Mini-Symposium: Early life origins of chronic diseaseImpact of prenatal and early life environmental exposures on normal human development
Introduction
In September 2000, the United Nations set eight ambitious targets, now referred to as the Millennium Development Goals, to be achieved by 2015 [1]. These goals largely concentrated on improving global health by eliminating or reducing traditional causes of all-age mortality and morbidity. As a result, the global pattern of disease has changed, with a reduction seen in early childhood deaths and deaths from communicable, maternal, neonatal, and nutritional disorders [2], [3]. However, deaths and disability from chronic non-communicable diseases (NCDs) have increased [2], [3]. In 2008, an estimated 36 million deaths were due to NCDs including cardiovascular disease, cancers, chronic respiratory diseases and diabetes [4]. While alcohol and tobacco use, physical inactivity and an unhealthy diet are known to increase the risk NCDs, a recent Lancet Commission report has found pollution to also be a major underlying cause of death, disability and NCDs [5]. As such, the World Health Organization has recognised exposure to adverse environments as a major contributor to NCDs, especially in children [6].
Our modern environments contain an increasing variety of chemicals and subsequent emissions that increase the risk of chronic disease development. Awareness of these risks, especially in the environments where children in early life spend most of their time (domestic, pre-school care, and school) and of avoidable exposures, is low. Low awareness amongst the public, childcare workers, teachers, and health care professionals contributes to human behaviours that perpetuate and even increase exposures to these pollutants. As such, the majority of populations around the world are exposed to varying amounts of environmental toxicants at any one time.
Growing evidence indicates that foetal and early-life exposure to air pollutants and other environmental contaminants increase life-long risk of chronic disease through mechanisms including endocrine disruption, epigenetic changes, and disturbance of innate immune defences [7], [8], [9]. Trans-placental transfer, breast milk, dermal transfer, and non-nutritive ingestion result in unique exposure pathways during foetal development and in early life. For young children, environmental interactions occur primarily at home and in educational/childcare establishments through breathing air, consuming food and water, and through “mouthing behaviours” whereby they put their hands, feet, and fomites into their mouth, resulting in non-nutritive ingestion of toxicants. Despite substantial literature indicating that adverse environmental exposures increase the risk of NCDs, many knowledge gaps exist, particularly with respect to impacts on the developing foetus and young children, and at what concentrations those risks occur [7], [8], [9], [10], [11], [12], [13], [14], [15], [16].
This article will first review normal human development during the foetal and early postnatal periods and discuss how this can be disrupted by adverse environmental exposures. We will outline exposure sources and pathways and discuss the mechanisms by which early life exposures increase the lifelong risk of chronic NCDs.
Section snippets
Normal human development
The process of growth and development in children is one that occurs from conception to adolescence. A large number of anatomical, biochemical and physiological changes occur prenatally and continue after birth [17]. These maturational processes are susceptible to alteration by physical, biological and chemical exposures at various points of time. The effects of any given exposure will be determined largely by the time in the developmental and maturational process that the exposure occurred [17]
Exposure pathways during foetal development and early postnatal life
Pollutants can enter the body via a variety of routes depending on their physical characteristics and source. Exposure pathways that are specific to, or more common during, foetal development and early postnatal life include:
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Trans-placental: the placenta does not provide a protective barrier for most xenobiotics and, as such, the foetus is exposed to whatever chemicals enter the maternal circulation. While many hazardous chemicals are metabolized in the maternal liver, usually into less toxic
Mechanisms by which environmental exposures adversely affect growth and development
Maternal environmental exposures during pregnancy can adversely affect the developing foetus through a variety of mechanisms [9]. The placenta, once considered a protective barrier, shielding the foetus from environmental exposures, allows relatively free passage to a wide variety of environmental chemicals [9]. Many of these chemicals induce adverse effects by altering foetal gene expression through a variety of epigenetic mechanisms including methylation of cytosine-phosphate-guanine (CpG)
Conclusion
Disruption of normal human growth and development, by adverse environmental exposures especially during foetal development and early postnatal life, increases life-long risk of chronic disease. The developmental timing of adverse exposures determines the likely impact on health and development. While many organ systems are structurally and functionally mature at birth, the CNS, respiratory and immune systems are not and undergo prolonged periods of postnatal growth and development. As such,
Practice points
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Deaths and disability from chronic non-communicable diseases (NCDs) has increased globally.
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Adverse environmental exposures during foetal and postnatal development increase risk of NCDs.
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CNS, respiratory and immune systems are more susceptible.
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Pathways include trans-placental, breast milk, non-nutritive ingestion, dermal and inhalation exposure.
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Exposures can impact gene expression, cause DNA damage, oxidative stress processes and maturation of precursor cells.
Educational aims
The reader will be able to:
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Provide a review of normal human development during the foetal and early postnatal periods
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Discuss how normal development can be disrupted by adverse environmental exposures.
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Outline the most common exposure sources and pathways.
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Discuss the mechanisms by which early life exposures increase the lifelong risk of chronic conditions.
Directions for future research
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Investigate how environmental exposures impact gene expression, induction of oxidative stress, epigenetic mechanisms.
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Investigate potential for anti-oxidant therapy to mitigate or prevent adverse consequences of environmental exposures on normal human development.
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There is a need for more evidence on the environmental exposures that are detrimental at each sensitive development period.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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