Christopher Martyn

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.

Maternal vitamin D status during pregnancy and child outcomes.

Objective:To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child.Design:Prospective study.Setting:Princess Anne Maternity Hospital, Southampton, UK.Subjects:A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years.Methods:Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed.Results:There were no associations between maternal 25(OH)-vitamin D concentrations and the childs body size or measures of the childs intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy >75 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15–9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09–26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l.Conclusion:Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the childs intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies.Sponsorship:The study was supported by the Medical Research Council and WellChild (previously known as Children Nationwide).

GEOGRAPHICAL RELATION BETWEEN ALZHEIMER'S DISEASE AND ALUMINIUM IN DRINKING WATER

In a survey of eighty-eight county districts within England and Wales, rates of Alzheimers disease in people under the age of 70 years were estimated from the records of the computerised tomographic (CT) scanning units that served these districts. Rates were adjusted to compensate for differences in distance from the nearest CT scanning unit and for differences in the size of the population served by the units. Aluminium concentrations in water over the past 10 years were obtained from water authorities and water companies. The risk of Alzheimers disease was 1.5 times higher in districts where the mean aluminium concentration exceeded 0.11 mg/l than in districts where concentrations were less than 0.01 mg/l. There was no evidence of a relation between other causes of dementia, or epilepsy, and aluminium concentrations in water.

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 mothers intercristal pelvic diameter was small or whose mothers 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.

Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension

There is much evidence that people who had low birthweight tend to have higher blood pressure in later life. However, the mechanisms that mediate this relation are unknown. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries may be deficient, and that this deficiency would lead to permanent changes in the mechanical properties of these vessels. Over a lifetime, such changes could predispose an individual to higher blood pressure, increased left-ventricular mass, and cardiovascular disease.

Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people

Abstract Objectives: To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over. Design: A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded. Setting: Eight areas in Britain (five in England, two in Scotland, and one in Wales). Subjects: 730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4. Results: Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease. Conclusion: In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease. Key messages Key messages Vitamin C is the most important dietary antioxidant in terms of intake Both dietary intake of vitamin C and plasma ascorbate concentrations were related to risk of death from stroke (but not from coronary heart disease) in 730 elderly people studied prospectively Vitamin C status was as strong a predictor of death from stroke as diastolic blood pressure Antioxidant vitamins are potentially important in the prevention of cerebrovascular disease

Cognitive impairment and mortality in a cohort of elderly people

Abstract Objectives: To investigate the relation between cognitive function and cause specific mortality in people aged 65 and over. Design: A 20 year follow up study of a cohort of randomly selected elderly people living in the community who in 1973-4 had taken part in a nutritional survey funded by the Department of Health and Social Security. Setting: Eight areas in Britain (five in England, two in Scotland, and one in Wales). Subjects: 921 men and women whose cognitive function was assessed by a geriatrician in 1973-4 and for whom data on health, socioeconomic circumstances, and diet had been recorded. Results: Cognitive impairment was associated with increased mortality, in particular death from ischaemic stroke. Those who scored 7 or less on the Hodkinson mental test had a relative risk of dying from stroke of 2.8 (95% confidence interval 1.4 to 5.5), compared with those who gained the maximum score (10), after adjustment for age, sex, blood pressure, serum cholesterol concentration, and vitamin C intake. These associations were independent of illness or social class. At the time of the nutritional survey, cognitive function was poorest in those with the lowest vitamin C status, whether measured by dietary intake or plasma ascorbic acid concentration. The relation between vitamin C status and cognitive function was independent of age, illness, social class, or other dietary variables. Conclusion: The relation between cognitive function and risk of death from stroke suggests that cerebrovascular disease is an important cause of declining cognitive function. Vitamin C status may be a determinant of cognitive function in elderly people through its effect on atherogenesis. A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease. Key messages Key messages In this prospective study of 921 elderly people cognitive impairment was a strong predictor of death from ischaemic stroke Low vitamin C intake and low plasma ascorbate concentrations were also important risk factors for death from stroke Cognitive performance was poorest in people with the lowest vitamin C status A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease

Migrant studies in multiple sclerosis

To re-evaluate how migrant studies contribute to our understanding of the epidemiology and aetiology of multiple sclerosis, we undertook a systematic review of all relevant studies published in English language journals, comparing rates of multiple sclerosis in migrant populations with those in the host country and in the country of origin. Interpretation of migrant studies is difficult. Migrants are seldom representative of the country of origin, tending to be younger, healthier and of higher socioeconomic status. Data quality may be poor, and lack of age-standardisation can mislead when rates are compared. Nevertheless, two consistent patterns can be discerned in these studies of the effect of migration on risk of multiple sclerosis. Migrants who move from an area where the disease is common to an area where it is rarer show a decrease in rate of disease. By contrast, people who migrate in the opposite direction tend to retain the low risk of their country of origin. Results from the few studies which have examined the effect of age at migration on risk of multiple sclerosis suggest that an individuals risk of the disease is largely established during the first two decades of life. Risk of multiple sclerosis can change rapidly between generations: although migrants from low risk countries to high risk countries retain their low risk, their children have a risk of multiple sclerosis that approaches that of the host country. Migrant studies add little to our understanding of the genetics of multiple sclerosis but they emphasise the importance of environmental factors. We discuss several possible interpretations of the patterns seen in migrant studies, including the hypothesis that multiple sclerosis is a sequel to delayed exposure to a common infectious agent. One candidate for such an infectious agent is Epstein-Barr virus.

The influence of head growth in fetal life, infancy, and childhood on intelligence at the ages of 4 and 8 years

OBJECTIVE. We investigated the effects of head growth prenatally, during infancy, and during later periods of development on cognitive function at the ages of 4 and 8 years. METHODS. We studied 633 term-born children from the Avon Longitudinal Study of Parents and Children cohort whose head circumference was measured at birth and at regular intervals thereafter. Their cognitive function was assessed with the Wechsler Preschool and Primary Scale of Intelligence at the age of 4 years and with the Wechsler Intelligence Scale for Children at the age of 8 years. Linear regression analysis was used to calculate postnatal head growth between successive time points, conditional on previous size, and to examine the relationship between head growth during different periods of development and later IQ. RESULTS. When the influence of head growth was distinguished for different periods, only prenatal growth and growth during infancy were associated with subsequent IQ. At 4 years, after adjustment for parental characteristics, full-scale IQ increased an average of 2.41 points for each 1-SD increase in head circumference at birth and 1.97 points for each 1-SD increase in head growth during infancy, conditional on head size at birth. At 8 years, head circumference at birth was no longer associated with IQ, but head growth during infancy remained a significant predictor, with full-scale IQ increasing an average of 1.56 points for each 1-SD increase in growth. CONCLUSION. The brain volume a child achieves by the age of 1 year helps determine later intelligence. Growth in brain volume after infancy may not compensate for poorer earlier growth.

The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex

Background: The aetiology of the learning difficulty in tuberous sclerosis is debated. It may be related to the amount of tubers in the brain or caused by the infantile spasms that occur in early life. Aims: To examine the relative contributions to final intelligence (IQ) made by both cerebral tubers and infantile spasms. Methods: As part of an epidemiological study of tuberous sclerosis in the south of England, patients were recruited who were able to undergo magnetic resonance imaging (MRI) without the need for an anaesthetic. Epilepsy history was determined by interview and review of clinical records. IQ was assessed using either Wechsler intelligence scales or Raven’s matrices. Results: A total of 41 patients consented to have an MRI scan. IQ scores were normally distributed about a mean of 91. Twenty six patients had a positive history of epilepsy, and 11 had suffered from infantile spasms. There was a significant relation between the number of tubers and IQ. Infantile spasm status partly confounded the relation between tubers and IQ, but did not render the relation statistically insignificant. The relation between infantile spasms and learning difficulty remained strong even when controlling for the number of tubers.