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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.  Assessing diets of 3 year old children: evaluation of a food frequency questionnaire 
Public health nutrition  2013;17(5):1069-1077.
Objective
To evaluate the use of an administered 80-item food frequency questionnaire (FFQ) to assess nutrient intake and diet quality in 3 year old children.
Design
Frequency of consumption and portion size of the foods listed on the FFQ during the 3 months preceding the interview were reported by the child’s main caregiver; after the interview a 2-day prospective food diary (FD) was completed on behalf of the child. Nutrient intakes from FFQ and FD were estimated using UK food composition data. Diet quality was assessed from the FFQ and FD, according to the child’s scores for a principal component analysis-defined dietary pattern (‘prudent’ pattern), characterised by high consumption of fruit, vegetables, water and wholemeal cereals.
Subjects
892 children aged 3 years in the Southampton Women’s Survey
Setting
Southampton, UK
Results
Intakes of all nutrients assessed by FFQ were higher than FD estimates, but there was reasonable agreement in terms of ranking of children (range for Spearman rank correlations for energy-adjusted nutrient intakes, rs=0.41 to 0.59). Prudent diet scores estimated from the FFQ and FD were highly correlated (r=0.72). Some family and child characteristics appeared to influence the ability of the FFQ to rank children, most notably the number of child’s meals eaten away from home.
Conclusion
The FFQ provides useful information to allow ranking of children at this age with respect to nutrient intake and quality of diet, but may overestimate absolute intakes. Dietary studies of young children need to consider family and child characteristics that may impact on reporting error associated with an FFQ.
doi:10.1017/S136898001300102X
PMCID: PMC3743718  PMID: 23635946
dietary assessment; young children; food frequency questionnaire
3.  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
5.  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
6.  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
7.  Specific psychological variables predict quality of diet in women of lower, but not higher, educational attainment 
Appetite  2010;56(1):46-52.
Our previous work found that perceived control over life was a significant predictor of the quality of diet of women of lower educational attainment. In this paper, we explore the influence on quality of diet of a range of psychological and social factors identified during focus group discussions, and specify the way this differs in women of lower and higher educational attainment. We assessed educational attainment, quality of diet, and psycho-social factors in 378 women attending Sure Start Children’s Centres and baby clinics in Southampton, UK. Multiple-group path analysis showed that in women of lower educational attainment, the effect of general self-efficacy on quality of diet was mediated through perceptions of control and through food involvement, but that there were also direct effects of social support for healthy eating and having positive outcome expectancies. There was no effect of self-efficacy, perceived control or outcome expectancies on the quality of diet of women of higher educational attainment, though having more social support and food involvement were associated with improved quality of diet in these women. Our analysis confirms our hypothesis that control-related factors are more important in determining dietary quality in women of lower educational attainment than in women of higher educational attainment.
doi:10.1016/j.appet.2010.11.003
PMCID: PMC3685814  PMID: 21078352
educational attainment; diet; disadvantage; self-efficacy; perceived control
8.  Patterns of fetal and infant growth are related to atopy and wheezing disorders at age 3 years 
Thorax  2010;65(12):1099-1106.
Background
Little is known about whether patterns of growth are associated with altered respiratory and immune development. This study relates prenatal and infant growth patterns to wheeze and atopy at age 3 years
Methods
Birth weight and length were measured in 1548 children born at term. Conditional fetal head and abdominal circumference growth velocities were calculated from antenatal ultrasound measurements. Conditional postnatal growth velocities were calculated from infant weight, length and adiposity data. .Measures of size and conditional growth were related to parentally-reported infant and early childhood wheeze and to atopic status at age 3.
Results
Atopy risk increased by 46% per standard deviation (SD) increase in abdominal circumference growth velocity from 11-19 weeks’ gestation but by 20% per SD decrease in abdominal growth velocity from 19-34 weeks (p=0.007 and p=0.011). Atopic wheeze risk increased by 20% per SD decrease in 19-34 week abdominal growth (p=0.046). Non-atopic wheeze risk increased by 10% per SD decrease in 11-19 week head circumference growth. Greater relative infant weight and adiposity gains were associated with both atopic and non-atopic wheeze.
Conclusions
Rapid growth during 11-19 weeks’ gestation followed by growth faltering is associated with atopy, suggesting that influences affecting fetal growth may also alter immune development. A lower early fetal growth trajectory is associated with non-atopic wheeze, possibly reflecting an association with smaller airways. An association between postnatal adiposity gain and wheeze may partly reflect prenatal influences that cause fetal growth to falter but are then followed by postnatal adiposity gain.
doi:10.1136/thx.2010.134742
PMCID: PMC3685135  PMID: 20956394
asthma; preschool-wheeze; allergic sensitisation; growth; nutrition
9.  Does living in a food insecure household impact on the diets and body composition of young children? Findings from the Southampton Women’s Survey 
Background
Little is known about food insecurity in the UK. The aims of this study were to assess the prevalence and factors associated with food insecurity in a UK cohort, and to examine whether the diets, reported health and anthropometry of young food insecure children differed from those of other children.
Methods
The Southampton Women’s Survey is a prospective cohort study in which detailed information about the diet, lifestyle and body composition of 3000 women was collected before and during pregnancy. Between 2002-2006, 1618 families were followed up when the child was 3 years old. Food insecurity was determined using the Household Food Security scale. The child’s height and weight were measured; diet was assessed by food frequency questionnaire.
Results
4.6% of the households were food insecure. Food insecurity was more common in families where the mothers were younger, smokers, of lower social class, in receipt of financial benefits, and who had a higher deprivation score (all p<0.05). In comparison with other 3-year-old children, those living in food insecure households were likely to have worse parent-reported health and to have a diet of poorer quality, characterised by greater consumption of white bread, processed meat and chips, and by a lower consumption of vegetables (all p<0.05). They did not differ in height or body mass index.
Conclusions
Our data suggest that there are significant numbers of food insecure families in the UK. The poorer reported health and diets of young food insecure children have important implications for their development and lifelong health.
doi:10.1136/jech.2010.125476
PMCID: PMC3679518  PMID: 21652519
food insecurity; body composition; dietary quality; children
10.  Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content 
Calcified tissue international  2011;90(2):120-127.
Aim
Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children.
Methods
We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument).
Results
Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass.
Conclusions
Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.
doi:10.1007/s00223-011-9554-5
PMCID: PMC3629299  PMID: 22159788
Epigenetic; methylation; umbilical cord; eNOS; DXA
11.  Correction of unexpected distributions of P values from analysis of whole genome arrays by rectifying violation of statistical assumptions 
BMC Genomics  2013;14:161.
Background
Statistical analysis of genome-wide microarrays can result in many thousands of identical statistical tests being performed as each probe is tested for an association with a phenotype of interest. If there were no association between any of the probes and the phenotype, the distribution of P values obtained from statistical tests would resemble a Uniform distribution. If a selection of probes were significantly associated with the phenotype we would expect to observe P values for these probes of less than the designated significance level, alpha, resulting in more P values of less than alpha than expected by chance.
Results
In data from a whole genome methylation promoter array we unexpectedly observed P value distributions where there were fewer P values less than alpha than would be expected by chance. Our data suggest that a possible reason for this is a violation of the statistical assumptions required for these tests arising from heteroskedasticity. A simple but statistically sound remedy (a heteroskedasticity–consistent covariance matrix estimator to calculate standard errors of regression coefficients that are robust to heteroskedasticity) rectified this violation and resulted in meaningful P value distributions.
Conclusions
The statistical analysis of ‘omics data requires careful handling, especially in the choice of statistical test. To obtain meaningful results it is essential that the assumptions behind these tests are carefully examined and any violations rectified where possible, or a more appropriate statistical test chosen.
doi:10.1186/1471-2164-14-161
PMCID: PMC3610227  PMID: 23496791
P values; Distributions; Statistical analysis; Statistical assumptions; Whole genome methylation promoter arrays; Epigenome
12.  Fetal Liver Blood Flow Distribution: Role in Human Developmental Strategy to Prioritize Fat Deposition versus Brain Development 
PLoS ONE  2012;7(8):e41759.
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.
doi:10.1371/journal.pone.0041759
PMCID: PMC3425554  PMID: 22927915
13.  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, 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.
doi:10.2337/db10-0979
PMCID: PMC3115550  PMID: 21471513
15.  Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination 
Background
Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.
Methods
We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.
We measured the length, weight and head circumference at birth and 12 months.
Results
IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.
At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.
Conclusions
Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.
doi:10.1186/1471-2334-12-6
PMCID: PMC3274427  PMID: 22243970
16.  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
17.  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
18.  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
19.  Dietary patterns in pregnant women: a comparison of food frequency questionnaires and four-day prospective diaries 
The British journal of nutrition  2007;99(4):869-875.
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.
doi:10.1017/S0007114507831746
PMCID: PMC3091014  PMID: 18005481
Dietary patterns; principal component analysis; food frequency questionnaire
20.  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
21.  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
22.  Dietary patterns in the Southampton Women’s Survey 
European journal of clinical nutrition  2006;60(12):1391-1399.
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.
doi:10.1038/sj.ejcn.1602469
PMCID: PMC3091020  PMID: 16804555
Dietary patterns; Principal component analysis; Cluster analysis
23.  OCCUPATIONAL PHYSICAL ACTIVITIES, WORKING HOURS AND OUTCOME OF PREGNANCY: FINDINGS FROM THE SOUTHAMPTON WOMEN’S SURVEY 
Objectives
To investigate risks of physical activity at work by pregnancy trimester, including the effects on head and abdominal circumference.
Method
At 34 weeks gestation we interviewed 1327 mothers from the prospective Southampton Women’s Survey (SWS); we asked about their activities (working hours, standing/walking, kneeling/squatting, trunk bending, lifting and night shifts) in jobs held at each of 11, 19 and 34 weeks gestation, and subsequently ascertained four birth outcomes – preterm delivery, small for gestational age (SGA) and reduced head or abdominal circumference – blinded to employment history.
Results
Risk of preterm delivery was elevated nearly three-fold in women whose work at 34 weeks entailed trunk bending for >1 hour/day. Small head circumference was more common in babies born to women who worked for >40 hours/week. However, no statistically significant associations were found with SGA or small abdominal circumference, and pre-term delivery showed little association with long working hours, lifting, standing, or shift work.
Conclusions
A need exists for more research on trunk bending late in pregnancy, and on the relation of work to reduced head circumference. Our findings on several other occupational exposures common among pregnant workers are reassuring.
doi:10.1136/oem.2008.043935
PMCID: PMC3088899  PMID: 19770355
24.  Epstein-Barr Virus but Not Cytomegalovirus Is Associated with Reduced Vaccine Antibody Responses in Gambian Infants 
PLoS ONE  2010;5(11):e14013.
Background
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.
Methodology/Principal Findings
Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.
Conclusions
The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.
doi:10.1371/journal.pone.0014013
PMCID: PMC2984441  PMID: 21103338
25.  Placental Malaria is associated with reduced early life weight development of affected children independent of low birth weight 
Malaria Journal  2010;9:16.
Background
Infection with Plasmodium falciparum during pregnancy contributes substantially to the disease burden in both mothers and offspring. Placental malaria may lead to intrauterine growth restriction or preterm delivery resulting in low birth weight (LBW), which, in general, is associated with increased infant morbidity and mortality. However, little is known about the possible direct impact of the specific disease processes occurring in PM on longer term outcomes such as subsequent retarded growth development independent of LBW.
Methods
In an existing West-African cohort, 783 healthy infants with a birth weight of at least 2,000 g were followed up during their first year of life. The aim of the study was to investigate if Plasmodium falciparum infection of the placenta, assessed by placental histology, has an impact on several anthropometric parameters, measured at birth and after three, six and 12 months using generalized estimating equations models adjusting for moderate low birth weight.
Results
Independent of LBW, first to third born infants who were exposed to either past, chronic or acute placental malaria during pregnancy had significantly lower weight-for-age (-0.43, 95% CI: -0.80;-0.07), weight-for-length (-0.47, 95% CI: -0.84; -0.10) and BMI-for-age z-scores (-0.57, 95% CI: -0.84; -0.10) compared to infants born to mothers who were not diagnosed with placental malaria (p = 0.019, 0.013, and 0.012, respectively). Interestingly, the longitudinal data on histology-based diagnosis of PM also document a sharp decline of PM prevalence in the Sukuta cohort from 16.5% in 2002 to 5.4% in 2004.
Conclusions
It was demonstrated that PM has a negative impact on the infant's subsequent weight development that is independent of LBW, suggesting that the longer term effects of PM have been underestimated, even in areas where malaria transmission is declining.
doi:10.1186/1475-2875-9-16
PMCID: PMC2841609  PMID: 20074331

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