Entangled lives: Implications of the developmental origins of health and disease hypothesis for bioarchaeology and the life course

In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course. Together, these data can ultimately help to elucidate mechanisms that underlie fetal metabolic programming. Finally, we review current gaps in knowledge and identify areas where the field of metabolomics is likely to provide insights into mechanisms linked to DOHaD in human populations.

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Analyzing Policies Through a DOHaD Lens: What Can We Learn?

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15122906 ◽

2018 ◽

Vol 15 (12) ◽

pp. 2906 ◽

Cited By ~ 2

Author(s):

Julia Goodman ◽

Janne Boone-Heinonen ◽

Dawn Richardson ◽

Sarah Andrea ◽

Lynne Messer

Keyword(s):

Life Course ◽

Life Experiences ◽

Evidence Base ◽

Policy Impact ◽

Full Potential ◽

Developmental Origins ◽

Health Trajectories ◽

Health And Disease ◽

Potential Impact ◽

The Life Course

Social, health, and environmental policies are critical tools for providing the conditions needed for healthy populations. However, current policy analyses fall short of capturing their full potential impacts across the life course and from generation to generation. We argue that the field of Developmental Origins of Health and Disease (DOHaD), a conceptual and research framework positing that early life experiences significantly affect health trajectories across the lifespan and into future generations, provides an important lens through which to analyze social policies. To illustrate this point, we synthesized evidence related to policies from three domains—family leave, nutrition, and housing—to examine the health implications for multiple generations. We selected these policy domains because they represent increasing distance from a reproductive health focus, each with a growing evidence base to support a potential impact on pregnant women and their offspring. Each of these examples represents an opportunity to extend our understanding of policy impact using a DOHaD lens, taking into account the potential life course and intergenerational effects that have previously been overlooked.

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Do the concepts of “life course approach” and “developmental origins of health and disease” underpin current maternity care? Study protocol

International Journal of Gynecology & Obstetrics ◽

10.1002/ijgo.12955 ◽

2019 ◽

Vol 147 (2) ◽

pp. 140-146 ◽

Cited By ~ 1

Author(s):

Chandni Maria Jacob ◽

Wendy T. Lawrence ◽

Hazel M. Inskip ◽

Fionnuala M. McAuliffe ◽

Sarah Louise Killeen ◽

...

Keyword(s):

Life Course ◽

Study Protocol ◽

Maternity Care ◽

Developmental Origins ◽

Life Course Approach ◽

Health And Disease ◽

Care Study

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Distal mediator-enriched, placental transcriptome-wide analyses illustrate the Developmental Origins of Health and Disease

10.1101/2021.04.12.21255170 ◽

2021 ◽

Author(s):

Arjun Bhattacharya ◽

Anastasia N. Freedman ◽

Vennela Avula ◽

Rebeca Harris ◽

Weifang Liu ◽

...

Keyword(s):

Association Studies ◽

Specific Gene ◽

Developmental Origins ◽

Functional Validation ◽

Intrauterine Environment ◽

Health And Disease ◽

Genomic Regulation ◽

The Life Course ◽

Omic Data ◽

Trait Associations

ABSTRACTAs the master regulator of the intrauterine environment, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) but is understudied in relation to tissue-specific gene and trait regulation. We performed distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 health traits across 5 physiological categories, using gene expression models trained with multi-omic data from the Extremely Low Gestational Age Newborn Study (N = 272). At P < 2.5 × 10−6, we detected 248 gene-trait associations (GTAs) across 176 genes, mostly for metabolic and neonatal traits and enriched for cell growth and immunological pathways. Of these GTAs, 89 showed significant mediation through genetic variants distal to the gene, identifying potential targets for functional validation. Functional validation of a mediator gene (EPS15) in human placenta-derived JEG-3 trophoblasts resulted in increased expression of its predicted targets, SPATA13 and FAM214A, both associated with the trait of waist-hip ratio in TWAS. These results illustrate the profound health impacts of placental genetic and genomic regulation in developmental programming across the life course.

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Characterizing the human methylome across the life course: findings from eight UK-based studies

10.1101/2021.09.18.460916 ◽

2021 ◽

Author(s):

Esther Walton ◽

Riccardo Marioni ◽

Hannah R Elliott ◽

Simon R Cox ◽

Ian R Deary ◽

...

Keyword(s):

Life Course ◽

Fold Increase ◽

Cross Sectional ◽

Cpg Sites ◽

Age Related ◽

Developmental Age ◽

Regression Framework ◽

Health And Disease ◽

The Life Course ◽

First Time

Variation in DNA methylation (DNAm) is associated with multiple biological processes that track growth and development, ageing and age-related diseases. However, there is little understanding of what constitutes typical patterns of DNAm variation and how these patterns change across the life course. In this study, we synthesised a map of the human methylome across the life course, focussing on changes in variability and mean DNAm. Harmonizing DNAm datasets across eight longitudinal and cross-sectional UK-based studies, we meta-analysed n=13,215 blood samples from n=7,037 unique individuals from birth to 98 years of age. Changes in CpG-specific variability and means were described across the life course using a meta-regression framework. CpG-specific associations of variability or mean DNAm in relation to the likelihood of association with 100 traits linked to environmental exposures, health and disease were tested within and across ten developmental age bins across the life course. Age was linked to DNAm variability at 29,212 CpG sites. On average, we observed a 1.26 fold increase in DNAm variability per year across the life course. 33,730 CpGs displayed changes in mean DNAm, with 64% of these loci showing decreases in DNAm over time. CpG sites linked to traits were in general more variable across the life course. Our study provides, for the first time, a map of the human methylome across the life course, which is publicly accessible through a searchable online database. This resource allows researchers to query CpG-specific trajectories from birth to old age and link these to health and disease.

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Beyond the dyad: making Developmental Origins of Health and Disease (DOHaD) interventions more inclusive

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174417000629 ◽

2017 ◽

Vol 9 (1) ◽

pp. 10-14 ◽

Cited By ~ 12

Author(s):

M. Pentecost ◽

F. C. Ross ◽

A. Macnab

Keyword(s):

Life Course ◽

Health Outcomes ◽

Pregnant Women ◽

South African ◽

Developmental Origins ◽

South African Context ◽

The South ◽

Windows Of Opportunity ◽

African Context ◽

Health And Disease

Pregnant women, children under 2 and the first thousand days of life have been principal targets for Developmental Origins of Health and Disease interventions. This paradigm has been criticized for laying responsibility for health outcomes on pregnant women and mothers and through the thousand days focus inadvertently deflecting attention from other windows for intervention. Drawing on insights from the South African context, this commentary argues for integrated and inclusive interventions that encompass broader social framings. First, future interventions should include a wider range of actors. Second, broader action frameworks should encompass life-course approaches that identify multiple windows of opportunity for intervention. Using two examples – the inclusion of men, and engagement with adolescents – this commentary offers strategies for producing more inclusive interventions by using a broader social framework.

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Pakistan Developmental Origins of Health and Disease (DOHaD) Society: addressing the ‘DO’ component of DOHaD

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174418000636 ◽

2018 ◽

Vol 10 (02) ◽

pp. 141-143

Author(s):

N. Mohammed ◽

R. Nuruddin ◽

A. Shoukat Ali

Keyword(s):

Fetal Programming ◽

In Utero ◽

Learning Disorders ◽

Developmental Origins ◽

Early Screening ◽

Future Health ◽

Double Burden ◽

Research Findings ◽

Health And Disease ◽

The Life Course

AbstractAdverse intrauterine environment could serve as an important stimulus for postnatal altered health status and for increased susceptibility to long-term non-communicable diseases (NCDs). The notion is now recognized as the Developmental Origins of Health and Disease (DOHaD), which was first proposed by Sir David Barker. Since then, several scientific disciplines have strived to measure the magnitude of the early fetal programming and later risk of diseases. Pakistan, with striking figures of morbidity and mortality from NCDs, is currently tackling with double burden of diseases and requires planned efforts to counteract the threat of NCDs. Considering the growing needs and available evidences, Pakistan DOHaD Society was officially instigated in September 2016. The Society aims to explicitly address the association of life in utero with future health and disease and to endorse early screening and interventions to reduce the burden of NCDs, mental health issues and learning disorders along the life course. It has shown significant progress toward investigating the influence of adverse in utero environment such as diabetes, maternal under-nutrition and pre-eclampsia on fetal programming under two major research lines, that is, cardiovascular and cerebrovascular programming. The Society has been successful in disseminating its research findings through several esteemed international scientific conferences. Pakistan DOHaD Society encourages scientific community for collaborative research aimed at improving the quality of life during early childhood, adolescence and adulthood through provision of appropriate pre-pregnancy and antenatal interventions targeted to address at-risk in utero conditions.

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