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Biomedical subjects

C Osmond

Publications and source records attributed to C Osmond.

At least 127 records · Page 7Linked to original sources

Growth in utero and serum cholesterol concentrations in adult life.

OBJECTIVE: To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN: Follow up study of men and women whose size at birth had been recorded. SETTING: Jessop and Northern General Hospitals, Sheffield. SUBJECTS: 219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES: Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS: Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION: Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.

Abdomen↗

Relation of fingerprints and shape of the palm to fetal growth and adult blood pressure.

OBJECTIVE: To examine how finger and palm prints are related to fetal growth and adult blood pressure. DESIGN: Follow up study of babies born around 50 years ago whose birth weight, placental weight, head circumference, and length at birth were recorded. SETTING: Preston, Lancashire. SUBJECTS: 139 men and women born in Sharoe Green Hospital in Preston during 1935-43 and still living in Lancashire. MAIN OUTCOME MEASURES: Finger and palm prints and current blood pressure. RESULTS: People who were thin at birth had more whorl patterns on their fingers. People who were short at birth in relation to their head circumference had longer hands and a narrower palmer angle. Mean systolic blood pressure was 8 mmHg higher (95% confidence interval 2 to 13; p = 0.01) in the 93 men and women with a whorl pattern on one or more fingers compared with the 46 who had no whorls. The greater the number of fingers with whorls the higher the systolic blood pressure. Whorls on the right hand were more strongly associated with higher systolic pressure than whorls on the left, mean systolic pressure rising by 2.2 mmHg (0.2 to 4.1; p = 0.03) for each additional whorl on the right hand. People with long hands and a narrow palmar angle also had higher systolic pressure. Again, these associations were stronger for the right hand. Mean systolic pressure rose by 0.49 mmHg (-0.03 to 1.01; p = 0.03) for each degree decrease in palmar angle on the right hand. CONCLUSIONS: Fingertip whorls and a narrow palmar angle are indelible markers of impaired fetal development at different stages in pregnancy. Both are associated with raised blood pressure in adult life.

Adolescent↗

The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life.

OBJECTIVE: To determine how fetal growth is related to death from cardiovascular disease in adult life. DESIGN: A follow up study of men born during 1907-24 whose birth weights, head circumferences, and other body measurements were recorded at birth. SETTING: Sheffield, England. SUBJECTS: 1586 Men born in the Jessop Hospital. MAIN OUTCOME MEASURE: Death from cardiovascular disease. RESULTS: Standardised mortality ratios for cardiovascular disease fell from 119 in men who weighed 5.5 pounds (2495 g) or less at birth to 74 in men who weighed more than 8.5 pounds (3856 g). The fall was significant for premature cardiovascular deaths up to 65 years of age (chi 2 = 5.0, p = 0.02). Standardised mortality ratios also fell with increasing head circumference (chi 2 = 4.6, p = 0.03) and increasing ponderal index (weight/length3) (chi 2 = 3.8, p = 0.05; for premature deaths chi 2 = 6.0, p = 0.01). They were not related to the duration of gestation. Among men for whom the ratio of placental weight to birth weight was in the highest fifths the standardised mortality ratio was 137. CONCLUSION: These findings show that reduced fetal growth is followed by increased mortality from cardiovascular disease. They suggest that reduction in growth begins early in gestation. They are further evidence that cardiovascular disease originates through programming of the body's structure, physiology, and metabolism by the environment during fetal life. Maternal nutrition may have an important influence on programming.

Adult↗

Initiation of hypertension in utero and its amplification throughout life.

OBJECTIVE: To determine whether the relation between high blood pressure and low birth weight is initiated in utero or during infancy, and whether it changes with age. DESIGN: A longitudinal study of children and three follow up studies of adults. SETTING: Farnborough, Preston, and Hertfordshire, England, and a national sample in Britain. SUBJECTS: 1895 children aged 0-10 years, 3240 men and women aged 36 years, 459 men and women aged 46-54 years, and 1231 men and women aged 59-71 years. The birth weight of all subjects had been recorded. MAIN OUTCOME MEASURE: Systolic blood pressure. RESULTS: At all ages beyond infancy people who had lower birth weight had higher systolic blood pressure. Systolic blood pressure was not related to growth during infancy independently of birth weight. The relation between systolic pressure and birth weight became larger with increasing age so that, after current body mass was allowed for, systolic pressure at ages 64-71 years decreased by 5.2 mm Hg (95% confidence interval 1.8 to 8.6) for every kg increase in birth weight. CONCLUSIONS: Essential hypertension is initiated in fetal life. A raised blood pressure is then amplified from infancy to old age, perhaps by a positive feedback mechanism.

Adult↗

Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth.

Two follow-up studies were carried out to determine whether lower birthweight is related to the occurrence of syndrome X-Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia. The first study included 407 men born in Hertfordshire, England between 1920 and 1930 whose weights at birth and at 1 year of age had been recorded by health visitors. The second study included 266 men and women born in Preston, UK, between 1935 and 1943 whose size at birth had been measured in detail. The prevalence of syndrome X fell progressively in both men and women, from those who had the lowest to those who had the highest birthweights. Of 64-year-old men whose birthweights were 2.95 kg (6.5 pounds) or less, 22% had syndrome X. Their risk of developing syndrome X was more than 10 times greater than that of men whose birthweights were more than 4.31 kg (9.5 pounds). The association between syndrome X and low birthweight was independent of duration of gestation and of possible confounding variables including cigarette smoking, alcohol consumption and social class currently or at birth. In addition to low birthweight, subjects with syndrome X had small head circumference and low ponderal index at birth, and low weight and below-average dental eruption at 1 year of age. It is concluded that Type 2 diabetes and hypertension have a common origin in sub-optimal development in utero, and that syndrome X should perhaps be re-named "the small-baby syndrome".

Aged↗

Fetal growth and impaired glucose tolerance in men and women.

A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p < 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p < 0.004), as did 2-h plasma insulin concentrations (p < 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition.

Birth Weight↗

Infant feeding, fetal growth and adult thyroid function.

Prolonged breast-feeding in humans is associated with increased low-density lipoprotein cholesterol and higher death rates from ischaemic heart disease in adult life. The reasons for this link are unclear. A possible explanation is that thyroid hormones present in breast milk and absorbed by the suckling infant could, by the process of hormonal imprinting, permanently down-regulate the set point of thyroid homeostasis. Thyroid hormones influence cholesterol metabolism, and could explain the link between infant feeding and the regulation of cholesterol levels in the adult. We therefore investigated whether infant feeding was related to adult thyroid function in 303 women aged 60-71 years who were born in the county of Hertfordshire, UK, where birthweight, the weight at 1 year and the method of infant feeding had been recorded routinely. Free thyroxine (FT4) concentrations but not free triiodothyronine (FT3) or thyrotrophin (TSH) were increased in the women who, as infants, had been breast-fed beyond 1 year of age (p < 0.01). In women who were bottle-fed, with or without breast-feeding, serum TSH rose and FT4 fell with increasing birthweight (p = 0.01 and p = 0.04, respectively). Although the metabolic significance of these findings is unclear, they suggest that the set point of thyroid function in the adult is determined by fetal growth and infant feeding.

Adult↗

Fetal growth and autoimmune thyroid disease.

To determine whether fetal and infant growth could influence susceptibility to autoimmune disease in adults, the occurrence of thyroid autoantibodies and autoimmune thyroiditis was studied in 305 women, aged 60-71, born in Hertfordshire and for whom details of birthweight, infant growth, and feeding were routinely recorded. Thyroglobulin autoantibody was detected in 37% of the women, thyroid peroxidase autoantibody in 41%, and autoimmune thyroiditis, defined as biochemical or clinical hypothyroidism in association with thyroid autoantibodies, in 5.6%. The proportion of women with thyroglobulin and thyroid peroxidase autoantibodies fell with increasing birthweight but was not related to weight at 1 year of age or the method of infant feeding. The prevalence of both autoantibodies rose with increasing adult body mass index but fell as the waist to hip ratio increased. These results demonstrate the importance of early environment in determining the susceptibility to autoimmune thyroid disease. The contrasting effects of adult body mass index and waist to hip ratio on antibody prevalence could be explained by their associations with different hormonal environments.

Aged↗

Life events and breast cancer prognosis.

OBJECTIVE: To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN: Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING: Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS: 204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES: Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS: After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION: These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.

Breast Neoplasms↗

Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.

OBJECTIVE: To examine whether method of infant feeding is associated with adult serum lipid concentrations and mortality from ischaemic heart disease. DESIGN: Follow up study of men born during 1911-30. SETTING: Hertfordshire, England. SUBJECTS: 5718 men, for 5471 of whom information on infant feeding had been recorded by health visitors and 1314 of whom had died. 485 of the men born during 1920-30 and still living in Hertfordshire who had blood lipid measurements. MAIN OUTCOME MEASURES: Death from ischaemic heart disease; serum cholesterol and apolipoprotein concentrations. RESULTS: 474 men had died from ischaemic heart disease. Standardised mortality ratios were 97 (95% confidence interval 81 to 115) in men who had been breast fed and had not been weaned at 1 year, 79 (69 to 90) in breast fed men who had been weaned at 1 year, and 73 (59 to 89) in men who had been breast and bottle fed. Compared with men weaned before one year men not weaned had higher mean serum concentrations of total cholesterol (6.9 (not weaned) v 6.6 (weaned) mmol/l), low density lipoprotein cholesterol (5.0 v 4.6 mmol/l) and apolipoprotein B (1.14 v 1.08 g/l). Men who had been bottle fed also had a high standardised mortality ratio for ischaemic heart disease (95; 68 to 130) and high mean serum concentrations of total cholesterol (7.0 mmol/l), low density lipoprotein cholesterol (5.1 mmol/l), and apolipoprotein B (1.14 g/l). In all feeding groups serum apolipoprotein B concentrations were lower in men with higher birth weight and weight at 1 year. CONCLUSIONS: Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischaemic heart disease. Adult serum apolipoprotein B concentrations are related to growth in fetal life and infancy.

Age Factors↗

Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life.

OBJECTIVE: To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life. DESIGN: Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail. SETTING: Hertfordshire and Preston, England. SUBJECTS: 591 men born in east Hertfordshire who still lived there and 148 men born in Preston who still lived in or close to the city. MAIN OUTCOME MEASURES: Plasma fibrinogen and factor VII concentrations. RESULTS: Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3.21 g/l in men of less than or equal to 18 lb to 2.93 g/l in men greater than or equal to 27 lb and from 122% of standard to 103%; p less than 0.001, p less than 0.005 respectively). The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p = 0.01). CONCLUSIONS: Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and factor VII. This may be a persisting response to impaired liver development during a critical early period.

Aged↗

The relation of fetal growth to plasma glucose in young men.

In a study of men aged 59 to 70 years plasma glucose levels 30 min and 2 h after a 75-g glucose load were inversely related to birthweight. To determine whether there are similar relations at a younger age the 30-min plasma glucose levels of 40 men aged 21 years, who were born in one hospital in the United Kingdom, were measured. Lower birthweight was associated with higher 30-min plasma glucose levels. This trend was independent of gestational age, and current body mass, height and social class.

Birth Weight↗

Space time clustering of births in SIDS: do perinatal infections play a role?

The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS.

Birth Intervals↗

The relation of fetal length, ponderal index and head circumference to blood pressure and the risk of hypertension in adult life.

The blood pressure of 327 men and women aged 46 to 54 years was related to birthweight, placental weight, length, ponderal index and head circumference at birth. All the subjects were born after 38 completed weeks of gestation. There were strong trends of higher blood pressure in adult life with lower birthweight (P = 0.04) and greater placental weight (P = 0.002). In subjects with placental weights of 1.25 lb or less, mean blood pressure, and the risk of hypertension, rose as ponderal index at birth fell (P = 0.0001). Mean systolic pressure rose by 13 mm Hg as ponderal index fell from greater than 14.75 to 12 or less. In those with placental weights above 1.25 lb, mean blood pressure, and the risk of hypertension, rose as length decreased and as the ratio of head circumference to length increased (P = 0.02). Mean systolic pressure rose by 14mm Hg as the head circumference to length ratio increased from less than 0.65 to greater than or equal to 0.7. These findings characterise the birth measurements of two groups of babies who are at increased risk of hypertension in adult life.

Birth Weight↗

Early growth and abdominal fatness in adult life.

STUDY OBJECTIVE: The aim was to determine whether abdominal fatness in adult men is associated with retarded growth in fetal life and infancy. DESIGN: This was a follow up study of (1) men born during 1920-30 whose birthweights and weights at one year were recorded at the time by health visitors; and (2) men born during 1935-43 whose size at birth was measured in detail. The main outcome measure was the ratio of waist circumference to hip girth. SETTING: Hertfordshire and Preston, England. SUBJECTS: Subjects were 845 men born in east Hertfordshire who still live there; and 239 men born in Preston who still live in or close to the city. MAIN RESULTS: After allowing for body mass index, mean waist to hip ratio fell with increasing birthweight and rose as the ratio of placental weight to birthweight increased. These trends were independent of duration of gestation and therefore reflected retarded fetal growth. Waist to hip ratio also fell with increasing weight at one year. All these trends were independent of adult height, alcohol consumption, smoking, social class, and age. CONCLUSIONS: The tendency to store fat abdominally, which is known to increase the risk of cardiovascular disease and diabetes independently of obesity, may be a persisting response to adverse conditions and growth failure in fetal life and infancy.

Abdomen↗