Early life influences on adult organ function, health and disease, including data from Swedish population-based cohorts

Sammanfattning: Prenatal insults or adverse events during the in-utero period may lead to suboptimal function of adult organs because of the impairment of critical organ development and growth, as linked to lower birth weight. This may ultimately predispose the individual to the later onset of some diseases in adulthood, a process known as Developmental Origins of Health and Disease (DOHaD). There is ample evidence of the link between early life factors and disease onset; however, the evidence of their associations with organ function and physiological traits is limited. The overall aim of the thesis was to elucidate the influence of early life factors, such as birth weight and gestational age, on adult organ traits and disease risk, based on a systematic review and meta-analysis, and data from three population-based cohorts, including Malmö Offspring Study (MOS) cohort, LifeGene Study cohort, and Malmö Birth Data cohort. We selected 11 peer-reviewed studies for qualitative synthesis in Paper I and had a sample size of 1995 individuals in Paper II, 2012 individuals in Paper III, and 10093 individuals in Paper IV. We found an increased risk of cancer (any) mortality and prostate cancer mortality with increased birth weight (Paper I). However, the association of birth weight with breast cancer mortality was statisticallyinsignificant. In the MOS cohort (Paper II), we found that adults born with low birth weight (LBW) but who attained a higher body mass index (BMI) at age 20 (mismatch) had significantly higher systolic and diastolic blood pressure (BP) compared to those born with LBW but continued to have low BMI at age 20. Birth weight z-score showed an inverse association with peripheral augmentation index and positive with pulse wave velocity, markers of aortic stiffness. Likewise, in the MOS cohort (Paper III), an average 0.054 arbitrary unit decrease in skin autofluorescence advanced glycation end products (sfAGE) value and 0.016 unit decrease in mean ankle-brachial index (ABI) value per 1 kg increase in birth weight (adjusted for gestational age and sex) were noted. In the LifeGene study cohort (Paper IV), we found a positive association between birth weight and apolipoproteins A1 (apoA1) but an inverse association with apolipoproteins B (apoB) (β-coefficient [95% Confidence Interval]: -0.023 [-0.034, -0.012]; p<0.001). An inverse association was also found between birth weight and the apoB/apoA1 ratio, a marker of cardiovascular risk.LBW, a surrogate marker of adverse intrauterine conditions, is associated with adult cardiometabolic risk traits (markers) such as hypertension, impaired glucose metabolism, and lipid disturbances, increasing the risk of developing cardiovascular diseases and type 2 diabetes. On the contrary, higher birth weight was associated positively with increased cancer mortality risk (i.e., cancer prognosis). Our findings highlight the key role of periconception care among young couples as well as the optimization of maternal health care forthe prevention of adult cardiometabolic disease.