The rapidly rising prevalence of non-communicable diseases (NCDs) represents a major challenge to public health and clinical medicine globally. NCDs are increasing rapidly in high-income countries, but even more rapidly in some low-middle-income countries with insufficient resources to meet the challenge. Whilst not identified in the Millennium Development Goals, there is much attention paid to NCDs in the discussions at many levels on the Sustainable Development Goals, as they underpin economic, social and environmental development in the post-2015 era. In this article, we discuss how a life-course approach to health, commencing of necessity in early development, can provide new opportunities for addressing this challenge. The approach can leverage human health capital throughout life and across generations. New insights into mechanisms, especially those processes by which the developmental environment affects epigenetic processes in the developing offspring, offer the prospect of identifying biomarkers of future risks. New interventions to promote health literacy, lifestyle and physical fitness in adolescents, young adults and their children hold great promise. In this respect, health-care professionals concerned with preconceptional, pregnancy and newborn care will have a vital role to play.
Highlights
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Leveraging health capital, even before conception, promotes resilience and reduces later dependency on health care.
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Biological and epigenetic processes operate across normal development, reflecting maternal health and lifestyle, and may provide biomarkers of NCD risk.
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Health literacy, lifestyle and physical fitness of couples, young adults and their children impact life-course health capital and that of the next generation.
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The Ob/Gyn community has a vital role to play in advocating and influencing health policy to deliver these messages.
The development of the Millennium Development Goals (MDGs) in the period leading up to the Millennium Summit at the United Nations (UN) in 2000, and the somewhat belated recognition almost a decade later that a concerted effort was needed to address the uneven progress towards meeting these goals, did much to change our perceptions of where effort was needed in global health. As the relationship between global health and social and economic development became better understood, governments, non-government organizations (NGOs), civil society organizations (CSOs), charities and philanthropic bodies started to pay greater attention to moving from isolated health-aid projects directed at specific targets to more coordinated approaches to fundamental issues such as infectious disease and sanitation. Amongst these issues is reproductive, maternal, neonatal and child health (RMNCH) and it is indisputable that the development of the MDGs played a major role in bringing attention to late gestation, birth and infancy as periods of the life course for both the mother and her infant associated with substantial mortality and morbidity. Perhaps this is best encapsulated in the UN Secretary General’s ‘Every Women, Every Child’ initiative . RMNCH issues were primarily viewed as problems of low-middle-income countries (LMICs) and there was universal acceptance that it raised important concerns about gender equality, women’s empowerment and access to education and health care as well as the rights of the child. Considerable progress in some parts of the world has been made towards MDGs 4, 5 and 6, for example, in terms of maternal and infant mortality , although there is still much to be done in this context and increased activity to meet the MDGs has been urged by the UN Secretary General. The most recent data estimates show a 45% reduction in maternal deaths associated with pregnancy from 523,000 in 1990 to 289,000 in 2010, but against this background is the finding that 27.5% of deaths are associated with pre-existing conditions, mainly human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), malaria, obesity and diabetes . The inclusion of these two last groups makes it clear that there is still much to be done to reduce the impact of NCDs on this generation and the next.
The MDGs were not however seen as being particularly relevant to high-income countries (HICs) and had effectively little impact in that context, although stillbirth, growth restriction, prematurity, pre-eclampsia and hypertension still affect >10% of all pregnancies in HICs. Furthermore, issues such as an unhealthy diet and body composition before and during pregnancy; antenatal and post-partum mood disorders and stress; drug, alcohol and tobacco abuse in pregnancy; low breastfeeding rates; and inappropriate weaning practices, which can have long-term consequences for both mother and infant, remain inadequately addressed in many HICs. Moreover, the MDGs did not recognize the importance of healthy early development for lifelong benefits in neurocognitive and executive function, social integration, productivity and lifetime earnings. The economic return on early life investment remains poorly understood in many quarters.
In retrospect, the most remarkable omission from the MDGs is non-communicable diseases (NCDs), namely diabetes, cardiovascular and chronic lung disease and some forms of cancer. NCDs are now the world’s biggest killers, accounting for 63% of all deaths globally. Eighty percent of these deaths occur in LMICs, especially those going through socio-economic transition, based on World Health Organization (WHO) data from several years ago ; the situation will have worsened since then. The prevalence of NCDs is increasing in many countries because they become more apparent with demographic changes that lead to a higher proportion of older members of society, with falling infant and child mortality and with urbanization and adoption of a Western lifestyle that leads to a greater mismatch between our evolved biology and our contemporary environments . Aggravating matters still further, there are other categories of chronic conditions that should be included under the heading of NCDs, including mental illness, cognitive decline, allergic and atopic diseases, and musculoskeletal disorders such as osteoporosis and frailty, all of which also have a developmental component .
The developmental origins of health and disease (DOHaD) concept points to the critical role of developmental factors in the risk of NCDs and in particular obesity, heart disease and diabetes. While the evidence for this is both compelling and long-standing , it has only been in the past decade that the concept has started to gain broader acceptance beyond the DOHaD research community. Broadly speaking, the DOHaD concept now posits that there are multiple ways in which the developmental environment can affect the risk of, for example, later obesity and its associated morbidities.
Two major types of developmental pathways to greater disease risk have been identified. One of these is normative and reflects the role of adaptive developmental plasticity as an evolved mechanism; this is reflected in the greater metabolic disease risk in the offspring associated with subtly unbalanced maternal nutrition, prematurity, growth retardation and primiparity. It involves the induction of stable epigenetic changes in the offspring. These prenatal cues, which may be interpreted as signals of a relatively poor environment, albeit one that lies within the evolutionary experience of the species, induce physiological changes in the offspring phenotype, especially in its responses to nutritional and other environmental challenges, which are thought to promote survival to reproductive age and thus Darwinian fitness. However, they also make the offspring more likely to be mismatched to its later life environment if the developmental cues are inaccurate, due to specific maternal conditions or environmental improvement between generations. Hence, they lead to a greater risk of NCDs, for example, in an obesogenic environment. Epigenetic analysis now allows an estimate of the size of these effects, which have been shown, even for some limited epigenetic marks measurable at birth, to account for ≥25% of the variation in adiposity in 6–9-year-old children in UK cohorts .
The second major pathway is a result of exposing the fetus and newborn to novel (in evolutionary terms) aspects of the environment and inducing responses that also create a greater risk of subsequent obesity and insulin resistance – these exposures include excessive infant formula feeding, inappropriate weaning, maternal obesity and gestational diabetes mellitus (GDM). GDM now complicates as many as 20% of pregnancies in parts of Asia and the Middle East. It confers an increased risk of diabetes and cardiovascular disease on the mother but also passes the risk of diabetes and obesity to her offspring . Maternal obesity, the prevalence of which is rising rapidly both in HICs and LMICs, and excessive weight gain during pregnancy also have intergenerational consequences.
Other aspects of the environment such as smoking and disordered sleep have also been shown to increase the risk of childhood obesity . In addition, there is currently much interest in the role that the exposure to endocrine disruptor chemicals may play in DOHaD .
This challenge posed by NCDs was recognized by the UN at the high-level meeting on the Prevention and Control of Non-communicable Diseases held in September 2011: the resulting Political Declaration focused on a wide range of underlying factors, and there was only some emphasis placed on the role of human development in setting the risk of NCDs. The principal reference to DOHaD which concerns us in this article is to be found in clause 26 of the Political Declaration, which states “{We} note also with concern that maternal and child health is inextricably linked with NCDs and their risk factors, specifically as prenatal malnutrition and low birth weight create a predisposition to obesity, high blood pressure, heart disease and diabetes later in life; and that pregnancy conditions, such as maternal obesity and gestational diabetes, are associated with similar risks in both the mother and her offspring.” Following the UN statement, WHO produced a draft Action Plan on NCDs, which was ratified at the World Health Assembly in May 2013. One of the overarching principles of this document concerns the life-course approach necessary to address the problem, which states, “A life-course approach is key to prevention and control of noncommunicable diseases. It starts with maternal health, including preconception, antenatal and postnatal care and maternal nutrition, and continues through proper infant feeding practices, including promotion of breastfeeding and health promotion for children, adolescents and youth followed by promotion of a healthy working life, healthy ageing and care for people with noncommunicable diseases in later life.” Only recently, the Director-General of WHO established a Commission on Ending Childhood Obesity (ECHO) that is focused directly on the early part of the life course and is informed by these concepts and evidence .
At their inception, the MDGs were intended to have been met by 2015. The post-2015 agenda is currently the subject of considerable discussion and it is envisaged that the global community will again endorse a limited but ambitious set of goals to challenge and focus international agencies, foundations, governments and civil society. As with the MDGs, the post-2015 goals will be set at a high level but underneath these will be a set of very specific indicators. A more structured approach is envisaged than with the MDGs and discussion has particularly been focused on integrating the pillars of economic, environmental and social development under the heading of ‘sustainability’: hence, the post-2015 goals are being labelled as Sustainable Development Goals (SDGs).
Whilst the United Nations Secretary-General (UNSG) urges accelerated progress to meet the MDGs , it is clear that the SDGs cannot merely be a continuation of this exercise. The SDGs will have to address, where possible, important global challenges not identified in the MDGs and in principle be applicable with modifications to all member states. However, as with the MDGs, the SDGs will focus the allocation of resources, not only in terms of international aid to low- and middle-income countries but also within countries themselves, and these will have to be related to local health-care budgets and priorities. For this reason alone, it will be important to define the SDGs carefully.
As part of preparing the SDG agenda, the UNSG established a High Level Panel of Eminent Persons which reported in 2013 . The focus of this report was very much on sustainable economic development, with an emphasis on poverty reduction. Health issues, including NCDs, received relatively little mention, and this was also true for issues relating to young people of reproductive age, although a statement on young people’s health was included. The major focus of other recent discussions, for example, at ECOSOC, has similarly been on youth, with the UNSG’s Envoy on Youth addressing the necessary underlying principles of such a focus: participation, advocacy, partnerships and harmonization .
There has been considerable discussion about the overall heading under which health might be promoted in the post-2015 era, with the Director-General of WHO identifying universal health coverage (see Ref. ) and linking it to poverty , although maximizing lifespan has been suggested as it is more easily quantified. Whilst the former is likely to focus largely on issues of access to affordable health care, attention also needs to be paid to early child development and adolescent health . This is particularly true as relatively less investment in health care for adolescents has been made over the last 50 years compared to younger children, and adolescence has been identified as a time that offers a second chance to reverse social inequalities in health .
There are a number of lifestyle or, more accurately, behavioural factors that contribute to NCD risk. Particular emphasis has been given to smoking; unbalanced diet with high fat, sugar and salt intake; lack of physical activity; and excessive alcohol consumption . However, in a very large meta-analysis, it was concluded that interventions to reduce high blood pressure, cholesterol and glucose, even if effective, might only reduce excess the risk of CHD by 50%, suggesting that there are many other factors involved. Obesity is recognized to be associated with high NCD risk, and many campaigns have been aimed at reducing its prevalence in HICs. These have met with only limited success, as weight loss is hard to achieve and even harder to maintain in many high-risk individuals, apparently because the mechanisms controlling appetite and satiety cannot easily be reset . Furthermore, there are major population and individual differences in the relationship between body fat and risks of metabolic disease . Clues to the underlying causes of this problem come from studies that examined appetite and the neuroendocrine control of eating in subjects who had maintained weight loss in a research programme: even a year after the inception of the weight loss, they still had continuously increased appetite and desire to eat even following a meal and accompanying changes in blood leptin and ghrelin . Importantly, it is now becoming clear that satiety, food preference and perhaps exercise capacity (at least in animals, see Ref. ) have major developmental and biologically based determinants. Once set points are established in early life (with both prenatal and early postnatal components), it may be effectively impossible to reverse these and this may explain why lifestyle interventions are difficult to sustain.
The adoption of a life-course approach to health and disease prevention, enshrined in the reports of the Sustainable Development Solutions Network (SDSN) , the UN Global Compact and the UNSG , has led to revision of ideas in this area. The role of the private sector is both important but complex and sensitive. A policy brief has recently been prepared jointly by the International Society for DOHaD, NCD Child, NCD Alliance and the Partnership for Maternal and Newborn Child Health (PMNCH) group , which encapsulates this new thinking, emphasizing that interventions in early life to reduce NCD risk and those in high-risk adults are not alternatives or mutually exclusive: quite the reverse, if, as the experimental evidence strongly suggests , early development sets the level of responses to interventions or therapies later. The newly announced Commission for ECHO provides a direct route for these perspectives to have a greater impact and utility on addressing this current gap in the NCD agenda.
We emphasize that NCD risk is graded across the normal range of factors such as diet, physical activity, etc. This is enshrined in the life-course model, in which risk, whilst low in early life, increases exponentially. Moreover, everyone is at a risk of NCDs, because these diseases are universal and are associated with normal human responses to a modern mismatched environment . They develop slowly and are essentially incurable although their progress can be slowed or perhaps halted. Thus, unlike the effects of teratogens or fixed genetic abnormalities, the pathology associated with NCDs does not start in early life but develops gradually as a result of declining plasticity and the accumulative effects of inadequate responses to unhealthy lifestyle. What the DOHaD concept offers is an explanation of how early life events generate a greater sensitivity to the adverse consequences of confronting the inevitable modern obesogenic world – the logical extension of this, confirmed experimentally and supported by epidemiological studies, is to focus on enhancing the developmental environment to make the individual more resilient to the obesogenic burden. Beyond that there is now compelling evidence that obesity in childhood is a strong predictor of obesity in later life, and thus the launch of the Commission on ECHO is both logical and very important.
Scientific endeavours across a range of fields, especially in DOHaD, child development, anthropology, social sciences and health economics in recent decades have compellingly demonstrated that adult physical and emotional health is related to the environment and health of the individual from conception through childhood and adolescence. The health capital which accrues throughout the life course is related to the attainment of physical structure and function in critical organ systems, in turn influencing resilience, the rate of decline with ageing and the likelihood of incurring medical and social costs ( Fig. 1 ). A healthy infant, first and foremost, depends on a healthy mother, both during pregnancy and through infancy. However, there is also now growing evidence for the importance of preconceptual and peri-conceptual influences and for paternal as well as maternal factors having intergenerational effects, and this greatly expands the challenge of effectively addressing RMNCH. Thus, there needs to be a continued focus on maternal health before and during pregnancy and at birth. This needs to be linked to initiatives aimed at HIV/AIDS, malaria, drugs and smoking during pregnancy but to extend to maternal nutrition and workloads and social–emotional support during pregnancy. As with many initiatives in communicable disease, progress will require working with young couples, to address issues of contraception, teenage pregnancy and girls’ attendance in school. We will have to devise innovative ways of doing this, as adolescents are usually a healthy section of the population and have other priorities. This may be one of the areas where the debated role of the private sector in health promotion could be harnessed to great effect through new social networking opportunities: after all, these sectors communicate with the younger population very effectively.
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