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Biomedical subjects

D J Barker

Publications and source records attributed to D J Barker.

At least 73 records · Page 4Linked to original sources
PubMed1998

In utero programming of chronic disease.

1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. 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. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.

Child↗
PubMed1997

Fetal growth, length of gestation, and polycystic ovaries in adult life.

BACKGROUND: Polycystic ovaries are a common disorder associated with menstrual irregularities, subfertility, hirsutism, acne, and a range of endocrine abnormalities, including high concentrations of plasma luteinising hormone (LH) and excessive androgen production. The pathophysiology is not understood. We investigated whether the disorder originates during intrauterine life. METHODS: We examined 235 women aged 40-42 years who were born in Sheffield, UK. We related the prevalence of polycystic ovaries and the plasma concentrations of gonadotropin hormones and androgens to the women's body size at birth, and the length of gestation. FINDINGS: 49 (21%) of the women had polycystic ovaries. We defined two groups of women with the disorder, which correspond to the two groups that commonly present clinically. The first group comprised obese women who were androgenised, with higher than normal concentrations of plasma LH and testosterone. These women had above-average birthweight and were born to overweight mothers. The second group comprised women of normal weight who had high plasma LH, but normal testosterone concentrations. These women were born after term (40 weeks' gestation). INTERPRETATION: The two common forms of polycystic ovary syndrome have different origins in intrauterine life. Obese, hirsute women with polycystic ovaries have higher than normal ovarian secretion of androgens that are associated with high birthweight and maternal obesity. Thin women with polycystic ovaries have altered hypothalamic control of LH release resulting from prolonged gestation.

Adult↗
PubMed1997

Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study.

OBJECTIVE: To determine whether restricted growth in utero is associated with an increased risk of coronary heart disease are among men in Finland, where rates of the disease are among the highest in the world. DESIGN: Follow up study. SETTING: Helsinki, Finland. SUBJECTS: 3302 men born in Helsinki University Central Hospital during 1924-33 who went to school in the city of Helsinki and were resident in Finalnd in 1971. MAIN OUTCOME MEASURES: Standardised mortality ratios for coronary heart disease. RESULTS: Men who were thin at birth, with low placental weight, had high death rates from coronary heart disease. Men whose mothers had a high body mass index in pregnancy also had high death rates. In a multivariate analysis the hazard ratio for coronary heart disease was 1.37 (95% confidence interval 1.20 to 1.57) (P < 0.0001) for every standard deviation decrease in ponderal index at birth and 1.24 (1.10 to 1.39) (P = 0.0004) for every standard deviation increase in mother's body mass index. The effect of mother's body mass index was restricted to mothers of below average stature. CONCLUSION: These findings suggest a new explanation for the epidemics of coronary heart disease that accompany Westernisation. Chronically malnourished women are short and light and their babies tend to be thin. The immediate effect of improved nutrition is that women become fat, which seems to increase the risk of coronary heart disease in the next generation. With continued improvements in nutrition, women become taller and heavier; their babies are adequately nourished; and maternal fatness no longer increases the risk of coronary heart disease, which therefore declines.

Aged↗
PubMed1997

Is the age of menopause determined in-utero?

OBJECTIVE: To determine whether age at menopause is related to size at birth. DESIGN: A follow-up study of two groups of women whose size at birth was recorded. SETTING: Hertfordshire and Sheffield, England. POPULATION: 755 women aged 60-71 years born in Hertfordshire; 235 women aged 40-42 years born in the Jessop Hospital, Sheffield. MAIN OUTCOME MEASURES: Age at natural menopause or serum follicle stimulating hormone concentration greater than 25 IU/ml. RESULTS: Age at menopause was unrelated to birth weight. However, it occurred at a younger age in women who had low weight at 1 year. This was independent of their body weight and smoking habits. In the population of younger women those who had had an early menopause tended to have been short at birth, with a high ponderal index (birth weight/length3). CONCLUSION: Growth retardation in late gestation, leading to shortness at birth and low weight gain in infancy, may be associated with a reduced number of primordial follicles in the ovary leading in turn to an earlier menopause.

Adult↗
PubMed1997

Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome?

To test the hypothesis that elevated sympathetic nervous system (SNS) activity could be determined in utero and be one of the processes mediating the link between size at birth and insulin resistance and raised blood pressure in adult life, we have studied the resting pulse rate of 449 men and women aged 46 to 54 (mean 50) years born in Preston, Lancashire, England whose birth size was recorded in detail. The subjects were visited at home by trained fieldworkers who measured resting pulse rate and blood pressure using an automated recorder. The resting pulse rate ranged from 44 to 108 (mean 73) beats min(-1). It rose with increasing body mass index (r = 0.14, p = 0.003) and waist to hip ratio (adjusted for sex r = 0.10, p = 0.003) and correlated significantly with systolic and diastolic blood pressures (p = 0.001), fasting glucose (p = 0.02), split proinsulin (p = 0.001), and triglyceride concentrations (p = 0.02). The pulse rate fell progressively from 76 beats min(-1) among subjects who weighed 5.5 lb (2.5 kg) or less at birth to 71 beats min(-1) among those who weighed 7.5 lb (3.3 kg) or more (decline in pulse rate per kg increase in birthweight = 2.7, 95 % CI 0.6 to 4.8 beats min(-1). The association was independent of current body mass index, waist to hip ratio and of potential confounding variables including smoking, alcohol consumption, and social class. Although the resting pulse rate is an imperfect index of SNS activity, these findings are consistent with the hypothesis that elevated SNS activity established in utero is one mechanism linking small size at birth with the insulin resistance syndrome in adult life.

Adult↗
PubMed1997

Maternal nutrition, fetal nutrition, and disease in later life.

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↗
PubMed1997

Fetal nutrition and cardiovascular disease in later life.

Recent finding suggest that many 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 life, including coronary heart disease and the related disorders stroke, diabetes and hypertension.

Aged↗
PubMed1997

Intra-uterine programming of the adult cardiovascular system.

We have become accustomed to the idea that the major disorders of adult life, including coronary heart disease, stroke and diabetes, arise through an interaction between influences in our adult lifestyle and a genetically determined susceptibility. Recent research, however, suggests that growth in utero may also play an important role.

Adult↗
PubMed1997

Maternal birthweight and diet in pregnancy in relation to the infant's thinness at birth.

OBJECTIVE: To examine how maternal diet in pregnancy and parental body size and birthweight influence an infant's thinness at birth measured by a low ponderal index. DESIGN: An observational study of newborn infants and their parents. SETTING: Southampton, England. POPULATION: Five hundred and thirty-eight infants born at term. MAIN OUTCOME MEASURE: Ponderal index at birth. RESULTS: Women who had a high intake of carbohydrate in early pregnancy and a low intake of dairy protein in late pregnancy tended to have infants that were thin at birth (P = 0.01 and P = 0.03, respectively, in a simultaneous analysis). Women who themselves had a low birthweight also tended to have thin infants, ponderal index falling from 28.3 kg/m3 to 26.2 kg/m3 as the women's birthweights decreased from more than 4.0 kg to 2.5 kg or less (P < 0.0001). Tall fathers had thin infants, but ponderal index was not related to the women's heights or the fathers' birthweights. CONCLUSION: These associations may reflect constraints on placental development imposed by a woman's nutrition in pregnancy and during her own intrauterine life. Effects of the father's height may be mediated through genetic influences on skeletal growth.

Adult↗
PubMed1997

The fetal origins of 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 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 coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations.

Animals↗
PubMed1997

Intrauterine programming of coronary heart disease and stroke.

We have become accustomed to the idea that the major disorders of adult life, including coronary heart disease, stroke and diabetes, arise from an interaction between influences in our adult lifestyle and a genetically determined susceptibility. Recent research, however, suggests that growth in utero may also play an important role.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Fetal undernutrition and disease in later life.

Recent findings suggest that coronary heart disease and stroke, and the associated conditions, hypertension and non-insulin dependent diabetes, originate through impaired growth and development during fetal life and infancy. These diseases may be consequences of 'programming', whereby a stimulus or insult at a critical, sensitive period of early life results in long-term changes in physiology or metabolism. Animal studies provide many examples of programming, which occurs because the systems and organs of the body mature during periods of rapid growth in fetal life and infancy. There are critical windows of time during which maturation must be achieved; and failure of maturation is largely irrecoverable.

Animals↗