Chronic inflammation is implicated in many diseases of aging, and it is a potentially important mechanism linking environments and health over the life course. But this understanding is based almost exclusively on research in affluent industrialized populations, which are epidemiologically and ecologically unique in comparison with most populations globally, and historically. A comparative, life course approach challenges key assumptions of the chronic inflammation paradigm, and points toward promising directions for future research into the developmental origins of health and disease.

Learning objectives

1. To appraise CVD risk across multiple domains and distinguish components of risk that nest within individuals and those that nest within communities
2. To integrate social determinants of health into overall CVD risk of individuals
3. To summarize CVD risk over the life course and across time windows of different durations:

Using a lifecourse epidemiology perspective, this presentation will highlight comparative analysis of birth cohorts followed into adulthood in diverse geographic and ecologic settings. Data from the Philippines, Guatemala, Brazil, South Africa, and India allow for exploration of the importance of the first 1000 days ---conception to age 2 years--- in shaping multiple aspects of health and well-being in young to middle adulthood, including socioemotional, cognitive and physical outcomes.

High blood pressure (BP) is the greatest single contributor to the global burden of disease, and is of increasing prevalence in populations transitioning to obesogenic lifestyles. In low- and middle-income countries, concern that high body mass index (BMI) in childhood will track into adulthood and elevate BP, has left a gap in knowledge about the role of undernutrition. Using data from a 20-year prospective cohort study in Mali (N = 1344), we show that for adults of normal weight, increased BP was substantially attributable to undernutrition in childhood. Catch-up growth was associated with lower adult BP and later exposure to undernutrition in childhood was more adverse than was exposure during the first 1000 days of life. The lowest BP (by > 7 mm Hg) in young adulthood was observed in participants whose BMI was larger in childhood, but smaller in adulthood. The policy implication is that interventions to alleviate undernutrition should extend beyond the first 1000 days of life.

Some phenotypes, and not always the most desirable ones, are transmitted between generations by epigenetic mechanisms. I will present results from our study aimed at understanding how pathologically short stature, or stunting, is transmitted from mothers to offspring. In undernourished populations, over 140 million children are stunted, predisposing them for poor health and reduced cognitive function in adulthood. Epidemiological evidence and studies in animals suggest that stunting, at least in part, is a phenotype passed from one generation to the next, but the mechanism of transmission is unknown. Imprinted genes have been identified experimentally and through theoretical considerations as candidates for regulating growth in mammals. Imprinted genes are preferentially expressed from either the maternal or the paternal allele, instead of the usual 50:50 expression. We hypothesized that the extent of expression bias in imprinted genes in the placenta affects offspring growth and transmits stunting. To test this hypothesis, we sequenced RNA and quantified the expression biases (allele specific expression) of imprinted genes in placentas from mothers in Mali, West Africa. By studying variation in allelic bias in this multi-generation cohort study, we can show for the first time an association between maternal phenotypes, birth phenotypes, and genomic imprinting.

Malthus believed humans to be naturally and consistently highly fertile, with disease and food shortage being the primary factors limiting human population growth. We now know that the human female reproductive system is dynamically responsive to signals indicative of environmental, psychosocial, and individual conditions, with substantial natural (non-pathological) variation in functioning from one ovarian cycle to another, from one woman to another within a population, and from one population to another. I’ll discuss the theoretical basis and empirical evidence for our current understanding of the sources of this natural variation including proximate biological mechanisms by which past and current conditions mediate fertility across individuals and populations. Viewed through an evolutionary lens, otherwise surprising findings regarding fecundity, reproductive hormone levels, ovulation, early pregnancy loss, and lifetime reproductive success make elegant sense.

The INCAP Nutrition Supplementation Trial Longitudinal Study is perhaps the longest-running prospective cohort study in any low- or middle-income country. Established in Guatemala in 1969 as a community-randomized nutrition intervention trial, cohort participants are now 50 years old on average. In this presentation Dr Stein will review the initial trial rationale and design, and describe some of the key findings that have emerged, including recent findings on the role of early-life nutrition on cardiometabolic disease risk in middle adulthood. https://www.ncbi.nlm.nih.gov/pubmed/30012268 https://www.ncbi.nlm.nih.gov/pubmed/18606931 https://www.ncbi.nlm.nih.gov/pubmed/18285366