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1.  Association of diarrhoea in childhood with blood pressure and coronary heart disease in older age: analyses of two UK cohort studies 
Background
There is a suggestion that acute dehydration in childhood may lead to elevated blood pressure. We examined if episodes of diarrhoea in childhood, a recognized proxy for acute dehydration, were related to measured blood pressure and coronary heart disease in older adults.
Methods
Data were pooled from two prospective UK cohort studies (participants born 1920–39) in which episodes of diarrhoea were ascertained from health visitor records from birth until 5 years of age. Blood pressure and coronary heart disease were assessed during medical examination in men and women over 64 years of age. In total, 5203 men and women had data on diarrhoea in early life, adult blood pressure and a range of covariates; 4181 of these also had data on coronary heart disease status.
Results
The prevalence of diarrhoea in infancy (3.3%) and between 1 and 5 years (1.1%) was low. There was no relation of diarrhoea from either period (age- and sex-adjusted results for diarrhoea in infancy presented here) with measured blood pressure [coefficient for systolic; 95% CI (confidence interval): 0.44; −2.88–3.76] or coronary heart disease (Odds ratio, OR; 95% CI: 0.91; 0.54–1.54) in adulthood. There was a similar lack of association when hypertension was the outcome of interest. These observations were unchanged after adjustment for a range of covariates.
Conclusions
In the largest study to date to examine the relation, there was no evidence that diarrhoea in early life had an influence on measured blood pressure, hypertension or coronary heart disease in older adults.
doi:10.1093/ije/dym178
PMCID: PMC3660699  PMID: 18056131
blood pressure; children; diarrhoea; hypertension; coronary heart disease
2.  Maternal vitamin D status during pregnancy and child outcomes 
Objective:
To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child.
Design:
Prospective study.
Setting:
Princess Anne Maternity Hospital, Southampton, UK.
Subjects:
596 pregnant women were recruited. 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years.
Methods:
Maternal (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a DXA scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed.
Results:
There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers' concentration of 25(OH)-vitamin D in pregnancy was >75 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, p=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, p=0.038) compared to children whose mothers' concentration was <30 nmol/l.
Conclusion:
Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies.
doi:10.1038/sj.ejcn.1602680
PMCID: PMC2629513  PMID: 17311057
pregnancy; diet; vitamin D; infant; child
3.  Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire Cohort Study 
OBJECTIVES
To examine relationships between diet and grip strength in older men and women, and to determine whether these relationships are modified by prenatal growth.
DESIGN
Cross-sectional and retrospective cohort study
SETTING
Hertfordshire, UK
PARTICIPANTS
Two thousand, nine hundred and eighty three men and women aged 59 to 73 years who were born and still live in Hertfordshire, UK
MEASUREMENTS
Weight at birth recorded in Health Visitor ledgers. Current food and nutrient intake assessed using an administered food frequency questionnaire, grip strength was measured with a hand-held dynamometer.
RESULTS
Grip strength was positively associated with height and weight at birth, and inversely related to age (all P<0.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43kg (95% CI 0.13 to 0.74) in men (P=0.005), and 0.48kg (95% CI 0.24 to 0.72) in women (P<0.001), was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength.
CONCLUSION
These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the anti-inflammatory actions of n-3 fatty acids may play a role in the prevention of sarcopenia.
doi:10.1111/j.1532-5415.2007.01478.x
PMCID: PMC2493054  PMID: 18005355
diet; sarcopenia; grip strength
4.  INTERACTION BETWEEN BIRTH-WEIGHT AND POLYMORPHISM IN THE CALCIUM SENSING RECEPTOR GENE IN DETERMINATION OF ADULT BONE MASS: THE HERTFORDSHIRE COHORT STUDY 
The Journal of rheumatology  2007;34(4):769-775.
Objective
We sought evidence of interaction between single nucleotide polymorphisms (SNPs) in the Calcium Sensing Receptor (CASR) gene and early life in determination of bone mineral density (BMD) among individuals from the Hertfordshire Cohort Study.
Methods
Four hundred and ninety eight men and 468 women aged 59-71 years were recruited. A lifestyle questionnaire was administered and BMD at lumbar spine and femoral neck was measured. DNA was obtained from whole blood samples using standard extraction techniques. Five SNPs of the CASR gene termed CASRV1 (rs1801725, G>T, S986A), CASRV2 (rs7614486, T>G, untranslated), CASRV3 (rs4300957, untranslated), CASRV4 (rs3804592 G>A, intron) and CASRV5 (rs1393189, T>C, intron) were analysed.
Results
Among women the 11 genotype of the CASRV3 SNP was associated with higher lumbar spine BMD within the lowest birth-weight tertile, while the opposite pattern was observed among individuals in the highest birth-weight tertile (test for interaction on 1df, p=0.005, adjusted for age, BMI, physical activity, dietary calcium intake, cigarette and alcohol consumption, social class, menopausal status and HRT use). Similar relationships were seen at the total femur (p=0.042, fully adjusted) with birth-weight and at the total femur according to weight at one year tertile among women (p<0.001, fully adjusted). One haplotype was associated with lumbar spine BMD in women (p=0.008, fully adjusted); these findings were replicated in a second cohort.
Conclusion
We have found evidence of an interaction between a SNP of the CASR gene and birth weight in determination of bone mass in a UK female population.
PMCID: PMC2136207  PMID: 17309124
bone; bone density; cohort studies; genetic studies
5.  Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study 
Background
Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data are available relating bone density, lipid profile and anthropometric measures. We addressed these relationships in a large well-characterised cohort of men and women (The Hertfordshire Cohort Study, UK).
Methods
Four hundred and sixty five men and 448 women from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur.
Results
BMD at the lumbar spine (males r=0.15, p=0.001; females r=0.14 p=0.003) and total femoral region (males r=0.18, p=0.0001; females r==0.16, p=0.0008) was related to serum triglyceride level, even after adjustment for waist hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r=−0.15, p=0.001) and total femoral BMD (males r=−0.15, p=0.002; females r=−0.23, p<0.0001); these relationships were also attenuated by adjustment for body fat percentage but not waist hip ratio. No relationships were seen between total or LDL cholesterol with BMD.
Conclusions
We have demonstrated relationships between lipid profile and BMD that are robust to adjustment for one measure of central obesity (waist-hip ratio) but not total body fat.
doi:10.1093/qjmed/hcm023
PMCID: PMC2080690  PMID: 17449479
lipid; bone; cohort; anthropometry; obesity
6.  Growth in early life predicts bone strength in late adulthood 
Bone  2007;41(3):400-405.
Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength.
We studied 313 men and 318 women born in Hertfordshire between 1931-39 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500).
Birthweight and conditional weight at one year were strongly related to radial and tibial length in both sexes (p<0.001), and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use and menopausal status in women. Among men, BMI was strongly positively associated with radial (r=0.46, p=0.001) and tibial (r=0.24, p=0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p=0.0002; tibia: p=0.08) and trabecular BMD (radius: p=0.08; tibia: p=0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p=0.0002; tibia: p=0.001) and trabecular (radius: p=0.008; tibia: p=0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p=0.006; fracture load x: p=0.005; fracture load y: p=0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p=0.0001), cortical (p<0.005) and trabecular (p=0.0002) BMD, poorer forearm bone strength [polar SSI (p=0.006), fracture load X & Y (p=0.02)], and lower tibial total (p<0.001), cortical (p=0.008) and trabecular (p=0.0001) BMD.
We have shown that growth in early life is associated with bone size and strength in a UK population aged 65-73 years. Lifestyle factors were associated with volumetric bone density in this population.
doi:10.1016/j.bone.2007.05.007
PMCID: PMC2080691  PMID: 17599849
Bone; Strength; Density; Programming; Epidemiology
7.  Maternal size in pregnancy and body composition in children 
Context:
Evidence suggests that babies' fat mass at birth is greater if their mothers were themselves fatter during pregnancy, but it is unclear whether this association persists into childhood.
Objective:
To examine the relation between maternal size in pregnancy, early growth and body composition in children.
Design:
Prospective cohort study
Setting:
Southampton, UK.
Participants:
216 nine-year-old children whose mothers had participated in a study of nutrition during pregnancy.
Main outcome measures:
Fat mass and lean mass measured by dual-energy X-ray absorptiometry, adjusted for height (“fat mass index” and “lean mass index”).
Results:
Fat mass index at age nine years was greater in children whose mothers had a larger mid-upper arm circumference in late pregnancy or a higher pre-pregnant body mass index. For one standard deviation (SD) increase in maternal mid-upper arm circumference in late pregnancy, fat mass index rose by 0.26 (95% CI 0.06-0.46) SD in boys and by 0.44 (95% CI 0.31-0.57) SD in girls. For one SD increase in maternal pre-pregnant BMI, fat mass index rose by 0.26 (95% CI 0.04-0.48) SD in boys and by 0.42 (95% CI 0.29-0.56) SD in girls.
Conclusions:
Mothers with a higher pre-pregnant body mass index or a larger mid-upper arm circumference during pregnancy tend to have children with greater adiposity at age nine. The extent to which this is attributable to genetic factors, the influence of maternal lifestyle on that of her child, or maternal adiposity acting specifically during pregnancy on the child's fat mass cannot be determined in this study.
doi:10.1210/jc.2007-0088
PMCID: PMC2066182  PMID: 17684051
child; body composition; pregnancy; birth weight; weight gain; infancy
8.  Growth in early life predicts bone strength in late adulthood: The Hertfordshire Cohort Study 
Bone  2007;41(3):400-405.
Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength.
We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500).
Birthweight and conditional weight at 1 year were strongly related to radial and tibial length in both sexes (p < 0.001) and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use, and menopausal status in women. Among men, BMI was strongly positively associated with radial (r = 0.46, p = 0.001) and tibial (r = 0.24, p = 0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p = 0.0002; tibia: p = 0.08) and trabecular BMD (radius: p = 0.08; tibia: p = 0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p = 0.0002; tibia: p = 0.001) and trabecular (radius: p = 0.008; tibia: p = 0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p = 0.006; fracture load X: p = 0.005; fracture load Y: p = 0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p = 0.0001), cortical (p < 0.005) and trabecular (p = 0.0002) BMD, poorer forearm bone strength [polar SSI (p = 0.006), fracture load X and Y (p = 0.02)], and lower tibial total (p < 0.001), cortical (p = 0.008), and trabecular (p = 0.0001) BMD.
We have shown that growth in early life is associated with bone size and strength in a UK population aged 65–73 years. Lifestyle factors were associated with volumetric bone density in this population.
doi:10.1016/j.bone.2007.05.007
PMCID: PMC2080691  PMID: 17599849
Bone; Strength; Density; Programming; Epidemiology

Results 1-8 (8)