The ENVIRONAGE birth cohort as a resource for further understanding of the Developmental Origins of Health and Disease

The Developmental Origins of Health and Disease (DOHaD) also called the Barker hypothesis, postulate that risk factors for age-related diseases such as coronary heart diseases, stroke, diabetes mellitus type 2 and hypertension, find their origin in childhood and even during the fetal period. It is believed that in utero life represents a critical time window in the early programming of diseases later in life. The interplay between environmental and maternal factors effects physiological processes during pregnancy and thereby potentially alters the programming of fetal growth and development. Associations between different prenatal environmental factors and clinical health outcomes in childhood and adulthood have been reported. However, studies on health effects of prenatal exposure to air pollution in newborns and children are scarce. In this thesis, the effect of prenatal and childhood exposure to air pollution on cardiovascular outcomes in newborns and in 4 to 6 year old children were investigated. This thesis consists of 3 parts: Part I of this thesis gives a general overview of the characteristics of the birth cohort ‘ENVIRONAGE’ and explains the rationale for the strong focus on the molecular mechanisms and clinical measurements to bridge the gap between exposure and health effects occurring in early life (Chapter 1). Part II of this thesis is focused on newborn outcomes. In chapter 2, we investigated the association between prenatal air pollution and cord plasma insulin concentrations. We found that exposure to particulate air pollution in late pregnancy is associated with increased levels of cord plasma insulin at birth. Chapter 3 focuses on the association between newborns blood pressure and prenatal air pollution exposure, traffic and land use indicators. We showed that a higher blood pressure in the first days of the neonate’s life was associated with higher prenatal air pollution concentrations, higher percentage industrial area, and lower greenness at maternal residence. Part III of this thesis focuses on the follow-up study within the ongoing ENVIRONAGE cohort. In chapter 4, we have established reference values of cardiovascular phenotypes in 4 to 6 year old children to understand the early cardiovascular health trajectory and to gain insight of life course changes of small and large arteries. In chapter 5, we investigated the association of pre- and postnatal air pollution exposure with carotid intima-media thickness and the arterial stiffness in children. We found that short-term exposure to PM2.5 and PM10 one month before follow-up visit was inversely associated with carotid arterial stiffness parameters including the distensibility coefficient and compliance coefficient and positively associated with Young’s Elastic Modulus. The persistence of my findings will be further investigated in the future. The ENVIRONAGE birth cohort has implemented follow-up visits at the age of 9 to understand potential long-term effects from exposures before birth towards healthy or unhealthy ageing and development. In summary, clustering findings of hormonal, molecular, and clinical measurements in early life leads to a better understanding of modifiable risk factors that influence CVD development. Addressing or preventing these modifiable risk factors may improve CVD outcomes in later life and decrease future morbidity and mortality in the general population.

Publication year:2019

Keywords:Air pollution, health, children, newborn

Accessibility:Embargoed