Search strategy

Publications for this literature review were obtained through searches of the Medline and Embase databases, as well as Google Scholar and Discovery at the University of Melbourne, using combinations of the following and related search terms: ‘epigenetics’, ‘genetics’, ‘attitudes to health’, ‘DOHaD’, ‘parents’, ‘opinions’, and ‘chronic health’.

Epigenetics

It is currently widely accepted that the developmental trajectory of an individual is not simply a competition between two opposing factors (nature and nurture), but rather represents a complex interaction between genetic and environmental factors. ^{Reference Morris, Gwinn, Clyne and Khoury2-Reference Dupras and Ravitsky4} Genetic (nature) and environmental (nurture) factors do not act independently of each other during development. ^{Reference Morris, Gwinn, Clyne and Khoury2} Instead, they interact in a number of different ways, one of these being through epigenetic mechanisms. Furthermore, this gene-environment interaction can change and evolve throughout a person’s life, ^{Reference Weaver3} suggesting that it is not only the initial developmental stages of life which influence an individual’s health and risk of disease. Epigenetics has provided the means for a paradigm shift in the nature versus nurture debate. ^{Reference Lappé5}

Conrad Waddington was the first to define epigenetics as ‘the interactions of genes with their environment, which bring the phenotype into being’ (p.298). ^{Reference Dolinoy, Weidman and Jirtle6} His idea was supported by the discovery of a potential underlying mechanism of epigenetic action, DNA methylation, in the 1970s by Holliday and Pugh. ^{Reference Dolinoy, Weidman and Jirtle6} The word ‘epigenetics’ has historically been ambiguous; its definition has changed dramatically over time as the science behind it has progressed. ^{Reference Greally7} Today, however, the term ‘epigenetics’ is generally used to describe more specifically modifications to DNA and gene expression that do not involve changes to the DNA sequence itself, ^{Reference Dolinoy, Weidman and Jirtle6-Reference Richardson, Daniels and Gillman10} or alternatively, ‘experience-dependent molecular alterations to DNA or to proteins that alter how genes behave without changing the information they contain’ (p.171). ^{Reference Nestler11}

Epigenetics plays a major role in mammals in phenomena such as genomic imprinting (where parent-of-origin epigenetic markers determine gene expression) and X-inactivation (the epigenetic process by which one X chromosome is deactivated in females). ^{Reference Dolinoy, Weidman and Jirtle6} Epigenetic markers (such as DNA methylation, histone modification, and DNA packaging) are involved in the regulation and expression of genes, both spatially (across different tissue types) and temporally (across developmental stages). ^{Reference Dolinoy, Weidman and Jirtle6,Reference Rothstein, Cai and Marchant8} Epigenetic markers control gene expression by affecting when and how genes are expressed. ^{Reference Rothstein, Cai and Marchant8} Epigenetic markers are unique compared to DNA sequence for a number of reasons, including their susceptibility to influence by the environment. ^{Reference Rothstein, Cai and Marchant8} It is also plausible that in some cases, they may be transmissible from parent to offspring. ^{Reference Dolinoy, Weidman and Jirtle6} In order to understand the influence that the environment has on epigenetic markers, and their potential inheritance, it is important to first understand the process of epigenetic reprogramming.

Epigenetic reprogramming

Epigenetic reprogramming occurs at several time points during development, including gametogenesis (when eggs and sperm are created) and in early embryogenesis ^{Reference Dolinoy, Weidman and Jirtle6,Reference Vanhees, Vonhogen, van Schooten and Godschalk12} (Fig. 1). Epigenetic reprogramming involves genome-wide ‘resetting’ of epigenetic markers, ^{Reference Dolinoy, Weidman and Jirtle6} the best understood of which is DNA methylation. Global demethylation is thought to occur in order to restore totipotency to the cell; however, some areas of the genome are protected from this global demethylation, such as imprinted genes. ^{Reference Dolinoy, Weidman and Jirtle6,Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} Epigenetic markers within these regions are known as ‘parent-of-origin methylation marks’ (p.272) ^{Reference Vanhees, Vonhogen, van Schooten and Godschalk12} and are essential for the correct expression of these genes. De novo methylation of the genome then occurs around the time of implantation, which coincides with the first cell lineage determination stage ^{Reference Dolinoy, Weidman and Jirtle6,Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} and establishes a new pattern of DNA methylation in the blastocyst. ^{Reference Vanhees, Vonhogen, van Schooten and Godschalk12} There are currently around 100 known imprinted genes; however, a growing consensus suggests there are likely other genes that also elude reprogramming through similar mechanisms. ^{Reference Hughes14} This is the basis of intergenerational epigenetic inheritance. ^{Reference Rothstein, Cai and Marchant8,Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} Because of this global demethylation and subsequent de novo methylation process, there are several time points at which the epigenome is most sensitive to disruptors, namely during gestation, neonatal development, adolescence, and late adulthood. However, the epigenome is at its most vulnerable during embryogenesis, ^{Reference Dolinoy, Weidman and Jirtle6} gestation and newborn stages ^{Reference Rothstein, Cai and Marchant8} due to high rates of cell division at these times. Furthermore, changes to epigenetic state can be sensitive and specific to the developmental stage at which they occur. ^{Reference Rothstein, Cai and Marchant8}

Fig. 1. Alterations in DNA methylation status during cell development. Reused with permission from Jirtle and Skinner ^{Reference Jirtle and Skinner16} . Global demethylation (and therefore epigenetic reprogramming) occurs at two key time points during development, during gametogenesis and early embryogenesis.

Although intergenerational epigenetic inheritance has been observed in mammals, ^{Reference Dolinoy, Weidman and Jirtle6,Reference Hughes14} the mechanism by which it occurs remains elusive. ^{Reference Gluckman, Hanson and Beedle15,Reference Jirtle and Skinner16} Knowledge of mitotic inheritance of epigenetic markers is well established; however, the global demethylation and reprogramming which occurs during gametogenesis and after conception poses a challenge for understanding the intergenerational inheritance of epigenetic markers. ^{Reference Gluckman, Hanson and Beedle15} It should be remembered that although the following concepts are described mostly in terms of intrauterine environment, both maternal and paternal effects have been observed in transgenerational epigenetic inheritance, ^{Reference Richardson, Daniels and Gillman10,Reference Vanhees, Vonhogen, van Schooten and Godschalk12} hence, ‘the paternal influence on epigenetic alterations in offspring should not be neglected’ (p.274). ^{Reference Vanhees, Vonhogen, van Schooten and Godschalk12}

Epigenetic exceptionalism

While there is much research focusing on the ethical issues of genetic concepts and genetic inheritance, there has been argument as to whether, ethically, epigenetics should be considered any differently. ^{Reference Rothstein, Cai and Marchant8,Reference Rothstein17} From a scientific point of view, it is clear that the two have both similarities and differences. The most obvious difference between genetics and epigenetics is that, unlike genetic changes, epigenetic changes can be reversible. ^{Reference Rothstein, Cai and Marchant8} Possibly less known is the fact that epigenetic changes occur more frequently than DNA mutations. ^{Reference Rothstein, Cai and Marchant8} Furthermore, unlike genetic mutations, excluding the mechanism of mutagenesis, epigenetic markers may be influenced by the environment. ^{Reference Rothstein, Cai and Marchant8,Reference Chadwick and O’Connor18} A similarity between genetics and epigenetics is that epigenetic changes may also be inherited. ^{Reference Rothstein, Cai and Marchant8} Some have suggested that, despite its differences, epigenetics poses the same ethical issues as genetics, albeit potentially more complex. ^{Reference Rothstein, Cai and Marchant8,Reference Chadwick and O’Connor18} However, because epigenetic variants can be reversible, and therefore more easily prevented or treated, responsibility on parents and societal blame for children’s epigenetic conditions could be greater than that for genetic conditions. ^{Reference Dupras and Ravitsky4}

Developmental plasticity and developmental mismatch

Developmental plasticity, sometimes referred to as phenotypic plasticity, ^{Reference Weaver3} biological embedding, ^{Reference Moore, Arefadib, Deery and Sue West19} or fetal programming ^{Reference Lumey, van Poppel, Lumey and Vaiserman20} is the process whereby a fetus ‘utilizes environmental cues to adjust individual phenotype to the current and predicted environment’ (p.8). ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} This allows the fetus to use information about the current environment as a ‘weather forecast’ for the future environment, and to develop and adapt accordingly. ^{Reference Moore, Arefadib, Deery and Sue West19} The process of developmental plasticity not only explains how one genotype can produce a range of phenotypes, ^{Reference Dolinoy, Weidman and Jirtle6,Reference Jablonka and Lamb21} but it also provides an evolutionary advantage. This is because developmental plasticity allows the fetus to become best adapted to the predicted environment by adjusting its phenotype to best match environmental demand. ^{Reference Weaver3} Developmental plasticity is therefore thought to help an individual more quickly adapt to their environment, bypassing the long process of genetic evolution. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13,Reference Barker22}

Because of developmental plasticity, the environmental factors acting during an individual’s early life set the trajectory for their developmental course, moulding the phenotype to those specific environmental inputs. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} It has therefore been suggested that the early life environment can affect the phenotype permanently and into adult life. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} At the molecular level, the concept of developmental plasticity describes an individual’s ability to ‘tune’ gene expression ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} through a ‘weather forecast’ ^{Reference Barker22} from the mother. This tuning can be achieved via epigenetic mechanisms. Epigenetic programming is therefore proposed as a mechanism for developmental plasticity, ^{Reference Weaver3,Reference Dupras and Ravitsky4,Reference Dolinoy, Weidman and Jirtle6,Reference Vanhees, Vonhogen, van Schooten and Godschalk12} as it affects regulation of gene expression, and is both influenced by early life environment, and consistent into adult life. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13}

Although epigenetics may have conferred a selective advantage throughout evolutionary history, today it instead exacerbates disease risk across generations. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} The reason for this can be explained through the ‘developmental mismatch’ theory, where the future environment does not reflect that which was predicted, resulting in the individual being at increased risk of disease. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} Although such adaptations may be beneficial in the short term, they may cause disease in the long term if the environment changes. ^{Reference Lumey, van Poppel, Lumey and Vaiserman20} Such dramatic changes in predicted and actual environment can result from circumstances such as inaccurate environmental cues during gestation, ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} or dramatic shifts in nutrition due to improved socio-economic status. Godfrey et al. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} also suggest that the degree of mismatch between the predicted and actual environment is directly related to the risk of disease. This is particularly relevant for societies undergoing rapid economic growth, ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} where one generation may experience a far richer environment than previous generations.

The developmental mismatch concept was shown most notably in a study conducted by Roseboom et al., ^{Reference Roseboom, van der Meulen, Ravelli, Osmond, Barker and Bleker24} who examined individuals who had been exposed to extreme famine in the Netherlands during World War II. Because the Dutch famine occurred over a short period of time (only a few months), records were kept immaculately, and the population were well-nourished both before and after the famine, this particular occurrence provided a unique opportunity to study the effects of undernutrition on pregnant women and their resulting children. ^{Reference Lumey, van Poppel, Lumey and Vaiserman20,Reference Roseboom, van der Meulen, Ravelli, Osmond, Barker and Bleker24} The study revealed that the undernutrition of mothers during pregnancy affected a child’s health in later life, ^{Reference Roseboom, van der Meulen, Ravelli, Osmond, Barker and Bleker24} and that the effect directly depended on both the timing during gestation at which the famine was experienced and on the specific systems under embryonic and fetal development at that time. ^{Reference Roseboom, van der Meulen, Ravelli, Osmond, Barker and Bleker24} Outcomes such as adult body size, diabetes, and schizophrenia showed the most association with prenatal exposure to famine. ^{Reference Lumey, van Poppel, Lumey and Vaiserman20} Epigenetic changes also showed an association with prenatal famine, providing a possible mechanism for the adult disease outcomes. ^{Reference Lumey, van Poppel, Lumey and Vaiserman20}

Developmental Origins of Health and Disease

A major implication of the developmental plasticity and developmental mismatch concepts is the overarching DOHaD theory. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} Sometimes referred to as the ‘fetal basis of adult disease’ or the ‘early origins’ theory, the DOHaD theory suggests that ‘nutrition and other environmental factors during prenatal and early postnatal development influence developmental plasticity, thereby altering susceptibility to adult chronic diseases’ (p.298). ^{Reference Dolinoy, Weidman and Jirtle6} In addition, the First 1000 Days concept builds on the DOHaD theory by suggesting that the first 1000 days of development (from conception until age two) are the most crucial in affecting future disease risk. ^{Reference Mameli, Mazzantini and Zuccotti25} The concept of the First 1000 Days has been described in the literature based on recent evidence emphasising the importance of this early life stage. ^{Reference Moore, Arefadib, Deery and Sue West19,Reference Mameli, Mazzantini and Zuccotti25}

Because of its implication in many common diseases, it is well accepted that the DOHaD concept has worldwide public health implications, ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} as the fetal environment impacts the developmental trajectory, and therefore disease risk, of every child across the globe. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} Additionally, environmental factors can affect multiple future generations through the inheritance of epigenetic markers, despite their continued lack of exposure to such factors, ^{Reference Dolinoy, Weidman and Jirtle6} further emphasising the importance of epigenetic concepts in global health strategy. Despite this recognised importance, translation of DOHaD knowledge into public health policy and guidelines has been limited. ^{Reference Jacob and Hanson26}

Epigenetics and NCD

Evidence suggests that epigenetics plays a significant role in disease susceptibility in adult life. ^{Reference Dolinoy, Weidman and Jirtle6} Changes in epigenetic regulation are associated with an increasing number of diseases, including but not limited to: type 2 diabetes, ^{Reference Lappé5,Reference Vanhees, Vonhogen, van Schooten and Godschalk12,Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13,Reference Jirtle and Skinner16} cancer, ^{Reference Lappé5,Reference Dolinoy, Weidman and Jirtle6,Reference Vanhees, Vonhogen, van Schooten and Godschalk12,Reference Jirtle and Skinner16} cardiovascular disease, ^{Reference Lappé5,Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13,Reference Jirtle and Skinner16} obesity, ^{Reference Lappé5,Reference Vanhees, Vonhogen, van Schooten and Godschalk12,Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13,Reference Jirtle and Skinner16,Reference Chadwick and O’Connor18,Reference Mameli, Mazzantini and Zuccotti25} and mental illness, ^{Reference Lappé5,Reference Dolinoy, Weidman and Jirtle6,Reference Scott9,Reference Jirtle and Skinner16} suggesting that the range of epigenetic influence across all aspects of human health is vast. There is widespread agreement that epigenetics plays a significant role in human health, ^{Reference Egger, Liang, Aparicio and Jones27-Reference Peedicayil29} and new evidence is emerging regularly linking epigenetic changes to increasingly more aspects of human disease. ^{Reference Peedicayil29}

Also known as chronic diseases, NCDs are non-infectious, long-lasting conditions which are caused by a combination of genetic and environmental factors. ³⁰ They include cardiovascular disease, cancer, chronic respiratory disease, and diabetes. ³⁰ The prevalence of NCDs across the globe is increasing, ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13,Reference Barker, Barker, Fleming and Lampl31} generating a significant burden on global economies and worldwide health. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} As of 2014, NCDs were more common worldwide than communicable diseases, a statistic which is likely only to worsen. ^{Reference Hanson, Gluckman, Godfrey, Seckl and Christen32} Particularly in Western countries, where they present one of the major health problems, ^{Reference Roseboom, van der Meulen, Ravelli, Osmond, Barker and Bleker24} NCDs are the modern-day epidemic. ^{Reference Gluckman, Hanson and Low33} For example, the global prevalence of type 2 diabetes is expected to double by the year 2030, and the prevalence of cardiovascular disease is expected to increase by 35%. ^{Reference Barker, Barker, Fleming and Lampl31} NCDs cause 41 million deaths worldwide each year, contributing to 71% of global mortality, and accounting for over 80% of premature mortality. ^{Reference Riley, Guthold and Cowan34} Furthermore, 85% of these premature deaths occur in low- and middle-income countries, ^{Reference Riley, Guthold and Cowan34} indicating the impact of social and economic deprivation on these diseases. There is a significant amount of evidence to suggest that environmental factors acting during the early stages of life are contributing to this rising epidemic. ^{Reference Barker, Barker, Fleming and Lampl31} Therefore, because the majority of these deaths are preventable, ^{Reference Riley, Guthold and Cowan34} there is an important need for appropriate interventions.

Predictive epigenetic testing

Some have suggested that early identification of those at increased risk of NCDs may help encourage individuals to undertake preventative measures. ^{Reference Hanson, Gluckman, Godfrey, Seckl and Christen32} Epigenetics provides new opportunities for biomarkers which identify those at increased risk of NCDs. ^{Reference Hanson, Gluckman, Godfrey, Seckl and Christen32,Reference Hanson and Gluckman35,Reference Park and Kobor36} In fact, potential epigenetic biomarkers predictive of future disease are already being discovered. ^{Reference Sharp and Relton37} For example, Murray ^{Reference Murray, Bryant and Titcombe38} showed that DNA methylation state at birth is predictive of cardiovascular disease in late childhood. Research has also shown that DNA methylation is also associated with prenatal alcohol consumption and tobacco use. ^{Reference Sharp and Relton37} Furthermore, advances in the field of cancer include the adoption of DNA methylation screening to help predict the efficacy of certain drugs. ^{Reference Heyn, Méndez-González and Esteller39} Of course, these kinds of discoveries require not only labour-intensive research, but often time-intensive longitudinal studies in order to determine causality, rather than simply correlation. ^{Reference Sharp and Relton37} However, these epigenetic biomarkers allow for predictive epigenetic testing for an increasing number of health conditions. This will have many benefits, including the opportunity to further the prospect of personalised medicine in everyday health care by targeting those individuals who are at an increased risk, and providing early interventions to mitigate that risk. ^{Reference Chadwick and O’Connor18,Reference Peedicayil29} In particular, inroads into personalised medicine will provide opportunities for therapies targeted to the individual’s epigenome. ^{Reference Heyn, Méndez-González and Esteller39,Reference Weber40} Godfrey et al. ^{Reference Godfrey, Lillycrop, Burdge, Gluckman and Hanson13} suggest that continuing research into epigenetic mechanisms will allow development of potential interventions. The reversibility of epigenetic markers provides a particularly promising opportunity for treatment and prevention of epigenetic disease, ^{Reference Rothstein, Cai and Marchant8,Reference Egger, Liang, Aparicio and Jones27,Reference Hanson, Gluckman, Godfrey, Seckl and Christen32} resulting in a push for the advent of new epigenetic therapies. ^{Reference Egger, Liang, Aparicio and Jones27}

While predictive epigenetic testing may provide information to inform early intervention, ^{Reference Hanson, Gluckman, Godfrey, Seckl and Christen32} it may not necessarily lead to positive behaviour change. The Health Belief Model suggests that there are multiple factors which influence people’s health behaviours, including their perceived risk of disease. ^{Reference Fang, Dunkel-Schetter and Tatsugawa41,Reference Rosenstock42} Risk perception is therefore an important consideration in assessing the personal and clinical utility of both testing and public health messaging, however there is limited research in this area in the context of epigenetic testing.

Public understanding and opinion of epigenetics

While there has been some research in exploring the public’s understanding of genetic and environmental susceptibility to disease, in line with the ‘nature versus nurture’ debate, ^{Reference Morris, Gwinn, Clyne and Khoury2,Reference Condit43} research in this area is lacking. Some suggest that the public views genetic factors as contributing only a small role to human disease and associated with only diseases which are viewed as severe or incurable. ^{Reference Morris, Gwinn, Clyne and Khoury2} This is contrary to other literature showing genetic susceptibility plays a role in a significant portion of human diseases which are generally considered to be caused by environmental factors, such as lung cancer caused by cigarette smoking, pesticide and lead toxicity, infectious diseases and the effects of certain drugs. In fact, the ‘gene-environment interaction is fundamental to nearly all diseases’ (p.27). ^{Reference Morris, Gwinn, Clyne and Khoury2} Despite this, the majority of people understand that both genetic and environmental factors contribute to an individual’s overall health; however, people tend to treat these as discrete factors without interaction. ^{Reference Condit43} This is contradictory to what epigenetic research suggests. Condit showed that the public tend to view genetics ‘through the lens of heredity’ (p.1) ^{Reference Condit43} rather than by understanding the underpinning biological mechanisms by which inheritance operates. While there is limited data about the public’s awareness and understanding of epigenetic concepts, epigenetics is highly prevalent throughout mainstream media, creating potential for widespread misconception and over-hype. ^{Reference Dubois, Louvel, Le Goff, Guaspare and Allard44} Ultimately, studies show that the public’s understanding of common disease genetics is low, ^{Reference Tercyak, Hensley Alford and Emmons45,Reference Smerecnik, Mesters, de Vries and de Vries46} suggesting that their knowledge of epigenetics is likely to be even more limited.

Testing in childhood

Because predictive epigenetic testing is likely to occur in early childhood in order for early interventions to be most effective, ethical issues arise which are similar to those relating to predictive genetic testing in children. There has been much professional discussion surrounding the ethical appropriateness of genetic testing in children. ^{Reference Fallat, Katz and Mercurio47} There has also been some research exploring parents’ views of this issue ^{Reference Tercyak, Hensley Alford and Emmons45,Reference Campbell and Ross48-Reference Shkedi-Rafid, Fenwick, Dheensa and Lucassen50} ; however, some have suggested that this research is insufficient to fully explore the attitudes of parents and health professionals towards the genetic testing of children. ^{Reference Segal, Polansky and Sankar49} The vast majority of consensus statements advise against genetic testing in children for adult-onset conditions for which there are no effective preventative measures available in childhood ^{Reference Fallat, Katz and Mercurio47,Reference Campbell and Ross48} ; however this is often in opposition to parents’ views. Campbell and Ross ^{Reference Campbell and Ross48} suggest that the views of parents vary greatly with regard to wanting to know their children’s genetic predispositions to adult conditions. Almost half of the sample surveyed by Shkedi-Rafid et al. ^{Reference Shkedi-Rafid, Fenwick, Dheensa and Lucassen50} were of the opinion that parents should be able to test their children for adult-onset conditions, even when there was no treatment or preventative measures available. Similarly, a study led by Tarini found that greater than one-third of parents expressed interest in predictive genetic testing for their children for untreatable adult-onset diseases. ^{Reference Tarini, Singer, Clark and Davis51} Tercyak et al. ^{Reference Tercyak, Hensley Alford and Emmons45} showed that parents saw the benefits of genetic testing in childhood to outweigh the risks. These benefits included the knowledge of the predisposition itself, and the associated preparedness that this knowledge provided, both emotionally and practically. ^{Reference Tercyak, Hensley Alford and Emmons45,Reference Shkedi-Rafid, Fenwick, Dheensa and Lucassen50} This may be in part due to the assumption of parents that although there were no known effective interventions, they may still be able to utilise the information (such as changing their child’s diet or being more open to new treatments when they become available). ^{Reference Shkedi-Rafid, Fenwick, Dheensa and Lucassen50}

Anticipating parents’ questions, reactions, and general knowledge about genetic testing is important in order to provide the best healthcare possible, and to facilitate effective informed decision making ^{Reference Tercyak, Hensley Alford and Emmons45,Reference Shkedi-Rafid, Fenwick, Dheensa and Lucassen50} by educating health professionals as to the motivations behind parents’ requests. ^{Reference Tarini, Singer, Clark and Davis51} Further research into this area may allow the discrepancies between public and professional opinion to become clearer, and the reasons behind such discrepancies to be addressed. ^{Reference Shkedi-Rafid, Fenwick, Dheensa and Lucassen50} As summarised by Etchegary et al., ‘optimal utilisation of any genetic testing depends on the knowledge and attitudes of the potential consumers of genetic tests and technologies’ (p.354). ^{Reference Etchegary, Dicks, Green, Hodgkinson, Pullman and Parfrey52} This will likely also be the case with epigenetic testing, by allowing health professionals to be better prepared for the implementation of such testing in childhood. However, ethical issues surrounding the use of predictive testing for children, as well as equity and access of testing, will need to be considered as epigenetic testing is adopted.

How knowledge of DOHaD concepts can improve health outcomes

While there have been limited attempts at knowledge translation of DOHaD concepts beyond the scientific community, ^{Reference McKerracher, Moffat, Barker, Williams and Sloboda53} early research suggests that educational interventions can influence health outcomes. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23,Reference Bay, Vickers, Mora, Sloboda and Morton54} An example which is relevant in the context of epigenetics is a study from Bay et al., ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23,Reference Bay, Vickers, Mora, Sloboda and Morton54} where adolescents’ knowledge of DOHaD concepts before and after an in-school educational intervention were examined, and it was found that both knowledge and health outcomes were improved immediately following the intervention, ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} and at 12 months’ post-intervention. ^{Reference Bay, Vickers, Mora, Sloboda and Morton54} The participants showed increased positive lifestyle and nutritional behaviours as well as a better understanding of the long-term and intergenerational impact of these behaviours. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} The overall conclusion suggested that these types of interventions may be more effective in early life, in comparison to more traditional mid-life changes, ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} providing better health as well as economic outcomes. This increased knowledge also has the potential to be passed down to future generations, providing further benefit to the extended family. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23}

For the evidence supporting DOHaD to benefit society as a whole, it must be understood by the public so they can make decisions about its use. ^{Reference Bay and Vickers55} Therefore, educational interventions such as the one used by Bay et al. ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} are likely to be an important step in the prevention of NCDs. These types of interventions have been suggested at the prenatal stage, ^{Reference Barker, Barker, Fleming and Lampl31,Reference Hanson and Gluckman35} during childhood, ^{Reference Bateson, Barker and Clutton-Brock56} or during adolescence. ^{Reference Hanson, Gluckman, Godfrey, Seckl and Christen32,Reference Bay and Vickers55} Alternatively, before and during pregnancy would be an optimal time to target women, as it is at this stage that they are most receptive to health advice for their future children. ^{Reference Roseboom, van der Meulen, Ravelli, Osmond, Barker and Bleker24} Others have recommended that addressing the challenge of NCDs will require a life-course approach, with interventions targeted at many life stages. ^{Reference Hanson and Gluckman35} Limited research into the knowledge translation of DOHaD concepts also points to the recommendation that interventions should be aimed at multiple generations simultaneously. ^{Reference McKerracher, Moffat, Barker, Williams and Sloboda53}

While increased knowledge is likely to lead to improved overall health outcomes, ^{Reference Bay, Mora, Sloboda, Morton, Vickers and Gluckman23} it is also important that we do not forget the large impact of socio-economic factors on NCD disease risk. ³⁰ Being impoverished greatly increases an individual’s risk of NCDs due to increased exposure to environmental factors such as tobacco use and poor diet. ³⁰ Educational interventions that shed light on human behaviour and its impact on transgenerational epigenetic inheritance should be careful not to place blame and increase stigma on communities – and particularly mothers within these communities – affected by such socio-economic factors. Additionally, improved public awareness and understanding of epigenetics and DOHaD concepts should be just one intervention in a suite of public health initiatives designed to combat the increasing prevalence of NCDs globally, with a focus on disadvantaged populations with potentially less control over environmental factors impacting the health of future generations.