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Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol. We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing). Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males' peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position. This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.

Background Adolescents are increasingly susceptible to obesity, and thus at risk of later non-communicable diseases, due to changes in food choices, physical activity levels and exposure to an obesogenic environment. This review aimed to synthesize the literature investigating the effectiveness of health education interventions delivered in school settings to prevent overweight and obesity and/ or reduce BMI in adolescents, and to explore the key features of effectiveness. Methods A systematic search of electronic databases including MEDLINE, CINAHL, PsychINFO and ERIC for papers published from Jan 2006 was carried out in 2020, following PRISMA guidelines. Studies that evaluated health education interventions in 10–19-year-olds delivered in schools in high-income countries, with a control group and reported BMI/BMI z-score were selected. Three researchers screened titles and abstracts, conducted data extraction and assessed quality of the full text publications. A third of the papers from each set were cross-checked by another reviewer. A meta-analysis of a sub-set of studies was conducted for BMI z-score. Results Thirty-three interventions based on 39 publications were included in the review. Most studies evaluated multi-component interventions using health education to improve behaviours related to diet, physical activity and body composition measures. Fourteen interventions were associated with reduced BMI/BMI z-score. Most interventions ( n  = 22) were delivered by teachers in classroom settings, 19 of which trained teachers before the intervention. The multi-component interventions ( n  = 26) included strategies such as environment modifications ( n  = 10), digital interventions ( n  = 15) and parent involvement ( n  = 16). Fourteen studies had a low risk of bias, followed by 10 with medium and nine with a high risk of bias. Fourteen studies were included in a random-effects meta-analysis for BMI z-score. The pooled estimate of this meta-analysis showed a small difference between intervention and control in change in BMI z-score (− 0.06 [95% CI -0.10, − 0.03]). A funnel plot indicated that some degree of publication bias was operating, and hence the effect size might be inflated. Conclusions Findings from our review suggest that school-based health education interventions have the public health potential to lower BMI towards a healthier range in adolescents. Multi-component interventions involving key stakeholders such as teachers and parents and digital components are a promising strategy.

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D 3 by endocytosis, placental metabolism of 25(OH)D 3 into 24,25-dihydroxyvitamin D 3 and active 1,25-dihydroxyvitamin D [1,25(OH) 2 D 3 ], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D 3 and synthesis of 1,25(OH) 2 D 3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D 3 . We demonstrate that 25(OH)D 3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.

Physical activity (PA) has many health benefits, but motherhood is often associated with reduced PA. Considering that ages and number of children may be associated with maternal PA, and that PA patterns may change as children transition to formal schooling, we aimed to investigate the associations between ages and number of children and device-measured maternal PA. Cross-sectional analyses were conducted using data from 848 mothers from the Southampton Women's Survey at two different timepoints. Two-level random intercept linear models were used to investigate associations between ages (≤4y(ears) (\"younger\"), school-aged, both age groups) and number (1, 2, ≥3) of children, and their interaction, and accelerometer-assessed minutes of maternal moderate or vigorous PA (log-transformed MVPA) and light, moderate or vigorous PA (LMVPA). Women with any school-aged children engaged in more MVPA than those with only ≤4y (e.g. % difference in minutes of MVPA [95% confidence interval]: 46.9% [22.0;77.0] for mothers with only school-aged vs only ≤4y). Mothers with multiple children did less MVPA than those with 1 child (e.g. 12.5% [-1.1;24.3] less MVPA for those with 2 children). For mothers with multiple children, those with any school-aged children did less LMVPA than those with only ≤4y (e.g. amongst mothers with 2 children, those with only school-aged children did 34.0 [3.9;64.1] mins/day less LMVPA). For mothers with any ≤4y, those with more children did more LMVPA (e.g. amongst mothers with only ≤4y, those with 2 children did 42.6 [16.4;68.8] mins/day more LMVPA than those with 1 child). Mothers with multiple children and only children aged ≤4y did less MVPA. Considering that many of these women also did more LMVPA than mothers with fewer or older children, interventions and policies are needed to increase their opportunities for higher intensity PA to maximise health benefits. ClinicalTrials.gov Identifier: NCT04715945.

Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001) and at age 4 years (r = 0.16, P = 0.02). In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02). This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04). We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

BackgroundSilver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%–10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS.MethodsA retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped.ResultsThe median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤−2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS.ConclusionHistorical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases.

ObjectivePremenstrual syndrome (PMS) is a very common disorder worldwide which carries an important economic burden. We conducted a systematic review and a meta-analysis to assess the role of alcohol in the occurrence of PMS.MethodsWe searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO, the Proceedings database and the Open Access Thesis and Dissertations (OATD) from inception to May 2017. We also reviewed the references of every article retrieved and established personal contact with researchers to trace further publications or reports. We did not include any language limitations. Studies were included if: (1) they presented original data from cohort, case-control or cross-sectional studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the exposure factors was alcohol consumption, (4) they provided estimates of odds ratios, relative risks, or any other effect measure and their confidence intervals, or enough data to calculate them.ResultsWe identified 39 studies of which 19 were eligible. Intake of alcohol was associated with a moderate increase in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32).DiscussionOur results suggest that alcohol intake presents a moderate association with PMS risk. Future studies should avoid cross-sectional designs and focus on determining whether there is a threshold of alcohol intake under which the harmful effect on PMS is non-existent.

It is recognised that eating habits established in early childhood may track into adult life. Developing effective interventions to promote healthier patterns of eating throughout the life course requires a greater understanding of the diets of young children and the factors that influence early dietary patterns. In a longitudinal UK cohort study, we assessed the diets of 1640 children at age 3 years using an interviewer-administered FFQ and examined the influence of maternal and family factors on the quality of the children's diets. To describe dietary quality, we used a principal components analysis-defined pattern of foods that is consistent with healthy eating recommendations. This was termed a ‘prudent’ diet pattern and was characterised by high intakes of fruit, vegetables and wholemeal bread, but by low intakes of white bread, confectionery, chips and roast potatoes. The key influence on the quality of the children's diets was the quality of their mother's diets; alone it accounted for almost a third of the variance in child's dietary quality. Mothers who had better-quality diets, which complied with dietary recommendations, were more likely to have children with comparable diets. This relationship remained strong even after adjustment for all other factors considered, including maternal educational attainment, BMI and smoking, and the child's birth order and the time spent watching television. Our data provide strong evidence of shared family patterns of diet and suggest that interventions to improve the quality of young women's diets could be effective in improving the quality of their children's diets.

BACKGROUND: Little is known about preschool-aged children’s levels of physical activity (PA) over the course of the day. Using time-stamped data, we describe the levels and patterns of PA in a population-based sample of four-year-old British children. METHODS: Within the Southampton Women’s Survey the PA levels of 593 4-year-old children (51% female) were measured using (Actiheart) accelerometry for up to 7 days. Three outcome measures: minutes spent sedentary (<20 cpm); in light (LPA: ≥20 – 399 cpm) and in moderate-to-vigorous activity (MVPA: ≥400 cpm) were derived. Average daily activity levels were calculated and then segmented across the day (morning, afternoon and evening). MVPA was log-transformed. Two-level random intercept models were used to analyse associations between activity level and temporal and demographic factors. RESULTS: Children were active for 67% (mean 568.5 SD 79.5 minutes) of their daily registered time on average, with 88% of active time spent in LPA. All children met current UK guidelines of 180 minutes of daily activity. There were no differences in children’s average daily levels of sedentary activity and LPA by temporal and demographic factors: differences did emerge when activity was segmented across the day. Sex differences were largest in the morning, with girls being more sedentary, spending fewer minutes in LPA and 18% less time in MVPA than boys. Children were more sedentary and less active (LPA and MVPA) in the morning if they attended childcare full-time compared to part-time, and on weekend mornings compared to weekdays. The reverse was true for weekend afternoons and evenings. Children with more educated mothers were less active in the evenings. Children were less sedentary and did more MVPA on summer evenings compared to winter evenings. CONCLUSIONS: Preschool-aged children meet current physical activity guidelines, but with the majority of their active time spent in LPA, investigation of the importance of activity intensity in younger children is needed. Activity levels over the day differed by demographic and temporal factors, highlighting the need to consider temporality in future interventions. Increasing girls’ morning activity and providing opportunities for daytime activity in winter months may be worthwhile.

Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking, physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development.