When a woman conceives, she has an estimated 26% chance of a miscarriage1 and an 11% chance of the child being born preterm,2 which may result in lifelong health problems such as allergies and/or a severe, chronic disease, neurological disorder, or developmental disability.3
Evidence increasingly suggests that childhood life surroundings may have a lasting effect on life chronic illness.4 Growing rates of chronic diseases in younger people mean that many people spend an increasing proportion of their lives coping with sickness.5 We know that children's health and development are a function of the complex interaction among biological and environmental influences.6
Many chronic conditions are believed to be caused by nutritional deficiencies exposure to toxins during gestation and in early infancy, and their incidence continues to increase ominously. They include cancer (now the second leading cause of death in children), asthma, autism, allergies, celiac disease, ADHD, and diabetes. Many children who suffer from some of these conditions also have significantly lower IQs, on average, than children in unaffected groups.7,8 9
The link between genes and environment
The human phenotype is the observable manifestation of one's genes and environment. This complex interaction plays a vital role in health and the risk of acquiring chronic diseases. Genetic, environmental, and gene–environment (GxE) interactions can be characterized and measured to identify associated disease biomarkers and biological mechanisms. It may be surprising, but current research has determined that genetic factors are not the major causes of chronic diseases. As much as 90% of chronic disease risk factors are due to non-genetic factors.10,11
Our genes are fixed at conception, but how they are expressed – our genome – can be influenced through changes such as chemical modifications and mutations. These modifications typically occur through environmental exposures throughout one's lifetime.
"When most people hear the terms 'environment' or 'environmental,' they often only consider external factors such as air and water pollution," states Anthony Macherone, Ph.D., strategic technical scientist at Agilent. "With respect to disease, the environment is far more complex. It incorporates external factors such as air, water, drugs, food, and internal factors such as pre-existing disease, oxidative stress, and microflora activity – especially in the gut. Therefore, the environment and its role in chronic disease are multidimensional and require a different definition."
The exposome12 – the environmental counterpart of the genome – encompasses the food and water we ingest, the air we breathe, the drugs we take, ionizing radiation from sunlight and other sources, our internal biochemistry, including the biosynthetic activity of our microbiome, and even where we work and live. Yet little is known about how these exposures affect humans or potentially influence the onset of cardiovascular disease, diabetes, asthma, Alzheimer's, many cancers, and other chronic diseases. To better understand disease risk, environmental factors that affect health and interact with the genome should be considered within the concept of the exposome paradigm.
The exposome paradigm and pregnancy
The old premise that many pregnancy issues and childhood chronic health conditions are unpredictable, random events and/or perhaps genetic in origin has been challenged. A mother's health and exposures during pregnancy have a profound effect on the health of her offspring, both in childhood and in later life. Under the exposome paradigm, a high incidence of problematic pregnancies and serious, chronic disorders among children are in large measure the common result of environmental factors.
Measuring the exposome to better understand chronic disease
Understanding how environmental factors affect health is a highly complex undertaking that would require measuring the countless exposures individuals experience over time and understanding how they influence disease. These measurements cannot be a one-time event because these exposures are in a constant state of flux, acutely and chronically influencing human health and biological processes. One way to evaluate the exposome paradigm would be to collect biological samples from a large number of individuals at birth, at 1 year of age, 5 years, 12 years, 21 years, and then once every 10 years over the lifetime. With such a vast repository of samples, researchers could then associate biomarkers and chemical predictors with various diseases.
Preconception to infancy
When women reduce toxins and follow proper nutrition before and during pregnancy, the incidence of both poor pregnancy outcomes and chronic disorders among their children can be dramatically reduced. The paradigm shift, now occurring among scientists who study pregnancies and links to chronic childhood health conditions, is the foundation of the Preconception to Infancy (P2i) vision.
The P2i program, sponsored by the nonprofit organization The Forum, aims to monitor and measure mother and child before, during, and after pregnancy and follow participants progress for the first five years postpartum. The P2i program will identify environmental exposures of the mother–child pair even before conception and mitigate these exposures through a regimen of prenatal care, nutrition, and reducing exposures to environmental factors through healthy lifestyle choices.
"In the last 50 years we've seen sharp increases in maternal death during pregnancy. So, we started to take a look at what's causing all of this, going from a rate of 5 percent to 38 percent," states David Humphrey, Esq., executive vice chairman and Board Member of the Autism Society of America and the Autism Research Institute. "We could attribute it to genetics, which could be a likely culprit. But with the rates of increases, there's no such thing as a genetic epidemic. Genetics takes a long time to modify conditions."
These measurements can make more accurate assessments and help prospective mothers strengthen their health profile with proper nutrition, avoid negative environmental factors, and reduce body burden. Understanding how exposures such as environment, diet, and lifestyle interact with our unique genetics, physiology, and epigenetics to impact health is how the exposome will be articulated.
Where technology fits in
The emerging technology of exposomics can be used to both qualify and quantify exposures of the mother and baby from preconception through infancy. Biological samples (plasma or serum) can be analyzed in testing laboratories by high-resolution mass spectrometry (MS) coupled to ultra-performance liquid chromatography (UPLC) or gas chromatography (GC) systems. Metabolic features characterizing exposed groups are identified by multivariate statistics, with appropriate corrections, and then the identification of the discriminating metabolites and biological pathways is undertaken. Once identified, these metabolites can be verified using a database of known biomarkers or with authentic reference standards.
The combination of exposomics and genetics will provide a path for a greater understanding of chronic diseases in children. Enabling scientists to study the interplay of genetics with the impact of environmental toxins will clear a path for studying the origins of disease and potentially take steps to prevent it from ever developing.
For more information, view this infographic: Preconception to Infancy (P2i) Program
Visit Agilent.com to discover and learn more about the complete set of integrated biology solutions that scientists can apply to unravel the exposome.
Find out more:
- Agilent ICP-MS
- Agilent GC/Q-TOF
- Agilent LC/Q-TOF
- Agilent Real-Time PCR
- Agilent MassHunter Profiler Professional
Anthony Macherone, Ph.D., is a strategic technical scientist at Agilent Technologies and co-editor, with Sonia Dagnino, of "Unravelling the Exposome: A Practical View" (Springer International Publishing AG, 2019).
David Humphrey, Esq., is an attorney, and CEO of a number of companies. He is a National Board Member of the Northwest Autism Foundation, The Forum, ACT Today!, and a co-founder of the Autism Treatment Network (ATN). He is also the co-founder and Director of the physician training group, Medical Academy of Pediatric Special Needs (MAPS), and executive vice chairman and Board Member of the Autism Society of America and the and the Autism Research Institute