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, retinoid X receptor-α (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [β] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and β = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (β = 10% [1–19], P = 0.023, n = 64 and β =12% [4–20], 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% [2–10] and β = 4% [1–7], 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.

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.

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.

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.

There is growing interest in the use of dietary patterns as measures of exposure in studies of diet-disease relationships. However, relatively little is known about the impact of the type of dietary assessment method on the patterns observed. Using food frequency questionnaire (FFQ) and food diary data collected from 585 women in early pregnancy we used principal component analysis to define dietary patterns. The first pattern was very similar in both datasets and was termed the ‘prudent’ diet. The second pattern, whilst comparable for the FFQ and food diaries, showed greater variation in coefficients than the prudent pattern; it was termed the ‘Western’ diet. Differences between the FFQ and diary scores were calculated for each woman for both the prudent and Western diet patterns. 95% of the differences in the prudent diet score lay within ±1.58 standard deviations of the mean, and 95% of the differences in the Western diet scores lay within ±2.22 standard deviations of the mean. Pearson’s correlation coefficients were 0.67 (P < 0.001) for the prudent diet score and 0.35 (P < 0.001) for the Western diet score. The agreement between the FFQ and diary scores was lowest amongst respondents who were younger, had lower educational attainment and whose diaries were coded as ‘poor, probably incomplete’, although these effects were small. The first two dietary patterns identified in this cohort of pregnant women appear to be defined similarly by both FFQ and diary data, suggesting that FFQ data provide useful information on dietary patterns.

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.

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.

Objective

Dietary pattern analysis is receiving increasing attention as a means of summarising the multi-dimensional nature of dietary data. This research aims to compare principal component analysis and cluster analysis using dietary data collected from young women in the UK.

Design

Diet was assessed using a 100-item interviewer-administered food frequency questionnaire. Principal component analysis and cluster analysis were used to examine dietary patterns.

Setting

Southampton, UK.

Subjects

6125 non-pregnant women aged 20 to 34 years

Results

Principal component analysis identified two important patterns: a ‘prudent’ diet, and a ‘high-energy’ diet. Cluster analysis defined two clusters, a ‘more healthy’ and a ‘less healthy’ cluster. There was a strong association between the prudent diet score and the two clusters, such that the mean prudent diet score in the less healthy cluster was −0.73 standard deviations and in the more healthy cluster was +0.83 standard deviations; the difference in the high-energy diet score between the two clusters was considerably smaller.

Conclusions

Both approaches revealed a similar dietary pattern. The continuous nature of the outcome of principal component analysis was considered to be advantageous compared with the dichotomy identified using cluster analysis.

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.

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.