• Home
  • News
  • Calendar
  • About DF/HCC
  • Membership
  • Visitor Center
 

Member Resources

Publications

International Journal of Epidemiology

International Journal of Epidemiology - RSS feed of current issue


This study was designed in 1962 to investigate the reformative effect of a particular punishment (caning) for a particular offence (smoking by schoolboys). In 1964, in the course of a larger study of juvenile offences, delinquency records were obtained from the police, and the relationship between smoking and delinquency is also discussed in this paper.






The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997–98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6–12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up.


We established Project Viva to examine prenatal diet and other factors in relation to maternal and child health. We recruited pregnant women at their initial prenatal visit in eastern Massachusetts between 1999 and 2002. Exclusion criteria included multiple gestation, inability to answer questions in English, gestational age ≥22 weeks at recruitment and plans to move away before delivery. We completed in-person visits with mothers during pregnancy in the late first (median 9.9 weeks of gestation) and second (median 27.9 weeks) trimesters. We saw mothers and children in the hospital during the delivery admission and during infancy (median age 6.3 months), early childhood (median 3.2 years) and mid-childhood (median 7.7 years). We collected information from mothers via interviews and questionnaires, performed anthropometric and neurodevelopmental assessments and collected biosamples. We have collected additional information from medical records and from mailed questionnaires sent annually to mothers between in-person visits and to children beginning at age 9 years. From 2341 eligible women, there were 2128 live births; 1279 mother-child pairs provided data at the mid-childhood visit. Primary study outcomes include pregnancy outcomes, maternal mental and cardiometabolic health and child neurodevelopment, asthma/atopy and obesity/cardiometabolic health. Investigators interested in learning more about how to obtain Project Viva data can contact Project_Viva@hphc.org.


The main aim of the Leucémies de l’Enfant et l’Adolescent (LEA) project (Childhood and Adolescent Leukaemia) is to study the determinants (medical, socioeconomic, behavioural and environmental) of medium- and long-term outcomes of patients treated for childhood acute leukaemia (AL). The LEA study began in 2004 and is based on a French multicentric prospective cohort. Included are children treated for AL since January 1980 (incident and prevalent cases), surviving at month 24 for myeloblastic AL and lymphoblastic AL grafted in first complete remission or at month 48 for lymphoblastic AL not grafted in first complete remission. Information is collected during specific medical visits and notably includes the following data: socioeconomic data, AL history, physical late effects (such as fertility, cardiac function and metabolic syndrome) and quality of life. Data are collected every 2 years until the patient is 20 years old and has had a 10-year follow-up duration from diagnosis or last relapse. Thereafter, assessments are planned every 4 years. In active centres in 2013, eligible patients number more than 3000. The cohort has already included 2385 survivors, with rate of exhaustiveness of almost 80%. Data access can be requested from principal coordinators and must be approved by the steering committee.


Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca).


Chronic diseases are a global problem, yet information on their determinants is generally scant in low- and middle-income countries. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information regarding the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes, in one such setting. At Visit 1, we enrolled 15 105 civil servants from predefined universities or research institutes. Baseline assessment (2008–10) included detailed interviews and measurements to assess social and biological determinants of health, as well as various clinical and subclinical conditions related to diabetes, cardiovascular diseases and mental health. A second visit of interviews and examinations is under way (2012–14) to enrich the assessment of cohort exposures and to detect initial incident events. Annual surveillance has been conducted since 2009 for the ascertainment of incident events. Biological samples (sera, plasma, urine and DNA) obtained at both visits have been placed in long-term storage. Baseline data are available for analyses, and collaboration via specific research proposals directed to study investigators is welcome.


TRAILS consists of a population cohort (N = 2230) and a clinical cohort (N = 543), both of which were followed from about age 11 years onwards. To date, the population cohort has been assessed five times over a period of 11 years, with retention rates ranging between 80% and 96%. The clinical cohort has been assessed four times over a period of 8 years, with retention rates ranging between 77% and 85%. Since the IJE published a cohort profile on the TRAILS in 2008, the participants have matured from adolescents into young adults. The focus shifted from parents and school to entry into the labour market and family formation, including offspring. Furthermore, psychiatric diagnostic interviews were administered, the database was linked to a Psychiatric Case Registry, and the availability of genome-wide SNP variations opened the door to genome-wide association studies regarding a wide range of (endo)phenotypes. With some delay, TRAILS data are available to researchers outside the TRAILS consortium without costs; access can be obtained by submitting a publication proposal (see www.trails.nl).


The original GAZEL cohort was composed of 20 625 employees of the French national gas and electricity companies (15 011 male employees then aged 40 to 50 years and 5614 women between 35 and 50 years old) at its inception in 1989. A Cohort Profile article was published in 2007. By the end of 2013, participants were aged 60–75, and almost all of them retired during follow-up. Accordingly, the main focus of research in the past decade was devoted to the study of the persistent, long-term effects of occupational exposures after retirement; of the transition between professionally active life and retirement; and on determinants of early ageing. Accordingly, in addition to the health, behavioural and social data collected yearly since the beginning of the follow-up, new data were thus collected on cognitive complaints, cognitive and physical functioning, limitations in daily activities, time use and social relationships of retirees. This update presents the main findings of research within the GAZEL Cohort Study during the past 7 years.

Any research group, in France or elsewhere, can submit a research proposal to work on the GAZEL cohort. To do this, interested researchers should contact one of the principal investigators of the GAZEL Cohort Study.


The Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes began in 1981 with data collected on 7223 pregnant woman-child pairs (6753 mothers, of whom 520 had 2 study children, less 50 who had multiple births). These women, and their children, were initially followed for up to 21 years. Since then there have been additional follow-ups of the mothers (27 years) and their children (30 years). There has also been a substantial increase in the breadth of topics addressed, with the collection of biological samples, the administration of structured clinical assessments of mental health and cognitive capacity, and markers of physical health such as lung function and blood pressure. MUSP was originally developed as a birth cohort study. It has become a longitudinal study of growth, development and ageing with an emphasis on the generational transmission of a wide range of factors impacting on adult health outcomes. We welcome interest in our study; for study background and publications visit [www.socialscience.uq.edu.au/musp] or contact [j.najman@uq.edu.au].


The Sentinel Panel of Districts (SPD) consists of 23 districts selected to provide nationally representative data on demographic and health indicators in Tanzania. The SPD has two arms: SAVVY and FBIS. SAVVY (SAmple Vital registration with Verbal autopsY) is a demographic surveillance system that provides nationally representative estimates of mortalities based on age, sex, residence and zone. SAVVY covers over 805 000 persons, or about 2% of the Tanzania mainland population, and uses repeat household census every 4–5 years, with ongoing reporting of births, deaths and causes of deaths. The FBIS (Facility-Based Information System) collects routine national health management information system data. These health service use data are collected monthly at all public and private health facilities in SPD districts, i.e. about 35% of all facilities in Mainland Tanzania. Both SAVVY and FBIS systems are capable of generating supplementary information from nested periodic surveys. Additional information about the design of the SPD is available online: access to some of SPD’s aggregate data can be requested by sending an e-mail to [hmasanja@ihi.or.tz].


The Taabo Health and Demographic Surveillance System (HDSS) is located in south-central Côte d’Ivoire, approximately 150 km north-west of Abidjan. The Taabo HDSS started surveillance activities in early 2009 and the man-made Lake Taabo is a key eco-epidemiological feature. Since inception, there has been a strong interest in research and integrated control of water-associated diseases such as schistosomiasis and malaria. The Taabo HDSS has generated setting-specific evidence on the impact of targeted interventions against malaria, schistosomiasis and other neglected tropical diseases.

The Taabo HDSS consists of a small town, 13 villages and over 100 hamlets. At the end of 2013, a total population of 42 480 inhabitants drawn from 6707 households was under surveillance. Verbal autopsies have been conducted to determine causes of death. Repeated cross-sectional epidemiological surveys on approximately 5–7% of the population and specific, layered-on haematological, parasitological and questionnaire surveys have been conducted.

The Taabo HDSS provides a database for surveys, facilitates interdisciplinary research, as well as surveillance, and provides a platform for the evaluation of health interventions. Requests to collaborate and to access data are welcome and should be addressed to the secretariat of the Centre Suisse de Recherches Scientifiques en Côte d’Ivoire: [secretariat@csrs.ci].


The Birbhum HDSS was established in 2008 and covers 351 villages in four administrative blocks in rural areas of Birbhum district of West Bengal, India. The project currently follows 54 585 individuals living in 12 557 households. The population being followed up is economically underprivileged and socially marginalized. The HDSS, a prospective longitudinal cohort study, has been designed to study changes in population demographic, health and healthcare utilization. In addition to collecting data on vital statistics and antenatal and postnatal tracking, verbal autopsies are being performed. Moreover, periodic surveys capturing socio-demographic and economic conditions have been conducted twice. Data on nutritional status (children as well as adults), non-communicable diseases, smoking etc. have also been collected in special surveys. Currently, intervention studies on anaemia, undernutrition and common preschool childhood morbidities through behavioural changes are under way. For access to the data, a researcher needs to send a request to the Data Manager [suri.shds@gmail.com]. Data are shared in common formats like comma-separated files (csv) or Microsoft Excel (xlsx) or Microsoft Access Database (mdb).The HDSS will soon upgrade its data management system to a more integrated platform, coordinated and guided by INDEPTH data sharing policy.


Background Systolic blood pressure, total cholesterol and smoking are known predictors of cardiovascular disease (CVD) mortality. Less is known about the effect of lifetime accumulation and changes of risk factors over time as predictors of CVD mortality, especially in very long follow-up studies.

Methods Data from the Finnish cohorts of the Seven Countries Study were used. The baseline examination was in 1959 and seven re-examinations were carried out at approximately 5-year intervals. Cohorts were followed up for mortality until the end of 2011. Time-dependent Cox models with regular time-updated risk factors, time-dependent averages of risk factors and latest changes in risk factors, using smoothing splines to discover nonlinear effects, were used to analyse the predictive effect of risk factors for CVD mortality.

Results A model using cumulative risk factors, modelled as the individual-level averages of several risk factor measurements over time, predicted CVD mortality better than a model using the most recent measurement information. This difference seemed to be most prominent for systolic blood pressure. U-shaped effects of the original predictors can be explained by partitioning a risk factor effect between the recent level and the change trajectory. The change in body mass index predicted the risk although body mass index itself did not.

Conclusions The lifetime accumulation of risk factors and the observed changes in risk factor levels over time are strong predictors of CVD mortality. It is important to investigate different ways of using the longitudinal risk factor measurements to take full advantage of them.


Background The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects.

Methods PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS).

Results In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS.

Conclusions PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population.


Background It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation.

Methods Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997–2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme).

Results During 11.6 million person-years of follow-up, 114 859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers’ lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR) = 1.04, 95% confidence interval (CI) 0.91–1.19).The strength of association differed markedly according to disease type: stable angina (HR = 1.08, 95% CI 1.01–1.15),transient ischaemic attack (HR = 1.41, 95% CI 1.28-1.55), unstable angina (HR = 1.54, 95% CI 1.38–1.72), intracerebral haemorrhage (HR = 1.61, 95% CI 1.37–1.89), heart failure (HR = 1.62, 95% CI 1.47–1.79), ischaemic stroke (HR = 1.90, 95% CI 1.72–2.10), MI (HR = 2.32, 95% CI 2.20–2.45), SAH (HR = 2.70, 95% CI 2.27–3.21), PAD (HR = 5.16, 95% CI 4.80–5.54) and abdominal aortic aneurysm (AAA) (HR = 5.18, 95% CI 4.61–5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR = 1.36, 1.47 and 2.74, respectively).

Conclusions The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction.


Background: Experimental studies suggest oxidative stress could lead to the development of hypertension. Serum bilirubin is a major contributor to the antioxidant capacity in blood plasma and has been identified as an independent cardiovascular risk factor in cohort studies. However, data on the relationship between bilirubin and blood pressure are scarce and inconclusive.

Methods: We analysed data from the National Health and Nutrition Examination Surveys (NHANES) 1999–2012 (N = 31 069). Fifty multiple imputed data sets were generated and analysed to avoid selection/confounding bias due to excluding individuals/variables with missing values. A minimal sufficient adjustment set of variables (MSAS) needed to estimate the unconfounded effect of bilirubin on blood pressure and hypertension (systolic/diastolic blood pressure ≥140/90 mmHg or using antihypertensive medication) was identified using the back-door criterion and included in all regression models.

Results: After adjustment for the MSAS variables, systolic blood pressure decreased progressively up to –2.5 mmHg (p < 0.001) and the prevalence of hypertension was up to 25% lower (P < 0.001) in those with bilirubin ≥1.0 mg/dl—the highest two deciles—compared with those with 0.1–0.4 mg/dl–the lowest decile. Sensitivity analyses showed these results were unlikely to be explained by residual confounding or selection bias.

Conclusions: High serum bilirubin may decrease the risk of hypertension by inactivating and inhibiting the synthesis of reactive oxygen species in vascular cells. Strategies to boost the bioavailability of circulating and tissue bilirubin or to mimic bilirubin's antioxidant properties could have a significant impact on prevention and control of hypertension as well as coronary heart disease.


Background: High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers.

Methods: We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity.

Results: Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours.

Conclusions: Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.


Background: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients.

Methods: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old (‘young adults’, 2010 cases and 4042 controls) and >45 years old (‘older adults’, 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

Results: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (–11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (–2.41%, 5.80%) in older adults.

Conclusions: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.


Background: The aetiology of pancreatic cancer (PC) has been extensively studied and is the subject of numerous meta-analyses and pooled analyses. We have summarized results from these pooled and meta-analytical studies to estimate the fraction of PCs attributable to each of the identified risk factors.

Methods: Using a comprehensive strategy, we retrieved 117 meta-analytical or pooled reports dealing with the association between specific risk factors and PC risk. We combined estimates of relative risk and estimates of exposure to calculate the fraction of PCs caused or prevented by a particular exposure.

Results: Tobacco smoking (‘strong’ evidence) and Helicobacter pylori infection (‘moderate’ evidence) are the major risk factors associated with PC, with respective estimated population attributable fractions of 11–32% and 4–25%. The major protective factors are history of allergy (‘strong’ evidence) and increasing fruit or folate intake (‘moderate’ evidence), with respective population preventable fractions of 3–7% and 0–12%.

Conclusions: We summarized results of 117 meta-analytical or pooled data reports dealing with 37 aetiological exposures, to obtain robust information about the suspected causes of PC. By combining these estimates with their prevalences in the population, we calculated population attributable or population preventable fractions. About two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.


Background: Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient.

Methods: A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring.

Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index ≥30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12–24 months of age.

Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model.

Results: The study included 85 509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98–1.06) and 1.20 (95% CI: 0.98–1.47) for hypertensive disorders; 1.09 (95% CI: 1.01–1.18) and 1.23 (95% CI: 1.07–1.43) for preeclampsia; 1.04 (95% CI: 0.97–1.13) and 1.24 (95% CI: 0.86–1.79) for diabetes; 1.08 (95% CI: 1.05–1.11) and 1.19 (95% CI: 1.12–1.26) for overweight; 1.12 (95% CI: 1.08–1.17) and 1.16 (95% CI: 0.97–1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P = 0.027).

Conclusions: Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring.


Background: Obstetric management of term breech infants changed dramatically following the Term Breech Trial which suggested increased serious neonatal morbidity following trial of labour. Short-term morbidity is a poor proxy of long-term neurological sequelae. We determined whether vaginal breech delivery was associated with educational outcomes.

Methods: We linked three Scotland-wide administrative databases at an individual level: the ScotXed school census; Scottish Qualifications Authority (SQA) examination results; and Scottish Morbidity Record (SMR02) maternity database. The linkage provided information on singleton children, born at term, attending Scottish schools between 2006 and 2011.

Results: Of the 456 947 eligible children, 1574 (0.3%) had vaginal breech deliveries, 12 489 (2.7%) planned caesarean section for breech presentation and 442 090 (96.9%) vaginal cephalic deliveries. The percentage of term breech infants delivered vaginally fell from 23% to 7% among children who started school in 2006 and 2011, respectively. Of children born by vaginal breech delivery, 1.5% had a low 5-min Apgar score (≤3) compared with only 0.4% of those born by either breech caesarean section [adjusted odds ratio (OR) 6.16, 95% confidence interval (CI) 4.44–8.54, p < 0.001] or cephalic vaginal delivery (adjusted OR 3.84, 95% CI 2.99–4.93, p < 0.001). Children born by vaginal breech delivery had lower examination attainment than those born by either planned caesarean section for breech presentation (adjusted OR 1.16, 95% CI 1.02–1.32, p = 0.020) or vaginal cephalic delivery (adjusted OR 1.14, 95% CI 1.01–1.28, p = 0.029).

Conclusions: Vaginal delivery of term breech infants was associated with lower examination attainment, as well as poorer Apgar scores, suggesting that the adverse effects are not just short-term.


Background: Parental investments in children are an important determinant of human capability formation. We investigated the causal effect of household expenditure on Indonesian children’s cognitive function between 2000 and 2007. We also investigated the effect of change in mean cognitive function from a simulation of a hypothetical cash transfer intervention.

Methods: A longitudinal analysis using data from the Indonesian Family Life Survey (IFLS) was conducted including 6136 children aged 7 to 14 years in 2000 and still alive in 2007. We used the inverse probability of treatment weighting of a marginal structural model to estimate the causal effect of household expenditure on children’s cognitive function.

Results: Cumulative household expenditure was positively associated with cognitive function z-score. From the marginal structural model, a 74534 rupiah/month (about US$9) increase in household expenditure resulted in a 0.03 increase in cognitive function z-score [β = 0.32, 95% confidence interval (CI) 0.30–0.35] Based on our simulations, among children in the poorest households in 2000 an additional US$6–10 of cash transfer resulted in a 0.01 unit increase in cognitive function z-score, equivalent to about 6% increase from the mean z-score prior to cash transfer. In contrast, children in the poorest household in 2007 did not benefit from an additional US$10 cash transfer. We found no overall effect of cash transfers at the total population level.

Conclusions: Greater household expenditure had a small causal effect on children’s cognitive function. Although cash transfer interventions had a positive effect for poor children, this effect was quite small. Multi-faceted interventions that combine nutrition, cash transfer, improved living conditions and women’s education are required to benefit children’s cognitive development in Indonesia.


Background: When comparing the health of two populations, it is not enough to compare the prevalence of chronic diseases. The objective of this study is therefore to propose a metric of health based on domains of functioning to determine whether the English are healthier than the Americans.

Methods: We analysed representative samples aged 50 to 80 years from the 2008 wave of the Health and Retirement Study (N = 10 349) for the US data, and wave 4 of the English Longitudinal Study of Ageing (N = 9405) for English counterpart data. We first calculated the age-standardized disease prevalence of diabetes, hypertension, all heart diseases, stroke, lung disease, cancer and obesity. Second, we developed a metric of health using Rasch analyses and the questions and measured tests common to both surveys addressing domains of human functioning. Finally, we used a linear additive model to test whether the differences in health were due to being English or American.

Results: The English have better health than the Americans when population health is assessed only by prevalence of selected chronic health conditions. The English health advantage disappears almost completely, however, when health is assessed with a metric that integrates information about functioning domains.

Conclusions: It is possible to construct a metric of health, based on data directly collected from individuals, in which health is operationalized as domains of functioning. Its application has the potential to tackle one of the most intractable problems in international research on health, namely the comparability of health across countries.



Background: Nickel exposure can induce hyperglycaemia in rodents, but little is known about its association with abnormal glucose metabolism in humans. We aimed to investigate the association of nickel exposure with the prevalence of type 2 diabetes in Chinese adults.

Methods: A total of 2115 non-institutionalized men and women aged 55 to 76 years from Beijing and Shanghai were included, and urinary nickel concentration was assessed by inductively coupled plasma mass spectroscopy. The prevalence of type 2 diabetes was compared across urinary nickel quartiles. Fasting plasma glucose, insulin, lipids, C-reactive protein and glycated haemoglobin A1c, as well as urinary albumin and creatinine were measured.

Results: The median concentration of urinary nickel was 3.63 µg/l (interquartile range: 2.29–5.89 µg/l), and the prevalence of diabetes was 35.3% (747 cases/2115 persons). Elevated levels of urinary nickel were associated with higher fasting glucose, glycated haemoglobin A1c, insulin and homeostatic model assessment of insulin resistance (all P < 0.01). The odds ratios (95% confidence interval) for diabetes across the increasing urinary nickel quartiles were 1.27 (0.97–1.67), 1.78 (1.36–2.32) and 1.68 (1.29–2.20), respectively (referencing to 1.00), after multivariate adjustment including lifestyle factors, body mass index and family history of diabetes (P for trend <0.001). The association remained unchanged after further controlling for urinary creatinine and C-reactive protein (P for trend <0.001).

Conclusions: Increased urinary nickel concentration is associated with elevated prevalence of type 2 diabetes in humans.



Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally.

Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years.

Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517–541] in North America, 494/µl (95% CI: 429–559) in West Africa, 515/µl (95% CI: 508–522) in Southern Africa, 503/µl (95% CI: 478–528) in Asia and 437/µl (95% CI: 425–449) in East Africa.

Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.


Background: Several popular screening tests, such as mammography and prostate-specific antigen, have met with wide controversy and/or have lost their endorsement recently. We systematically evaluated evidence from randomized controlled trials (RCTs) as to whether screening decreases mortality from diseases where death is a common outcome.

Methods: We searched three sources: United States Preventive Services Task Force (USPSTF), Cochrane Database of Systematic Reviews, and PubMed. We extracted recommendation status, category of evidence and RCT availability on mortality for screening tests for diseases on asymptomatic adults (excluding pregnant women and children) from USPSTF. We identified meta-analyses and individual RCTs on screening and mortality from Cochrane and PubMed.

Results: We selected 19 diseases (39 tests) out of 50 diseases/disorders for which USPSTF provides screening evaluation. Screening is recommended for 6 diseases (12 tests) out of the 19. We assessed 9 non-overlapping meta-analyses and 48 individual trials for these 19 diseases. Among the results of the meta-analyses, reductions where the 95% confidence intervals (CIs) excluded the null occurred for four disease-specific mortality estimates (ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer; fecal occult blood test and flexible sigmoidoscopy for colorectal cancer) and for none of the all-cause mortality estimates. Among individual RCTs, reductions in disease-specific and all-cause mortality where the 95% CIs excluded the null occurred in 30% and 11% of the estimates, respectively.

Conclusions: Among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and reductions in all-cause mortality are very rare or non-existent.





The prevalence of vitamin A (VA) deficiency, which affects about one-third of children in developing countries, is falling only slowly. This is despite extensive distribution and administration of periodic (4– to 6-monthly) high-dose VA capsules over the past 20 years, now covering a reported 80% of children in developing countries. This massive programme was motivated largely by an expectation of reducing child mortality, stemming from findings in the 1980s and early 90s. Efficacy trials since 1994 have in most cases not confirmed a mortality impact of VA capsules. Only one large scale programme evaluation has ever been published, which showed no impact on 1–6–year-old mortality (the DEVTA trial, ending in 2003, in Uttar Pradesh, India). Periodic high-dose VA capsules may have less relevance now with changing disease patterns (notably, reductions in measles and diarrhoea). High-dose VA 6-monthly does not reduce prevalence of the deficiency itself, estimated by low serum retinol. It is proposed that: (i) there is no longer any evidence that intermittent high-dose VA programmes are having any substantial mortality effect, perhaps due to changing disease patterns; (ii) frequent intakes of vitamin A in physiological doses —e.g. through food-based approaches, including fortification, and through regular low-dose supplementation—are highly effective in increasing serum retinol (SR) and reducing vitamin A deficiency; (iii) therefore a policy shift is needed, based on consideration of current evidence. A prudent phase-over is needed towards increasing frequent regular intakes of VA at physiological levels, daily or weekly, replacing the high-dose periodic capsule distribution programmes. Moving resources in this direction must happen sooner or later: it should be sooner.





Background: This article is part of a series commissioned by the International Epidemiological Association, aimed at describing population health and epidemiological resources in the six World Health Organization (WHO) regions. It covers 32 of the 53 WHO European countries, namely the Western European countries, the Balkan countries and the Baltic countries.

Methods: The burdens of mortality and morbidity and the patterns of risk factors and inequalities have been reviewed in order to identify health priorities and challenges. Literature and internet searches were conducted to stock-take epidemiological teaching, research activities, funding and scientific productivity.

Findings: These countries have among the highest life expectancies worldwide. However, within- and between-country inequalities persist, which are largely due to inequalities in distribution of main health determinants. There is a long tradition of epidemiological research and teaching in most countries, in particular in the Western European countries. Cross-national networks and collaborations are increasing through the support of the European Union which fosters procedures to standardize educational systems across Europe and provides funding for epidemiological research through framework programmes. The number of Medline-indexed epidemiological research publications per year led by Western European countries has been increasing. The countries accounts for nearly a third of the global epidemiological publication.

Conclusions: Although population health has improved considerably overall, persistent within- and between-country inequalities continue to challenge national and European health institutions. More research, policy and action on the social determinants of health are required in the region. Epidemiological training, research and workforce in the Baltic and Balkan countries should be strengthened. European epidemiologists can play pivotal roles and must influence legislation concerning production and access to high-quality data.


In many biomedical studies, the event of interest can occur more than once in a participant. These events are termed recurrent events. However, the majority of analyses focus only on time to the first event, ignoring the subsequent events. Several statistical models have been proposed for analysing multiple events. In this paper we explore and illustrate several modelling techniques for analysis of recurrent time-to-event data, including conditional models for multivariate survival data (AG, PWP-TT and PWP-GT), marginal means/rates models, frailty and multi-state models. We also provide a tutorial for analysing such type of data, with three widely used statistical software programmes. Different approaches and software are illustrated using data from a bladder cancer project and from a study on lower respiratory tract infection in children in Brazil. Finally, we make recommendations for modelling strategy selection for analysis of recurrent event data.


Backgound: The term ‘joint modelling’ is used in the statistical literature to refer to methods for simultaneously analysing longitudinal measurement outcomes, also called repeated measurement data, and time-to-event outcomes, also called survival data. A typical example from nephrology is a study in which the data from each participant consist of repeated estimated glomerular filtration rate (eGFR) measurements and time to initiation of renal replacement therapy (RRT). Joint models typically combine linear mixed effects models for repeated measurements and Cox models for censored survival outcomes. Our aim in this paper is to present an introductory tutorial on joint modelling methods, with a case study in nephrology.

Methods: We describe the development of the joint modelling framework and compare the results with those obtained by the more widely used approaches of conducting separate analyses of the repeated measurements and survival times based on a linear mixed effects model and a Cox model, respectively. Our case study concerns a data set from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS). We also provide details of our open-source software implementation to allow others to replicate and/or modify our analysis.

Results: The results for the conventional linear mixed effects model and the longitudinal component of the joint models were found to be similar. However, there were considerable differences between the results for the Cox model with time-varying covariate and the time-to-event component of the joint model. For example, the relationship between kidney function as measured by eGFR and the hazard for initiation of RRT was significantly underestimated by the Cox model that treats eGFR as a time-varying covariate, because the Cox model does not take measurement error in eGFR into account.

Conclusions: Joint models should be preferred for simultaneous analyses of repeated measurement and survival data, especially when the former is measured with error and the association between the underlying error-free measurement process and the hazard for survival is of scientific interest.


Only 60–70% of fertilized eggs may result in a live birth, and very early fetal loss mainly goes unnoticed. Outcomes that can only be ascertained in live-born children will be missing for those who do not survive till birth. In this article, we illustrate a common bias structure (leading to ‘live-birth bias’) that arises from studying the effects of prenatal exposure to environmental factors on long-term health outcomes among live births only in pregnancy cohorts. To illustrate this we used prenatal exposure to perfluoroalkyl substances (PFAS) and attention-deficit/hyperactivity disorder (ADHD) in school-aged children as an example. PFAS are persistent organic pollutants that may impact human fecundity and be toxic for neurodevelopment. We simulated several hypothetical scenarios based on characteristics from the Danish National Birth Cohort and found that a weak inverse association may appear even if PFAS do not cause ADHD but have a considerable effect on fetal survival. The magnitude of the negative bias was generally small, and adjusting for common causes of the outcome and fetal loss can reduce the bias. Our example highlights the need to identify the determinants of pregnancy loss and the importance of quantifying bias arising from conditioning on live birth in observational studies.