Prenatal fever and autism risk.

Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.

Identification of patients with recent-onset psychosis in KwaZulu Natal, South Africa: a pilot study with traditional health practitioners and diagnostic instruments.

PURPOSE: There is considerable variation in epidemiology and clinical course of psychotic disorders across social and geographical contexts. To date, very little data are available from low- and middle-income countries. In sub-Saharan Africa, most people with psychoses remain undetected and untreated, partly due to lack of formal health care services. This study in rural South Africa aimed to investigate if it is possible to identify individuals with recent-onset psychosis in collaboration with traditional health practitioners (THPs). METHODS: We developed a strategy to engage with THPs. Fifty THPs agreed to collaborate and were asked to refer help-seeking clients with recent-onset psychosis to the study. At referral, the THPs rated probability of psychosis ("maybe disturbed" or "disturbed"). A two-step diagnostic procedure was conducted, including the self-report Community Assessment of Psychic Experiences (CAPE) as screening instrument, and a semi-structured interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Accuracy of THP referrals, and test characteristics of the THP rating and the CAPE were calculated. RESULTS: 149 help-seeking clients were referred by THPs, of which 44 (29.5%) received a SCAN DSM-IV diagnosis of psychotic disorder. The positive predictive value of a THP "disturbed" rating was 53.8%. Test characteristics of the CAPE were poor. CONCLUSION: THPs were open to identifying and referring individuals with possible psychosis. They recognized "being disturbed" as a condition for which collaboration with formal psychiatric services might be beneficial. By contrast, the CAPE performed poorly as a screening instrument. Collaboration with THPs is a promising approach to improve detection of individuals with recent-onset psychosis in rural South Africa.

Fever and infections during pregnancy and psychosis-like experiences in the offspring at age 11. A prospective study within the Danish National Birth Cohort.

BACKGROUND: Maternal exposures to fever and infections in pregnancy have been linked to subsequent psychiatric morbidity in the child. This study examined whether fever and common infections in pregnancy were associated with psychosis-like experiences (PLEs) in the child. METHODS: A longitudinal study of 46 184 children who participated in the 11-year follow-up of the Danish National Birth Cohort was conducted. Pregnant women were enrolled between 1996 and 2002 and information on fever, genitourinary infections, respiratory tract infection, and influenza-like illness during pregnancy was prospectively collected in two interviews during pregnancy. PLEs were assessed using the seven-item Adolescent Psychotic-Like Symptom Screener in a web-based questionnaire completed by the children themselves at age 11. RESULTS: PLEs were reported among 11% of the children. Multinomial logistic regression models with probability weights to adjust for potential selection bias due to attrition suggested that maternal fever, genitourinary infections and influenza-like illness were associated with a weak to moderate increased risk of subclinical psychosis-like symptoms in the offspring, whereas respiratory tract infections were not. No clear pattern was observed between the strengths of the associations and the timing of exposure, or the type of psychosis-like symptom. CONCLUSIONS: In this study, maternal exposures to fevers and common infections in pregnancy were generally associated with a subtle excess risk of PLEs in the child. A more pronounced association was found for influenza-like illness under an a priori definition, leaving open the possibility that certain kinds of infections may constitute important risk factors.

Autism risk associated with parental age and with increasing difference in age between the parents.

Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985-2004 and followed up to the end of 2004-2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent's age (mothers 40-49 years vs 20-29 years, RR=1.15 (95% confidence interval (CI): 1.06-1.24), P-value<0.001; fathers⩾50 years vs 20-29 years, RR=1.66 (95% CI: 1.49-1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20-29 years, RR=1.18 (95% CI: 1.08-1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.

Three decades of eating disorders in Dutch primary care: decreasing incidence of bulimia nervosa but not of anorexia nervosa.

BACKGROUND: Whether the incidence of eating disorders in Western, industrialized countries has changed over time has been the subject of much debate. The purpose of this primary-care study was to examine changes in the incidence of eating disorders in The Netherlands during the 1980s, 1990s and 2000s. METHOD: A nationwide network of general practitioners (GPs), serving a representative sample (~1%) of the total Dutch population, recorded newly diagnosed patients with anorexia nervosa (AN) and bulimia nervosa (BN) in their practice during 1985-1989, 1995-1999, and 2005-2009. GPs are key players in the Dutch healthcare system, as their written referral is mandatory in order to get access to specialized (mental) healthcare, covered by health insurance. Health insurance is virtually universal in The Netherlands (99% of the population). A substantial number of GPs participated in all three study periods, during which the same case identification criteria were used and the same psychiatrist was responsible for making the final diagnoses. Incidence rates were calculated and for comparison between periods, incidence rate ratios. RESULTS: The overall incidence rate of BN decreased significantly in the past three decades (from 8.6 per 100,000 person-years in 1985-1989 to 6.1 in 1995-1999, and 3.2 in 2005-2009). The overall incidence of AN remained fairly stable during three decades, i.e. 7.4 per 100,000 person-years in 1985-1989, 7.8 in 1995-1999, and 6.0 in 2005-2009. CONCLUSIONS: The incidence rate of BN decreased significantly over the past three decades, while the overall incidence rate of AN remained stable.

Maternal weight gain in excess of pregnancy guidelines is related to daughters being overweight 40 years later.

BACKGROUND: Exceeding the Institute of Medicine guidelines for pregnancy weight gain increases childhood and adolescent obesity. However, it is unknown if these effects extend to midlife. OBJECTIVE: We sought to determine if exceeding the Institute of Medicine guidelines for pregnancy weight gain increases risk of overweight/obesity in daughters 40 years later. STUDY DESIGN: This cohort study is based on adult offspring in the Child Health and Development Studies and the Collaborative Perinatal Project pregnancy cohorts originally enrolled in the 1960s. In 2005 through 2008, 1035 daughters in their 40s were recruited to the Early Determinants of Mammographic Density study. We classified maternal pregnancy weight gain as greater than vs less than or equal to the 2009 clinical guidelines. We used logistic regression to compare the odds ratios of daughters being overweight/obese (body mass index [BMI] ≥25) at a mean age of 44 years between mothers who did not gain or gained more than pregnancy weight gain guidelines, accounting for maternal prepregnant BMI, and daughter body size at birth and childhood. We also examined potential family related confounding through a comparison of sisters using generalized estimating equations, clustered on sibling units and adjusted for maternal age and race. RESULTS: Mothers who exceeded guidelines for weight gain in pregnancy were more likely to have daughters who were overweight/obese in their 40s (odds ratio [OR], 3.4; 95% confidence interval {CI}, 2.0-5.7). This magnitude of association translates to a relative risk (RR) increase of 50% (RR = 1.5; 95% CI, 1.3-1.6). The association was of the same magnitude when examining only the siblings whose mother exceeded guidelines in 1 pregnancy and did not exceed the guidelines in the other pregnancy. The association was stronger with increasing maternal prepregnancy BMI (P trend < .001). Compared to mothers with BMI <25 who did not exceed guidelines, the relative risks (RR) for having an overweight/obese adult daughter were 1.3 (95% CI, 1.1-1.7), 1.7 (95% CI, 1.4-2.1) and 1.8 (95% CI, 1.5-2.1), respectively, if mothers exceeded guidelines and their prepregnancy BMI was <25, overweight (BMI 25-<30), or obese (BMI >30). This pattern held irrespective of daughters' weight status at birth, at age 4 years, or at age 20 years. CONCLUSION: Our findings support that obesity prevention before pregnancy and strategies to maintain weight gain during pregnancy within the IOM guidelines might reduce the risk of being overweight in midlife for the offspring.

Social disorganization of neighborhoods and incidence of psychotic disorders: a 7-year first-contact incidence study.

BACKGROUND: Environmental factors such as urban birth and ethnic minority position have been related to risk for psychotic disorders. There is some evidence that not only individual, but also neighborhood characteristics influence this risk. The aim of this study was to investigate social disorganization of neighborhoods and incidence of psychotic disorders. METHOD: The research was a 7-year first-contact incidence study of psychotic disorders in The Hague. Neighborhood characteristics included continuous, dichotomous and cumulative measures of socio-economic level, residential mobility, ethnic diversity, proportion of single person households, voter turnout, population density and crime level. Using multilevel Poisson regression analysis, incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of psychotic disorders were calculated for the indicators of neighborhood social disorganization. RESULTS: A total of 618 incident cases were identified. Neighborhood socio-economic level and residential mobility had the strongest association with incidence of psychotic disorders [individual-level adjusted Wald χ2 1 = 13.03 (p = 0.0003) and 5.51 (p = 0.02), respectively]. All but one (proportion of single person households) of the dichotomous neighborhood indicators were significantly associated with a higher IRR. The cumulative degree of neighborhood social disorganization was strongly and linearly associated with the incidence of psychotic disorders (trend test, Wald χ2 5 = 25.76, p = 0.0001). The IRR in neighborhoods with the highest degree of social disorganization was 1.95 (95% CI 1.38-2.75) compared with the lowest disorganization category. CONCLUSIONS: The findings suggest that the risk for developing a psychotic disorder is higher for people living in socially disorganized environments. Longitudinal studies are needed to investigate causality.

Prevalence, impact and cultural context of psychotic experiences among ethnic minority youth.

BACKGROUND: The risk for psychotic disorders is increased for many ethnic minority groups and may develop in early childhood. This study investigated whether the prevalence of psychotic experiences (PE) with high impact is higher among ethnic minority youth compared to majority youth and examined the significance of these PE. METHOD: A school-based study assessed a large community sample of 1545 ethnic minority and majority children in The Netherlands (mean age 12.98 ± 1.81 years). The Dutch (n = 702, 45.4%), Moroccan-Dutch (n = 400, 25.9%) and Turkish-Dutch (n = 170, 11.0%) ethnic groups could be studied separately. Self-report questionnaires on PE, impact and cultural context were administered. RESULTS: Prevalence of PE with high impact was 3.1% in Dutch, 9.5% in Moroccan-Dutch and 7.1% in Turkish-Dutch youth. Compared to Dutch youth, odds ratios were 3.0 [95% confidence interval (CI) 1.7-5.1] for Moroccan-Dutch youth and 2.2 (95% CI 1.1-4.6) for Turkish-Dutch youth. Differences were not explained by cultural or religious differences. CONCLUSIONS: The increased risk for psychotic disorders in ethnic minorities may already be detectable in childhood, since PE with high impact were more common among ethnic minority youth compared to majority youth. The additional measurement of impact of PE appears to be a valid approach to identify those children at risk to develop psychotic or other more common psychiatric disorders.

Associations of prenatal maternal smoking with offspring hyperactivity: causal or confounded?

BACKGROUND: The relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common. METHOD: Data were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961-1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory. RESULTS: Unadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [ß = 0.22, 95% confidence interval (CI) 0.11-0.33] and, to a similar degree, when the father smoked (ß = 0.18, 95% CI 0.07-0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (ß = 0.25, 95% CI 0.09-0.40) but father smoking was not (ß = 0.02, 95% CI -0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (ß = 0.26, 95% CI 0.03-0.49) or did not smoke (ß = 0.30, 95% CI 0.04-0.57). By number of cigarettes, associations with hyperactivity were present for 10-19 and 20+ cigarettes per day among mothers. CONCLUSIONS: In a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.

Direct comparison of first-contact versus longitudinal register-based case finding in the same population: early evidence that the incidence of schizophrenia may be three times higher than commonly reported.

BACKGROUND: The incidence of schizophrenia is commonly estimated by screening for psychosis among subjects presenting to psychiatric services. This approach (using a first-contact sampling frame) cannot account for cases that did not meet criteria for schizophrenia at first contact. We compared the usual approach directly with a register-based approach (using a longitudinal sampling frame) that also includes subjects initially diagnosed with other non-schizophrenic disorders. METHOD: We compared data from the Longitudinal Psychiatric Register (LPR) of The Hague over 1980-2009 with data previously collected in a first-contact study, and applied both methods to calculate the incidence of schizophrenia for subjects aged 20-54 years in the same catchment area and over the same period (October 2000 to September 2005). We reconstructed treatment pathways and diagnostic histories up to the end of 2009 and performed sensitivity analyses. RESULTS: The LPR identified 843 first onsets of schizophrenia, corresponding to a treated incidence rate (IR) of 69 per 100,000 person-years [95% confidence interval (CI) 64-74]. The first-contact study identified 254 first onsets, corresponding to a treated IR of 21 per 100,000 person-years (95% CI 18-23). Two-thirds of the difference was accounted for by subjects treated for other disorders before the onset of psychosis, and by patients in older age groups. CONCLUSIONS: The incidence of schizophrenia was three times higher in a longitudinal register study than in a high-quality first-contact study conducted in the same population. Risk estimates based only on first-contact studies may have been affected by selection bias.

Degree of fetal growth restriction associated with schizophrenia risk in a national cohort.

BACKGROUND: Accumulating evidence suggests that fetal growth restriction may increase risk of later schizophrenia but this issue has not been addressed directly in previous studies. We examined whether the degree of fetal growth restriction was linearly related to risk of schizophrenia, and also whether maternal pre-eclampsia, associated with both placental dysfunction and poor fetal growth, was related to risk of schizophrenia. METHOD: A population-based cohort of single live births in the Medical Birth Registry of Norway (MBRN) between 1967 and 1982 was followed to adulthood (n=873 612). The outcome was schizophrenia (n=2207) registered in the National Insurance Scheme (NIS). The degree of growth restriction was assessed by computing sex-specific z scores (standard deviation units) of ' birth weight for gestational age' and ' birth length for gestational age'. Analyses were adjusted for potential confounders. Maternal pre-eclampsia was recorded in the Medical Birth Registry by midwives or obstetricians using strictly defined criteria. RESULTS: The odds ratio (OR) for schizophrenia increased linearly with decreasing birth weight for gestational age z scores (p value for trend=0.005). Compared with the reference group (z scores 0.01­1.00), the adjusted OR [95% confidence interval (CI)] for the lowest z-score category (

Severity and persistence of asthma and mental health: a birth cohort study.

BACKGROUND: The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link. Method Data were drawn from the Raine Study, a population-based birth cohort study in Western Australia. Logistic regression models and generalized estimating equations were used to examine the relationship between asthma at age 5 years and the range of internalizing and externalizing mental health problems at ages 5-17 years. Analyses were stratified by asthma severity and persistence, and adjusted for a range of potential confounders. RESULTS: More severe and persistent asthma at age 5 was associated with significantly increased odds of affective, anxiety, somatic, oppositional defiant and conduct problems at ages 5-17. Mild asthma and remitted asthma were not associated with heightened vulnerability to mental disorders. CONCLUSIONS: Our results suggest that youth with symptomatic asthma are more likely to suffer from a wide range of mental health problems, and that the likelihood of mental health problems appears to increase as a function of asthma severity. Youth with poorly controlled and/or more severe and persistent asthma may be considered a vulnerable group who might benefit from mental health screening in clinical, school and community settings.

The use of well controls: an unhealthy practice in psychiatric research.

BACKGROUND: Studies comparing cases with controls to uncover the causes of psychiatric disorders are common in biological research. The validity of these studies depends upon adherence to the methodological principles underlying the case-control design. However, these principles are often violated. One common practice that violates these principles is the use of well controls. In this paper we describe the bias that it can cause and discuss why the use of well controls leads to invalidity in case-control studies. METHOD: Using hypothetical numerical examples we illustrate the consequences of using well controls. RESULTS: The results illustrate that the use of well controls can cause substantial bias. In no instance does the use of well controls improve validity. CONCLUSIONS: We conclude that the use of well controls is an unhealthy practice in psychiatric research.

The Autism Birth Cohort: a paradigm for gene-environment-timing research.

The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.

Genetics of schizophrenia in the South African Xhosa.

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

RedeAmericas: building research capacity in young leaders for sustainable growth in community mental health services in Latin America.

The purpose of this paper is to describe the development and initial accomplishments of a training program of young leaders in community mental health research as part of a Latin American initiative known as RedeAmericas. RedeAmericas was one of five regional 'Hubs' funded by the National Institute of Mental Health (NIMH) to improve community mental health care and build mental health research capacity in low- and middle-income countries. It included investigators in six Latin American cities - Santiago, Chile; Medellín, Colombia; Rio de Janeiro, Brazil; and Córdoba, Neuquén, and Buenos Aires in Argentina - working together with a team affiliated with the Global Mental Health program at Columbia University in New York City. One component of RedeAmericas was a capacity-building effort that included an Awardee program for early career researchers in the mental health field. We review the aims of this component, how it developed, and what was learned that would be useful for future capacity-building efforts, and also comment on future prospects for maintaining this type of effort.

Monitoring and evaluating capacity building activities in low and middle income countries: challenges and opportunities.

BACKGROUND: Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional 'hubs' established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs. METHODS: The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants. RESULTS: Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful. CONCLUSIONS: The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.

Developing mental health research in sub-Saharan Africa: capacity building in the AFFIRM project.

BACKGROUND: There remains a large disparity in the quantity, quality and impact of mental health research carried out in sub-Saharan Africa, relative to both the burden and the amount of research carried out in other regions. We lack evidence on the capacity-building activities that are effective in achieving desired aims and appropriate methodologies for evaluating success. METHODS: AFFIRM was an NIMH-funded hub project including a capacity-building program with three components open to participants across six countries: (a) fellowships for an M.Phil. program; (b) funding for Ph.D. students conducting research nested within AFFIRM trials; (c) short courses in specialist research skills. We present findings on progression and outputs from the M.Phil. and Ph.D. programs, self-perceived impact of short courses, qualitative data on student experience, and reflections on experiences and lessons learnt from AFFIRM consortium members. RESULTS: AFFIRM delivered funded research training opportunities to 25 mental health professionals, 90 researchers and five Ph.D. students across 6 countries over a period of 5 years. A number of challenges were identified and suggestions for improving the capacity-building activities explored. CONCLUSIONS: Having protected time for research is a barrier to carrying out research activities for busy clinicians. Funders could support sustainability of capacity-building initiatives through funds for travel and study leave. Adoption of a train-the-trainers model for specialist skills training and strategies for improving the rigor of evaluation of capacity-building activities should be considered.

ViPAR: a software platform for the Virtual Pooling and Analysis of Research Data.

BACKGROUND: Research studies exploring the determinants of disease require sufficient statistical power to detect meaningful effects. Sample size is often increased through centralized pooling of disparately located datasets, though ethical, privacy and data ownership issues can often hamper this process. Methods that facilitate the sharing of research data that are sympathetic with these issues and which allow flexible and detailed statistical analyses are therefore in critical need. We have created a software platform for the Virtual Pooling and Analysis of Research data (ViPAR), which employs free and open source methods to provide researchers with a web-based platform to analyse datasets housed in disparate locations. METHODS: Database federation permits controlled access to remotely located datasets from a central location. The Secure Shell protocol allows data to be securely exchanged between devices over an insecure network. ViPAR combines these free technologies into a solution that facilitates 'virtual pooling' where data can be temporarily pooled into computer memory and made available for analysis without the need for permanent central storage. RESULTS: Within the ViPAR infrastructure, remote sites manage their own harmonized research dataset in a database hosted at their site, while a central server hosts the data federation component and a secure analysis portal. When an analysis is initiated, requested data are retrieved from each remote site and virtually pooled at the central site. The data are then analysed by statistical software and, on completion, results of the analysis are returned to the user and the virtually pooled data are removed from memory. CONCLUSIONS: ViPAR is a secure, flexible and powerful analysis platform built on open source technology that is currently in use by large international consortia, and is made publicly available at [http://bioinformatics.childhealthresearch.org.au/software/vipar/].