Early origins of cardiometabolic risk factors: Life course epidemiology and pathways

Adverse experiences since early life play an important role in increasing susceptibility for cardio-metabolic diseases, chiefly cardiovascular diseases and type 2 diabetes (T2D), that confer the major burden of non-communicable diseases globally. It remains unknown how interaction between biological health, social status, psychological wellbeing and environmental factors aggregate at multiple time points during the life course to determine cardio-metabolic risk factors and their outcomes.

This thesis work was based on increasing the depth of understanding and gain new insight on the role of long-term effect of early life adversities, due to direct biological effects combined with inherited behavioral and psychosocial factors and their underlying epigenetic mechanism. The research was designed primarily on the Northern Finland Birth Cohort 1966 and 1986 with data available at multiple time points, pregnancy, birth, childhood, adolescence, and adulthood. However, multiple cohorts from Europe, US and Australia were also included with large international collaboration linking data to validate generalizability of the findings and understand country-specific factors.

The first work included in the thesis focused on the role of exposure to maternal smoking during pregnancy on child’s cardiometabolic risk factors in adulthood through epigenetic changes. It identified that differential DNA methylation at GFI1 (a compelling smoking-related epigenetic locus), associated with higher risk for adult adiposity, hypertension and hypertriglyceridemia. In the second work maternal risk factors during pregnancy were studied, which clustered into two biological and two psychosocial factors and showed comparable associations with birth outcomes in the two ethnically diverse populations (Finnish and Dutch). The aggregate of adverse biopsychosocial risk factors was found to be associated with lower birth weight. The third study provided clear evidence that lower birth weight remains a major risk for T2D. The longitudinal risk (from pregnancy to adult life) of changes in overweight patterns on T2D was higher when adiposity in childhood continues in adulthood. No smoking and higher education attainment level were important adult lifestyle modifiers in reducing the risk. This is an important finding considering the acceleration in the trend of obesity and metabolic diseases at the global level. Early detection of at-risk individuals in childhood can provide opportunity for health interventions and individual-level personalized policy recommendations.

Collectively, the body of evidence inferred that the risk factors intermingle throughout the life course (from pregnancy to adulthood), and multiple biological to psychological to social dimensions, showing immediate influence on birth outcomes and on the development of cardiometabolic risk factors in adulthood. DNA methylation emerged as a biomarker linking smoking with development of hypertension, hypertriglyceridemia, and adiposity. This research work provided strong foundation for further works that can help unravel emerging epigenetic markers related to other health-related risk factors (e.g. BMI, obesity, education etc.). The biopsychosocial model is important in the clinical settings to identify mothers and child with an increased risk of adversities. It is noteworthy that the measures used in this research are systematically obtained at the maternal clinics and Finnish Neuvola system, and the findings could have immediate clinical application to detect biological and psychosocial risk factors and inform on the possible way to prevent them.