Sarah Crozier

Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study.

BACKGROUND Vitamin D insufficiency is common in women of childbearing age and increasing evidence suggests that the risk of osteoporotic fracture in adulthood could be determined partly by environmental factors during intrauterine and early postnatal life. We investigated the effect of maternal vitamin D status during pregnancy on childhood skeletal growth. METHODS In a longitudinal study, we studied 198 children born in 1991-92 in a hospital in Southampton, UK; the body build, nutrition, and vitamin D status of their mothers had been characterised during pregnancy. The children were followed up at age 9 years to relate these maternal characteristics to their body size and bone mass. FINDINGS 49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy. Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (r=0.21, p=0.0088) and lumbar-spine (r=0.17, p=0.03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0.0001 and p=0.0110, respectively) and childhood bone mass (p=0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0.0286). INTERPRETATION Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

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.

Women's Dietary Patterns Change Little from Before to During Pregnancy

Principal component analysis (PCA) is a popular method of dietary patterns analysis, but our understanding of its use to describe changes in dietary patterns over time is limited. Using a FFQ, we assessed the diets of 12,572 nonpregnant women aged 20-34 y from Southampton, UK, of whom 2270 and 2649 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. PCA at each time point produced 2 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 2 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.

Impact of educational attainment on the quality of young women's diets

Objective: New findings, that relate poor foetal growth to long-term outcomes, highlight the need to understand more about the nature of womens diets before and during pregnancy. This study examines the influence of sociodemographic and anthropometric factors on the quality of the diets of young women in the UK.Design: Diet was assessed by an interviewer-administered food frequency questionnaire. A single diet score was calculated for each woman using the first component defined by principal components analysis.Setting: Southampton, UK.Subjects: A total of 6125 non pregnant women aged 20–34 y.Results: The diets of women with low diet scores were characterised by low intakes of fruit and vegetables, wholemeal bread, rice and pasta, yogurt, and breakfast cereals, but high intakes of chips and roast potatoes, sugar, white bread, red, and processed meat and full-fat dairy products. Educational attainment was the most important factor related to the diet score. In all, 55% (95% CI 50–59%) of women with no educational qualifications had scores in the lowest quarter of the distribution, compared with only 3% (95% CI 2–4%) of those who had a degree. Smoking, watching television, lack of strenuous exercise, and living with children were also associated with lower diet scores. After taking these factors into account, no other factor including social class, the deprivation score of the neighbourhood, or receipt of benefits added more than 1% to the variance in the diet score.Conclusions: Poor achievement at school defines a substantial group of women in the UK who may be vulnerable. Many of these women have poor diets that are not simply a result of the level of deprivation in their neighbourhood, or of living at a level of poverty that entitles them to benefits. We suggest that it is a priority to identify and to address the barriers that prevent these women from improving the quality of their diets.Sponsorship: The study was funded by the Dunhill Medical Trust, the University of Southampton and the Medical Research Council.

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.

Maternal vitamin D status in pregnancy is associated with adiposity in the offspring: findings from the Southampton Women's Survey

BACKGROUND Low vitamin D status has been linked to adiposity, but little is known of the effects of low status in pregnancy on offspring body composition. OBJECTIVE The objective was to determine how maternal vitamin D status relates to lean and fat mass of the offspring. DESIGN The offspring of 977 pregnant women, who had serum 25-hydroxyvitamin D [25(OH)D] measured at 34 wk gestation, were followed up within 3 wk of birth and at 4 and 6 y of age for dual-energy X-ray absorptiometry assessment of lean and fat mass. RESULTS The median maternal serum 25(OH)D concentration was 62 nmol/L (IQR: 43-89 nmol/L); 35% of the women studied had values <50 nmol/L. Lower vitamin D status was associated with lower fat mass in the offspring at birth but with greater fat mass at ages 4 and 6 y. It was not associated with lean mass at any of the ages studied. The opposing associations seen between maternal 25(OH)D (SDs) and fat mass (SDs) in the offspring at birth and at age 6 y were robust to adjustment for a range of confounding factors, including maternal BMI and weight gain in pregnancy [β (95% CI): 0.08 (0.02, 0.15) and -0.10 (-0.17, -0.02), respectively]. The key independent predictors of higher maternal vitamin D status were season of assessment and use of vitamin D supplements. CONCLUSIONS Lower maternal vitamin D status may be linked to programmed differences in offspring fat mass. The findings require replication but add to a growing evidence base for a role of vitamin D in the origins of adiposity.

Fetal Liver-Sparing Cardiovascular Adaptations Linked to Mother’s Slimness and Diet

Fetal adaptations to impaired maternoplacental nutrient supply include altered regional blood flow. Whether such responses operate within the normal range of maternal body composition or diet is unknown, but any change in fetal liver perfusion could alter hepatic development, with long-term consequences for the risk of cardiovascular and metabolic disease. In 381 low-risk pregnancies, we found that the fetuses of slimmer mothers with lower body fat stores and those eating an unbalanced diet had greater liver blood flow and shunted less blood away from the liver through the ductus venosus at 36 weeks gestation. Consequences of such “liver-sparing” may underlie the increased cardiovascular risk of people whose mothers were slimmer and had lower body fat stores in pregnancy.

Portal and umbilical venous blood supply to the liver in the human fetus near term.

To determine the contribution of the umbilical (UV) and portal (PV) veins to blood supply to the human fetal liver in a low‐risk population near term, and to assess the distribution between the left and right lobes.

Maternal dietary patterns during pregnancy and childhood bone mass: a longitudinal study.

Maternal nutrition is a potentially important determinant of intrauterine skeletal development. Previous studies have examined the effects of individual nutrients, but the pattern of food consumption may be of greater relevance. We therefore examined the relationship between maternal dietary pattern during pregnancy and bone mass of the offspring at 9 yr of age. We studied 198 pregnant women 17–43 yr of age and their offspring at 9 yr of age. Dietary pattern was assessed using principal component analysis from a validated food frequency questionnaire. The offspring underwent measurements of bone mass using DXA at 9 yr of age. A high prudent diet score was characterized by elevated intakes of fruit, vegetables, and wholemeal bread, rice, and pasta and low intakes of processed foods. Higher prudent diet score in late pregnancy was associated with greater (p < 0.001) whole body and lumbar spine BMC and areal BMD in the offspring, after adjustment for sex, socioeconomic status, height, arm circumference, maternal smoking, and vitamin D status. Associations with prudent diet score in early pregnancy were weaker and nonsignificant. We conclude that dietary patterns consistent with current advice for healthy eating during pregnancy are associated with greater bone size and BMD in the offspring at 9 yr of age.

Dietary patterns in the Southampton Women's Survey.

Objective:Dietary pattern analysis is receiving increasing attention as a means of summarizing the multidimensional nature of dietary data. This research aims to compare principal component analysis (PCA) 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. PCA and cluster analysis were used to examine dietary patterns.Setting:Southampton, UK.Subjects:A total of 6125 non-pregnant women aged 20–34 years.Results:PCA 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 PCA was considered to be advantageous compared with the dichotomy identified using cluster analysis.Sponsorship:The study was funded by the Dunhill Medical Trust, the University of Southampton and the Medical Research Council.