Understanding early life determinants and mechanisms to preventing life course multimorbidity

The early part of life-from tiny embryo, to baby in the womb, to birth, through infancy and early childhood-is a time when many events happen that can have important, lasting effects on our lives. We want to find ways to make these early parts of our lives as good as they can be, so that we enter adulthood healthy and able to cope well with things that life may throw at us.

Our research will investigate the early life events that affect our hearts, blood vessels, mental health, and metabolism (how our bodies convert food to energy and to building blocks such as proteins, and eliminate waste). We want to find ways to prevent early life events that lead us to have several health problems in later life. We call this "multi-morbidity", meaning two or more long-term conditions or disabilities.

The idea of looking at health from early life into adulthood has been around for a while, but it is still fairly rare to actually link information from early life events with multimorbidity. We are a new group of people with complementary expertise in early life and adult health. For example, we have lab scientists studying hearts and blood vessels; psychologists investigating how movement and physical activity affects mothers and children; children's doctors providing front line care while also researching the best ways to help their patients; a data engineer; and public health researchers working on studies that follow people's health for decades. We know that to answer the big questions about early life events and multimorbidity we need to collaborate in new ways across our areas of expertise. We are now proposing a 6-month project to bring together what we know and our different techniques ('methods'), and to refine our bigger 4-year plan. Our bigger plan has four related parts:

A. We will find and make sense of different types of existing evidence about early life drivers of multimorbidity. We will work with stakeholders (parents, carers, children, policy makers, professionals) to draw up a map that will help people to think more clearly about early life events that cause or prevent multimorbidity, see the gaps in our knowledge, and decide which questions to answer next.
B. To answer these questions, we will electronically link up existing UK-based data (e.g. heel prick samples, red book questions) and use new methods, such as artificial intelligence, to explore it. We will also collect new data to fill gaps.
C. As the data helps us better understand early life events and how they affect later health, we will co-design new 'interventions' to alter these events. For example, we may develop medicines, health monitors, or ways for people to do things differently. They may be for individuals or populations.
D. We will involve patients and the public throughout to ensure focus on what matters and that the interventions work well in real life.

In the initial 6 months, we will use three particular areas to pilot our ideas and techniques. These are areas where: early life events are already known to affect later life multimorbidity but how this happens is not clear; there is great potential for better interventions; and we have substantial expertise. The areas are:
- mother's heart and blood vessel health, and influence on baby
- stressful events for the mother/child, and effects on hormones and later child health
- mother/child movement and physical activity, and effects on mother/child heart and blood health and stress

This research will change the way health and care is provided, moving from diagnosing and treating individual conditions as they appear to intervening on early life psychological, social and medical issues. This will prevent multiple problems later in life for large numbers of people. This will improve child and parent health, and reduce the burden on families and services. This research will also help inform what information is important for governments to collect in early life to monitor public health.

We seek to prevent life course multimorbidity (any two or more chronic conditions or disabilities) through early life biopsychosocial interventions. We focus on two multimorbidity clusters: cardiometabolic and mental health. Our aims are to:
1 Identify biological and behavioural mechanisms underlying drivers of multimorbidity from preconception through first years of life
2 Assess the involvement of regional clustering
3 Generate proof-of-concept interventions

Our plan has four integrated streams:
1 Synthesising existing evidence about early life drivers of multimorbidity using causal modelling and presenting the results in a dynamic map co-designed with stakeholders (parents, children, policy, providers). This enables clear understanding of mechanisms to multimorbidity and knowledge gaps.
2 Charting and linking up existing UK-based biopsychosocial data, and using novel statistical and machine learning methods to process and analyse it to address the knowledge gaps from stream 1.
3 Developing health technologies for targeting the multimorbidity mechanisms established in streams 1-2.
4 Engaging all stakeholders to co-design the research and maximise real-world relevance and translation.

In the first 6 months' Consolidator phase, we will pilot methods and build shared theory in three areas where the mechanisms to multimorbidity are not yet clear, there is great potential for innovation and we have substantial expertise: influence of mother's cardiovascular health on foetus/child; effect of stress on hormones and child health; effect of mother/child physical activity on cardiometabolic and mental health.

This research can shift health and care systems from single conditions to preventing multiple problems, and will directly improve child and parent health, reduce burden on families and the system, and inform governments on early life data to collect to monitor public health.