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Biomedical subjects

D J Barker

Publications and source records attributed to D J Barker.

At least 109 records · Page 6Linked to original sources

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↗

Weight in infancy and prevalence of coronary heart disease in adult life.

OBJECTIVE: To determine whether low birth weight and low weight at 1 year are followed by an increased prevalence of coronary heart disease in adult life. DESIGN: A follow up study of men born during 1920-30 whose birth weights and weights at 1 year were recorded. SETTING: Hertfordshire, England. SUBJECTS: 290 men born and still living in East Hertfordshire. MAIN OUTCOME MEASURE: The prevalence of coronary heart disease, defined by the Rose/WHO chest pain questionnaire, standard electrocardiographic criteria, or history of coronary artery angioplasty or graft surgery. RESULTS: 42 (14%) men had coronary heart disease. Their mean birth weight, 7.9 lb (3600 g), was the same as that of the other men. Their mean weight at 1 year, 21.8 lb (9.9 kg), was 1 lb (454 g) lower (95% confidence interval 0.1 to 1.8, P = 0.02). Percentages of men with coronary heart disease fell from 27% in those who weighed 18 lb (8.2 kg) or less at 1 year to 9% in those who weighed more than 26 lb (11.8 kg) (P value for trend = 0.03). This trend occurred in both smokers and non-smokers and within each social class. CONCLUSION: These findings add to the evidence that coronary heart disease is "programmed" during early growth.

Birth Weight↗

Maternal nutrition in relation to fetal and placental growth.

Babies who are small or disproportionate at birth, or who have altered placental growth are now known to be at an increased risk of developing coronary heart disease, hypertension and diabetes during adult life. This has led to the suggestion that these diseases are 'programmed' by an inadequate supply of nutrients to the developing fetus. The phenomenon of 'programming', whereby undernutrition in early life permanently changes body structure and function, is well documented in animals. As yet, relatively little is known about the maternal influences that alter fetal and placental growth, and underlie the programming of adult cardiovascular disease during fetal development. There are, however, interesting indications that maternal nutrition may be important.

Adult↗

Conference report: fetal origins of adult disease--report of the First International Study Group, Sydney, 29-30 October 1994.

The epidemiological observations that prenatal and perinatal events lead to adult disease are now well supported by animal data. The events in the periconceptual period, in early and late pregnancy and in infancy can effect programming of cardiovascular, endocrine and metabolic regulatory systems. However, the mechanisms underlying these pathological changes remain to be elucidated. Until this is addressed in experimental animals, clinical trials in human pregnancy are premature.

Embryo Implantation↗

Plasma concentrations of fibrinogen and factor VII in adult life and their relation to intra-uterine growth.

To examine the relation between fetal development and plasma concentrations of fibrinogen and factor VII in adult life we followed up 202 men and women, now aged around 50 years, who had been measured in detail at birth. Plasma concentrations of fibrinogen were related to weight and abdominal circumference at birth. In men, after adjustment for cigarette smoking and current obesity, plasma concentrations of fibrinogen fell by 0.12 g/l (95% CI 0.05-0.19) for each pound increase in birthweight and by 0.10 g/l (95% CI 0.03-0.17) for each inch increase in abdominal circumference. In contrast, analysis of the data for women showed no statistically significant relation between plasma fibrinogen concentration and weight or abdominal circumference at birth. No relation was seen between concentrations of factor VII and measurements made at birth in either sex. These findings suggest that, in men, reduced growth of the liver in fetal life has a long-term influence on fibrinogen metabolism.

Abdomen↗

Fetal growth and glucose and insulin metabolism in four-year-old Indian children.

Studies in Britain have shown that adults who had a low birthweight have high plasma glucose concentrations 30 and 120 min after an oral glucose load, and an increased risk of Type 2 diabetes and impaired glucose tolerance. Both Type 2 diabetes and low birthweight are common in India. To determine whether low birthweight is associated with reduced glucose tolerance in Indian children, glucose tolerance tests were carried out on 379 4-year-old children, whose birthweights were recorded, in Pune, India. Among 201 children who had been looked after on the routine postnatal wards at birth, those with lower birthweights had higher plasma glucose and insulin concentrations 30 min after an oral glucose load, independently of their current size (p = 0.01 and 0.04, respectively). Mean glucose and insulin concentrations were 8.1 mmol l-1 and 321 pmol l-1 in children whose birthweight had been 2.4 kg or less, compared with 7.5 mmol l-1 and 289 pmol l-1 in those who weighted more than 3.0 kg. Among 178 children who had been looked after in the Special Care Baby Unit, those with lower birthweights also had higher plasma insulin concentrations at 30 min but there were no trends with plasma glucose. Our findings suggest that Indian children with reduced intra-uterine growth have reduced glucose homeostasis after a glucose challenge. This is consistent with the hypothesis that Type 2 diabetes mellitus in India may be programmed in fetal life.

Adult↗

Thinness at birth and glucose tolerance in seven-year-old children.

Adults who had low birthweight and were thin at birth have an increased risk of Type 2 diabetes and impaired glucose tolerance. To discover whether thinness at birth is associated with reduced glucose tolerance in children, 250 7-year-old children underwent an abbreviated oral glucose tolerance test. Children who were thin at birth, as measured by a low ponderal index (birthweight length-3) had higher plasma glucose concentrations. Plasma glucose concentration 30 min after a glucose load rose by 0.07 mmol l-1 (95% confidence interval 0.00 to 0.14; p = 0.04) for every unit (kg m-3) fall in ponderal index. Children in the lowest quarter of the distribution of ponderal index (23 kg m-3 or less) had a mean 30 min plasma glucose concentration of 8.49 mmol l-1 compared to a mean of 7.97 mmol l-1 for those in the highest quarter (> 27.5 kg m-3). These associations were independent of duration of gestation, gender, social class or the child's current weight. This is consistent with the hypothesis that Type 2 diabetes originates in utero.

Adult↗

Size at birth and plasma insulin-like growth factor-1 concentrations.

OBJECTIVE: To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like growth factor-1 (IGF-1) concentrations in childhood. DESIGN: A follow up study of 4 year old children whose birth weights were recorded, and of 7 year old children whose weight, length, head circumference, and placental weight were measured at birth. SETTING: Pune, India, and Salisbury, England. SUBJECTS: 200 children born during October 1987 to April 1989 in the King Edward Memorial Hospital, Pune, weighing over 2.0 kg at birth and not requiring special care, and 244 children born during July 1984 to February 1985 in the Salisbury Health District and still living there. MAIN OUTCOME MEASURE: Plasma IGF-1 concentrations. RESULTS: In both groups of children, and consistent with findings in other studies, plasma IGF-1 concentrations were higher in taller and heavier children, and higher in girls than boys. Allowing for sex and current size, concentrations were inversely related to birth weight (Pune p = 0.002; Salisbury p = 0.003). Thus at any level of weight or height, children of lower birth weight had higher IGF-1 concentrations. The highest concentrations were in children who were below average birth weight and above average weight or height when studied. Systolic blood pressures were higher in children with higher IGF-1 concentrations (Pune p = 0.01; Salisbury p = 0.04). CONCLUSIONS: Children of lower birth weight develop higher circulating concentrations of IGF-1 than expected for their height and weight. This is consistent with the hypothesis that under-nutrition in utero leads to reprogramming of the IGF-1 axis. The increase of plasma IGF-1 concentrations in low birthweight children may also be linked to postnatal catch-up growth. High IGF-1 concentrations may be one of the mechanisms linking reduced fetal growth and high blood pressure in later life.

Anthropometry↗

Growth in utero, adult blood pressure, and arterial compliance.

OBJECTIVES: To examine the relation between disproportionate fetal growth and adult blood pressure and to investigate whether arterial compliance in adult life is related to early development. DESIGN: A follow up study of a group of men and women whose birth weights and other measurements of body size had been recorded at birth. SETTING: Home and outpatient study. SUBJECTS: 337 men and women born in the Jessop Hospital, Sheffield, between 1939 and 1940. MAIN OUTCOME: Adult systolic and diastolic blood pressures and arterial compliance as measured by pulse wave velocity in two arterial segments. RESULTS: Both systolic and diastolic blood pressures were higher in people whose birth weight was low, who were short or who had small abdominal or head circumferences at birth. Systolic blood pressure decreased by 2.7 mm Hg (95% CI 0.8 to 4.6) for each pound (454 g) gain in birth weight and by 3.4 mm Hg (95% CI 1.4 to 5.4) for each inch (2.54 cm) increase in crown-heel length. Diastolic pressure fell by 1.9 mm Hg (95% CI 0.9 to 2.9) for each pound (454 g) gain in birth weight and by 2.4 mm Hg (95% CI 1.4 to 3.5) for each inch (2.54 cm) increase in length. Systolic blood pressure was also higher in individuals whose mother's intercristal pelvic diameter was small or whose mother's blood pressure had been raised during pregnancy but these effects were statistically independent of the effects of low birth weight and other measurements that indicate fetal growth retardation. Arterial compliance was lower in those who had been small at birth. CONCLUSION: Impairment of fetal growth is associated with raised blood pressure in adult life and decreased compliance in the conduit arteries of the trunk and legs.

Arteries↗

Birth weight, weight at one year, and left ventricular mass in adult life.

OBJECTIVE: To examine how fetal and infant growth are related to left ventricular mass in adult life. DESIGN: A follow up study of men born during 1920-30 whose birth weights and weights at 1 year were recorded. SETTING: Hertfordshire, England. SUBJECTS: 290 men born and still living in East Hertfordshire, England. MAIN OUTCOME MEASURE: Left ventricular mass calculated from measurements of interventricular septal thickness and left ventricular posterior wall thickness and left ventricular internal diameter at end diastole measured by M mode echocardiography. RESULTS: Left ventricular mass was highest in men with the lowest weight at 1 year and fell with increasing weight at 1 year (r = 0.18, P = 0.01). Left ventricular mass was not related to birth weight. The relation with weight at 1 year was independent of factors in adult life known to influence left ventricular mass, including body size, systolic blood pressure, and age. The enlarged left ventricular mass associated with reduced growth in infancy was concentric, affecting both the interventricular septum and the left ventricular posterior wall. Concentric left ventricular hypertrophy is known to be associated with increased death rates from coronary artery disease. CONCLUSION: Low weight at 1 year is associated with concentric enlargement of the left ventricle in adult life. This is consistent with a previous finding of higher mortality from cardiovascular disease in men of low weight at 1 year, and provides further evidence that cardiovascular disease may be partly programmed in early life. The left ventricular enlargement may be a long term result of haemodynamic changes in utero or of persisting changes in growth factor concentrations.

Aged↗

Do lower respiratory tract infections in early childhood cause chronic obstructive pulmonary disease?

The hypothesis that lower respiratory tract infections (LRTI) in early childhood lead to chronic obstructive pulmonary disease (COPD) in late adult life has been difficult to test. However, a unique opportunity arose when records were discovered in the counties of Hertfordshire and Derbyshire, England, that contained information about childhood LRTI recorded 60 to 70 years ago. The lung function of some men still living in these counties was examined. In Hertfordshire men, bronchitis or pneumonia in infancy was associated with reduced mean FEV1, adjusted for age and height. In Derbyshire men, pneumonia before 2 yr of age was associated with a large and highly significant reduction in mean FEV1, adjusted for age and height. These findings were independent of smoking and social class. These data support a causal relationship between LRTI in early life and subsequent COPD.

Adult↗

Thinness at birth and insulin resistance in adult life.

Type 2 (non-insulin-dependent) diabetes mellitus may originate through impaired development in fetal life. Both insulin deficiency and resistance to the action of insulin are thought to be important in its pathogenesis. Although there is evidence that impaired fetal development may result in insulin deficiency, it is not known whether insulin resistance could also be a consequence of reduced early growth. Insulin resistance was therefore measured in 81 normoglycaemic subjects, and 22 subjects with impaired glucose tolerance, who were born in Preston, UK, between 1935 and 1943. Their birth measurements had been recorded in detail. Insulin resistance was measured by the insulin tolerance test which uses the rate of fall in blood glucose concentrations after intravenous injection of insulin as an index of insulin resistance. Men and women who were thin at birth, as measured by a low ponderal index, were more insulin resistant. The association was statistically significant (p = 0.01) and independent of duration of gestation, adult body mass index and waist to hip ratio and of confounding variables including social class at birth or currently. Thinness at birth and in adult life has opposing effects such that resistance fell with increasing ponderal index at birth but rose with increasing adult body mass index. It is concluded that insulin resistance is associated with impaired development in fetal life.

Adult↗

Disproportionate fetal growth and raised IgE concentration in adult life.

A follow-up study was carried out to determine whether either impaired or disproportionate fetal growth are associated with a raised total serum IgE concentration in men and women aged 50 years. The serum IgE concentration was measured in 146 men and 134 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Sixty-two subjects were found to have an IgE concentration above 80 IU/ml. Compared with subjects with a normal IgE on average they had a 0.30 inch larger head circumference at birth (P = 0.004) and weighted 5.6 ounces more at birth (P = 0.04). People with a raised and with a normal IgE were of similar crown-heel length at birth, indicating that in utero those with a raised IgE had had disproportionate growth of the head in relation to the trunk and limbs. The prevalence of a raised IgE rose from 14% in subjects whose head circumference at birth was 13 inches or less to 37% in those whose head circumference was more than 14 inches. This association was independent of gestational age at birth and of the mother's pelvic size and parity. It was also independent of adult physique, social class and smoking, and was similar in men and women. In multiple logistic regression analyses odds ratios of a raised IgE rose progressively to more than 4 as head circumference at birth increased from 13 inches or less to more than 14 inches.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Constitution↗