What is the First 1000 Days Program of the Giovanni Lorenzini Foundation?

A cutting-edge technologies-and-knowledge integration model for the prevention of Non-Communicable Diseases (NCDs) implemented in real-world settings. The project focuses on the identification and application of effective prevention interventions in the early phases of human development through multi-disciplinary approaches including clinical/molecular evaluation, empowerment/education, and use of portable devices for application in Public/Private Health & Wellness sectors.

Situational Analysis

Historically, research and clinical knowledge surrounding the “first one thousand days of life” has primarily centered on the nutritional component of this critical period in early human development. Evidence clearly shows how a holistic approach towards prevention is the most effective means to halt the NCDs crisis worldwide. This includes healthy lifestyles (physical exercise, nutrition…); supported by clinical/molecular insights and personalized intervention targeting individuals (and their parents) in the pre-conception, infancy and early childhood stages of life. Moreover, mounting evidence from interdisciplinary fields now point to the undeniable importance of understanding the full contextual environment in which new life is conceived and developed.

The 1,000 days between pregnancy and a child’s 2nd birthday are the most critical time for a child’s cognitive, physical and social development. The health and well-being of a woman (in the pre-conception/conception/pregnancy and lactation) is directly connected to the growth and health of her infant, both in earl, and in the late life stages. The right lifestyle for the child and surrounding environment during this time can have a profound impact on the child’s growth and development, and reduce disease risk in the years to follow.

An integral part of the first 1,000 days project promoted by the Giovanni Lorenzini Medical Foundation is the development of specific interventions targeting the relationship between the infant and the surrounding environment (including family, living place, educational activities etc…) and encouraging integrated strategies contributing to the intergenerational transmission of healthy lifestyle choices to lay the foundation for the child’s future cognition, motor/social skills and, ultimately, productivity.

Foreword

The ongoing reshaping of the demographic structure of the population with an increasing proportion of people over 65 and a decreasing proportion of children and young adults is tragically impacting our healthcare systems, both from the social, and the economic point of view. On one side the rise,chronic diseases is compromising the quality of life especially in the elderly; on the other, the cost of care for morbidity is challenging the efficiency and the sustainability of the healthcare system. Moreover, the contextual drop in the birth rate, in both developed and developing countries, hits the most critical pillars of civil society including health, welfare, and finance in a trans-generational fallout.

The growing rate of developmental disorders in the young generation is also triggered by the environmental factors to which the early life is highly more sensitive and exposed in the current context.

The epigenetics-environment interaction and its impact on health and wellbeing

During the process of human development an innate plasticity induces biological variations to provide a fit adaptation to an ever-changing environment. Through a complex network of molecular mechanisms, an organism can respond to environmental stimuli in an integrated and coordinated manner. The interplay between inherited genes and the exogenous stimuli (gene-environment interaction) has been previously described as developmental plasticity, representing the organism’s effort to fine-tune the genome to produce phenotypic profiles adapted to the predicted changing environment: this phenomenon is known as Adaptive Developmental Plasticity.

The plasticity of tissues is particularly affected by environmental exposure during development in utero, although in some cases (respiratory, immune systems, and the brain) the window of susceptibility extends into childhood because of the time-extended tissue development. Growing evidence indicates that the exposure during the sensitive window of developmental stages of the individual to nutritional imbalance, or environmental contaminants, including environmental noise organic pollutants, pesticides, metals, and chemicals in drinking water, may determine epigenetic alterations with a potential impact on adult life.

Therefore early life exposure can program the onset of chronic diseases, and especially neurodegenerative disorders, in the adult and old age. Considering that the new generations were exposed already, during conception, and have not reached their later and more disease-prone stages of life, poses additional concern on the expected unsustainable increase of chronic diseases.

The predisposition to pathological conditions is further influenced by the parental epigenetic inheritance that has been either inherited or built in responses to environmental exposure(s) experienced from the time spanning parental conception (grandparental) to the time of conception of the new progeny, affecting the offspring’s clinical features such as metabolic control, neuronal reserve, kidney size, reproductive maturation, and behavior. Well-characterized epigenetic alterations such as DNA methylation, histone modifications, and non-coding RNAs expression drive these phenomena during both early and later life through cell reprogramming and can be transmitted transgenerationally.

The effects of molecular insults

The effect of the parental epigenetic inheritance on many syndromes is an established phenomenon that now is starting to produce experimental evidences. Several major neurodevelopmental syndromes are linked to paternal and/or maternal epigenetic inheritance or even both. During pregnancy instead, environmental exposures such that to maternal prenatal stress has been recurrently associated with offspring’s onset of cardiovascular (atherosclerosis, hypertension, coronary heart disease and heart failure), metabolic (reduced fetal growth, obesity and diabetes) and neurological diseases (visuomotor disorders, attention deficit, impaired cognition, potential delay of temporal processing acuity, and reduced brain volume in children) with remarkable gender differences. The interaction between the environment, including both endogenous (such as hormone levels or immune status) and exogenous factors (such as nutritional and chemical exposures) and the epigenome has been defined as “environmental epigenomics”.

The Developmental Origins of Health and of Non-Communicable Diseases

The Developmental Origins of Health and Disease (DOHaD) theory suggests that targeted interventions on early-life stages, including individual behavior, optimization of nutrition, reduction of stress, noise exposure, monitoring of drugs and environmental pollutants, such as endocrine disruptors, represent a global need in order to tackle the increasing prevalence of NCDs. According to the WHO, NCDs currently cause more deaths than all other causes combined and NCD deaths are projected to increase from 38 million in 2012 to 52 million by 2030 worldwide. Four major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes) are responsible for 82% of NCD deaths. The substantial increase in the incidence of many NCDs over recent decades has been attributed to environmental changes and their interplay with individual genomic and epigenetic features.

Strategies targeting early developmental stages including pre-pregnancy, pregnancy, and the first few years of postnatal life represent the most cost-effective opportunity to tackle NCD incidence with immediate results over the short, medium, and long term. Vast evidence suggests that improvement of nutrition, reduced exposure to pollutants (including environmental noise), and healthy lifestyles affect favorably both health outcomes (in terms of reduced incidence of diseases and quality of life) and costs (in terms of productivity and use of resources). Such big challenges need primarily a change of mindset which, involves most of society starting with a significant reorientation in the education of healthcare professionals, but also the individual through individual empowerment approaches and improved health and wellbeing literacy.

The development of risk-prediction tools that might be applied throughout the life course could be very useful for future public health policies. A global vision and an inclusive strategy can be developed only by the active participation of all stakeholders to address the challenges of an aging society and the disruptive increase in incidence of chronic diseases. Innovative perspectives provided by the DOHaD theory may provide a wide, evidence-based understanding of the determinants of NCDs and the most effective interventions to generate meaningful responses to health and economic burden posed by these determinants.

The epidemics of Non-Communicable Diseases (NCDs) resulting from complex interactions between health, economic growth, and development, have been consistently linked with global trends such as population ageing, indiscriminate urbanization, climate changes and the worldwide spread of unhealthy lifestyles. The consequent paradigm shift from acute care (on which western care models have been built in the previous century) to a chronic care and the evolving concept of health boosted by unprecedented technological advancements, healthcare systems are facing global threats that require urgent interventions. For example in terms of healthcare access; universal health coverage aims to provide essential health services with the best standards to all people without risking financial hardship from unaffordable out-of-pocket payments. Reducing poverty and income inequalities will improve access to health services. Furthermore, education and empowerment of individuals could effectively provide people with the awareness needed to make informed decisions. Also quality of care represents a global critical issue; regional and national differences in healthcare provision due to a lack of standardization negatively affect both quality and costs. Ultimately, in most countries national health spending is projected to continue to grow faster than the GDP; at the current level and rate of growth, and healthcare costs will make many systems unsustainable in the very near future. Healthcare cost containment represents a compelling challenge to be tackled with improved standardization of healthcare services, together with more effective and more integrated strategies of patient management.

The relative size of the working-age segment of the population (ages 15-64) is dramatically dropping due to youth population stagnation and the rise in the number of elderly, contributing to the worsening threat that NCDs constitute for social welfare and health systems. This has additional implications for decreased productivity, in the workplace, and also for prolonged disability and diminished resources within families.

Rational preventive interventions in the first 1000 days

Effective preventive interventions for populations can be created to significantly lower the burden of healthcare costs and increase the quality of life, but these require a perspectives change. The target of interventions need to focus on an individual (the fetus/infant) who is not responsible for his or her own lifestyle, and involves an environment (that often times can be rarely or only narrowly be changed) and that is much wider than his or her immediate surroundings.

Evidence supports the idea that prevention, particularly primary prevention, could be the only medium and long term answer to the sustainability problem; for example vaccine-preventable infections may influence the development and/or the course of NCDs. Human papillomaviruses (HPV) and Hepatitis B virus (HBV) are necessary elements for the development of cancers; Influenza and S. Pneumoniae infections can worsen metabolic, cardiovascular and respiratory chronic diseases.

On the other hand among the most cost-effective preventive intervention is the promotion of breastfeeding; the benefits of breastfeeding for the infant include increased intelligence and protection against overweight and diabetes with long-term positive effects on later life. Moreover breastfeeding benefits mothers too, preventing breast cancer, improving birth spacing, and reducing the risk of diabetes and ovarian cancer. Breastfeeding generates both direct (from a reduced use of health resources) and indirect (being a “natural, renewable food that is environmentally safe and produced and delivered to the consumer without generating additional pollution, using unnecessary packaging, or producing waste”) cost savings. The protection, promotion, and support of breastfeeding are both an individual and a societal responsibility achievable through adequate education and intervention in both developed and developing countries

So far a wide spectrum of preventive interventions has been proposed including nutritional/dietary management (including reduced consumption of salt and sugar and increased consumption of fruit and vegetables and alignment to the circadian clock); increased physical activity; promotion of smoking cessation and reduction of excessive alcohol intake (increasing tobacco and alcohol taxes, and information, education, and communication campaigns, such as the ASSIST project – Alcohol, Smoking and Substance, transforming medical training to address the changing nature and burden of diseases.

Such efforts require a systemic approach representing a challenge for governments and stakeholders and it may generate a dramatic social, health and economic impact. It is clear how the private sector shares with public institutions common responsibilities while foreseeing an opportunity to redesign market strategies toward more ethical products. Technological development societal advances walk in parallel with education for a structural establishment of the social importance of prevention.

The implementation of integrated and systemic interventions

Preventive efforts should continue to focus on the 1,000 days, providing a game-changing perspective shift to develop more efficient healthcare systems. A consistent, sustainable, and timely commitment, and active investment by governments, industry, academic and civil society represents a prerogative to tackle preventable health issues and inequities globally.

So far, priority efforts to prevent NCDs have primarily focused on adult individuals’ risk factors (poor diet, physical inactivity, smoking and alcohol consumption) while almost ignoring early stages of development for individuals.

Innovation in health technologies can support the DOHaD theory shift, providing effective tools for a continuous monitoring of routine indicators, such as parental preconception, metabolic status, weight gain during pregnancy, stunting and wasting prevalence and weight gain in relation to length during infancy as well as exposure to environmental risk factors. More efforts are needed to monitor epigenetic alterations in a cost-effective way.

Ultimately, the assessment of the feasibility, efficacy, effectiveness and efficiency of preventive strategies, inspired by the first 1,000 days paradigm with a life-course and multilevel outcome perspective represent an essential step to objectively support specific policy activities.

The Giovanni Lorenzini Medical Foundation is leading the way we understand how health and physical/mental wellness is perceived. By developing such an innovative program to prevent chronic disease onset, we will continue to be an agent for change, in real world-settings. By applying multidisciplinary and sustainable approaches – including lifestyle choices, molecular and portable technologies – we will implement the latest knowledge today to maximize health and wellbeing for tomorrow.”

The First 1000 Days aspires to be this agent of change.

Join us on this journey!