The DOHaD Society has passed its 10th birthday, so it seems an appropriate time to reflect on what has been achieved and the Society’s aspirations. At the 10th International Congress in Rotterdam in November 2017, Peter Gluckman (the Society’s first President) delivered a plenary lecture entitled ‘DOHaD – addressing the science-policy nexus: a reality check’; in opening the Congress, Mark Hanson (second, and outgoing President) not only highlighted the success of the Society but also the challenges it now faces in achieving impact for its work in the global health arena, that is beyond the research agenda; and in assuming the role of third President, Lucilla Poston highlighted the need for the Society to grasp opportunities to change healthcare policy, while persevering with basic research and well-planned intervention studies. In this review we summarize the points made in these three presentations and issue a call to action to the membership to take up the challenge of taking the Society’s work to the next level of translating science to policy.

The field of Developmental Origins of Health and Disease (DOHaD) has grown considerably in recent decades and is receiving increasing recognition from health policymakers. Today, DOHaD research aims to offer a comprehensive perspective on health and disease that traces how different life experiences shape health and disease risks over the entire life course. This integrative perspective opens up distinct possibilities for improving health. At the same time, it raises questions regarding the specific social responsibilities of DOHaD as a field and about possible pathways to a socially just and scientifically robust implementation of DOHaD knowledge in society. In this article, we review the history and key characteristics of DOHaD as a field of scientific knowledge production. We argue that based on its key assumptions – that life circumstances, health and disease are closely linked on a molecular scale – DOHaD is an inherently political research field. When tracing how life environments affect health and disease, it is of utmost social and political importance to specify how DOHaD understands and frames these life environments, which aspects of life worlds are included and which excluded, and how research results are interpreted and translated into health recommendations at individual, societal and policy levels. We suggest a number of ways by which the DOHaD community can constructively and responsibly meet the demands that these inherent characteristics place on knowledge production and dissemination in the field.

Maternal psychological distress is common in pregnancy and may influence the risk of adverse outcomes in children. Psychological distress may cause a suboptimal intrauterine environment leading to growth and developmental adaptations of the fetus and child. In this narrative review, we examined the influence of maternal psychological distress during pregnancy on fetal outcomes and child cardiometabolic, respiratory, atopic and neurodevelopment-related health outcomes. We discussed these findings from an epidemiological and life course perspective and provided recommendations for future studies. The literature in the field of maternal psychological distress and child health outcomes is extensive and shows that exposure to stress during pregnancy is associated with multiple adverse child health outcomes. Because maternal psychological distress is an important and potential modifiable factor during pregnancy, it should be a target for prevention strategies in order to optimize fetal and child health. Future studies should use innovative designs and strategies in order to address the issue of causality.

There is increasing evidence linking maternal diet and physical activity before and during pregnancy with offspring’s cardiovascular health. Although many studies examined this association, the evidence has not been reviewed systematically. We therefore undertook a systematic review to synthesize evidence examining the association of maternal diet and physical activity before and during pregnancy with offspring’s blood pressure and vascular health. We systematically searched the databases MEDLINE and EMBASE from inception to June 30, 2017. Eligibility screening, data extraction and quality assessment were performed by two independent reviewers. A total of 19 articles were included comprising three randomized controlled trials and 16 observational studies. Of the studies that examined the association of interest, 60% (three out of five studies) showed that high maternal carbohydrate intake was associated with higher offspring’s blood pressure. Maternal protein intake during pregnancy was negatively associated with offspring carotid intima-media thickness in two out of two studies. No consistent findings for maternal fatty acid intake were found. There were too few studies to draw conclusions on energy intake, fibre intake, protein/carbohydrate ratio, specific foods, dietary patterns and maternal physical activity. Heterogeneity in exposure and outcome assessment hampered pooling. Also, owing to the observational nature of most studies, causality cannot be established. Harmonization of valid exposure and outcome measurements, and the development of core outcome sets are needed to enable more robust conclusions.

In epidemiologic analytical studies, the primary goal is to obtain a valid and precise estimate of the effect of the exposure of interest on a given outcome in the population under study. A crucial source of violation of the internal validity of a study involves bias arising from confounding, which is always a challenge in observational research, including life course epidemiology. The increasingly popular approach of meta-analyzing individual participant data from several observational studies also brings up to discussion the problem of confounding when combining data from different populations. In this study, we review and discuss the most common sources of confounding in life course epidemiology: (i) confounding by indication, (ii) impact of baseline selection on confounding, (iii) time-varying confounding and (iv) mediator–outcome confounding. We also discuss the issue of addressing confounding in the context of an individual participant data meta-analysis.

Epigenetic changes represent a potential mechanism underlying associations of early-life exposures and later life health outcomes. Population-based cohort studies starting in early life are an attractive framework to study the role of such changes. DNA methylation is the most studied epigenetic mechanism in population research. We discuss the application of DNA methylation in early-life population studies, some recent findings, key challenges and recommendations for future research. Studies into DNA methylation within the Developmental Origins of Health and Disease framework generally either explore associations between prenatal exposures and offspring DNA methylation or associations between offspring DNA methylation in early life and later health outcomes. Only a few studies to date have integrated prospective exposure, epigenetic and phenotypic data in order to explicitly test the role of DNA methylation as a potential biological mediator of environmental effects on health outcomes. Population epigenetics is an emerging field which has challenges in terms of methodology and interpretation of the data. Key challenges include tissue specificity, cell type adjustment, issues of power and comparability of findings, genetic influences, and exploring causality and functional consequences. Ongoing studies are working on addressing these issues. Large collaborative efforts of prospective cohorts are emerging, with clear benefits in terms of optimizing power and use of resources, and in advancing methodology. In the future, multidisciplinary approaches, within and beyond longitudinal birth and preconception cohorts will advance this complex, but highly promising, the field of research.

Adverse exposures during fetal life and the postnatal period influence physical, cognitive and emotional development, and predispose to an increased risk of various chronic diseases throughout the life course. Findings from large observational studies in various populations and experimental animal studies have identified different modifiable risk factors in early life. Adverse maternal lifestyle factors, including overweight, unhealthy diet, sedentary behavior, smoking, alcohol consumption and stress in the preconception period and during pregnancy, are the most common modifiable risk factors leading to a suboptimal in-utero environment for fetal development. In the postnatal period, breastfeeding, infant growth and infant dietary intake are important modifiable factors influencing long-term offspring health outcomes. Despite the large amount of findings from observational studies, translation to lifestyle interventions seems to be challenging. Currently, randomized controlled trials focused on the influence of lifestyle interventions in these critical periods on short-term and long-term maternal and offspring health outcomes are scarce, have major limitations and do not show strong effects on maternal and offspring outcomes. New and innovative approaches are needed to move from describing these causes of ill-health to start tackling them using intervention approaches. Future randomized controlled lifestyle intervention studies and innovative observational studies, using quasi-experimental designs, are needed focused on the effects of an integrated lifestyle advice from preconception onwards on pregnancy outcomes and long-term health outcomes in offspring on a population level.

Complications of pregnancy remain key drivers of morbidity and mortality, affecting the health of both the mother and her offspring in the short and long term. There is lack of detailed understanding of the pathways involved in the pathology and pathogenesis of compromised pregnancy, as well as a shortfall of effective prognostic, diagnostic and treatment options. In many complications of pregnancy, such as in preeclampsia, there is an increase in uteroplacental vascular resistance. However, the cause and effect relationship between placental dysfunction and adverse outcomes in the mother and her offspring remains uncertain. In this review, we aim to highlight the value of gestational hypoxia-induced complications of pregnancy in elucidating underlying molecular pathways and in assessing candidate therapeutic options for these complex disorders. Chronic maternal hypoxia not only mimics the placental pathology associated with obstetric syndromes like gestational hypertension at morphological, molecular and functional levels, but also recapitulates key symptoms that occur as maternal and fetal clinical manifestations of these pregnancy disorders. We propose that gestational hypoxia provides a useful model to study the inter-relationship between placental dysfunction and adverse outcomes in the mother and her offspring in a wide array of examples of complicated pregnancy, such as in preeclampsia.