Epidemiological observations have led to the hypothesis that the risk of developing some chronic noncommunicable diseases in adulthood is influenced not only by genetic and adult life-style factors but also by environmental factors acting in early life. Research in evolutionary biology, developmental biology, and animal and human physiology provides support for this idea and suggests that environmental processes influencing the propensity to disease in adulthood operate during the periconceptual, fetal, and infant phases of life. This "developmental origins of health and disease" concept may have important biological, medical, and socioeconomic implications. It has been proposed that the risk of suffering chronic diseases depends in part on environmental influences acting early in life (1). The "developmental origins of health and disease" model arose largely from retrospective epidemiological studies of human populations (1-3). The relative size and importance of such developmental and nongenetic effects have been disputed (4, 5). We review the clinical and experimental data and the mechanisms involved, and evaluate the wider implications arising from this concept. Epidemiological and Clinical StudiesRetrospective epidemiological analysis of causal factors in a disease process spanning most of a lifetime is challenging because concurrent risk factors carry greater weight and it is difficult to identify or attribute risk to distant, early-life factors. In addition, direct study of the potential impact of development on later disease outcomes is difficult because of the need for unbiased cohorts with both perinatal data and health outcomes documented well into middle age. Thus, most studies have used surrogate (i.e., indirect or proxy) measures of disease risk, such as systolic blood pressure or fasting insulin/ glucose ratios. Although the definition of the health/disease boundary is inevitably arbitrary, where clinical cardiovascular or metabolic disease is the measured outcome, the effect of early environmental influences is clear (Fig. 1).There are now many epidemiological studies (1-3) relating impaired fetal growth (deduced from birth weight or body proportions) to an increased incidence of cardiovascular disease or type 2 diabetes mellitus (T2D) or their precursors: dyslipidemia, impaired glucose tolerance, or vascular endothelial dysfunction. Disease risk is higher in those born smaller who become relatively obese as adolescents or adults (1). Interpretation of these studies has led to debate about the magnitude of the effect (4), although the only published estimate based upon a longterm Finnish cohort (3) suggests it to be substantial. Prospective clinical studies on children born small also provide support for the concept (6, 7).In evaluating the relative role of genetic and environmental factors, it is useful to note that birth size has only a small genetic component and primarily reflects the quality of the intrauterine environment. The observed relationship between disease risk and birth size does n...

The Sustainable Development Goals (SDGs) provide a historic opportunity to implement at scale interventions to promote Early Childhood Development (ECD). While the evidence base for the importance of ECD has grown, the research is distributed across sectors, populations, and settings with diversity noted in the scope and focus. In this paper, we provide a comprehensive updated analyses of ECD interventions across five sectors: health; nutrition; education; child protection; and social protection. Our review concludes that to make interventions, successful, smarter and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in "nurturing care". The recommendations emphasize that intervention packages should be applied at developmentally appropriate times during the life-course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence is now strong that parents, caregivers, and families need to be supported in providing nurturing care and protection for young children to achieve their developmental potential.