Showing papers by "George Davey Smith published in 2006"

Indicators of socioeconomic position (part 1)

Abstract: This glossary presents a comprehensive list of indicators of socioeconomic position used in health research. A description of what they intend to measure is given together with how data are elicited and the advantages and limitation of the indicators. The glossary is divided into two parts for journal publication but the intention is that it should be used as one piece. The second part highlights a life course approach and will be published in the next issue of the journal.

Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review

Abstract: OBJECTIVE: To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. DATA SOURCES: Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. REVIEW METHODS: Review of RCTs of omega 3 intake for (3) 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. RESULTS: Of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. CONCLUSION: Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

Measuring Multiple Deprivation at the Small-Area Level

Abstract: Indices to measure deprivation at a small-area level have been used in the United Kingdom to target regeneration policy for over thirty years. The development of the Indices of Deprivation 2000 for England and comparable indices for Northern Ireland, Wales, and Scotland, involved a fundamental reappraisal and reconceptualisation of small-area level multiple deprivation and its measurement. Multiple deprivation is articulated as an accumulation of discrete dimensions or ‘domains’ of deprivation. This paper presents the key principles that were taken into consideration when constructing these four indices and the more recent English Indices of Deprivation 2004, and provides an account of the statistical techniques that were used to operationalise them.

Life expectancy: women now on top everywhere

Abstract: During 2006, even in the poorest countries, women can expect to outlive men > “Women who seek to be equal with men lack ambition.” > > Timothy Leary (1920-1996) T he year 2006 should not be allowed to pass without at least a quiet celebration that this is the first year in human history when—across almost all the world—women can expect to enjoy a longer life expectancy than men. That the trend is moving in this direction will probably be confirmed this week in the 2006 world health report. In its world health report of 2002, the World Health Organization, using data for 2001, reported that male life expectancy exceeded female life expectancy in only six countries: Nepal, Botswana, Zimbabwe, Lesotho, Bangladesh, and Swaziland.1 A year later, the situation seemed to have reversed in all six countries, with two other countries (Qatar and the Maldives) reporting that men were living slightly longer than women.2 In its …

Epidemiologic Evidence for the Fetal Overnutrition Hypothesis: Findings from the Mater-University Study of Pregnancy and Its Outcomes

Abstract: The fetal overnutrition hypothesis proposes that greater maternal adiposity results in increased obesity throughout life in the offspring. The authors examined the associations between parental prepregnancy body mass index (BMI; weight (kg)/height (m)(2)), based on height and weight reported by the mother at her first antenatal clinic visit, and offspring BMI (height and weight measured at age 14 years) in 3,340 parent-offspring trios from a birth cohort based in Brisbane, Australia (mothers were recruited in 1981-1984). The maternal-offspring BMI association was stronger than the paternal-offspring BMI association. In the fully adjusted model, the increase in standardized offspring BMI at age 14 for a one-standard-deviation (SD) increase in maternal BMI was 0.362 SD (95% confidence interval: 0.323, 0.402), and the corresponding result for a one-SD increase in paternal BMI was 0.239 SD (95% confidence interval: 0.197, 0.282). There was statistical support for a difference in the magnitude of the association between maternal-offspring BMI and paternal-offspring BMI in all confounder-adjusted models tested (all p's < 0.0001). In sensitivity analyses taking account of different plausible levels of nonpaternity (up to 15%), the greater maternal effect remained. These findings provide some support for the fetal overnutrition hypothesis.

A road map for efficient and reliable human genome epidemiology.

Abstract: Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.

Advanced paternal age: How old is too old?

Abstract: Average paternal age in the UK is increasing. The public health implications of this trend have not been widely anticipated or debated. This commentary aims to contribute to such a debate. Accumulated chromosomal aberrations and mutations occurring during the maturation of male germ cells are thought to be responsible for the increased risk of certain conditions with older fathers. Growing evidence shows that the offspring of older fathers have reduced fertility and an increased risk of birth defects, some cancers, and schizophrenia. Adverse health outcomes should be weighed up against advantages for children born to older parents, mindful that these societal advantages are likely to change over time.

The mortality divide in India: the differential contributions of gender, caste, and standard of living across the life course.

Abstract: Objectives. We investigated the contributions of gender, caste, and standard of living to inequalities in mortality across the life course in India.Methods. We conducted a multilevel cross-sectional analysis of individual mortality, using the 1998–1999 Indian National Family Health Survey data for 529321 individuals from 26 states.Results. Substantial mortality differentials were observed between the lowest and highest standard-of-living quintiles across all age groups, ranging from an odds ratio (OR) of 4.61 (95% confidence interval [CI]=2.98, 7.13) in the age group 2 to 5 years to an OR of 1.97 (95% CI=1.68, 2.32) in the age group 45 to 64 years. Excess mortality for girls was evident only for the age group 2 to 5 years (OR=1.33, 95% CI=1.13, 1.58). Substantial caste differentials were observed at the beginning and end stages of life. Area variation in mortality is partially a result of the compositional effects of household standard of living and caste.Conclusions. The mortality burden, across the life...

Explaining the social gradient in coronary heart disease: comparing relative and absolute risk approaches

Abstract: Study objectives: There are contradictory perspectives on the importance of conventional coronary heart disease (CHD) risk factors in explaining population levels and social gradients in CHD. This study examined the contribution of conventional CHD risk factors (smoking, hypertension, dyslipidaemia, and diabetes) to explaining population levels and to absolute and relative social inequalities in CHD. This was investigated in an entire population and by creating a low risk sub-population with no smoking, dyslipidaemia, diabetes, and hypertension to simulate what would happen to relative and social inequalities in CHD if conventional risk factors were removed. Design, setting, and participants: Population based study of 2682 eastern Finnish men aged 42, 48, 54, 60 at baseline with 10.5 years average follow up of fatal (ICD9 codes 410–414) and non-fatal (MONICA criteria) CHD events. Main results: In the whole population, 94.6% of events occurred among men exposed to at least one conventional risk factor, with a PAR of 68%. Adjustment for conventional risk factors reduced relative social inequality by 24%. However, in a low risk population free from conventional risk factors, absolute social inequality reduced by 72%. Conclusions: Conventional risk factors explain the majority of absolute social inequality in CHD because conventional risk factors explain the vast majority of CHD cases in the population. However, the role of conventional risk factors in explaining relative social inequality was modest. This apparent paradox may arise in populations where inequalities in conventional risk factors between social groups are low, relative to the high levels of conventional risk factors within every social group. If the concern is to reduce the overall population health burden of CHD and the disproportionate population health burden associated with the social inequalities in CHD, then reducing conventional risk factors will do the job.

Indigenous health and socioeconomic status in India.

Abstract: Background Systematic evidence on the patterns of health deprivation among indigenous peoples remains scant in developing countries. We investigate the inequalities in mortality and substance use between indigenous and non-indigenous, and within indigenous, groups in India, with an aim to establishing the relative contribution of socioeconomic status in generating health inequalities. Methods and Findings Cross-sectional population-based data were obtained from the 1998–1999 Indian National Family Health Survey. Mortality, smoking, chewing tobacco use, and alcohol use were four separate binary outcomes in our analysis. Indigenous status in the context of India was operationalized through the Indian government category of scheduled tribes, or Adivasis, which refers to people living in tribal communities characterized by distinctive social, cultural, historical, and geographical circumstances. Indigenous groups experience excess mortality compared to non-indigenous groups, even after adjusting for economic standard of living (odds ratio 1.22; 95% confidence interval 1.13–1.30). They are also more likely to smoke and (especially) drink alcohol, but the prevalence of chewing tobacco is not substantially different between indigenous and non-indigenous groups. There are substantial health variations within indigenous groups, such that indigenous peoples in the bottom quintile of the indigenous-peoples-specific standard of living index have an odds ratio for mortality of 1.61 (95% confidence interval 1.33–1.95) compared to indigenous peoples in the top fifth of the wealth distribution. Smoking, drinking alcohol, and chewing tobacco also show graded associations with socioeconomic status within indigenous groups. Conclusions Socioeconomic status differentials substantially account for the health inequalities between indigenous and non-indigenous groups in India. However, a strong socioeconomic gradient in health is also evident within indigenous populations, reiterating the overall importance of socioeconomic status for reducing population-level health disparities, regardless of indigeneity.

Serum cholesterol, haemorrhagic stroke, ischaemic stroke, and myocardial infarction: Korean national health system prospective cohort study

Abstract: Objective To investigate risk factors, such as heavy alcohol consumption, that might explain any increased risk of haemorrhagic stroke associated with low blood cholesterol. Design Prospective cohort study. Setting Korea. Participants 787 442 civil servants (661 700 men, 125 742 women) aged 30-64. Main outcome measures Cardiovascular risk factors were assessed at biennial health check. Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems. Results 6328 cases of ischaemic stroke (6021 men, 307 women), 3947 cases of haemorrhagic stroke (3748 men, 199 women), 3170 cases of undefined stroke (2902 men, 268 women), and 4417 cases of myocardial infarction (4305 men, 112 women) occurred. Ischaemic stroke and myocardial infarction were strongly and positively associated with blood cholesterol (hazard ratio per 1 mmol/l cholesterol 1.20 (95% confidence 1.16 to 1.24) and 1.48 (1.43 to 1.53), respectively). Haemorrhagic stroke showed an inverse association in fully adjusted models (0.91, 0.87 to 0.95). This inverse association was confined to participants with hypertension. When stratified by concentration of γ glutamyl transferase (GGT), an indicator of alcohol consumption, the association was not seen in participants with low concentrations of GGT, and it was independent of hypertension in those with high concentrations of GGT (> 80 U/l).

Association of Childhood Socioeconomic Position with Cause-specific Mortality in a Prospective Record Linkage Study of 1,839,384 Individuals

Abstract: Previous studies have lacked sufficient power to assess associations between early-life socioeconomic position and adult cause-specific mortality. The authors examined associations of parental social class at age 0-16 years with mortality among 1,824,064 Swedes born in 1944-1960. Females and males from manual compared with nonmanual childhood social classes were more likely to die from smoking-related cancers, stomach cancer, respiratory disease, cardiovascular disease, and diabetes. Males from manual compared with nonmanual social classes were more likely to die from unintentional injury, homicide, and alcoholic cirrhosis. The association with stomach cancer was little affected by adjustment for parental later-life and own adult social class or education. For other outcomes, educational attainment resulted in greater attenuation of associations than did adjustment for adult social class. Early-life social class was not related to suicide or to melanoma, colon, breast, brain, or lymphatic cancers or to leukemia. With the exception of stomach cancer, caused by Helicobacter pylori infection acquired in childhood, poorer social class in early life was associated with diseases largely caused by behavioral risk factors such as smoking, physical inactivity, and an unhealthy diet. Educational attainment may be important in reducing the health inequalities associated with early-life disadvantage.

Reverse Causality and Confounding and the Associations of Overweight and Obesity with Mortality

Abstract: Objective: To examine the effect of reverse causality and confounding on the association of BMI with all-cause and cause-specific mortality. Research Methods and Procedures: Data from two large prospective studies were used. One (a community-based cohort) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972–1976; the other (an occupational cohort) included 4016 men working in the central belt of Scotland at the time of the baseline assessment in 1970–1973. Participants in both cohorts were ages 45 to 64 years at baseline; the follow-up period was 28 to 34 years. Results: In age-adjusted analyses that did not take account of reverse causality or smoking, there was no association between being overweight (BMI 25 to <30 kg/m2) and mortality, and weak to modest associations between obesity (BMI ≥30 kg/m2) and mortality. There was a strong association between smoking and lower BMI in women and men in both cohorts (all p < 0.0001). Among never-smokers and with the first 5 years of deaths removed, overweight was associated with an increase in all-cause mortality (relative risk ranging from 1.12 to 1.38), and obesity was associated with a doubling of risk in men in both cohorts (relative risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk, 1.56). In both never-smokers and current smokers, being overweight or obese was associated with important increases in the risk of cardiovascular disease. Discussion: These findings demonstrate that with appropriate control for smoking and reverse causality, both overweight and obesity are associated with important increases in all-cause and cause-specific mortality, and in particular with cardiovascular disease mortality.

Meta-analyses of Observational and Genetic Association Studies of Folate Intakes or Levels and Breast Cancer Risk

Abstract: Background: Evidence from case – control studies suggests that increasing dietary folate intake is associated with a reduced risk of breast cancer. However, large cohort studies have found no such association, and animal studies suggest that folate supplementation may promote tumorigenesis. We conducted a meta-analysis to summarize the available evidence from observational studies on this issue and a metaanalysis of the association between a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate metabolism, and breast cancer risk. Methods: We searched Medline and ISI Web of Knowledge databases for relevant studies that were published through May 31, 2006. We used random-effects analysis to calculate odds ratios (ORs) for case – control studies or relative risks (RRs) for cohort studies for a 100- μ g/d increase in folate intake. Unadjusted odds ratios were calculated for the studies of MTHFR genotype based on published genotype frequencies. Results: A total of 13 case – control studies and nine cohort studies were included in the meta-analysis of folate intake and breast cancer risk. We found a summary OR of 0.91 (95% confi dence interval [CI] = 0.87 to 0.96) from the case – control studies and a summary RR of 0.99 (95% CI = 0.98 to 1.01) from the cohort studies for a 100- μ g/d increase in folate intake. We found evidence that the case – control studies may have suffered from substantial publication bias. The case – control and cohort studies may have been subject to measurement error, confounding, and possibly spurious associations arising from subgroup analyses; in addition, the case – control studies were potentially subject to recall bias and publica tion bias. Seventeen studies were included in the meta-analysis of MTHFR C677T genotype and breast cancer risk. We found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk. Conclusion: A lack of dietary folate intake is not associated with the risk of breast cancer. [J Natl Cancer Inst 2006;98: 1607 – 22 ]

ZIP-Code-based versus Tract-based Income Measures as Long-Term Risk-adjusted Mortality Predictors

Abstract: There is a well-established, strong association between socioeconomic position and mortality. Public health mortality analyses thus routinely consider the confounding effect of socioeconomic position when possible. Particularly in the absence of personally reported data, researchers often use area-based measures to estimate the effects of socioeconomic position. Data are limited regarding the relative merits of measures based on US Census tract versus ZIP code (postal code). ZIP-code measures have more within-unit variation but are also more easily obtained. The current study reports on 293,138 middle-aged men screened in 14 states in 1973-1975 for the Multiple Risk Factor Intervention Trial and having 25-year mortality follow-up. In risk-adjusted proportional hazards models containing either ZIP-code-based or tract-based median household income, all-cause mortality hazard ratios were 1.16 (95% confidence interval: 1.14, 1.17) per Dollars 10,000 less ZIP-code-based income and 1.15 (95% confidence interval: 1.13, 1.16) per Dollars 10,000 less tract-based income; adding either income variable to a risk-adjusted model improved model fit substantially. Both were significant independent predictors in a combined model; tract-based income was a slightly stronger mortality predictor (hazard ratios = 1.05 and 1.11 for ZIP-code-based and tract-based income, respectively). These patterns held across various causes of death, for both Blacks and non-Blacks, and with or without adjustment for ZIP-code-based income diversity or tract-based proportion below poverty.

Smoking during pregnancy and offspring fat and lean mass in childhood.

Abstract: Maternal smoking during pregnancy has been shown to be associated with obesity in the offspring, but findings have been based mainly on BMI, which is derived from height and weight. This study examined the association between maternal and partner smoking during pregnancy and offspring total fat, truncal fat, and lean mass in childhood.

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Abstract: Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance ( P =10 −9 ). rs3757840 was also highly significantly associated with fasting glucose ( P =8×10 −7 ), but haplotype analysis revealed that this is explained by linkage disequilibrium ( r 2 =0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11–53 g) increase in offspring birth weight ( P =.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Association Between Birth Weight and Blood Pressure Is Robust, Amplifies With Age, and May Be Underestimated

Abstract: Data on the early life origins of adult hypertension have been widely reported: however, recent research shows that the strength of association between small size at birth and higher blood pressure weakens as study size increases. In this article, we retest the association between birth weight and systolic blood pressure in a large cohort, examine whether age interacts with birth weight to predict blood pressure, and explore reasons why birth weight-blood pressure associations tend to weaken with increasing study size. Measurements from 25874 employees of a large United Kingdom company (mean [SD] age: 38.0 [7.9] years), undertaking voluntary occupational health screening, were available. Using linear regression analysis, we observed that systolic blood pressure changed −0.8 (95% CI: −1.1 to −0.5) mmHg per 1-kg increase in birth weight ( P P P

Measurement of temperature rises in the femtosecond laser pulsed three-dimensional atom probe

Abstract: A previous Letter [B. Gault et al., Appl. Phys. Lett. 86, 094101 (2005)] interpreted measurements of the field evaporation enhancement under femtosecond pulsed laser irradiation of a field emitter in terms of a direct electric field enhancement by the intrinsic field of the laser light. We show that, on the contrary, the field evaporation enhancement is predominantly a thermal heating effect. Indirect measurements of the peak specimen temperature under irradiation by femtosecond laser pulses are consistent with temperature rises obtained using longer laser pulses in a range of earlier work.

Early Socioeconomic Position and Blood Pressure in Childhood and Adulthood: The Cardiovascular Risk in Young Finns Study

Abstract: Studies have found an association between low socioeconomic position in childhood and high adult blood pressure. It is unclear whether this association is explained by a pathway directly linking disadvantage to elevated blood pressure in childhood and adolescence, which then tracks into adulthood. We assessed parental socioeconomic position and systolic blood pressure in 1807 children and adolescents ages 3 to 18 years at baseline. Adult systolic blood pressure was measured 21 years later at ages 24 to 39 years. There was strong tracking of blood pressure from childhood to adulthood. Lower parental socioeconomic position was associated with higher blood pressure in childhood, adolescence (P<0.01), and adulthood (P<0.0001), with the mean age- and sex-adjusted systolic pressure differences between the highest and lowest socioeconomic groups varying between 2.9 and 4.3 mm Hg. With adjustment for blood pressure in childhood and adolescence, the regression coefficient between parental socioeconomic position and adult blood pressure attenuated by 32%. A similar level of attenuation (28%) occurred with adjustment for adult body mass index (BMI). With adjustment for both preadult blood pressure and adult BMI, the association between parental socioeconomic position and adult blood pressure was attenuated by 45%. Other factors, including birth weight and BMI in childhood and adolescence, had little impact on the association between parental socioeconomic position and adult blood pressure. These data suggest that early socioeconomic disadvantage influences later blood pressure in part through an effect on blood pressure in early life, which tracks into adulthood, and in part through an effect on BMI.

Global inequality of life expectancy due to AIDS

Abstract: Global inequality in both health and wealth began to rise worldwide in the early 1980s and has been exacerbated by AIDS in Africa. This trend is not inevitable, and historical trends show that inequality can be reduced

Nutritional interventions and outcome in patients with cancer or preinvasive lesions : Systematic review

Abstract: Background: Dietary modifi cations and supplements are used widely by patients with cancer and preinvasive lesions as an adjunct to standard treatment. Given the widespread use of nutritional modifi cations and supplements by such patients and concerns about the lack of benefi t and possible harm, we conducted a systematic review of randomized controlled trials to examine the effect of nutritional interventions on patients with cancer or preinvasive lesions. Methods: We searched electronic databases and reference lists to locate all eligible trials and analyzed trial quality. Outcome measures were all-cause and cancer mortality, disease-free survival, cancer recurrence, second primary cancer, recurrence of a preinvasive lesion, or progression to cancer. Results of individual trials were combined by use of random-effects meta-analyses. Results: We identifi ed 59 eligible trials, 25 in patients with cancer and 34 in patients with preinvasive lesions, respectively. Trial quality was generally low; only three trials (two of cancer and one of preinvasive lesions) had adequate methods for generating the allocation sequence, allocation concealment, and masking both outcome assessors and participants. The combined odds ratio (OR) for the effect of a healthy diet — given alone or with dietary supplements, weight loss, or exercise — on all-cause mortality was 0.90 (95% confi dence interval [CI] = 0.46 to 1.77). There was no evidence of an association between the use of antioxidant (OR = 1.01, 95% CI = 0.88 to 1.15) or retinol (OR = 0.97, 95% CI = 0.83 to 1.13) supplements and all-cause mortality. Meta-analyses of all other outcomes did not show clear evidence of benefi t or harm. Conclusions: The impact of most nutritional interventions cannot be reliably estimated because of the limited number of trials, many of which were of low quality. There is no evidence that dietary modifi cation by cancer patients improves survival and benefi ts disease prognosis. [J Natl Cancer Inst 2006;98: 961 – 73 ]

Intrauterine Growth and Intelligence Within Sibling Pairs: Findings From the Aberdeen Children of the 1950s Cohort

Abstract: OBJECTIVE The objective of this study was to examine whether the established positive association between birth weight and childhood psychometric intelligence is seen within singleton sibling pairs from the same family as well as between nonsiblings METHODS We examined the association of intrauterine growth (measured as birth weight standardized for gender and gestational age) with psychometric intelligence (measured using the Moray House picture test) at 7 years old in a birth cohort of 9792 individuals who were singleton births occurring in Aberdeen, Scotland, between 1950 and 1956 We further compared this association within siblings with that between nonsiblings in the cohort; this family-based analysis included 1645 sibling pairs (N = 3290 individuals) RESULTS There was a positive linear association between birth weight and childhood psychometric intelligence at age 7 in the whole cohort, which remained with adjustment for a range of potential confounding factors A one standard deviation increase in birth weight for gestational age z score was associated with a greater intelligence score in a regression model adjusting for sex, year of birth, paternal social class, maternal height, age, gravidity, and birth outside of marriage The mean age difference between the siblings within each family pair was 22 years In the family-based analysis there was no strong association between birth weight for gestation age z score and intelligence within sibling pairs from the same family, but there was a positive association between nonsiblings; the difference in these effects being unlikely to be due to chance With additional adjustment for social class, maternal height, age, gravidity, and birth outside of marriage, the within-sibling pair effect was unaltered and the nonsibling effect attenuated, although an apparently robust positive association remained In these adjusted analyses there was still evidence that the within-sibling effect differed from that between nonsiblings We found no evidence that the main effects or the family-based analyses differed between males and females DISCUSSION Our family-based analyses are consistent with one previous large family-based study that included >2500 sibling pairs and found no within-sibling-pairs association between birth weight and childhood intelligence, but did not make a direct statistical comparison between the within-sibling-pairs association and that between nonsiblings In a second large study that included only sibling pairs of the same sex, in males there was a within-sibling-pairs association between birth weight and childhood intelligence However, for females there was no within-sibling-pairs association The authors commented that this sex difference was puzzling and needed replication Although we had less power than this earlier study to assess sex differences, the point estimates and statistical tests in our study suggested that there was no sex difference CONCLUSIONS The lack of any association within sibling pairs from the same family suggests that the association between birth weight and childhood intelligence in the general population of singletons is largely explained by fixed family factors that are closely matched in siblings of a similar age These factors include family socioeconomic characteristics, parental education and intelligence, genetic factors and fixed maternal factors, such as her behaviors, size, and metabolic and cardiovascular health that are constant from one pregnancy to the next and could therefore affect her offspring growth and intelligence across all pregnancies

Associations of adiposity from childhood into adulthood with insulin resistance and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr Cohort.

Abstract: Context: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and IGF metabolism. Objective: Our objective was to investigate associations of adiposity at different stages of life with insulin and the IGF system. Design, Setting, and Participants: The study was a 65-yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally surveyed between 1937 and 1939. Main Outcomes: Outcomes included homeostasis model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood. Results: Childhood body mass index (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, −3.4 ng/ml; 95% confidence interval, −7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95% confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4 to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), a...