Overview of the Raine Study

The Raine Study has a vision of ‘Advancing knowledge, Enhancing lives’. Its mission is ‘To improve lifelong health and quality of life through ground-breaking, impactful research that examines influences, pathways and outcomes from before birth and throughout life’s course’. The Raine Study has grown from its early foundations into a multigenerational, longitudinal research study, encompassing pregnancy, childhood, adolescence and adulthood. It was established in 1989–1991 in Perth/Boorloo with the then stated purpose: to develop a large cohort of Western Australian children studied from 18 weeks’ gestation to ascertain the relative contributions of familial risk factors, foetal growth, placental development and environmental insults to outcome in infancy and to the precursors of adult morbidity. Initially, 2,900 pregnant women were recruited from King Edward Memorial Hospital, which at the time was Perth’s only public maternity hospital, at 18 weeks’ gestation, resulting in 2868 live births. Their offspring have completed assessments starting in-utero to their current age of 33–36 years. The Raine Study includes the mothers and fathers originally recruited in 1989–1991 – Generation 1 (Gen1), and the index participants, who were the babies born into the study between 1989 and 1992 – Generation 2 (Gen2). The Gen2 participants reflect the diversity of WA’s population, with varied health, socioeconomic, educational, and wellbeing profiles.

The Raine Study is currently recruiting the children of the Gen2 participants as its third generation – Generation 3 (Gen3), as well as collecting information on the non-Raine study biological parents of the Gen3 children (Gen2B). Fig. 1 provides a visual representation of the Raine Study participant generations. Over 37 years, the Raine Study has conducted 17 follow-ups at key life stages, and is currently recruiting for the 18^th, making its participants among the most extensively phenotyped individuals globally. Data spans prenatal to adult life, covering physical and mental health, development, lifestyle, and environment. The study has collected: over 30,000+ biopsychosocial variables, 200,000+ biological samples and over 30 million+ genomic data points. This data set provides a myriad of opportunities for researchers to access rich and valuable sources of evidence from pre-pregnancy into adulthood and older age to support DOHaD research. Additional details of the data available can be found in Supplementary Table S1 and Table S2.

Figure 1.

The Raine Study participant generations.

This is a unique opportunity to create a multigenerational cohort perfectly positioned to answer research questions pertinent to the health of the population of Western Australia and the local factors influencing disease development.

The conceptual paradigm for the Raine Study is based around the DOHaD framework, and over time has evolved into a broader life-course approach encompassing the multiple interacting domains of genetics, phenotypes, behaviours, the environment, and other developmental outcomes.^{Reference Straker, Mountain and Jacques5}

Research highlights

The Raine Study has made substantial contributions to the scientific understanding of the DOHaD. As one of the world’s longest-running and most comprehensively phenotyped cohort studies, it has generated over 790 publications, informed more than 530 national and international policies and guidelines,⁷ and supports a vibrant network of over 400 researchers across Australia and overseas.

The research generated by the Raine Study data has produced influential scientific knowledge across a range of disciplines intersecting with life course and disease development. Analysis of the key topics of scientific publications between 2015 to 2025 demonstrates the highly interconnected research areas in which the Raine Study has contributed evidence and insights from multigenerational life-course data (Fig. 2). These include important fields in health and disease burden, such as cardiovascular disease, liver disease, diabetes, respiratory disease, sleep disorders, metabolic health, mental health, and the determinant factors influencing those diseases, such as gestational age, birth weight, breastfeeding, blood pressure and body composition.

Figure 2.

A visual representation of the interconnected key research areas where the Raine Study data has contributed invaluable multigenerational life-course insights. Data taken from publications from 2015 to 2025.

The Raine Study ensures that all research outputs are scientifically sound through robust governance processes. During review, expert methodological feedback is provided to strengthen analyses and minimise bias. Researchers are expected to identify and account for relevant confounding through appropriate design and analytical approaches, including multivariable adjustment and sensitivity analyses, where relevant. Selection of confounders and analytical methods ultimately remains the responsibility of the research team and is subject to peer review upon publication.

The first major finding from the Raine Study was in 1996 and provided evidence establishing the safety of routine prenatal ultrasound.^{Reference Newnham, Doherty and Kendall8,Reference Macdonald, Newnham and Gurrin9} A randomised controlled trial carried out between 1989 and 1991 observed that although initially increased proportions of birthweights in lower percentiles were observed in babies exposed to multiple prenatal ultrasounds, these findings did not persist upon examination at 1 year of age.^{Reference Newnham, Evans and Michael10} These findings influenced international guidelines governing the use of ultrasound during pregnancy which has provided decades of improved prenatal care and reassurance.^{Reference Dry, Pedretti and Nathan11}

Preterm and early term birth has major impact on life course outcomes. In Western Australia, more than 3,000 babies are born too soon each year – approximately 1 in 12 pregnancies do not progress to full term. This rate is more than double amongst Aboriginal and Torres Strait Islander and disadvantaged communities.^{Reference Brown, Cotaru and Binks12} In 2013, research using the Raine Study data provided evidence suggesting that children born at 37 weeks are at increased risk of learning and behavioural problems,^{Reference Robinson, Whitehouse and Zubrick13} and subject to other long-term impacts including respiratory conditions, infectious disease complications, and negative cardiometabolic health outcomes in later life.^{Reference White and Newnham14} This indicated that 37 weeks, which was historically deemed as the safe defined cutoff for perinatal risk, may not be optimal for behavioural development. These findings have driven regional and national policy change, underpinning the Western Australian Preterm Birth Prevention Initiative that was established in 2014. This statewide programme was introduced to lower the rate of preterm birth across WA and in 2018 its success resulted in a national extension via the Australian Preterm Birth Prevention Alliance, which is the first programme of its kind globally. Between 2018 and 2021, these strategies resulted in a 10% reduction in preterm births.^{Reference Newnham, Vernon and Ward15} Prevention of early planned births without medical or obstetric indication is also a priority in the fourth Australian Atlas of Healthcare Variation (2021).¹⁶

The Raine Study has contributed evidence to inform treatment of Attention Deficit Hyperactivity Disorder (ADHD), a neurodevelopmental condition characterised by persistent patterns of hyperactivity, impulsivity, and/or inattention that impair social, academic, and occupational functioning.¹⁷ Considerable debate persists regarding the nature and prevalence of ADHD, as well as the appropriateness of stimulant-based medication as treatment. The use of stimulant medications remains contentious, particularly given their frequent prescription to young children and the substantial increase in prescribing rates observed in recent years. Notably, the rate of Dexamphetamine Sulphate prescriptions in Western Australia is approximately four times higher than the national Australian average.¹⁷ Longitudinal data collected as part of the Raine Study were used to examine the long-term social, emotional, school-based, growth, and cardiovascular outcomes associated with the use of stimulant medication in the treatment of ADHD. There were no significant differences based on medication use on depression, self-perception, and social functioning at 14 years of age. However, while not statistically significant a trend was present towards slightly higher depression scores with the use of medication and improved self-perception and social functioning. Overall, it was found there was little long-term benefit of stimulant medication in reducing the core symptoms of ADHD and improving social, emotional and school based outcomes. These findings provided the evidence base for the Western Australian Department of Health’s ADHD policy and contributed to national clinical guideline development.¹⁸ Further research into ADHD associations using the Raine Study participants also found evidence to suggest a Western-style diet is associated with increased risk of having an ADHD diagnosis in adolescents aged14.^{Reference Howard, Robinson and Smith19} These findings prompted further investigations that have most recently identified the potential for alternative approaches such as nutritional psychiatry rather than medications.^{Reference Lewis, Lagopoulos and Villani20}

Obesity is a significant factor in disease burden worldwide. A study on the Gen2 Raine Study participants showed that approximately 30% of the children were already at higher risk of obesity-related disorders by age eight years.^{Reference Huang, Stanley and Beilin21} This correlates with recent data showing that 28% of children aged 5–17 years are overweight or obese, significantly contributing to rising health and wellbeing risks. Research using Raine Study data continues to make a significant impact in this research area, including how early exposures such as diet, physical activity, lifestyle and sedentary behaviours influence obesity and later cardiometabolic, hepatic, and cardiovascular health.

Steatotic liver disease (SLD) is the most common chronic liver disease in children and is expected to become the leading cause of liver cirrhosis, failure, and transplantation.^{Reference Temple, Cordero and Li22} Results from a study using Raine Study participants at age 17 identified that childhood adiposity trajectories from age 3 years are associated with the diagnosis and severity of SLD in late adolescence, with 15.2% of participants receiving a diagnosis. This increases the risks of type 2 diabetes, heart attack, liver cirrhosis, and cancer in later life.^{Reference Ayonrinde, Olynyk and Marsh23} These findings have not only informed prevention strategies such as extended breastfeeding and lower maternal weight but also highlighted the importance of the rising prevalence of SLD in children and adolescents. It was also found that the Western dietary pattern, lower rates of physical activity, and longer television-watching duration at age 14 years were associated with SLD at age 17 years in Gen2 participants.^{Reference Oddy, Herbison and Jacoby24}

Three decades of movement and behaviour data collected from the Raine Study Gen2 participants enabled mapping of physical activity trajectory patterns that have contributed to novel evidence regarding physical activity and cardiorespiratory fitness (CRF), artery function, insulin resistance and mental health outcomes. These studies have contributed to guidelines aimed at addressing some of the current chronic disease and wellbeing issues, such as obesity and mental health. CRF is a strong independent predictor of all-cause and cardiovascular mortality in adults. Studies using Raine Study data have shown that physical activity level as an adult, as well as low exposure to television watching in early life, are key factors that influence CRF at age 28.^{Reference Haynes, McVeigh and Lester25}

Television watching in childhood and adolescence has also been found to be associated with negative impacts on artery function in adulthood, supporting current screen-time based guidelines for children and adolescents. This may be an important finding for the current and future generations of children and adolescents, since contemporary screen time has drastically increased through the generations, and is predicted to be a major contributor to early onset dementia.^{Reference Manwell, Tadros and Ciccarelli26} In addition, a study showed that a group of Gen2 participants who watched less television during childhood and adolescence had lower body fat percentage and greater bone mass at age 20 and 22, compared to those who watched more television, and also self-reported better physical health.^{Reference McVeigh, Smith and Howie27} These findings contributed to the 2019 World Health Organization guidelines on Physical Activity and sedentary behaviour, and sleep for Children under 5 years of Age.²⁸ These recommendations offer evidence-based guidance for national policies to promote population-level physical activity. They also reinforce public health messaging with relevance to parents, schools and government, focused on minimising sedentary behaviour during development and maintaining regular physical activity throughout the lifespan.

There is growing evidence that the health burden associated with sleep is not limited to those with a diagnosed sleep disorder, with multiple dimensions of poor sleep, including insufficient or excessive duration, irregularity and dissatisfaction, recognised as modifiable risk factors for chronic conditions including cardiovascular diseases and diabetes. Young adults may be particularly vulnerable to poor sleep that persists into adulthood and, as a result, are a priority population for chronic disease prevention efforts.^{Reference Metse, Eastwood and Ree29} Findings from the Raine Study have contributed to this body of research and have revealed that a substantial proportion of young adults (41.1% of females; 42.3% of males) experience suboptimal sleep, with sleep dissatisfaction strongly associated with poorer mental and physical health outcomes.^{Reference Metse, Eastwood and Ree29} At age 22 years, 1 in 5 (14.9% of females; 26.9% of males) met diagnostic criteria for obstructive sleep apnoea (OSA), and 1 in 7 had chronic insomnia (19.3% of females; 10.6% of males). These were the first published data on the prevalence of OSA in young adults in the community.^{Reference Eastwood, Ward and Bucks30} Such important insights can be used to inform public health interventions to improve sleep health and therefore the physical and mental health of young adults. Research into sleep health in middle-age using the Raine Study’s Gen1 participants also provided evidence that those with OSA and severely irregular sleep were at increased risk of hypertension. These findings highlight sleep irregularity as a modifiable target for reducing hypertension risk in individuals with OSA, reinforcing the Study’s contribution to early preventive cardiometabolic medicine.^{Reference Sansom, Reynolds and Windred31} Findings from Gen1 and Gen2 were presented to the Parliamentary Inquiry into Sleep Health Awareness in Australia.³²

These examples of major areas of research outcomes of the Raine Study demonstrate the value of a multi-generational longitudinal cohort study in identification of factors influencing heath and determinants of disease burden. They show that cohort data provides significant insights into how early life; including before conception, during pregnancy, and in childhood, shapes health across the life course and across generations. The continued impact of the Raine Study in policy and clinical practice is fundamental to identification of factors inferencing health and wellbeing. This requires innovative research using data and biosamples collected in assessments of participants across time in an integrated approach that maximises the value of all parts of the cohort study.

Participant involvement

Participant engagement and consumer involvement are central to the Raine Study and have contributed to the success and longevity of the cohort. The Raine Study operates in ongoing partnership with participants to support research, governance and strategic decision-making. This section outlines the mechanisms used to engage and involve participants, incorporate consumer perspectives into research prioritisation and governance, and maintain the strong relationships that underpin long-term participant retention and involvement.

The strong relationships between cohort participants, staff, and researchers, that have been fostered through the years are critical to the success of the Raine Study. Since its inception in 1989, the Raine Study has been guided by the principle that research is most robust when shaped by the people it serves, with participant engagement central to its approach. The Raine Study continues to set an exemplary standard for how participants should be included and engaged in cohort studies. The Raine Study participants are involved at all levels of the leadership and are key members of governance bodies within the study, from idea to implementation of operations and governance, ensuring their voices shape our research and strategic decision-making processes. Relationships with participants and their families have been prioritised and nurtured, ensuring on-going support from the cohort. This consistency in participant engagement has resulted in exceptional participant retention over the past 37 years, which has been critical to the longevity of this multigenerational cohort study.

One challenge when discussing attrition in the Raine Study, is that participation is not a simple ‘in or out’ process. Unlike many studies where participants permanently leave upon missing a single assessment, participation in the Raine Study is fluid. As can be expected during such a lengthy period, there have been fluctuations in participation rates over the years particularly in early adulthood where life events such as attending university, work and travel make it more difficult to attend. For example, while 1029 participants did not participate in the 22-year follow-up, many of these individuals subsequently returned and participated in later follow-ups. Participants can choose whether to take part in any given follow-up and often re-engage at later assessments. Participants who are definitively lost to follow up include only those that have died. As a result, lower attendance at a particular follow-up should not be interpreted as permanent loss from the cohort. Consequently, apparent declines in participation at individual waves cannot be interpreted as cohort attrition. A more informative measure is long-term participant engagement and retention across multiple follow-ups, which demonstrates the ongoing commitment of Raine Study participants over time.

Gen2 participants are due to complete their 18^th follow-up in December 2026 and of these 18 follow-ups over the last 37 years, 75% of participants have returned to complete five or more follow-ups with over a third returning to complete ten or more.

In 2026 we currently have over 2000 eligible Gen2, over 2000 Gen1 mothers, over 1200 Gen1 fathers and over 1000 Gen3 participants, noting that active recruitment for Gen3 remains ongoing. These numbers reflect the on-going and continued value of the Raine Study as a multigenerational cohort study.

Past cohort profiles for both Gen1^{Reference Dontje and Eastwood6} and Gen2^{Reference Straker, Mountain and Jacques5} have previously been described in detail, including detailed recruitment numbers, assessment methods, and the examination of attrition bias. In the Gen1 cohort, attrition bias based on age, education, ethnicity, income and socioeconomic status (SES) were assessed. It was found that, in general, the differences between those who attended and those who did not were small and limited to lower education, income and SES.^{Reference Dontje and Eastwood6} In the Gen2 cohort, the proportions of participants vs non-participants across infant characteristics remained constant across all follow-ups, with the exception of a gradual reduction in the participation rate of infants of Aboriginal and Torres Strait Islander ancestry.^{Reference Straker, Mountain and Jacques5}

The recruitment numbers reported in past cohort profiles show minor differences to the current cohort profile due to extensive data cleaning and harmonisation projects conducted in recent years.

The Raine Study has a dedicated Participant Engagement Team, which facilitates cohort consultation utilising various methods, which can be seen in Fig. 3, to maximise participant engagement and involvement.

Figure 3.

A visual representation of the methods utilised by the Raine Study to facilitate cohort consultation to maximise participant engagement and involvement.

In 2024 the Participant Engagement Team, facilitated by the Raine Study Community Advisory Committee, instigated the Participant Priority Setting Project (PPSP),^{Reference De Paolis, Abdul and McKenzie33} one of our largest and most comprehensive consumer engagement projects to date. The Raine Study is one of a growing number of Australian cohort studies that directly involve participants in setting future research priorities, reflecting an increasing commitment to meaningful consumer involvement in research. The PPSP framework allowed participants to collectively inform the future research direction of the Raine Study, identifying key research areas that participants wanted prioritised, including mental health, reproductive health, and generational impact.

Researchers utilising the Raine Study data are also expected to initiate cohort consultation and involve participant representatives in their studies. This collaborative approach ensures that research priorities are informed by the perspectives of the broader community, making the work more relevant and impactful.

In addition to formal committees, workshops and participant surveys, the Raine Study maintains strong connections with participants through regular newsletters, social media platforms including Facebook, Instagram and LinkedIn, direct mail communications, and invitations to participate as co-creators in research activities. Participants are also invited to community events such as Breakfast by the Bay, Telethon Family Festival and the Raine Study Symposium, where they can connect with researchers, staff and fellow participants.

Maintaining this strong relationship with participants and their families has ensured that they remain immensely supportive of the Raine Study’s vision and purpose. This sustained engagement has been essential in achieving the study’s impact to date and remains critical to advancing the next generation and broader multigenerational research priorities.

The future of the Raine Study

The Raine Study’s enduring impact lies in its unique capacity to follow individuals from before birth into adulthood and the inclusion of multiple generations. Since 2023, the Raine Study has been committed to creating a multigenerational cohort positioning it as a unique resource for future DOHaD research. The ongoing recruitment of Gen3 and Gen2B participants will further strengthen the Raine Study’s long-term relevance. This will enable researchers to deepen our understanding of how health behaviours, exposures, and outcomes are transmitted across generations, and how early interventions can disrupt cycles of disadvantage and disease. In addition, it will provide a powerful longitudinal resource for understanding how health and well-being are established across the life-course and through generations.

The ongoing multigenerational recruitment will also enable the creation of complete family genetic profiles, offering a rare opportunity to identify genetic variants linked to disease risk and to examine epigenetic inheritance, transgenerational effects of lifestyle and environmental exposures, and gene–environment interactions. These advances will enhance understanding of the mechanisms underlying the intergenerational transmission of chronic health conditions affecting the WA population. Expanding the study’s multigenerational genetic database will support the future of precision medicine through more tailored prevention and treatment strategies informed by individual and familial genetic profiles.

Building on our multigenerational research capacity, the Raine Study is perfectly placed to deliver intergenerational control groups to provide information on typical community health for those without a condition or disadvantage. Many health studies recruit children with a particular disorder or disability, and to understand the impact, causes and consequences of that condition, a control group is required. For example, while not directly involved in assisted reproductive technologies (ART), the Raine Study served as a reference population enabling robust benchmarking for a series of outcomes in 5 landmark studies on adolescents conceived via ART.^{Reference Wijs, Doherty and Keelan34–Reference Penova-Veselinovic, Melton and Huang38} Findings showed no differences in cardiometabolic outcomes, respiratory health, thyroid function, or DNA methylation signatures between ART and naturally conceived adolescents – providing global reassurance to children and adults born from In Vitro Fertilisation (IVF) treatment, to couples considering or embarking on IVF treatment and clinicians counselling their patients.

The Raine Study is currently in the process of linking its dataset with Commonwealth and Western Australian administrative data across multiple datasets, which includes education, justice, policing, health and mental health, disability, child protection, live events and public housing datasets. Data linkage will complement and maximise the value of our data holdings, enabling epidemiological research across the healthcare system throughout the participant’s lifespan. This will augment traditional approaches to data collection, consequently increasing the potential to drive policy-relevant research, find participants lost to follow-up and link family members to further facilitate and strengthen intergenerational research.

The Raine Study is integrated into major international consortia and is currently collaborating with 20 global consortia across diverse areas of health and biomedical research (further details can be found in List S1 in Supplementary Material). The study contributes high-quality longitudinal data that supports innovative, interdisciplinary investigations with the potential to advance scientific knowledge and improve public health outcomes worldwide. This international engagement further amplifies scientific value and impact of the research conducted in this multigenerational cohort study.

The Raine Study contributes to regional and national collaborative initiatives, including the WA Cohorts Network, a partnership with the ORIGINS project (https://origins.thekids.org.au) and the Busselton Health Study (https://bpmri.org.au) and the Australasian Longitudinal Leaders Forum (ALLF; https://www.uts.edu.au/about/faculties/health/research/insight/allf). These partnerships provide opportunities to share expertise, explore data harmonisation approaches, and strengthen the broader longitudinal research ecosystem in Oceania.

Collectively, these developments ensure that the Raine Study remains a globally significant, future-focused platform for advancing understanding of health and disease across the life course and across generations.

Conclusion

Over the last 37 years, the Raine Study has evolved from a single-generation, place-based Western Australian pregnancy cohort grounded in the DOHaD framework into a comprehensive, multigenerational life-course cohort with demonstrated global reach and impact. The continued growth and resulting national and international significance highlight the importance of individual localised studies and their immense research value. These studies not only offer unique population perspectives but also contribute meaningfully to global DOHaD research.

Entering its next phase by expanding multigenerational recruitment, the Raine Study will further strengthen its role as a research enabling platform providing capacity for researchers to address emerging health challenges and understand how health and well-being are established across the life-course and across generations.

Central to the Raine Study’s longevity and success is its deeply embedded commitment to participant partnership. Sustained, meaningful consumer involvement across governance, priority-setting, and research implementation has fostered exceptional retention and ensured that the study remains ethically grounded, community-centred, and scientifically relevant.

Together, these attributes ensure that the Raine Study remains a cornerstone of global DOHaD and life-course research and a vital resource for improving the health and wellbeing of current and future generations. The approaches taken by the Raine Study can be used in developing countries to establish local cohort studies supporting investigation of local factors influencing health and disease development.