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Biomedical subjects

D J Barker

Publications and source records attributed to D J Barker.

At least 91 records · Page 5Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Cell mediated immunity after measles in Guinea-Bissau: historical cohort study.

OBJECTIVE: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles. DESIGN: Historical cohort study. SETTING: Bissau, Guinea-Bissau. SUBJECTS: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles. MAIN OUTCOME MEASURES: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens. RESULTS: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the case of measles. CONCLUSION: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.

Adolescent↗
PubMed1996

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↗
PubMed1996

Measles and atopy in Guinea-Bissau.

BACKGROUND: Epidemiological studies have led to speculation that infections in early childhood may prevent allergic sensitisation but evidence to support this hypothesis is lacking. We investigated whether measles infection protects against the development of atopy in children of Guinea-Bissau, West Africa. METHODS: We conducted a historical cohort study in Bandim, a semi-rural district of Bissau, the capital of Guinea-Bissau. 395 young adults, first surveyed in 1978-80 aged 0-6 years, were followed up in 1994. Our analyses were restricted to 262 individuals still living in Bandim for whom a measles history, documented in childhood, was judged to be reliable. We defined atopy as skin-prick test positivity (> or = 3 mm weal) to one or more of seven allergens. FINDINGS: 17 (12.8 percent) of 133 participants who had had measles infection were atopic compared with 33 (25.6 percent) of 129 of those who had been vaccinated and not had measles (odds ratio, adjusted for potential confounding variables 0.36 [95 percent CI 0.17-0.78], p=O.O1). Participants who had been breastfed for more than a year were less likely to have a positive skin test to housedust mite. After adjustment for breastfeeding and other variables, measles infection was associated with a large reduction in the risk of skin-prick test positivity to housedust mite (odds ratio for Dermatophagoides pteronyssinus 0.20 [0.05-0.81], p=0.02; D farinae 0.20 [0.06-0.71], p=0.01). INTERPRETATION: Measles infection may prevent the development of atopy in African children.

Allergens↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Size at birth and adrenocortical function in childhood.

OBJECTIVE: The mechanisms underlying the association between reduced size at birth and cardiovascular disease and non-insulin-dependent diabetes mellitus in adult life are not known. One possibility is that the intra-uterine environment has permanent effects on the function or activity of the hypothalamo-pituitary-adrenal axis. We tested this by relating size at birth to the urinary excretion of adrenal androgen and glucocorticoid metabolites in a population sample of 9-year-old children. SUBJECTS AND METHODS: One hundred and ninety children (89 boys and 101 girls) of known present height, weight and size at birth collected a 24-hour urine sample. The urinary breakdown products of dehydroepiandrosterone sulphate and of cortisol and cortisone were measured by gas chromatography and their respective breakdown products summed ('adrenal androgen metabolites' and 'glucocorticoid metabolites'). Excretion was expressed in microgram/day. RESULTS: Urinary adrenal androgen metabolite excretion was higher in children who had been light at birth. A 1-kg decrease in birthweight was associated with a 40% (95% CI 9-79%) increase in metabolite excretion. Excretion was positively associated with current weight and age, but the relation with birth weight was independent of weight, age or sex. Urinary glucocorticoid metabolite excretion was positively associated with current weight, but not independently with age. The urinary excretion of total glucocorticoid metabolites was higher in children who had been light at birth, but the relation was best described as U-shaped, with the highest average urinary glucocorticoid metabolite excretion being found in children who had been either light or heavy at birth. The U-shaped (quadratic) relation persisted after adjustment for sex and current weight (P for quadratic term 0.006). CONCLUSION: These findings suggests that the intra-uterine environment, as measured by fetal size at birth, has long-lasting effects on the function of the hypothalamo-pituitary-adrenal axis.

Adrenal Cortex↗
PubMed1996

Diet in pregnancy and the offspring's blood pressure 40 years later.

OBJECTIVE: To determine how diet of the mother in pregnancy influences the blood pressure of the offspring in adult life. DESIGN: A follow up study of men and women born during 1948-1954 whose mothers had taken part in a survey of diet in late pregnancy. SETTING: Aberdeen, Scotland. POPULATION: Two hundred and fifty-three men and women born in Aberdeen Maternity Hospital. MAIN OUTCOME MEASURE: Systolic and diastolic blood pressure. RESULTS: The relations between the diet of mothers and their offsprings' blood pressure were complex. When the mothers' intake of animal protein was less than 50 g daily, a higher carbohydrate intake was associated with a higher blood pressure in the offspring (a 100 g increase in carbohydrate being associated with a 3 mmHg increase in systolic pressure (P = 0.02)). At daily animal protein intakes above 50 g, lower carbohydrate intake was associated with higher blood pressure (a 100 g decrease in carbohydrate being associated with an 11 mmHg rise in systolic blood pressure (P = 0.004)). These increases in blood pressure were associated with decreased placental size. CONCLUSION: Mothers' intakes of animal protein and carbohydrate in late pregnancy may influence their offsprings' adult blood pressure. This may be mediated through effects on placental growth.

Adult↗
PubMed1996

The fetal origins of hypertension.

UNLABELLED: RESULTS OF UNDERNUTRITION BEFORE BIRTH: Animal studies have shown that undernutrition before birth leads to persisting changes in blood pressure and in a range of other physiological, metabolic and structural parameters. Studies in humans have shown that men and women whose birthweights were at the lower end of the normal range, who were thin or short at birth, or small in relation to placental size, have increased rates of hypertension and coronary heart disease. CONCLUSIONS: We are beginning to understand something of the mechanisms underlying these associations. Elevation of blood pressure may be a fetal response to undernutrition and may initiate hypertension in adult life.

Animals↗
PubMed1995

The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease.

Recent findings suggest that many human fetuses have to adapt to a limited supply of nutrients and in doing so they permanently change their physiology and metabolism. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders: stroke, diabetes and hypertension.

Aged↗
PubMed1995

Fetal origins of coronary heart disease.

The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.

Adolescent↗
PubMed1995

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↗