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Biomedical subjects

C Osmond

Publications and source records attributed to C Osmond.

At least 91 records · Page 5Linked to original sources

Birth weight and body fat distribution in adolescent girls.

OBJECTIVE: To examine the association between birth weight and body fat distribution in a group of adolescent girls. DESIGN: A total of 216 white girls who were born in Southampton had their heights, weights, waist and hip circumferences, and skinfold thicknesses measured when they were aged between 14 and 16 years. RESULTS: The girls who were smallest at birth, but who were fattest at time of measurement were the most centrally obese. In girls whose body mass index was above the median (21 kg/m2), the subscapular to triceps skinfold ratio rose by 9% for every kilogram decrease in birth weight. Among overweight girls, with a body mass index over 25, the ratio rose by 27% for every kilogram decrease in birth weight. CONCLUSION: In adolescent girls, the tendency to store fat on the trunk rather than the limbs, seems to be programmed by growth in fetal life, and is most evident in those who are overweight.

Adipose Tissue↗

The effects of genotype and infant weight on adult plasma levels of fibrinogen, factor VII, and LDL cholesterol are additive.

High circulating levels of cholesterol, particularly low density lipoprotein (LDL) cholesterol and the clotting factors fibrinogen and factor VII, are associated with increased risk of myocardial infarction. Variations in the plasma levels of these factors are determined in part by polymorphisms in the genes concerned and also by weight at 1 year (infant weight). We have looked at the possibility of interactions between these genetic factors and infant weight in a sample of 290 men and 192 women from Hertfordshire using the beta-fibrinogen G/A-455, factor VII R353Q, and ApoE polymorphisms. The rare allele frequencies of the three polymorphisms were 0.19 for beta-fibrinogen, 0.10 for factor VII, and 0.07 and 0.13 for the 2 and 4 alleles of ApoE, and these frequencies were not different in subjects of different infant weight. In this sample, the polymorphisms showed the expected effects on plasma levels of fibrinogen, factor VII, and LDL cholesterol. The A-455 allele was associated with higher fibrinogen levels but the effect was only statistically significant in women (p = 0.003). The R353 allele was associated with higher factor VII activity in both men and women (p < 0.0001 for both). The ApoE2 allele was associated with lower levels of LDL cholesterol (p = 0.03 in men, p = 0.006 in women), while the ApoE4 allele was associated with higher levels (p < 0.001 in men, not significant in women). In this sample of men and women the effect of low infant weight was only associated with significant effects on fibrinogen and LDL cholesterol in the group of men (p = 0.005 and p = 0.008 respectively). Compared with the E3E3 subjects, the LDL lowering effect of the E2 allele and the raising effect of the E4 allele was greater in those with low infant weight compared with those with high infant weight (low v high infant weight for E2: 12.7% v 9.4%; for E4 12.7% v 8.5%). Although in this sample the interactive effect did not reach statistical significance, the additive effect of ApoE genotype and low infant weight on determining plasma LDL cholesterol levels, if confirmed, may be of relevance in determining a person's future risk of atherosclerosis.

Adult↗

Relation of fetal growth to adult lung function in south India.

BACKGROUND: Follow up studies in Britain have shown that low rates of fetal growth are followed by reduced lung function in adult life, independent of smoking and social class. It is suggested that fetal adaptations to undernutrition in utero result in permanent changes in lung structure, which in turn lead to chronic airflow obstruction. India has high rates of intrauterine growth retardation, but no study has examined the association between fetal growth and adult lung function in Indian people. We have related size at birth to lung function in an urban Indian population aged 38-59 years. METHODS: Two hundred and eighty six men and women born in one hospital in Mysore City, South India, during 1934-1953 were traced by a house-to-house survey of the city. Their mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured using a turbine spirometer. These measurements were linked to their size at birth, recorded at the time. RESULTS: In both men and women mean FEV1 fell with decreasing birthweight. Adjusted for age and height, it fell by 0.09 litres with each pound (454 g) decrease in birthweight in men (95% confidence interval (CI) 0.01 to 0.16) and by 0.06 (95% CI -0.01 to 0.13) in women. Likewise, mean FVC fell by 0.11 litres (95% CI 0.02 to 0.19) with each pound decrease in birthweight in men, and by 0.08 litres (95% CI 0.002 to 0.16) in women. FEV1 and FVC were lower in men who smoked, but the associations with size at birth were independent of smoking. Small head circumference at birth was associated with a low FEV1/FVC ratio in men which may reflect restriction in airway growth in early gestation. CONCLUSION: This is further evidence that adult lung function is "programmed" in fetal life. Smoking may be particularly detrimental to the lung function of populations already disadvantaged by poor rates of fetal growth.

Adult↗

Peak and trough growth hormone concentrations have different associations with the insulin-like growth factor axis, body composition, and metabolic parameters.

GH is secreted in a pulsatile fashion, promoting growth and anabolism. The components of the pulsatile signal involved in these diverse effects are unclear. We constructed (20-min sampling interval) and analyzed 24-h serum GH profiles in 45 adult male volunteers, 59.4-69.9 yr old, body mass index (BMI) 21.9-36.5 Kg/m2, using Fourier transformation and a concentration distribution analysis that determines the concentration at or below which the serum GH concentrations in the 24-h profile spend a percentage of the total time. The observed concentrations (OC) below which 95% and 5% of the values in the time series lie [lsb]OC95 (peaks) and OC5 (troughs)] and mean 24-h serum GH concentrations were related to measures of the insulin-like growth factor (IGF) family, parameters of body composition, fasting insulin and cholesterol measures, and GH-binding protein concentrations. Mean 24-h serum GH concentrations ranged between 0.19 and 2.15 mU/L (1 microgram/L = 2.6 mU/L). Pulse periodicity was between 180 and 200 min. There was a positive relationship between peak GH levels and serum IGF-1 and IGFBP-3 levels (r = 0.39; P = 0.009 and r = 0.32; P = 0.03, respectively). GH trough levels were unrelated to these measures of the IGF family. In contrast, GH troughs were related inversely to BMI (r = -0.31; P = 0.04) and waist-hip ratio (r = -0.4; P = 0.006). Peak GH levels were not related to these measures. Factors known to influence these measures, fasting insulin concentration, or cortisol secretion did not alter the trough GH relationship in multiple regression analysis. All GH parameters were related inversely to fasting insulin concentration. Although GH parameters were related inversely to cholesterol and low-density lipoprotein-cholesterol, this effect disappeared when age and fasting insulin levels were introduced into the regression. GH-binding protein levels related most strongly to BMI (r = 0.60; P < 0.001), with no effect of any GH parameter observed in multiple regression analysis. These results suggest that the peak values of a GH concentration profile may influence the IGF axis, whereas trough values may influence body composition and metabolic parameters of GH action.

Aged↗

Mothers' pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK.

BACKGROUND: People who have a low birthweight show increased death rates from coronary heart disease and a higher prevalence for its risk factors. These findings have led to the hypothesis that the disease is programmed in fetal life. The aim of this study was to explore whether risk of stroke in adult life was linked to impaired fetal growth. METHODS: We ascertained deaths from stroke and coronary heart disease in 13 249 men in two cohorts from Hertfordshire and Sheffield, UK. We related death rates from these disease to body size at birth, weight at 1 year, and to measurements of the mothers' pelvises. FINDINGS: Death rates from both stroke and coronary heart disease tended to be highest in men whose birthweight had been low. Standardised mortality ratios (SMRs) for stroke fell by 12% (95% Cl 1-22) and for coronary heart disease by 10% (6-14) between each of five groupings of increasing birthweight (< or = 5.5 lb, 5.6-6.5 lb, 6.6-7.5 lb, 7.6-8.5 lb, and > 8.5 lb). Mortality from stroke was most strongly associated with low birthweight in relation to head size, and low placental weight in relation to head size. These patterns of growth occurred in offspring of mothers with flat bony pelvises. The SMR in sons of these women was 184 (67-396) compared with 104 (78-138) in the remainder of the cohort. In contrast, mortality from coronary heart disease was associated with small head circumference, thinness or shortness at birth and an altered ratio of placental weight to birthweight. INTERPRETATION: Stroke may originate in poor nutrition during the mother's childhood, which deforms the bony pelvis and subsequently impairs her ability to sustain the growth of the placenta and fetus in late pregnancy. Coronary heart disease, on the other hand, seems to originate in adaptations made by the fetus to inadequate delivery of nutrients when it occurs for reasons other than failure of placental growth.

Adult↗

Fetal growth and coronary heart disease in south India.

BACKGROUND: Coronary heart disease is predicted to become the commonest cause of death in india within 15 years People from India living overseas already have high rates of the disease that are not explained by known coronary risk factors. Small size at birth is a newly described risk factor for coronary heart disease, but associations between size at birth and the disease have not been examined in India. METHODS: We studied 517 men and women who were born between 1934 and 1954 in a mission hospital in Mysore, South India, and who still lived near to the hospital. We related the prevalence of coronary heart disease, defined by standard criteria, to their birth size. FINDINGS: 25 (9%) men and 27 (11%) women had coronary heart disease. Low birthweight, short birth length, and small head circumference at birth were associated with a raised prevalence of the disease. Prevalence fell from 11% in people whose birthweights were 5.5 lb (2.5 kg) or less to 3% in those whose birthweights were more than 7 lb (3.1 kg), p for trend = 0.09. The trends were stronger and statistically significant among people aged 45 years and over (p = 0.03 for birthweight, 0.04 for length, and 0.02 for head circumference). High rates of disease were also found in those whose mothers had a low body weight during pregnancy. The highest prevalence of the disease (20%) was in people who weighted 5.5 lb (2.5 kg) or less at birth and whose mothers weighted less than 100 lb (45 kg) in pregnancy. These associations were largely independent of known coronary risk factors. INTERPRETATION: In India, as in the UK, coronary heart disease is associated with small size at birth, suggesting that its pathogenesis is influenced by events in utero. The association with low maternal bodyweight is further evidence that the disease originates through fetal undernutrition. Prevention of the rising epidemic of the disease in India may require improvements in the nutrition and health of young women.

Birth Weight↗

Relation of cord plasma concentrations of proinsulin, 32-33 split proinsulin, insulin and C-peptide to placental weight and the baby's size and proportions at birth.

Small and disproportionate size at birth are associated with type 2 diabetes and coronary heart disease in adult life. Insulin has an important role in controlling growth in utero and we hypothesised that reduced fetal insulin secretion could be one factor underlying these associations. We therefore measured cord plasma concentrations of proinsulin, 32-33 split proinsulin, insulin and C-peptide in 391 babies born at term and related them to the weight of the placenta and to the babies' size and proportions at birth. Babies with a small placental weight and a lower birth weight had lower cord plasma concentrations of split proinsulin and insulin. Babies who were disproportionate, either having a high ratio of head to abdominal circumference or being thin, had lower concentrations of split proinsulin, split proinsulin and insulin. The relations with split proinsulin were especially strong, the geometric mean concentration (pmol/l) falling from 14.2 in babies with a head to abdominal circumference ratio of 101.6% or less to 7.2 in those with a ratio above 107.3% (P < 0.0001), and from 17.4 in babies with a ponderal index above 28.5 kg/m3 to 7.4 in those with a ponderal index of 25.5 kg/m3 or less (P < 0.0001). These findings support the hypothesis that reduced fetal insulin secretion may be one factor underlying the associations between reduced growth in utero and type 2 diabetes and coronary heart disease in adult life.

Anthropometry↗

Maternal nutrition in early and late pregnancy in relation to placental and fetal growth.

OBJECTIVE: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. DESIGN: Prospective observational study. SETTING: Princess Anne Maternity Hospital, Southampton. SUBJECTS: 538 mothers who delivered at term. MAIN OUTCOME MEASURES: Placental and birth weights adjusted for the infant's sex and duration of gestation. RESULTS: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g(95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother's height and body mass index and of strong relations between the mother's birth weight and the placental and birth weights of her offspring. CONCLUSION: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring's risk of cardiovascular disease.

Adolescent↗

Fetal growth and cardiovascular risk factors in Jamaican schoolchildren.

OBJECTIVE: To determine relation between schoolchildren's blood pressure, glycated haemoglobin level, and cholesterol concentration and their anthropometry, socioeconomic status, and birth measurements. DESIGN: Retrospective cohort study. SETTING: 27 schools closest to University Hospital of the West Indies, Kingston, Jamaica. SUBJECTS: 2337 children aged 6-16 years who were born at university hospital were recruited, and their birth records were recovered: 1610 had suitable records, 659 had records including birth length, and 610 of these were prepubertal. MAIN OUTCOME MEASURES: Blood pressure, glycated haemoglobin level, serum cholesterol concentration, anthropometry at birth, current anthropometry, and socioeconomic status. RESULTS: Multiple regression analysis showed that children's systolic blood pressure was inversely related to their birth weight (P < 0.0001) and directly related to their current weight. Glycated haemoglobin level was higher in children with thicker triceps skinfolds (P < 0.001) and who had been shorter at birth (P = 0.003). Serum cholesterol concentration was inversely related to current height (P = 0.001) and to length at birth (P = 0.09) and was directly related to triceps skinfold thickness and higher socioeconomic status (P < 0.001). CONCLUSIONS: Blood pressure in childhood was inversely related to birth weight and directly to current weight. Glycaemic control and serum cholesterol were related to short length at birth, height deficit in childhood, and childhood obesity.

Adolescent↗

Nutrition in pregnancy and the concentrations of proinsulin, 32-33 split proinsulin, insulin, and C-peptide in cord plasma.

As insulin is a major fetal growth hormone, we have related the mother's nutrient intakes (assessed by a food frequency questionnaire) and other influences associated with fetal growth to the baby's concentrations of insulin and its propeptides in umbilical cord plasma. Among 391 term babies studied, those whose mothers had high energy intakes in early pregnancy and low protein intakes in late pregnancy had lower cord plasma concentrations of 32-33 split proinsulin, insulin, and C-peptide. Concentrations of split proinsulin fell by 0.66 (95% Cl 0.29 to 1.03, p = 0.0006) log pmol l-1 for each log kcal increase in the mother's energy intake in early pregnancy and by 0.005 (95% Cl 0.000 to 0.010, p = 0.04) log pmol l-1 for each g decrease in protein intake in late pregnancy. Insulin and propeptide concentrations were however unrelated to the mother's height and body mass index, and to smoking during pregnancy. These observations parallel recent studies relating the same pattern of dietary intakes to impaired fetal and placental growth. Although dietary intakes assessed by food frequency questionnaires allow only cautious conclusions, our findings could have implications for the offspring's risk of Type 2 diabetes mellitus in adult life.

Adolescent↗

Evaluation of a food frequency questionnaire used to assess nutrient intakes in pregnant women.

OBJECTIVE: To compare nutrient intakes assessed by food frequency questionnaire (FFQ) with those determined from food diaries. DESIGN: A 100-item FFQ was administered to women at 15 weeks of pregnancy. Food diaries were kept for a 4-day period at 16 weeks of pregnancy. SETTING: Community-based study of a general population sample of pregnant women booked for delivery at the Princess Anne Maternity Hospital, Southampton, UK. SUBJECTS: 603 women were recruited. Complete dietary data were provided by 569 women. RESULTS: Nutrient intakes determined by FFQ were greater than those from food diaries. Spearman rank correlation coefficients for macronutrients ranged from 0.27 (protein and starch) to 0.37 (fat). Stronger correlations for energy, fat and carbohydrate were seen in women who did not experience nausea, suggesting that the level of agreement observed between the FFQ and food diary in the whole group may be an underestimate of the true agreement. The percentage of individuals classified to the same quarter of the distribution of nutrient intake by the FFQ and diaries ranged from 30% (starch) to 41% (calcium), with between 4% (riboflavin) and 8% (energy, protein and vitamin E) classified to the opposite quarters. Using serum vitamin C as an independent biomarker of intake, the percentage of individuals classified to the correct quarter of intake was similar for the FFQ and diary (34% and 37%), with 8% (FFQ) and 6% (diary) misclassified to the opposite quarter. CONCLUSION: The FFQ appears to give meaningful estimates of nutrient intake in early pregnancy which can be used to rank individuals within the distribution.

Adult↗

Weight gain in infancy and cancer of the ovary.

The geographic association between ovarian cancer and tall stature suggests a link with rapid growth in early childhood. Among 5585 women born in Hertfordshire, UK, 41 who died from ovarian cancer had had a high rate of weight gain in infancy. Whereas their mean birthweight was the same as that of the other women, their mean weight at 1 year was higher (22.3 pounds [10.1 kg] vs 21.4 pounds [9.7 kg], p = 0.01). These observations are consistent with the hypothesis that ovarian cancer is linked to altered patterns of gonadotropin release established in utero when the fetal hypothalamus is imprinted.

Adult↗

Fetal and infant growth and cardiovascular risk factors in women.

OBJECTIVE: To examine whether cardiovascular risk factors in women are related to fetal and infant growth. DESIGN: Follow up study of women born 1923-30 whose birth weights and weights at one year were recorded. SETTING: Hertfordshire. SUBJECTS: 297 women born and still living in East Hertfordshire. MAIN OUTCOME MEASURES: Plasma glucose and insulin concentrations during a standard oral glucose tolerance test; fasting plasma proinsulin and 32-33 split proinsulin concentrations; blood pressure; fasting serum total, low density lipoprotein and high density lipoprotein cholesterol, triglyceride, and apolipoprotein A I and B concentrations; and plasma fibrinogen and factor VII concentrations. RESULTS: Fasting plasma concentrations of glucose, insulin, and 32-33 split proinsulin fell with increasing birth weight (P = 0.04, P = 0.002, and P = 0.0002 respectively, when current body mass index was allowed for). Glucose and insulin concentrations 120 minutes after an oral glucose load showed similar trends (P = 0.03 and P = 0.02). Systolic blood pressure, waist:hip ratio, and serum triglyceride concentrations also fell with increasing birth weight (P = 0.08, P = 0.07, and P = 0.07 respectively), while serum high density lipoprotein cholesterol concentrations rose (P = 0.04). At each birth weight women who currently had a higher body mass index had higher levels of risk factors. CONCLUSION: In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women.

Apolipoproteins↗