Suzanne Butterworth

Early growth and type 2 diabetes: evidence from the 1946 British birth cohort

Aims/hypothesisWe assessed whether low birthweight or early adiposity rebound was more strongly associated with type 2 diabetes, and whether any effect of low birthweight or early adiposity rebound was explained by adult BMI, adult height, social class of subject or of his/her father, or maternal or paternal diabetes.MethodsCox’s proportional hazard models were used on data from the National Birth Cohort Study (the MRC National Survey of Health and Development), which was begun in 1946 and had self-reported physician-diagnosed diabetes with age at onset ranging from 31 to 53 years (n=78 cases, and n=47 cases in the multivariate analysis) as the outcome.ResultsA U-shaped association between birthweight and type 2 diabetes rates was close to statistical significance (quadratic term p value=0.08). Younger age at adiposity rebound was associated with increased rates of type 2 diabetes (test for trend p=0.002), the association being robust to adjustment for each of sex, birthweight, weight at 2 years, father’s social class, parental diabetes, and own social class. The effect of early adiposity rebound was very slightly reduced by adjustment for sex and adult height (p=0.003), but considerably reduced after adjustment for sex and adult BMI (test for trend p=0.1), and further reduced (p=0.4) after additional adjustment for birthweight, weight at 2 years, adult height, social class of subject and of his/her father, and parental diabetes.Conclusions/interpretationEarly adiposity rebound was associated with an increased rate of type 2 diabetes independently of birthweight, but its effect was mostly through high adult BMI. Parental diabetes and possibly low weight at 2 years were also risks.

MUC7 haplotype analysis: results from a longitudinal birth cohort support protective effect of the MUC7*5 allele on respiratory function

The mucin MUC7 is a glycoprotein that plays a role in bacterial clearance and has candidacidal activity. There are two common allelic forms with 5 or 6 tandem repeats (TR) of a 23 amino acid motif within the highly glycosylated (mucin) domain. The MUC7*5 allele has previously been shown to be less prevalent in patients with asthma, suggesting a protective role in respiratory function. Here we report the characterisation of other frequent genetic variation within and in the vicinity of the gene MUC7. A total of 26 polymorphisms were identified of which 5 are located in transcribed regions. A subset of 8 polymorphisms was selected to represent the major haplotypes, and allelic association was studied in individuals of Northern European ancestry, including known asthmatics. There was low haplotype diversity and strong association between each of the loci, and the MUC7*5 allele‐carrying haplotype remained the one most strongly associated with asthma. Five of these polymorphisms have also been tested in the 1946 longitudinal birth cohort, for whom developmental, environmental and respiratory health data are available. We show that the haplotype carrying MUC7*5 is associated with higher FEV1 at 53 years, reduced age‐related decline of FEV1, and also reduced incidence of wheeze.

Childhood cognitive ability and age at menopause: evidence from two cohort studies.

Objective:To investigate whether poorer cognitive ability in childhood is associated with an earlier menopause. Design:Two cohorts were included: a nationally representative British birth cohort study of 1,350 women born in March 1946 and followed up to age 54 years, and an Aberdeen cohort study of 3,465 women born in Aberdeen from 1950 to 1956 and followed up to age 44 to 50 years. Both cohorts had prospective information on childhood cognitive ability at age 7 or 8 years. Results:In both cohorts, women with lower cognitive scores in childhood reached menopause earlier than women with higher scores. With follow-up of menopause to 49 years, the hazard ratio (HR) for one standard deviation of the cognitive score was 0.80 (95% CI, 0.72-0.90) in the Aberdeen cohort and 0.84 (95% CI, 0.73-0.97) in the older 1946 birth cohort. The effect was still evident in the 1946 birth cohort with follow-up of menopause to 53 years (HR = 0.87; 95% CI, 0.79-0.95). These ratios were weakly attenuated by adjustment for potential confounding effects of lifetime socioeconomic circumstances, parity, and smoking. Conclusions:The association between early cognitive ability and timing of menopause only partially reflects common risk factors, although residual confounding remains a possibility. Alternatively, early environmental or genetic programming may explain this association, perhaps through setting lifelong patterns of hormone release or causing transient hormonal changes at sensitive periods of development. These findings have implications for the interpretation of studies investigating an association between age at menopause and adult cognitive function.

Reduced midlife physical functioning among never married and childless men: evidence from the 1946 British birth cohort study.

Background and aims: Marital and parental role characteristics are important factors in both men and women’s health. Most studies to date have either focused on disease specific outcomes or summary measures of self-reported health rather than using functional tests of performance. The goal of this study is to investigate the extent to which marital and parental role characteristics are associated with midlife physical function. Methods: A prospective birth cohort study was carried out with reference to births that took place in England, Scotland, and Wales during one week in March of 1946. Regular assessment of 1353 men and 1411 women were made from six weeks after birth throughout childhood and adulthood. Handgrip strength, timed chair rising, and standing balance tests at age 53 years were used to calculate an aggregate physical performance score that ranged from 0 (poorest score) to 2.81. Results: The mean physical performance score was 1.42 (SD 0.42) for men and 1.30 (SD 0.37) for women. By age 53 years, 11% of men and 8% of women had married but remained childless; 6% of men and 4% of women had never married. Never married (x 1.15; 95% CI 1.06, 1.24) and childless married men (

Breast cancer in relation to childhood parental divorce and early adult psychiatric disorder in a British birth cohort

⋏r x

Grip Strength, Postural Control, and Functional Leg Power in a Representative Cohort of British Men and Women: Associations With Physical Activity, Health Status, and Socioeconomic Conditions

1.36; 95% CI 1.30, 1.42) had significantly poorer physical performance scores than married men with children (

Childhood Socioeconomic Status Predicts Physical Functioning a Half Century Later

⋏r x

Developmental Origins of Midlife Grip Strength: Findings From a Birth Cohort Study

1.46; 95% CI 1.43, 1.48). These relationships remained after adjustment for adult social class and employment status, own educational attainment and body mass index at 53 years (beta=−0.18, 95% CI −0.27, −0.09 for never married and beta=−0.09, 95% CI −0.16, −0.03 for childless married, compared with married men with children). Of those men who had never married, 28% reported they were not working due to long-term health problems compared to 5% in both childless married men and married men with children. There were no marked differences in functional outcomes among women. Conclusions: In this representative middle-aged population, unmarried and childless men faced greater risk of poor midlife physical function, even after adjustment for confounders. These findings suggest that for men, marriage and parenthood protect against functional decline in midlife. Alternatively, physical performance may be a marker of poorer health in earlier life, which affects the chance of marriage and parenthood.

Developmental Origins of Midlife Physical Performance: Evidence from a British Birth Cohort

BACKGROUND Jacobs and Bovasso reported (Psychological Medicine 2000, 30, 669-678) that maternal death in childhood and chronic severe depression in adulthood were associated with subsequent breast cancer. We have examined the effects of parental loss in childhood and psychiatric disorder in adult life on breast cancer risk using a national birth cohort study. METHOD Eighty-three cases of breast cancer were diagnosed in a study of 2253 women followed from birth to age 59 years. Cox proportional hazards models were used to test whether breast cancer rates were higher in women who experienced parental death and divorce before age 16, psychiatric disorders between 15 and 32 years, symptoms of anxiety and depression at 36 years, or use of antidepressant medication at 31 or 36 years than in women who did not have these experiences. RESULTS There was no overall association between parental death, parental divorce or psychiatric disorder and the incidence of breast cancer. There was some evidence that women with more severe psychiatric disorders between the ages of 15 and 32 years were more likely to develop breast cancer early. The interaction between parental divorce and severe psychiatric disorder was non-significant (p=0.1); however, the group who experienced both these events had an increased breast cancer risk compared with those who experienced neither [hazard ratio (HR) 2.64, 95% confidence interval (CI) 1.13-6.19]. CONCLUSIONS Our study does not provide strong support for the hypothesis that early loss or adult psychiatric disorders are associated with breast cancer. A meta-analysis is needed that uses data from all available cohort studies and investigates possible interactive effects on breast cancer risk.