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Programming effects of early life stress exposure to bereavement on future health: a perspective in 6.7 million subjects in 3 European countries

Final Report Summary - PROGEURO (Programming effects of early life stress exposure to bereavement on future health: a perspective in 6.7 million subjects in 3 European countries)

There have been significant challenges in the four research areas of:
1. Foetal Programming /Developmental origins of Health and Disease (DOHaD). The widely use of growth variables as the indicators of foetal environment remains the major methodological limitation. And no research in humans has been able to examine the biomarkers at different programming stages from exposure itself to disease in one single study.
2. Stress. It remains difficult to assess stress and to obtain data on long-term health in a large study. The biological programming effects of prenatal stress need to be elucidated.
3. Bereavement. There is a significant knowledge gap in health of children bereaved by the death of a close relative.
4. Register-based research. To combine the multi-national data is necessary to understand the aetiology and the impact of rare disease and the effects of certain risk factors. But such a first attempt will face many obstacles.

The novel approaches in this study are designed to meet all the above challenges. By the support from of ProgEuro, we have set up a very large study including data from more than 25 registers in three Nordic countries (Denmark, Sweden, and Finland). The overall study cohort includes 7.3 million children born between 1968 to 2008 and their 26.9 million family relatives in the three Nordic countries. The objective of full population cohort is to examine the programming effects of an early stress exposure, bereavement during prenatal or early years in life, on a wide range of health outcomes. The overall specific aims are to systematically examine the effects of stress exposure to bereavement during prenatal/postnatal life on both common and rare health outcomes. The second biological component is a proof of concept for foetal programming, examining biomarkers along the pathway from prenatal stress to diseases. The study is the first of its kind, resting upon the existing infrastructure for register-based studies with a long-term follow-up up to four decades. Combination of main database with biobanks will permit investigations of gene-environmental interactions at a large scale with a relatively low cost. The study makes better value of the register system for the public, in terms of knowledge, disease prevention / treatment, public health services, and policy-making.

This study is feasible only in European settings, which will strengthen the European leadership in epidemiology and public health. It starts a new era for joint European research in public health. The challenges in 'ProgEuro' have also been the source of new scientific insights, hypotheses, and probably new theories.

The project has led to more than 50 peer-reviewed publications, including in top scientific journals like PLos Medicine, JAMA, JAMA psychiatry, etc.

The project have supported five PhD students, who are becoming independent researchers in related areas, and each of them have published 4- 8 papers in their PhD periods.

The project has established a strong collaborative team representing leading experts from multi-disciplinary scientific fields from all the five Nordic countries, UK, Ireland, China, and USA.