Differentiation of patient-specific void urine-derived human induced pluripotent stem cells to fibroblasts and skeletal muscle myocytes.

Cell-based therapy is a major focus for treatment of stress urinary incontinence (SUI). However, derivation of primary cells requires tissue biopsies, which often have adverse effects on patients. A recent study used human induced pluripotent stem cells (iPSC)-derived smooth muscle myocytes for urethral sphincter regeneration in rats. Here, we establish a workflow using iPSC-derived fibroblasts and skeletal myocytes for urethral tissue regeneration: (1) Cells from voided urine of women were reprogrammed into iPSC. (2) The iPSC line U1 and hESC line H9 (control) were differentiated into fibroblasts expressing FSP1, TE7, vinculin, vimentin, αSMA, fibronectin and paxillin. (3) Myogenic differentiation of U1 and H9 was induced by small molecule CHIR99021 and confirmed by protein expression of myogenic factors PAX7, MYOD, MYOG, and MF20. Striated muscle cells enriched by FACS expressed NCAM1, TITIN, DESMIN, TNNT3. (4) Human iPSC-derived fibroblasts and myocytes were engrafted into the periurethral region of RNU rats. Injected cells were labelled with ferric nanoparticles and traced by Prussian Blue stain, human-specific nuclear protein KU80, and human anti-mitochondria antibody. This workflow allows the scalable derivation, culture, and in vivo tracing of patient-specific fibroblasts and myocytes, which can be assessed in rat SUI models to regenerate urethral damages and restore continence.

Validity and application of immunoturbidimetric and enzyme-linked immunosorbent assays for the measurement of adiponectin concentration in ponies.

BACKGROUND: Circulating adiponectin concentrations were lower in ponies with a history of endocrinopathic laminitis and in nonlaminitic ponies that subsequently developed laminitis. The assays used in these studies have been discontinued or are no longer valid. OBJECTIVES: (1) to determine the validity of immunoturbidimetric (IT) and enzyme linkedimmunosorbent (ELISA) assays for equine total and high molecular weight (HMW) [adiponectin] measurement and (2) to investigate the association between [adiponectin] measured using these assays and endocrinopathic laminitis. STUDY DESIGN: Method validation and cohort study. METHODS: Accuracy and precision of IT and ELISA assays for measuring total (TAC) and HMW (HMWAC) [adiponectin] were determined. Using the IT assay, the effects of anti-coagulant and storage temperature were assessed, TAC was measured in previously laminitic (PL) and never laminitic (NL) ponies (n = 6/group). Comparison with a previously validated radioimmunoassay was made in NL ponies (n = 223). Association between TAC and subsequent laminitis development in NL ponies was investigated using univariable logistic regression and ROC curve analysis. RESULTS: The IT assay was precise and demonstrated good agreement with the previously validated radioimmunoassay. TAC was significantly (P<0.01) lower in PL (mean ± s.d. 8.9 ± 2.9 µg/mL) compared to NL (24.2 ± 11.8 µg/mL) ponies and in NL ponies that developed laminitis within 12 months (median 4.8 µg/mL; IQR 2.65-13.4 µg/mL) compared to those that remained nonlaminitic (19.9 µg/mL; 9.95-31.5 µg/mL). TAC was significantly (P = 0.01) associated with laminitis occurrence within 12 months. Use of the area under the ROC curve to distinguish animals that did and did not develop laminitis showed good accuracy (0.76). None of the ELISA methods validated satisfactorily. MAIN LIMITATIONS: Laminitis risk is based on data from ponies in one region. CONCLUSIONS: The IT method is suitable for measurement of equine TAC. TAC is lower in ponies with previous or future laminitis. The ELISA methods are not suitable for measurement of equine HMWAC or TAC.

Micro-techniques for analysis of human adipose tissue fatty acid composition in dietary studies.

BACKGROUND AND AIMS: Adipose tissue (AT) fatty acid (FA) composition is considered to be the gold standard long-term biomarker of dietary fatty acid intake. Typically this measurement is made directly from samples collected via large-needle-biopsy or incision. However, with growing interest in the role of AT in relation to health, ideally the fatty acid composition would be analysed along with other measurements, such as gene expression or histology, on a single AT sample. Here we assess alternative ways of obtaining AT for measuring FA composition, in some cases in conjunction with other measurements. METHODS AND RESULTS: The FA composition of tissue obtained via different methods was compared to that of tissue collected via large-needle or surgical biopsy. Fatty acid composition was not significantly different in AT collected by small-needle mini-biopsy (n = 10), from an RNA 'lipid layer' (obtained during RNA extraction, 2 sites, n = 6 for each), or from cryosectioned tissue prepared for histology (n = 10). We also assessed the usefulness of the composition of plasma NEFA as a surrogate marker of subcutaneous AT (n = 58-80). Most FAs in plasma NEFA correlated strongly with those in AT (P < 0.05). CONCLUSION: It is feasible to measure the FA composition of AT on very small amounts of tissue. Additionally, it is possible to measure FA composition on the lipid rich 'by-product' of AT samples undergoing RNA extraction for gene expression. Samples sectioned for histology are also suitable. This provides further opportunities for multidisciplinary collaborations that may lead to a better application of dietary biomarkers.

Targeting cancer stem cell lines as a new treatment of human cancer.

Many studies have demonstrated that most cancers are clonal and are maintained by a cancer stem cell. Cancer stem cells have been identified in blood, breast, brain, lungs, gastrointestinal, prostate and ovarian cancer. Under normal homeostasis tissue specific stem cell division would be under strict control. When proliferation becomes independent of normal cellular controls, cancer develops. Studies indicate that cancer stem cells maintain their ability to differentiate, which explains the variety of cell types observed in tumors. Most therapies are directed at the fast growing tumor mass but not the slow dividing cancer stem cells and therefore the cancer is not eradicated. Understanding the process of transformation from a highly regulated stem cell to a cancer stem cell requires an understanding of genetic and epigenetic processes as well as having an understanding of the stem cell niche and the interaction of the stem cells with supportive cells in the niche. Current research is helping us to understand stem cells and stem cell regulation and in turn this will help to develop novel therapies to eliminate cancer and the initiating cancer stem cell. The relevant patents on the stem cell regulation and cancer therapy by stem cells are discussed.

Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth.

OBJECTIVES: The aim of this study was to determine whether normal human embryonic stem cells (hESC) would secrete factors that arrest growth of human epithelial cancer cell lines. MATERIALS AND METHODS: Cell proliferation was examined using the MTT assay then haemocytometer cell counts. Staining with propidium iodide followed by flow cytometry was used to detect cell cycle stages. Heat denaturation and molecular fractionation experiments were also performed. RESULTS: We found that hESC conditioned medium (hESC CM) inhibited SKOV-3 and HEY cell proliferation. Similar results were also obtained when we used breast and prostate cancer cell lines, whereas little or no inhibitory effect was observed when human fibroblasts were tested. Moreover, a co-culture model confirmed that inhibition of cancer cell proliferation is mediated by soluble factors produced by hESCs. We also determined that the proportion of cancer cells in G(1) phase was increased by hESC CM treatment, accompanied by decrease in cells in S and G(2)/M phases, suggesting that the factors slow progression of cancer cells by cell cycle inhibition. Heat denaturation and molecular fractionation experiments indicated a low molecular weight thermostable factor was responsible for these properties. CONCLUSIONS: Our findings provide evidence that the human embryonic microenvironment contains soluble factor(s) that are capable of inhibiting growth of cancer cells, and that exposure to such factors may represent a new cancer treatment strategy.

Dietary patterns related to attainment in school: the importance of early eating patterns.

OBJECTIVES: To empirically test the impact of dietary intake at several time points in childhood on children's school attainment and to investigate whether any differences in school attainment between children who ate packed lunches or school meals was due to who these children were, their pre-school dietary patterns, or to what they ate at school. DESIGN: Using longitudinal data available in the Avon Longitudinal Study of Parents and Children (ALSPAC), multivariate linear regression was used to assess the relative importance of diet at different ages for school attainment. MAIN OUTCOME MEASURES: Three indicators of school attainment were used: at ages 4-5 entry assessments to school, at ages 6-7 Key Stage 1 national tests and at ages 10-11 Key Stage 2 national tests. These outcome variables were measured in levels as well as in changes from the previous educational stage. RESULTS: The key finding at age 3 was that "junk food" dietary pattern had a negative association with the level of school attainment. A weak association remained after controlling for the impact of other dietary patterns at age 3, dietary patterns at ages 4 and 7 and other confounding factors. The authors did not find evidence that eating packed lunches or eating school meals affected children's attainment, once the impact of junk food dietary pattern at age 3 was accounted for in the model. CONCLUSIONS: Early eating patterns have implications for attainment that appear to persist over time, regardless of subsequent changes in diet.

Magnetic resonance imaging of abdominal adiposity in a large cohort of British children.

OBJECTIVE: To describe abdominal adipose tissue distribution in a large sample of contemporary British children; to determine the influence of gender, stage of maturation and body mass index (BMI) on abdominal adipose tissue distribution; and to compare the ability of BMI and waist circumference to predict abdominal adipose tissue. SUBJECTS AND METHODS: A total of 74 boys (mean age 13.4+/-0.4 years) and 96 girls (mean age 13.5+/-0.5 years) were selected from volunteer children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Height, weight and waist circumference were measured and BMI calculated. Stage of sexual maturation was available for 113 children using a self-report questionnaire based on Tanner's criteria. Magnetic resonance imaging was used to assess subcutaneous abdominal adipose tissue (SAAT) and intra-abdominal adipose tissue (IAAT) volumes and patterning. RESULTS: Boys had lower levels of IAAT (P=0.036) and SAAT (P=0.003) than girls. IAAT and SAAT were higher in overweight and obese boys and girls when compared with normal weight children (P<0.0001). This pattern was also reflected in waist circumference groups. Boys had higher IAAT/SAAT ratios than girls, indicating proportionately more adipose tissue deposited intra-abdominally (P=0.002). However, both boys and girls deposited less than 10% of their abdominal fat as internal adipose tissue. WC predicted 67.4% of the variance in IAAT (P<0.001), and BMI predicted 84.8% of the variance in SAAT (P<0.001). However, BMI as the best single predictor explained only 8.4% of the variance in the IAAT/SAAT ratio (P<0.001). CONCLUSIONS: At this age and stage of sexual maturation, the amount of IAAT remains relatively small. WC and BMI offer a feasible alternative to the MRI estimation of IAAT and SAAT, respectively, in a population-based sample of boys and girls. International Journal of Obesity (2008) 32, 91-99; doi:10.1038/sj.ijo.0803780; published online 27 November 2007.

Sodium intake in infancy and blood pressure at 7 years: findings from the Avon Longitudinal Study of Parents and Children.

BACKGROUND: Infancy may be a sensitive period regarding effects of sodium intake on future blood pressure (BP). This has only been demonstrated in one randomized trial of low sodium formulae with follow-up in adolescence in one-third of participants. OBJECTIVE: To prospectively assess associations between sodium intake in infancy and BP at 7 years in the Avon Longitudinal Study of Parents and Children (ALSPAC). SUBJECTS: A total of 533 children with sodium data at 4 months and 710 children with sodium at 8 months. RESULTS: 0.4% of participants at 4 months and 73.0% at 8 months exceeded recommended levels for infant sodium intake. After minimal adjustment (child age, sex, energy), sodium intake at 4 months was positively associated with systolic blood pressure (SBP) at 7 years (beta=0.54 mm Hg/mmol; 95% CI: 0.09, 0.98 mm Hg; P=0.02). This changed little following adjustment for confounders but attenuated after adjusting for breastfeeding. This association was not mediated by sodium intake at 7 years. Due to high sodium-potassium correlations, effects of sodium independent of potassium could not be estimated with reasonable precision. Sodium intake neither at 8 months nor at 7 years was associated with SBP at 7 years. CONCLUSION: The association between sodium intake at 4 months and future SBP requires replication in studies that can control for effects of potassium before we can conclude that early infancy is a sensitive period with respect to effects of sodium on future BP. The majority of infants exceeded recommended levels of sodium intake at 8 months, and interventions to reduce sodium in infants' diets should be considered.

Adjusting for energy intake in dietary pattern investigations using principal components analysis.

OBJECTIVE: The effect of energy adjustment on variables entered into principal component analysis (PCA) to derive dietary patterns has received little attention. DESIGN AND METHODS: As part of regular self-completion questionnaires, used in the Avon Longitudinal Study of Parents and Children, pregnant women were asked to record the frequency of consumption of a variety of food items. A total of 12 053 women completed the questionnaire. Individual dietary types were identified using PCA, before and after adjusting the food variables for energy intake. Associations with estimated nutrient intakes and with birthweight were examined for the two solutions and when energy adjustment was performed at a later stage of the analysis. RESULTS: Slight differences were seen in terms of the components extracted and the factor loadings obtained. The associations with nutrient intakes showed that there was a general reduction in the size of the correlation coefficients for the energy-adjusted components compared to the unadjusted components. There did not appear to be any difference in the size of the effects of the dietary pattern scores on birthweight, whether energy was adjusted for before entry into the PCA or after. CONCLUSIONS: In this sample, it is not necessary to adjust for energy intake before entry into a PCA analysis to determine dietary patterns when using food frequency questionnaire data. Effects of energy intake can be determined at a later stage in the analytical process.This study determines the effect of adjusting for energy on dietary patterns resulting from PCA and the subsequent effect on future outcomes.

Dietary patterns in pregnancy and associations with socio-demographic and lifestyle factors.

OBJECTIVE: To obtain distinct dietary patterns in the third trimester of pregnancy using principal components analysis (PCA); to determine associations with socio-demographic and lifestyle factors. DESIGN AND METHODS: A total of 12 053 pregnant women partaking in a population-based cohort study recorded current frequency of food consumption via questionnaire in 1991-1992. Dietary patterns identified using PCA were related to social and demographic characteristics and lifestyle factors. RESULTS: Five dietary patterns were established and labelled to best describe the types of diet being consumed in pregnancy. The 'health conscious' component described a diet based on salad, fruit, rice, pasta, breakfast cereals, fish, eggs, pulses, fruit juices, white meat and non-white bread. The 'traditional' component loaded highly on all types of vegetables, red meat and poultry. The 'processed' component was associated with high-fat processed foods. The 'confectionery' component was characterized by snack foods with high sugar content and the final 'vegetarian' component loaded highly on meat substitutes, pulses, nuts and herbal tea and high negative loadings were seen with red meat and poultry. There were strong associations between various socio-demographic variables and all dietary components; in particular, a 'health conscious' diet was positively associated with increasing education and age and non-white women. There was a negative association with increased parity, single, non-working women, those who smoked and who were overweight pre-pregnancy. Opposite associations were seen with the 'processed' component. CONCLUSIONS: Distinct dietary patterns in pregnancy have been identified. There is clear evidence of social patterning associated with the dietary patterns, these social factors need to be accounted for in future studies using dietary patterns. This study will form the basis for further work investigating pregnancy outcome.

Quality of food eaten in English primary schools: school dinners vs packed lunches.

OBJECTIVE: To compare the food and nutrient intakes of primary school children eating school dinners and packed lunches. SUBJECTS: Six-hundred and twenty-one 7-year-old children participating in the Avon Longitudinal Study of Parents and Children in South West England. METHODS: Diet was assessed by 3-day unweighed food record. RESULTS: The composition of both types of school meals compared unfavourably with dietary guidelines. Intakes of energy, non-starch polysaccharides (NSP), calcium, iron, folate, retinol equivalents, zinc, copper, magnesium, iodine and riboflavin were too low, and intakes of total and saturated fat were too high. However, children who ate school dinners had higher lunchtime intakes of protein, starch, NSP and most vitamins and minerals and lower intakes of sugar (14.2 and 20.9% of energy in school dinners and packed lunches, respectively, P<0.001) and saturated fat (12.0 and 16.2%, P<0.001). Only around half of the recommended amount of fruit and vegetables was eaten by children having either type of school meal. There were also differences in the whole day's nutrient intake according to school meal type. Children eating packed lunches had lower daily intakes of potassium and zinc, and higher intakes of sugar and saturated fat. Differences in nutrient intake were independent of maternal education. CONCLUSIONS: The food and nutrient content of both school dinners and packed lunches needed improvement. However, the standard of food brought from home by children was, if anything, worse than that served at school. Recent moves to improve school dinners will need to be complemented by education about what constitutes a healthy packed lunch.

Qualitative evaluation of a formal bedside clinical teaching programme in an emergency department.

BACKGROUND: Bedside clinical teaching in emergency departments is usually opportunist or ad hoc. A structured bedside clinical teaching programme was implemented, where a consultant and registrar were formally allocated to teaching and learning roles separated from the usual departmental management or clinical roles. Themes emphasised included clinical reasoning, practical clinical knowledge, communication, physical examination, procedural and professional skills. AIM: To evaluate the perceived educational value, effects on patient care and areas for ongoing development. METHODS: The study setting was an urban, tertiary referral, university-affiliated emergency department with prospectively allocated educational shifts of 4 or 5 h duration over a 6-month period. Evaluation was by session and course evaluation questionnaires, with respondents ranking predetermined themes and giving free-text responses. Qualitative presentation of results allowed exploration of the themes identified. RESULTS: Learners ranked history taking and physical examination technique as the most frequently learnt item, but clinical reasoning as the most important theme learnt. Informal discussion and performance critique or constructive feedback were the most frequent teaching methods. The biggest obstacle to learning was learner apprehension. The most frequent positive effect on patient care was faster management, decision making or disposition. Most often, no negative effect on patient care was identified. CONCLUSION: Formal bedside teaching is effective if organised with adequate staffing to quarantine the teacher and learner from routine clinical duties, and concentrating on themes best taught in the patient setting. Clinical reasoning and clinical knowledge were perceived to be most important, with positive effects on patient care through more thorough assessment and faster decision making.

Early life risk factors for obesity in childhood: cohort study.

OBJECTIVE: To identify risk factors in early life (up to 3 years of age) for obesity in children in the United Kingdom. DESIGN: Prospective cohort study. SETTING: Avon longitudinal study of parents and children, United Kingdom. PARTICIPANTS: 8234 children in cohort aged 7 years and a subsample of 909 children (children in focus) with data on additional early growth related risk factors for obesity. MAIN OUTCOME MEASURES: Obesity at age 7 years, defined as a body mass index (3) 95th centile relative to reference data for the UK population in 1990. RESULTS: Eight of 25 putative risk factors were associated with a risk of obesity in the final models: parental obesity (both parents: adjusted odds ratio, 10.44, 95% confidence interval 5.11 to 21.32), very early (by 43 months) body mass index or adiposity rebound (15.00, 5.32 to 42.30), more than eight hours spent watching television per week at age 3 years (1.55, 1.13 to 2.12), catch-up growth (2.60, 1.09 to 6.16), standard deviation score for weight at age 8 months (3.13, 1.43 to 6.85) and 18 months (2.65, 1.25 to 5.59); weight gain in first year (1.06, 1.02 to 1.10 per 100 g increase); birth weight, per 100 g (1.05, 1.03 to 1.07); and short (< 10.5 hours) sleep duration at age 3 years (1.45, 1.10 to 1.89). CONCLUSION: Eight factors in early life are associated with an increased risk of obesity in childhood.

Food and nutrient intakes of a population sample of 7-year-old children in the south-west of England in 1999/2000 - what difference does gender make?

OBJECTIVES: To describe the diet of schoolchildren aged 7 years, and identify gender differences in food and nutrient intakes. SUBJECTS: A cohort of children resident in the south-west of England in 1999/2000. METHODS: Diet was assessed using three 1-day unweighed food diaries. Nutrient intakes were compared with dietary reference values for this age group, and with children aged 7-10 years in the British National Diet and Nutrition Survey. Food and nutrient intakes were contrasted between boys and girls. RESULTS: Median nutrient intakes exceeded the reference nutrient intake (RNI) for most nutrients. Median intakes of iron and zinc were below the RNI. Median sodium intake was greater than the maximum set by the Scientific Advisory Committee on Nutrition. The mean energy intake for boys and girls, respectively, were 7.3 and 6.8 MJ, this is below the estimated average requirement. The percentage of energy from fat was 35.3% for boys and 36.1% for girls. Boys had higher iron intakes than girls, even after adjustment for energy intake. There were differences in the types of foods eaten between boys and girls; girls ate more fruit and vegetables (P = 0.001) and boys ate more breakfast cereals (P = 0.016). CONCLUSIONS: The dietary intakes of these 7-year-old children were adequate for most nutrients. However, a reduction in the sodium content of the diet would be advantageous. Fruit and vegetable consumption should be encouraged particularly among boys.

Trends in waist circumferences in young British children: a comparative study.

OBJECTIVE: To compare waist circumference (a measure of central fatness) and body mass index (BMI, a measure of general fatness) between a contemporary cohort and similar aged British children measured in 1987. DESIGN: : Comparative study of two cohorts. The first was a cross-sectional survey and the second an ongoing longitudinal survey. SETTING: : The cross-sectional study was conducted throughout Great Britain during 1987. The ongoing longitudinal study was conducted in the Avon region between 1995 and 1998. PARTICIPANTS: A total of 1821 children were measured in the cross-sectional study, and around 1000 children were measured in the longitudinal study. Ages ranged between 2 and 5 y. MAIN OUTCOME MEASURES: Waist circumference, height, weight and BMI. Values were expressed as mean+/-s.d. Age-related measures were compared. RESULTS: At equivalent ages, mean waist circumference values were greater in the contemporary children, compared with children measured in the earlier cross-sectional study in 1987 (P<0.05). Although boys from the contemporary cohort had the larger absolute waist circumference measurements, the absolute and percentage differences in waist circumference between the cohorts were greater for the girls. Mean BMI values were slightly but significantly higher in the contemporary children compared with children measured in the earlier cross-sectional study (P<0.05). The proportional increase in waist circumference for each age-sex group generally exceeded the proportional increase in BMI. CONCLUSION: These results suggest that central fatness in young British children has increased over the period of 1987-97 to a greater extent than general fatness. This should be of concern since evidence associates greater central adiposity with adverse levels of cardiovascular risk factors in children. Furthermore, the study highlights important shortcomings of the BMI measurement, in that it provides no information on body fat distribution and can mask true obesity-related risk in children.

Maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation in a cohort of British infants.

OBJECTIVE: To investigate the relation between maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation (IUGR). PARTICIPANTS: 11 585 pregnant women in south west England. METHODS: Information on fish intake was obtained from a food frequency questionnaire sent to the women at 32 weeks' gestation, and used to calculate n-3 fatty acid (n-3FA) intake from fish. IUGR was defined as a birth weight for gestational age and sex below the 10th centile. Confounding variables considered included maternal age, height, weight, education, parity, smoking and drinking in pregnancy, and whether the mother was living with a partner. Only singleton, liveborn infants were included. MAIN RESULTS: Mean daily intakes of fish and n-3FAs were 32.8 g and 0.147 g respectively. In unadjusted analyses there were positive associations between mean birth weight and fish intake or n-3FA intake, but these disappeared on adjustment for potential confounders. The frequency of IUGR decreased with increasing fish intake-the OR (95%CI) of IUGR in those eating no fish was 1.85 (1.44 to 2.38) compared with those in the highest fish intake group. On adjustment this relation was attenuated (adjusted OR 1.37 (1.02 to 1.84)), but the decline in the frequency of IUGR with increasing fish intake remained statistically significant. No relation was observed between mean gestation and fish or n-3FA intake. CONCLUSIONS: These results lend some support to the hypothesis that raising fish or n3-FA intake during pregnancy may increase fetal growth rate. However, they provide no evidence that increasing fish consumption is associated with an increase in mean gestation.

The effect of maternal smoking status, educational level and age on food and nutrient intakes in preschool children: results from the Avon Longitudinal Study of Parents and Children.

OBJECTIVE: Studies in adults have demonstrated that smoking status is associated with dietary quality, with smokers tending to have diets that conform less closely to guidelines on healthy eating than nonsmokers. However, there is very little information on the relation between children's dietary quality and parental smoking status. The objective of this study was to investigate the relation between maternal smoking status and nutrient intake in preschool children, allowing for the possible confounding effects of maternal educational level and age at delivery. SUBJECTS: In total, 993 children aged 18 months participating in the Avon Longitudinal Study of Parents and Children. METHODS: Diet was assessed by a 3-day food record. Maternal smoking status and educational level and age at delivery were assessed by questionnaire. RESULTS: In multivariate analysis, the children of smokers had significantly higher intakes of monounsaturated fatty acids and starch, and lower intakes of nonstarch polysaccharides (NSP). They were also less likely to have eaten poultry, buns, cakes and puddings, wholemeal bread and fruit, and more likely to have drunk sugar-sweetened soft drinks. Intakes of NSP and most vitamins and minerals increased significantly with increasing maternal education. Children of more highly educated mothers were less likely to have eaten chocolate, crisps and white bread, and more likely to have consumed wholemeal bread, fruit and fruit juice. CONCLUSIONS: The children of nonsmokers and more highly educated mothers consumed a diet that conformed more closely to current guidelines on healthy eating. These dietary differences may contribute to the excess of ill-health observed in the children of smokers and of less-educated mothers.

The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life.

OBJECTIVE: To review the literature on the association between birthweight and body mass index (BMI) and obesity in later life. METHODS: Included in the review were papers appearing in Medline since 1966 and identified using the search terms obesity, body fat, waist, body constitution, birthweight and birth weight. Further papers were identified by examining bibliographies. RESULTS: There is good evidence that there is an association between birthweight and subsequent BMI and overweight in young adults and children, which is linear and positive in some studies and J- or U-shaped in others. The evidence is less strong for middle-aged subjects. Studies that have assessed lean body mass (LBM) and fat body mass have tended to find that birthweight is positively associated with LBM and negatively associated with relative adiposity. This suggests that the association between birthweight and BMI/overweight does not necessarily reflect increased adiposity at higher birthweights. On controlling for current body mass there is fairly consistent evidence of a negative association between birthweight and a central pattern of fat distribution as measured by central:peripheral skinfold ratios. It has been suggested that the prenatal period is a 'critical' period for the development of adiposity, but it is unclear how far associations between birthweight and subsequent body habitus are genetic in origin and how far they result from intrauterine 'programming'. Two lines of evidence would suggest that the association is predominantly genetic. Studies of monozygotic twins have found environmentally determined differences in birthweight to be unrelated to subsequent BMI, and the association between birthweight and BMI is substantially reduced on controlling for parental BMI. However, some evidence of an influence of intrauterine environment on later obesity comes from studies of subjects who were exposed in utero to the effects of diabetes, famine conditions or smoking. CONCLUSIONS: The reasons for the positive association between birthweight and BMI remain unclear. More studies including accurate measurement of body composition are needed to assess how far this relation is accounted for by changes in fat mass or by changes in lean mass. Studies with accurate measures of parental BMI would also be useful in assessing the importance of this confounder.