Chained Risk Assessment for Life-Long Disease Burden of Early Exposures–Demonstration of Concept Using Prenatal Maternal Smoking

Traditional risk factors and environmental exposures only explain less than half of the disease burden. The developmental origin of the health and disease (DOHaD) concept proposes that prenatal and early postnatal exposures increase disease susceptibility throughout life. The aim of this work is to demonstrate the application of the DOHaD concept in a chained risk assessment and to provide an estimate of later in life burden of disease related to maternal smoking. We conducted three systematic literature searches for meta-analysis and reviewed the literature reporting meta-analyses of long-term health outcomes associated with maternal smoking and intermediate risk factors (preterm birth, low birth weight, childhood overweight). In the chained model the three selected risk factors explained an additional 2% (34,000 DALY) of the total non-communicable disease burden (1.4 million DALY) in 2017. Being overweight in childhood was the most important risk factor (28,000 DALY). Maternal smoking was directly associated with 170 DALY and indirectly via the three intermediate risk factors 1000 DALY (1200 DALY in total). The results confirm the potential to explain a previously unattributed part of the non-communicable diseases by the DOHAD concept. It is likely that relevant outcomes are missing, resulting in an underestimation of disease burden

The MATEX cohort – a Finnish population register birth cohort to study health effects of prenatal exposures

Abstract Background The prevalence of chronic diseases, such as immune, neurobehavioral, and metabolic disorders has increased in recent decades. According to the concept of Developmental Origin of Health and Disease (DOHaD), developmental factors associated with environmental exposures and maternal lifestyle choices may partly explain the observed increase. Register-based epidemiology is a prime tool to investigate the effects of prenatal exposures over the whole life course. Our aim is to establish a Finnish register-based birth cohort, which can be used to investigate various (prenatal) exposures and their effects during the whole life course with first analyses focusing on maternal smoking and air pollution. In this paper we (i) review previous studies to identify knowledge gaps and overlaps available for cross-validation, (ii) lay out the MATEX study plan for register linkages, and (iii) analyse the study power of the baseline MATEX cohort for selected endpoints identified from the international literature. Methods/design The MATEX cohort is a fully register-based cohort identified from the Finnish Medical Birth Register (MBR) (1987–2015). Information from the MBR will be linked with other Finnish health registers and the population register to link the cohort with air quality data. Epidemiological analyses will be conducted for maternal smoking and air pollution and a range of health endpoints. Discussion The MATEX cohort consists of 1.75 million mother-child pairs with a maximum follow up time of 29 years. This makes the cohort big enough to reach sufficient statistical power to investigate rare outcomes, such as birth anomalies, childhood cancers, and sudden infant death syndrome (SIDS). The linkage between different registers allows for an extension of the scope of the cohort and a follow up from the prenatal period to decades later in life