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1.  Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention1234 
Background: Early life may be a “critical period” when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects.
Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey).
Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m2) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry–assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003.
Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001).
Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.
doi:10.3945/ajcn.114.094268
PMCID: PMC4307207  PMID: 25646335
adiposity; childhood obesity; early life; obesity; lifecourse; prevention
2.  Association of early childhood abdominal circumference and weight gain with blood pressure at 36 months of age: secondary analysis of data from a prospective cohort study 
BMJ Open  2014;4(7):e005412.
Objectives
To assess whether changes in measures of fat distribution and body size during early life are associated with blood pressure at 36 months of age.
Design
Analysis of data collected from a prospective cohort study.
Setting
Community-based investigation in Southampton, UK.
Participants
761 children with valid blood pressure measurements, born to women participating in the Southampton Women’s Survey.
Primary and secondary outcome measures
Anthropometric measurements were collected at 0, 6, 12, 24 and 36 months and conditional changes between the time points calculated. Blood pressure was measured at 36 months. Factors possibly influencing the blood pressure were assessed using linear regression. All independent variables of interest and confounding variables were included in stepwise multiple regression to identify the model that best predicted blood pressure at 36 months.
Results
Greater conditional gains in abdominal circumference (AC) between 0–6 and 24–36 months were associated with higher systolic and diastolic blood pressures at 36 months (p<0.001). Subscapular skinfold and height gains were weakly associated with higher blood pressures, while greater weight gains between 0–6, 12–24 and 24–36 months were more strongly associated, but the dominant influences were AC gains, particularly from 0–6 to 24–36 months. Thus one SD score increases in AC between 0–6 and 24–36 months were associated with 1.59 mm Hg (95% CI 0.97 to 2.21) and 1.84 mm Hg (1.24 to 2.46) higher systolic blood pressures, respectively, and 1.04 mm Hg (0.57 to 1.51) and 1.02 mm Hg (0.56, 1.48) higher diastolic pressures, respectively.
Conclusions
Conditional gains in abdominal circumference, particularly within 6 months of birth and in the year preceding measurement, were more positively associated with blood pressure at 36 months than gains in other anthropometric measures. Above-average AC gains in early childhood may contribute to adult hypertension and increased cardiovascular disease risk.
doi:10.1136/bmjopen-2014-005412
PMCID: PMC4091398  PMID: 24993768
EPIDEMIOLOGY
4.  Fetal and infant growth predict hip geometry at six years old: Findings from the Southampton Women’s Survey 
Pediatric research  2013;74(4):450-456.
Background
We investigated relationships between early growth and proximal femoral geometry at age six years in a prospective population-based cohort, the Southampton Women’s Survey.
Methods
In 493 mother-offspring pairs we assessed linear size (individual measure dependent on developmental stage) using high-resolution ultrasound at 11, 19 and 34 weeks gestation (femur length) and at birth, 1, 2, 3, 4 and 6 years (crown-heel length/height). Standard deviation (SD)-scores were created and conditional regression modelling generated mutually independent growth variables. Children underwent hip DXA (Dual X-ray absorptiometry) at 6 years (Hologic Discovery, Hologic Inc., MA); hip structure analysis software yielded measures of geometry and strength.
Results
There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 years, with the strongest relationships observed for femur growth from 19-34 weeks gestation (β=0.26 cm3/SD, p<0.0001), and for height growth from birth to 1 year (β=0.25 cm3/SD, p<0.0001) and 1-2 years (β=0.33 cm3/SD, p<0.0001), with progressively weaker relationships over years 3 (β=0.23 cm3/SD, p=0.0002) and 4 (β=0.10 cm3/SD, p=0.18).
Conclusions
These results demonstrate that growth before age 3 years predicts proximal femoral geometry at six years old. The data suggest critical periods in which there is capacity for long term influence on the later skeletal growth trajectory.
doi:10.1038/pr.2013.119
PMCID: PMC3797011  PMID: 23857297
5.  Different Indices of Fetal Growth Predict Bone Size and Volumetric Density at 4 Years of Age 
We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks’ gestation from ultrasound measurements in participants in the Southampton Women’s Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks’ gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.
doi:10.1359/jbmr.091022
PMCID: PMC3793299  PMID: 20437610
EPIDEMIOLOGY; OSTEOPOROSIS; PROGRAMMING; DEVELOPMENTAL ORIGINS
6.  Epigenetic gene promoter methylation at birth is associated with child’s later adiposity 
Diabetes  2011;60(5):1528-1534.
Objective
Fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.
Research Design and Methods
Using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5′ from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ≥5% and a 5-95% range ≥10% we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.
Results
In cohort 1, RXRA chr9:136355885+ and eNOS chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient (β) 17% per standard deviation change in methylation (95% confidence interval (CI) 4 to 31%), P=0.009, n=64 and β=20% (9 to 32%), P<0.001, n=66, respectively) and %fat mass (β=10% (1 to 19%), P=0.023, n=64 and β=12% (4 to 20%), P=0.002, n=66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (β=6% (2 to 10%) and β=4% (1 to 7%), respectively, both P=0.002, n=239).
Conclusions
Our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease.
doi:10.2337/db10-0979
PMCID: PMC3115550  PMID: 21471513
7.  Dietary patterns change little from before to during pregnancy1 
The Journal of nutrition  2009;139(10):1956-1963.
Principal component analysis is a popular method of dietary patterns analysis, but our understanding of its use to describe changes in dietary patterns over time is limited. We assessed the diets of 12,572 non-pregnant women aged 20-34 from Southampton, UK using a food frequency questionnaire, of whom 2,270 and 2,649 became pregnant and provided complete dietary data in early and late pregnancy respectively. Intakes of white bread, breakfast cereals, cakes and biscuits, processed meat, crisps, fruit and fruit juices, sweet spreads, confectionery, hot chocolate drinks, puddings, cream, milk, cheese, full-fat spread, cooking fats and salad oils, red meat and soft drinks increased in pregnancy. Intakes of rice and pasta, liver and kidney, vegetables, nuts, diet cola, tea and coffee, boiled potatoes and crackers decreased in pregnancy. Principal component analysis at each time point produced two consistent dietary patterns, labeled ‘prudent’ and ‘high-energy’. At each time point in pregnancy, and for both the prudent and high-energy patterns, we derived two dietary pattern scores for each woman: a ‘natural’ score, based on the pattern defined at that time point, and an ‘applied’ score, based on the pattern defined before pregnancy. Applied scores are preferred to natural scores to characterize changes in dietary patterns over time because the scale of measurement remains constant. Using applied scores there was a very small mean decrease in prudent diet score in pregnancy, and a very small mean increase in high-energy diet score in late pregnancy, indicating little overall change in dietary patterns in pregnancy.
doi:10.3945/jn.109.109579
PMCID: PMC3113465  PMID: 19710161
Diet; Dietary patterns; Pregnancy; Principal component analysis
8.  Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey 
Background
Intrauterine life may be a critical period for the programming of later obesity, but there is conflicting evidence about whether pregnancy weight gain is an important determinant of offspring adiposity.
Objective
The purpose of this study was to examine the relationship of pregnancy weight gain with neonatal and childhood body composition.
Design
The participants (n=948) were children born to women in the Southampton Women’s Survey who had dual-energy x-ray absorptiometry measurements of body composition at birth, 4 or 6 years. Pregnancy weight gain was derived from the mothers’ measured weights before pregnancy and at 34 weeks gestation, analyzed using 2009 Institute of Medicine (IOM) categories (inadequate, adequate or excessive), and as a continuous measure.
Results
Almost half (49%) the children were born to women who gained excessive weight in pregnancy. In comparison with children born to women with adequate weight gain, they had a greater fat mass in the neonatal period (0.17 SD (95% CI 0.02, 0.32), P=0.03), at 4 years (0.17 SD (0.00, 0.34), P=0.05) and at 6 years (0.30 SD (0.11, 0.49), P=0.002). Greater pregnancy weight gain, as a continuous measure, was associated with greater neonatal fat mass (0.10 SD per 5kg weight gain (0.04, 0.15), P=0.0004) and, weakly, with fat mass at 6 years (0.07 SD per 5kg (0.00, 0.14), P=0.05), but not at 4 years (0.02 SD per 5kg (−0.04, 0.08), P=0.55).
Conclusions
Appropriate pregnancy weight gain, as defined by 2009 IOM recommendations, is linked to lower levels of adiposity in the offspring.
doi:10.3945/ajcn.2009.29128
PMCID: PMC3091013  PMID: 20375187
9.  Do women change their health behaviours in pregnancy? Findings from the Southampton Women’s Survey 
SUMMARY
A woman’s lifestyle choices before and during pregnancy have important implications for her unborn child, but information on behaviour can be unreliable when data are collected retrospectively. In particular there are no large longitudinal datasets that include information collected prospectively before pregnancy to allow accurate description of changes in behaviour into pregnancy.
The Southampton Women’s Survey is a longitudinal study of women in Southampton, UK, characterised when they were not pregnant and again during pregnancy. The objective of the analyses presented here is to describe the degree to which women comply with diet and lifestyle recommendations before and during pregnancy, and changes between these time points.
The analyses are based on 1490 women who delivered between 1998 and 2003 and who provided information before pregnancy and at 11 and 34 weeks gestation. At each time point a trained research nurse ascertained smoking status and assessed food and drink consumption using a food frequency questionnaire. We derived the proportions of women who complied with recommendations not to smoke, to eat five portions of fruit and vegetables per day and to drink no more than four units of alcohol per week and 300mg of caffeine per day.
There was a notable reduction in smoking when women became pregnant; before pregnancy 27% of women smoked, whereas in early pregnancy 15% smoked. Similarly there were significant reductions in alcohol consumption and intake of caffeinated drinks; before pregnancy 54% of women drank more than 4 units of alcohol per week and 39% had estimated intakes of caffeine in drinks of more than 300mg per day, whereas comparable figures for early pregnancy were 10% and 16% respectively. However, there was little change in fruit and vegetable intake; the percentages of women who did not achieve the recommendation to eat at least five portions of fruit and vegetables per week were 47% before pregnancy and 46% in early pregnancy. Younger women and those with fewer educational qualifications were less likely to comply with public health recommendations. 81% of women in early pregnancy complied with at least three of the recommendations. Although there is encouraging evidence of changed health behaviours in pregnancy, young women and those with few educational qualifications may particularly benefit from targeted health initiatives.
doi:10.1111/j.1365-3016.2009.01036.x
PMCID: PMC3091015  PMID: 19689495
Pregnancy; smoking; alcohol drinking; fruit and vegetables; caffeinated drinks
10.  Development of a 20-item food frequency questionnaire to assess a ‘prudent’ dietary pattern amongst young women in Southampton 
Objective
To develop a short food frequency questionnaire (FFQ) that can be used amongst young women in Southampton to assess compliance with a prudent dietary pattern characterised by high consumption of wholemeal bread, fruit and vegetables, and low consumption of sugar, white bread, and red and processed meat.
Methods
Diet was assessed using a 100-item interviewer-administered FFQ in 6,129 non-pregnant women aged 20-34 years. 94 of these women were re-interviewed two years later using the same FFQ. Subsequently diet was assessed in 378 women attending SureStart Children’s Centres in the Nutrition and Well-being Study using a 20-item FFQ. The 20 foods included were those that characterised the prudent dietary pattern.
Results
The 20-item prudent diet score was highly correlated with the full 100-item score (r=0.94) in the Southampton Women’s Survey. Both scores were correlated with red blood cell folate (r=0.28 for the 100-item score and r=0.25 for the 20-item score). Amongst the women re-interviewed after two years, the change in prudent diet score was correlated with change in red cell folate for both the 20-item (rS=0.31) and 100-item scores (rS=0.32). In the Nutrition and Well-being Study a strong association between the 20-item prudent diet score and educational attainment (r=0.41) was observed, similar to that seen in the Southampton Women’s Survey (r=0.47).
Conclusions
The prudent diet pattern describes a robust axis of variation in diet. A 20-item FFQ based on the foods that characterise the prudent diet pattern has clear advantages in terms of time and resources, and is a helpful tool to characterise the diets of young women in Southampton.
doi:10.1038/ejcn.2009.114
PMCID: PMC3091018  PMID: 19756032
Food frequency questionnaire; Principal component analysis
11.  Women’s compliance with nutrition and lifestyle recommendations before pregnancy: general population cohort study 
Objective To examine the extent to which women planning a pregnancy comply with recommendations for nutrition and lifestyle.
Design Prospective cohort study.
Setting Southampton, United Kingdom.
Participants 12 445 non-pregnant women aged 20-34 recruited to the Southampton Women’s Survey through general practices, 238 of whom became pregnant within three months of being interviewed.
Main outcome measures Folic acid supplement intake, alcohol consumption, smoking, diet, and physical activity before pregnancy.
Results The 238 women who became pregnant within three months of the interview were only marginally more likely to comply with recommendations for those planning a pregnancy than those who did not become pregnant in this period. Among those who became pregnant, 2.9% (95% confidence interval 1.2% to 6.0%) were taking 400 μg or more of folic acid supplements a day and drinking four or fewer units of alcohol a week, compared with 0.66% (0.52% to 0.82%) of those who did not become pregnant. 74% of those who became pregnant were non-smokers compared with 69% of those who did not become pregnant (P=0.08). Women in both groups were equally likely to consume five or more portions of fruit and vegetables a day (53% in each group, P=1.0), but only 57% of those who became pregnant had taken any strenuous exercise in the past three months compared with 64% in those who did not become pregnant (P=0.03).
Conclusion Only a small proportion of women planning a pregnancy follow the recommendations for nutrition and lifestyle. Greater publicity for the recommendations is needed, but as many pregnancies are unplanned, improved nutrition and lifestyles of women of childbearing age is also required.
doi:10.1136/bmj.b481
PMCID: PMC2643441  PMID: 19213768

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