellitus when pregnant. This systematic review and meta-analysis was performed to clarify any trends in this association in published observational population studies. We searched online databases for relevant studies, entered into them up until June 21st 2017. Five eligible studies were found and a pooled random effects dose response meta-analysis of results from these was conducted. This included coverage of 58,133 pregnancies, from which 3,035 women developed gestational diabetes. There was evidence of a non-linear association between age at menarche and gestational diabetes (overall p = 1.4 × 10−8; p for non-linearity = 2.4 × 10−4), along with evidence of relatively low heterogeneity (I2 = 25.5%). The largest predicted risk of gestational diabetes was associated with having a low age at menarche; the mean (95% confidence interval) risk relative to that associated with menarche at age 13 years being: 9 years 2.0 (1.6, 2.4), 10 years 1.6 (1.4, 1.9), 11 years 1.3 (1.2, 1.4), 12 years 1.1 (1.1, 1.1), 13 years was the reference, 14 years 1.0 (1.0, 1.0), 15 years 1.1 (0.9, 1.2), 16 years 1.1 (0.9, 1.4). There was evidence of potential publication bias, such that the maximal true relative risk of gestational diabetes, associated with an age at menarche of 9 years, may be closer to 1.6 than 2. Nevertheless, the curvilinear relationship between age at menarche and the future risk of gestational diabetes in pregnancy appears robust. [ABSTRACT FROM AUTHOR]

Background: The rising prevalence of obesity has made hepatic steatosis an increasingly common issue. Ultrasound is generally used in clinical practice to assess steatosis, but its accuracy has been inconsistent across studies. We aimed to determine the validity of ultrasound to diagnose hepatic steatosis when compared to the criterion method proton magnetic resonance spectroscopy (MRS) in older individuals. Methods: A total of 72 healthy white European individuals (n = 42 men; n = 30 women aged 67–76 years) participating in the Hertfordshire Birth Cohort Physical Activity trial had hepatic steatosis assessed by ultrasound and MRS. The ultrasound scans were graded as normal, mild, moderate and severe steatosis, while hepatic fat content above 5.5% by MRS was used as a cut-off for steatosis. Results: 18 participants (25%) had a level of hepatic fat measured by MRS consistent with diagnosis of steatosis. The sensitivity and specificity of ultrasound in diagnosing hepatic steatosis (mild/moderate/severe vs normal) were 96% (95% CI: 87–99.6%) and 94% (95% CI: 73–100%) respectively, although overlap in MRS hepatic fat content was observed between the ultrasound categories. Conclusions: Ultrasound is a valid method for detecting the presence or absence of hepatic steatosis in older adults and can be used as an alternative tool in both clinical investigations and epidemiological studies, when other imaging techniques are not feasible. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of a theory-based behavioural intervention to prevent rapid weight gain in formula milk-fed infants.Design: In this single (assessor) blind, randomised controlled trial, 669 healthy full-term infants receiving formula milk within 14 weeks of birth were individually randomised to intervention (n=340) or attention-matched control (n=329) groups. The intervention aimed to reduce formula milk intakes, and promote responsive feeding and growth monitoring to prevent rapid weight gain (≥+0.67 SD scores (SDS)). It was delivered to mothers by trained facilitators up to infant age 6 months through three face-to-face contacts, two telephone contacts and written materials.Results: Retention was 93% (622) at 6 months, 88% (586) at 12 months and 94% attended ≥4/5 sessions. The intervention strengthened maternal attitudes to following infant feeding recommendations, reduced reported milk intakes at ages 3 (-14%; intervention vs control infants), 4 (-12%), 5 (-9%) and 6 (-7%) months, slowed initial infant weight gain from baseline to 6 months (mean change 0.32 vs 0.42 SDS, baseline-adjusted difference (intervention vs control) -0.08 (95% CI -0.17 to -0.004) SDS), but had no effect on the primary outcome of weight gain to 12 months (baseline-adjusted difference -0.04 (-0.17, 0.10) SDS). By 12 months, 40.3% of infants in the intervention group and 45.9% in the control group showed rapid weight gain (OR 0.84, 95% CI 0.59 to 1.17).Conclusions: Despite reducing milk intakes and initial weight gain, the intervention did not alter the high prevalence of rapid weight gain to age 12 months suggesting the need for sustained intervention.Trial Registration Number: ISRCTN20814693. [ABSTRACT FROM AUTHOR]

The article discusses the associations between maternal Traditional dietary pattern adherence, antiretroviral HIV infection treatment exposure, neonatal size, and adiposity in urban, black South Africans, and it mentions maternal factors such as body mass index and gestational weight gain.

Background/Aims: Exposure to obesity during pregnancy may lead to adverse changes in the offspring’s metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). Methods: Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. Results: At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. Conclusions: Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin. [ABSTRACT FROM AUTHOR]

Aims: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy.Methods: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy.Results: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10−4; quadratic term: p = 1.0 × 10−3; n = 889; overall model p = 8.1 × 10−3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = −0.13, p = 5.2 × 10−4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = −0.11, p = 2.8 × 10−3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771).Conclusions: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance. [ABSTRACT FROM AUTHOR]