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International Journal of Epidemiology

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The Quebec Longitudinal Study of Kindergarten Children (QLSKC) is an ongoing population-based prospective longitudinal study presently spanning ages 6–29 years, designed to study the prevalence, risk factors, development and consequences of behavioural and emotional problems during elementary school. Kindergarten boys and girls attending French-speaking public schools in the Canadian province of Quebec during the 1986–87 and 1987–88 school years were included in the cohort: 2000 children representative of the population and 1017 children exhibiting disruptive behaviour problems. To date, 12 waves of data have been collected, and three generations of participants have been involved in the study (i.e. the study child, his parents and the first child of the study child). Information on demographics, psycho-social and lifestyle factors, child and family member characteristics (physical and mental health), and outcomes such as psychiatric diagnoses, delinquency or school diploma were assessed during three important developmental stages (childhood, adolescence and early adulthood). Blood samples were also collected in early adulthood for genetic analyses. Information on publications, available data and access to data can be found on the following website (http://www.gripinfo.ca/Grip/Public/www/).


The Wisconsin Longitudinal Study (WLS) is a longitudinal study of men and women who graduated from Wisconsin high schools in 1957 and one of their randomly selected siblings. Wisconsin is located in the upper midwest of the United States and had a population of approximately 14 000 000 in 1957, making it the 14th most populous state at that time. Data spanning almost 60 years allow researchers to link family background, adolescent characteristics, educational experiences, employment experiences, income, wealth, family formation and social and religious engagement to midlife and late-life physical health, mental health, psychological well-being, cognition, end of life planning and mortality. The WLS is one of the few longitudinal data sets that include an administrative measure of cognition from childhood. Further, recently collected saliva samples allow researchers to explore the inter-relationships among genes, behaviours and environment, including genetic determinants of behaviours (e.g. educational attainment); the interactions between genes and environment; and how these interactions predict behaviours. Most panel members were born in 1939, and the sample is broadly representative of White, non-Hispanic American men and women who have completed at least a high school education. Siblings cover several adjoining cohorts: they were born primarily between 1930 and 1948. At each interview, about two-thirds of the sample lived in Wisconsin, and about one-third lived elsewhere in the United States or abroad. The data, along with documentation, are publicly accessible and can be accessed at http://www.ssc.wisc.edu/wlsresearch/. Requests for protected data or assistance should be sent to wls@ssc.wisc.edu.


The Boston Area Community Health (BACH) Survey is a community-based, random sample, epidemiologic cohort of n = 5502 Boston (MA) residents. The baseline BACH Survey (2002–05) was designed to explore the mechanisms conferring increased health risks on minority populations with a particular focus on urologic signs/symptoms and type 2 diabetes. To this end, the cohort was designed to include adequate numbers of US racial/ethnic minorities (Black, Hispanic, White), both men and women, across a broad age of distribution. Follow-up surveys were conducted ~5 (BACH II, 2008) and 7 (BACH III, 2010) years later, which allows for both within- and between-person comparisons over time. The BACH Survey’s measures were designed to cover the following seven broad categories: socio-demographics, health care access/utilization, lifestyles, psychosocial factors, health status, physical measures and biochemical parameters. The breadth of measures has allowed BACH researchers to identify disparities and quantify contributions to social disparities in a number of health conditions including urologic conditions (e.g. nocturia, lower urinary tract symptoms, prostatitis), type 2 diabetes, obesity, bone mineral content and density, and physical function. BACH I data are available through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories (www.niddkrepository.org). Further inquiries can be made through the New England Research Institutes Inc. website (www.neriscience.com/epidemiology).


A cohort comprising residents of a housing regeneration and health programme was created from routinely collected data using a system which allows us to anonymously link housing data to individuals and their health. The regeneration programme incorporating four rolling work packages runs from 2009 to 2014. The main intervention cohort we describe here contains the 18 312 residents of 9051 residences at baseline. The cohort will be followed continuously through routine health data (demographics, mortality, hospital admissions and general practitioner records including prescriptions) with periodic updates of housing regeneration intervention data. Here, we describe the baseline data for the primary health outcomes of emergency hospital admissions for cardiovascular and respiratory conditions and injuries for those aged ≥60 years. We will compare the health of residents within the homes before and after the housing regeneration work has taken place, and we will calculate the change in health service costs with use of hospital and General Practitioners (GP) services. We will also use a difference in differences approach to assess changes in comparison with comparator cohorts. These data will be accessible at the end of the study period in 2016. Further information about this study can be obtained from Ronan Lyons; r.a.lyons@swansea.ac.uk


The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative longitudinal survey of persons in China 45 years of age or older and their spouses, including assessments of social, economic, and health circumstances of community-residents. CHARLS examines health and economic adjustments to rapid ageing of the population in China. The national baseline survey for the study was conducted between June 2011 and March 2012 and involved 17 708 respondents. CHARLS respondents are followed every 2 years, using a face-to-face computer-assisted personal interview (CAPI). Physical measurements are made at every 2-year follow-up, and blood sample collection is done once in every two follow-up periods. A pilot survey for CHARLS was conducted in two provinces of China in 2008, on 2685 individuals, who were resurveyed in 2012. To ensure the adoption of best practices and international comparability of results, CHARLS was harmonized with leading international research studies in the Health and Retirement Study (HRS) model. Requests for collaborations should be directed to Dr Yaohui Zhao (yhzhao@nsd.edu.cn). All data in CHARLS are maintained at the National School of Development of Peking University and will be accessible to researchers around the world at the study website. The 2008 pilot data for CHARLS are available at: http://charls.ccer.edu.cn/charls/. National baseline data for the study are expected to be released in January 2013.


The Korea National Health and Nutrition Examination Survey (KNHANES) is a national surveillance system that has been assessing the health and nutritional status of Koreans since 1998. Based on the National Health Promotion Act, the surveys have been conducted by the Korea Centers for Disease Control and Prevention (KCDC). This nationally representative cross-sectional survey includes approximately 10 000 individuals each year as a survey sample and collects information on socioeconomic status, health-related behaviours, quality of life, healthcare utilization, anthropometric measures, biochemical and clinical profiles for non-communicable diseases and dietary intakes with three component surveys: health interview, health examination and nutrition survey. The health interview and health examination are conducted by trained staff members, including physicians, medical technicians and health interviewers, at a mobile examination centre, and dieticians’ visits to the homes of the study participants are followed up. KNHANES provides statistics for health-related policies in Korea, which also serve as the research infrastructure for studies on risk factors and diseases by supporting over 500 publications. KCDC has also supported researchers in Korea by providing annual workshops for data users. KCDC has published the Korea Health Statistics each year, and microdata are publicly available through the KNHANES website (http://knhanes.cdc.go.kr).




Background High maternal pre-pregnancy body mass index (BMI) is associated with increased risk of offspring attention deficit hyperactivity disorder (ADHD). However, the role of unmeasured familial confounding for this association remains unclear.

Methods We conducted a population-based cohort study via linkage of Swedish national and regional registers to investigate maternal pre-pregnancy BMI (underweight: BMI <18.5; overweight: 25≤ BMI <30; obesity: BMI ≥30) in relation to offspring ADHD. We followed 673 632 individuals born in Sweden between 1992 and 2000, with prospectively collected information on maternal pre-pregnancy BMI, until they received an ADHD diagnosis or ADHD medication, death, emigration or 31 December 2009. Hazard ratios (HRs) were estimated by Cox proportional hazards models. Stratified Cox proportional hazards models were applied to data on full siblings to control for unmeasured familial confounding.

Results At the population level, pre-pregnancy overweight/obesity was associated with increased risk of offspring ADHD (HRoverweight = 1.23, 95% CI = 1.18–1.27, P = 0.01; HRobesity = 1.64, 95% CI = 1.57–1.73, P = 0.01), after adjustment for measured covariates. In full sibling comparisons, however, previously observed associations no longer remained (HRoverweight = 0.98, 95% CI = 0.83–1.16, P = 0.82; HRobesity = 1.15, 95% CI = 0.85–1.56, P = 0.38).

Conclusions The results suggested that the association between maternal pre-pregnancy overweight/obesity and offspring ADHD could be ascribed to unmeasured familial confounding.



Background There are concerns about negative effects of relocations between asylum-seeker centres on the mental health of asylum-seeking children. However, empirical evidence comes from cross-sectional studies only. In this longitudinal medical record study, we aimed to assess: (i) whether relocations during the asylum process are associated with the incidence of newly recorded mental distress in asylum-seeking children; and (ii) whether this association is stronger among vulnerable children.

Methods Data were extracted from the electronic medical records database of the Community Health Services for Asylum Seekers in The Netherlands (study period: 1 January 2000–31 December 2008). Included were 8047 children aged 4 to 17 years. Case attribution was done using International Classification of Primary Care codes for mental, behavioural or psychosocial problems. The association between annual relocation rate and incidence of mental distress was measured using relative risks (RR) estimated with multivariate Cox regression models.

Results A high annual relocation rate (>1 relocation/year) was associated with increased incidence of mental distress [RR = 2.70; 95% confidence interval (CI) 2.30–3.17]. The relative risk associated with a high annual relocation rate was larger in children who had experienced violence (RR = 3.87; 95% CI 2.79–5.37) and in children whose mothers had been diagnosed with post-traumatic stress disorder or depression (RR = 3.40; 95% CI 2.50–4.63).

Conclusions The risk of mental distress was greater in asylum-seeking children who had undergone a high annual relocation rate. This risk increase was stronger in vulnerable children. These findings contribute to the appeal for policies that minimize the relocation of asylum seekers.



Background: The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID).

Methods: The sample consisted of 417 303 Swedish children born 1984–2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD.

Results: Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63–1.89] at ages 40–45. For fathers, compared with the median age of 32 years, the OR for ages 55–59 was 1.39 (1.29–1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40–45 (≥97.2th percentile) had an estimated 18.63 (95% CI: 17.25–20.01) ASD cases per 1000 births, whereas fathers aged 55–59 (≥99.7th percentile) had 16.35 (95% CI: 15.11–17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers ≤35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID.

Conclusions: We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.


Background This study uses data from the World Health Organization’s Study on Global Ageing and Adult Health (SAGE) to examine patterns of hypertension prevalence, awareness, treatment and control for people aged 50 years and over in China, Ghana, India, Mexico, the Russian Federation and South Africa.

Methods The SAGE sample comprises of 35 125 people aged 50 years and older, selected randomly. Hypertension was defined as ≥140 mmHg (systolic blood pressure) or ≥90 mmHg (diastolic blood pressure) or by currently taking antihypertensives. Control of hypertension was defined as blood pressure below 140/90 mmHg on treatment. A person was defined as aware if he/she was hypertensive and self-reported the condition.

Results Prevalence rates in all countries are broadly comparable to those of developed countries (52.9%; range 32.3% in India to 77.9% in South Africa). Hypertension was associated with overweight/obesity and was more common in women, those in the lowest wealth quintile and in heavy alcohol consumers. Awareness was found to be low for all countries, albeit with substantial national variations (48.3%; range 23.3% in Ghana to 72.1% in the Russian Federation). This was also the case for control (10.2%; range 4.1% in Ghana to 14.1% India) and treatment efficacy (26.3%; range 17.4% in the Russian Federation to 55.2% in India). Awareness was associated with increasing age, being female and being overweight or obese. Effective control of hypertension was more likely in older people, women and in the richest quintile. Obesity was associated with poorer control.

Conclusions The high rates of hypertension in low- and middle-income countries are striking. Levels of treatment and control are inadequate despite half those sampled being aware of their condition. Since cardiovascular disease is by far the largest cause of years of life lost in these settings, these findings emphasize the need for new approaches towards control of this major risk factor.


Background Ethnic health inequalities are substantial. One explanation relates to socioeconomic differences between groups. However, socioeconomic variables need to be comparable across ethnic groups as measures of socioeconomic position (SEP) and indicators of health outcomes.

Methods We linked self-reported SEP and ethnicity data on 4.65 million individuals from the 2001 Scottish Census to hospital admission and mortality data for cardiovascular disease (CVD). We examined the direction, strength and linearity of association between eight individual, household and area socioeconomic measures and CVD in 10 ethnic groups and the impact of SEP adjustment.

Results There was wide socioeconomic variation between groups. All eight measures showed consistent, positive associations with CVD in White populations, as did educational qualification in non-White ethnic groups. For other SEP measures, associations tended to be consistent with those of White groups though there were one or two exceptions in each non-White group. Multiple SEP adjustment had little effect on relative risk of CVD for most groups. Where it did, the effect varied in direction and magnitude (for example increasing adjusted risk by 23% in Indian men but attenuating it by 11% among Pakistani women).

Conclusions Across groups, SEP measures were inconsistently associated with CVD hospitalization or death, with effect size and direction of effect after adjustment varying across ethnic groups. We recommend that researchers systematically explore the effect of their choice of SEP indicators, using standard multivariate methods where appropriate, to demonstrate their cross-ethnic group validity as potential confounding variables for the specific groups and outcomes of interest.


Background Observationally lower testosterone is associated with an unhealthier cardiovascular (CVD) risk profile, but this association is open to confounding and reverse causality. The authors examined the association of testosterone with well-established cardiovascular disease (CVD) risk factors (blood pressure, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)cholesterol and fasting glucose) and the Framingham score using a Mendelian randomization analysis with a separate-sample instrumental variable estimator.

Methods To minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on three selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). Multivariable censored and linear regressions were used to examine the association of genetically predicted testosterone levels with CVD risk factors and Framingham score among 4212 older Chinese men from the Guangzhou Biobank Cohort Study.

Results Predicted testosterone was unrelated to systolic blood pressure [–0.11 mmHg, 95% confidence interval (CI) –0.70 to 0.48], diastolic blood pressure (0.04 mmHg, 95% CI –0.27 to 0.36), fasting glucose (0.02 mmol/l, 95% CI –0.02 to 0.06) or Framingham score (0.02, 95% CI –0.0001 to 0.03) but associated with higher LDL-cholesterol (0.02 mmol/l, 95% CI 0.01 to 0.04) and lower HDL-cholesterol (–0.01 mmol/l, 95% CI –0.02 to –0.001), after adjustment for potential confounders (age, education, smoking status, use of alcohol and body mass index).

Conclusions Our findings did not corroborate observed protective effects of testosterone on cardiovascular risk factors or risk of ischaemic heart disease among men, but raises the possibility that higher testosterone may be associated with an unhealthier lipid profile.


Background In children being taller is associated with higher blood pressure (BP), but few studies have divided height into its components: trunk and leg length. We examined the associations of total height, trunk length and leg length with systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) at early childhood and mid-childhood visits, as well as change between the two visits.

Methods We obtained five measures of SBP and DBP at the early childhood visit (N = 1153, follow-up rate = 54%) and at the mid-childhood visit (N = 1086, follow-up rate = 51%) respectively, in Project Viva, a US cohort study. We measured total height and sitting height (a measure of trunk length that includes head and neck) and calculated leg length as the difference between the two. Using mixed models, we adjusted the cross-sectional analyses for leg length when trunk length was the exposure of interest, and vice versa. We also adjusted for maternal race/ethnicity, child age, sex, overall adiposity and BP measurement conditions.

Results At the mid-childhood visit, total height was positively associated with SBP [0.34 (0.24; 0.45) mmHg/cm] but not with DBP [0.07 (–0.003; 0.15)]. In models examining trunk and leg length separately, each was positively associated with SBP [0.72 (0.52; 0.92) and 0.33 (0.16; 0.49) respectively]. In a fully adjusted model with both leg and trunk length, only trunk length remained associated with BP. For a given leg length, a 1-cm increment in trunk length was associated with a 0.63-mmHg (0.42; 0.83) higher SBP and a 0.17-mmHg (0.02; 0.31) higher DBP. For a given trunk length, however, the associations of leg length with SBP [0.13 (–0.03; 0.30)] and with DBP [0.002 (–0.11; 0.12)] were null. These patterns were similar at the early childhood visit.

Conclusions Children with greater trunk lengths have higher BPs, perhaps because of the additional pressure needed to overcome gravity to perfuse the brain.


Background: Recent studies have suggested that retirement may have beneficial effects on health outcomes. In this study we examined whether the risk of myocardial infarction (MI) was reduced following retirement in a Danish population sample.

Methods: Participants were 617 511 Danish workers, born between 1932 and 1948, entering the study at the age of 60, without previous known incidents of ischaemic heart disease. Information on retirement and MI were obtained from Danish national registers. A Cox proportional hazard model was used to address the relation between retirement and onset of MI, while adjusting for age, sex, income, occupational position, education, cohabitation and immigrant status. The participants were followed for up to 7 years.

Results: Of the study population, 3% were diagnosed with MI during follow-up. Retirement was associated with a modestly higher risk of MI with a hazard ratio of 1.11 (95% confidence interval: 1.06, 1.16) when comparing retirees with active workers of the same age.

Conclusions: This study does not support the hypothesis that retirement reduces risk of MI. On the contrary, we find that retirement is associated with a modestly increased risk of MI.


Background During pregnancy, woman and fetus exchange small quantities of cells, and their persistence at later times is termed microchimerism. Microchimerism is known to substantially impact on women’s later health. This study examined the survival of women according to male microchimerism status.

Methods Male microchimerism presence, measured as Y chromosome in peripheral blood samples, was determined in 272 women from the large Danish Diet, Cancer and Health cohort when aged 50–64 years during 1993–97. Women were followed up for cause-specific death in national Danish registers until the end of 2009. Survival was analysed using Cox regression.

Results A total of 190 women (70%) were male microchimerism positive. During follow-up 21 women died, of whom 11 (52%) were male microchimerism positive at enrolment and 10 were negative. Of the 21 deaths, 13 (62%) were due to cancer and 5 (24%) were due to cardiovascular disease. Male microchimerism presence was associated with a reduced hazard ratio of all-cause mortality of 0.42 (95% CI 0.17–1.03). The hazard ratio of death from cancer and cardiovascular disease was 0.24 (95% CI 0.08–0.79) and 1.66 (95% CI 0.18–15.48), respectively, among male microchimerism positive compared with negative women.

Conclusions Although the biological mechanisms are not precisely known, male microchimerism presence in peripheral blood of women is associated with substantially improved survival in women. The results also indicate that the association with male microchimerism may vary between different causes of death.


Background Women planning to conceive are often advised to take multivitamins. Whether this affects the survival of the fetus is not known.

Methods We used data from 35 914 women in the Danish National Birth Cohort who at recruitment had reported the number of weeks of supplement use during a 12-week periconceptional period. A telephone interview provided information about maternal characteristics and data on fetal death came from registers. The associations between periconceptional multivitamin or folate-only use and early (<20 weeks) and late (≥20 weeks) fetal death were estimated by hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at 8 completed weeks of gestation, and comparisons were made with no supplement use at any time during the periconceptional period.

Results Any multivitamin use was associated with a small increased crude risk of fetal death [HR 1.12 (1.01–1.25)], which was restricted to early losses [HR 1.18 (1.05–1.33)] compared with late losses [HR 0.82 (0.62–1.10)]. Adjustment for maternal factors increased this excess risk further. Whereas regular users of multivitamins (4–6 weeks of 6) before conception had more early losses [HR 1.29 (1.12–1.48)], a decreased risk of late losses was indicated when use started after conception [HR 0.65 (0.39–1.09)]. Folate-only use was not associated with fetal death.

Conclusions Multivitamin use was associated with a modest increased risk of early fetal death. For late fetal death, regular supplement use after conception may decrease risk, but numbers were small. Further studies on preconceptional multivitamin use are needed to guide public health recommendations.



Background Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), commonly used as markers of liver dysfunction, have been implicated with risk of all-cause mortality. The prospective evidence on the associations in general populations has not been reliably quantified.

Methods We conducted a systematic review and meta-analysis of published prospective cohort studies evaluating the associations of baseline levels of these enzymes with all-cause mortality in general populations. Relevant studies were identified in a literature search of MEDLINE, EMBASE and Web of Science up to March 2013. Authors of unpublished studies provided data on request.

Results Nineteen unique cohort studies with aggregate data on over 9.24 million participants and 242 953 all-cause mortality outcomes were included. In a comparison of extreme thirds of baseline GGT and ALP levels, relative risks (RRs) (95% confidence intervals) for all-cause mortality were 1.60 (1.42-1.80) and 1.38 (1.17-1.63), respectively. The corresponding RRs for ALT were 0.82 (0.78-0.86) and 1.43 (1.08-1.90) in North American and Asian populations, respectively. There was no strong evidence of an association of AST with all-cause mortality: RR 1.23 (0.80-1.88). The pooled RRs per 5 U/l increment in GGT and ALP levels were 1.07 (1.04-1.10) and 1.03 (1.01-1.06), respectively.

Conclusions Available data indicate positive independent associations of baseline levels of GGT and ALP with all-cause mortality, consistent with linear dose-response relationships. There were geographical variations in the association of ALT with all-cause mortality which require further investigation. The potential incremental prognostic values of GGT and ALP in mortality risk assessment need evaluation.



Background Between 1997 and 2009, a number of key malaria control interventions were implemented in the Kilombero and Ulanga Districts in south central Tanzania to increase insecticide-treated nets (ITN) coverage and improve access to effective malaria treatment. In this study we estimated the contribution of these interventions to observed decreases in child mortality.

Methods The local Health and Demographic Surveillance Site (HDSS) provided monthly estimates of child mortality rates (age 1 to 5 years) expressed as cases per 1000 person-years (c/1000py) between 1997 and 2009. We conducted a time series analysis of child mortality rates and explored the contribution of rainfall and household food security. We used Poisson regression with linear and segmented effects to explore the impact of malaria control interventions on mortality.

Results Child mortality rates decreased by 42.5% from 14.6 c/1000py in 1997 to 8.4 c/1000py in 2009. Analyses revealed the complexity of child mortality patterns and a strong association with rainfall and food security. All malaria control interventions were associated with decreases in child mortality, accounting for the effect of rainfall and food security.

Conclusions Reaching the fourth Millenium Development Goal will require the contribution of many health interventions, as well as more general improvements in socio-environmental and nutritional conditions. Distinguishing between the effects of these multiple factors is difficult and represents a major challenge in assessing the effect of routine interventions. However, this study suggests that credible estimates can be obtained when high-quality data on the most important factors are available over a sufficiently long time period.


Background Data from West Africa indicate that a small thymus at birth and at 6 months of age is a strong and independent risk factor for infection-related mortality up to 24 and 36 months of age, respectively. We investigated the association between thymus size (thymic index, TI) in infancy and subsequent infant and child survival in a contemporary South Asian population.

Methods The study focused on the follow-up of a randomized trial of prenatal nutritional interventions in rural Bangladesh (ISRCTN16581394), with TI measured longitudinally in infancy (at birth and weeks 8, 24 and 52 of age) and accurate recording of mortality up to 5 years of age.

Results A total of 3267 infants were born into the Maternal and Infant Nutrition Interventions, Matlab study; data on TI were available for 1168 infants at birth, increasing to 2094 infants by 52 weeks of age. TI in relation to body size was largest at birth, decreasing through infancy. For infants with at least one measure of TI available, there were a total of 99 deaths up to the age of 5 years. No association was observed between TI and subsequent mortality when TI was measured at birth. However, an association with mortality was observed with TI at 8 weeks of age [odds ratio (OR) for change in mortality risk associated with 1 standard deviation change in TI: all deaths: OR = 0.64, 95% confidence interval (CI) 0.41, 0.98; P = 0.038; and infection-related deaths only: OR = 0.32, 95% CI 0.14, 0.74; P = 0.008]. For TI when measured at 24 and 52 weeks of age, the numbers of infection-related deaths were too few (3 and 1, respectively) for any meaningful association to be observed.

Conclusion These results confirm that thymus size in early infancy predicts subsequent survival in a lower mortality setting than West Africa. The absence of an effect at birth and its appearance at 8 weeks of age suggests early postnatal influences such as breast milk trophic factors.


Background: Artificial fluoridation of drinking water to improve dental health has long been a topic of controversy. Opponents of this public health measure have cited the possibility of bone cancer induction. The study objective was to examine whether increased risk of primary bone cancer was associated with living in areas with higher concentrations of fluoride in drinking water.

Methods: Case data on osteosarcoma and Ewing sarcoma, diagnosed at ages 0–49 years in Great Britain (GB) (defined here as England, Scotland and Wales) during the period 1980–2005, were obtained from population-based cancer registries. Data on fluoride levels in drinking water in England and Wales were accessed through regional water companies and the Drinking Water Inspectorate. Scottish Water provided data for Scotland. Negative binomial regression was used to examine the relationship between incidence rates and level of fluoride in drinking water at small area level.

Results: The study analysed 2566 osteosarcoma and 1650 Ewing sarcoma cases. There was no evidence of an association between osteosarcoma risk and fluoride in drinking water [relative risk (RR) per one part per million increase in the level of fluoride = 1·001; 90% confidence interval (CI) 0·871, 1·151] and similarly there was no association for Ewing sarcoma (RR = 0·929; 90% CI 0·773, 1·115).

Conclusions: The findings from this study provide no evidence that higher levels of fluoride (whether natural or artificial) in drinking water in GB lead to greater risk of either osteosarcoma or Ewing sarcoma.


Background Needle and syringe programmes (NSP) aim to reduce the risk of HIV by providing people who inject drugs (PWID) with sterile injecting equipment. A recent review of reviews (ROR) concluded that there was only tentative evidence to support the effectiveness of NSP in reducing HIV. We carried out a systematic review and meta-analysis to assess the association between NSP and HIV transmission.

Methods Relevant primary articles presenting data on the risk of HIV transmission associated with NSP were identified in two stages: (i) from reviews identified in two published RORs (covering the period 1980–2008); and (ii) a literature search of CINAHL, Cochrane Library, EMBASE, MEDLINE and PsychINFO for primary articles published since the most recent high quality review (covering the period 2008–12). Study results were synthesized using random-effects meta-analysis.

Results There were 12 studies comprising at least 12 000 person-years of follow-up. Exposure to NSP was associated with a reduction in HIV transmission: pooled effect size 0·66 [95% confidence interval (CI) 0·43, 1·01] across all studies, and 0·42 (95% CI 0·22, 0·81) across six higher quality studies (according to the Newcastle-Ottawa tool).

Conclusions There is evidence to support the effectiveness of NSP in reducing the transmission of HIV among PWID, although it is likely that other harm reduction interventions have also contributed to the observed reduction in HIV risk. NSP should be considered as just one component of a programme of interventions to reduce both injecting risk and other types of HIV risk behaviour.


Background There is evidence that South Asian individuals have higher fat mass for a given weight than Europeans. One study reported that the greater fatness for a given birthweight may increase with increasing birthweight, suggesting that any attempt to increase mean birthweight in South Asians would markedly increase their fatness.

Objective Our objective was to examine whether differences in cord leptin values between White British and Pakistani infants vary by birthweight category.

Method We examined the difference in cord leptin levels between 659 White British and 823 Pakistani infants recruited to the Born in Bradford cohort study, by clinical categories and thirds of the birthweight distribution.

Results Pakistani infants had a lower mean birthweight but higher cord leptin levels than White British infants [ratio of geometric mean (RGM) of cord leptin adjusted for birthweight = 1.36 (95% CI 1.26, 1.46)]. Birthweight was positively associated with cord leptin levels in both groups, with no evidence that the regression lines in the two groups diverged from each other with increasing birthweight. The relative ethnic difference in cord leptin was similar in low (<2500 g), normal and high (≥4000 g) birthweight infants (P-value for interaction = 0.91). It was also similar across thirds of the birthweight distribution [RGM (95% CI) in lowest, mid and highest thirds were 1.37 (1.20, 1.57), 1.36 (1.20, 1.54) and 1.31 (1.16, 1.52), respectively, P-interaction = 0.51].

Conclusions We found marked differences in cord leptin levels between Pakistani and White British infants but no evidence that this difference increases with increasing birthweight.


Background Endometriosis has been associated with a higher risk of cutaneous melanoma, but the mechanisms underlying this association are unknown. Some constitutional factors known to influence melanoma risk have been associated with endometriosis in some retrospective studies. However, prospective data are scarce, and more research is needed to confirm this potentially novel endometriosis risk profile.

Methods To investigate the relationships between pigmentary traits, family history of melanoma and endometriosis risk, we analysed data from the Nurses’ Health Study II, a cohort of 116 430 female US nurses aged 25–42 years at inclusion in 1989. Data were collected every 2 years with 20 years of follow-up for these analyses. We used Cox proportional hazards regression models to compute relative risks (RRs) and 95% confidence intervals (CIs).

Results During 1 212 499 woman-years of follow-up, 4763 cases of laparoscopically-confirmed endometriosis were reported among premenopausal Caucasian women. Endometriosis risk was increased with presence of naevi on the lower legs (RR = 1.08, 95% CI = 1.02–1.14) and higher level of skin’s burning reaction to sun exposure in childhood/adolescence (‘burn with blisters’: RR = 1.20, 95% CI = 1.06–1.36) compared with ‘practically none’; Ptrend = 0.0006) and family history of melanoma (RR = 1.13, 95% CI = 1.01–1.26).

Conclusion This assessment reports modest associations between several pigmentary traits, family history of melanoma and endometriosis risk, corroborating the results from previous retrospective studies. Our findings call for further research to better understand the mechanisms underlying these associations.


The analysis of repeated measures or panel data allows control of some of the biases which plague other observational studies, particularly unmeasured confounding. When this bias is suspected, and the research question is: ‘Does a change in an exposure cause a change in the outcome?’, a fixed effects approach can reduce the impact of confounding by time-invariant factors, such as the unmeasured characteristics of individuals. Epidemiologists familiar with using mixed models may initially presume that specifying a random effect (intercept) for every individual in the study is an appropriate method. However, this method uses information from both the within-individual/unit exposure-outcome association and the between-individual/unit exposure-outcome association. Variation between individuals may introduce confounding bias into mixed model estimates, if unmeasured time-invariant factors are associated with both the exposure and the outcome. Fixed effects estimators rely only on variation within individuals and hence are not affected by confounding from unmeasured time-invariant factors. The reduction in bias using a fixed effects model may come at the expense of precision, particularly if there is little change in exposures over time. Neither fixed effects nor mixed models control for unmeasured time-varying confounding or reverse causation.