The Developmental Origins of Health and Disease: Adolescence as a Critical Lifecourse Period to Break the Transgenerational Cycle of NCDs-A Narrative Review.

Noncommunicable diseases (NCDs), including type 2 diabetes and cardiovascular disease, represent a significant and growing global health burden. To date, a primary focus has been on treatment approaches to NCDs once manifested rather than strategies aimed at prevention. In this context, there is clear evidence that a range of adverse early life exposures can predispose individuals towards a greater risk of developing NCDs across the lifecourse. These risk factors can be passed to future generations, thus perpetuating a cycle of disease. This concept, preferentially termed "developmental programming", forms the basis of the Developmental Origins of Health and Disease (DOHaD) framework. To date, DOHaD has focused on preconception, pregnancy, lactation and, more recently, paternal health at the time of conception. However, it is becoming increasingly clear that investment in the window of adolescence is perhaps the most critical developmental window. Adolescence is a period where lifestyle behaviours become entrained. Therefore, a focus on adolescent behaviours, health literacy and emotional development may afford the best opportunity to break the cycle of NCDs. As the next generation of parents, adolescents should therefore be considered a priority group in advancing appropriate and informed actions aimed at reducing NCD risk factors across the lifecourse. This advancement requires a more comprehensive community understanding and uptake of DOHaD knowledge and concepts. NCD prevention strategies have typically entailed siloed (and often disease-specific) approaches with limited efficacy in curbing NCD prevalence and breaking the transgenerational transmission of disease traits. Recent findings across various disciplines have highlighted that a lifecourse systems approach is required to establish a comprehensive and sustainable framework for NCD intervention. A whole community approach with a particular focus on adolescents as potential agents of change is necessary to break the disease cycle.

Utility of preclinical models of altered maternal nutrition to support the developmental origins of health and disease hypothesis.

A clear link has been established between alterations in the early life environment and the risk for developing a range of cardiometabolic diseases in later life, a process preferentially termed developmental programming. In particular, alterations in the maternal nutritional environment have been associated with a range of adverse health outcomes in offspring across the lifecourse; effects that can be passed on to future generations. Following from the early epidemiological observations that provided the basis for the developmental origins of health and disease (DOHaD) hypothesis, a range of animal models were developed to examine the impact of early life programming and provide empirical data to support the emerging framework. These models became key tools to aid in our understanding of developmental programming as allowed investigation of potential mechanisms, strategies for intervention and transgenerational effects. The study published by Langley and Evans (Clin. Sci. 1994;86(2):217-222; DOI:10.1042/CS0860217), using a rat model of maternal low protein exposure, was one of the first to highlight the impact of an altered maternal nutritional environment on programming of elevated blood pressure in offspring. This work became a hallmark study in the DOHaD field by demonstrating key proof of principle to support the early epidemiological associations and characterizing a key preclinical model that has contributed greatly to our understanding of mechanisms underpinning developmental programming-particularly in the area of cardiovascular and renal function.

Circulatory amino acid responses to milk consumption in dairy and lactose intolerant individuals.

BACKGROUND/OBJECTIVES: Self-reported digestive intolerance to dairy foods is common. As dairy can be an important source of dietary protein, this study aimed to identify whether milk protein digestion is compromised in individuals with digestive intolerance. SUBJECTS/METHODS: Adult women (n = 40) were enroled in this double-blinded, randomised cross-over trial, with digestive symptoms characterised using a lactose challenge and self-reported digestive symptom questionnaire. Participants were classified as either lactose intolerant (LI, n = 10), non-lactose dairy intolerant (NLDI, n = 20) or dairy tolerant (DT, n = 10). In a randomised sequence, participants consumed three different kinds of milk (750 ml); conventional milk (CON), a2 Milk™ (A2M), and lactose-free conventional milk (LF-CON). Circulatory plasma amino acid (AA) concentrations were measured at baseline and every 30 min until 3 h post-ingestion. RESULTS: In all participants across all milk types, plasma AA concentrations (AUC0-180) increased after milk ingestion with no significant differences in responses observed between milk types or participants (P > 0.05), with the exception of the suppressed lysine response in the DT group following A2M ingestion, relative to the other two groups and milk types (P < 0.05). CONCLUSION: Milk protein digestion, as determined by circulatory AAs, is largely unaffected by dairy- and lactose- intolerances.

Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years.

Background: Human milk bioactives may play a role in infant health and development. Although the variability in their concentrations in milk is well-established, the impact of differential milk profiles on infant growth outcomes remains unclear. Thus, the aim of the present study was to investigate whether different concentrations of metabolic hormones are associated with different weight and BMI in infants beyond the first year of life. Methods: Milk samples at 2.6 (±0.4) months after birth and anthropometric measures at 13 months, 2, 3, and 5 years were collected as part of the Finnish STEPS cohort study from 501 mothers and the respective 507 infants. Leptin, adiponectin, insulin-like growth factor (IGF)-1 and cyclic glycine-proline (cGP) in milk were analyzed. Multiple regression models and a repeated measures mixed model were used to examine associations between milk hormone concentrations and weight and BMI z-scores across time, at each time-point, and weight gain from birth to each follow-up visit. All models were corrected for birth weight, infant sex, duration of exclusive and total breastfeeding, time of introduction of solid foods and maternal pre-pregnancy BMI. Results: Higher milk IGF-1 was associated with higher weight at 13 months (p = 0.004) but lower weight at 3 (p = 0.011) and 5 years of age (p = 0.049). Higher cGP was associated with lower weight across the 5 years (p = 0.019) but with higher BMI at 5 years (p = 0.021). Leptin and adiponectin did not display associations with infant growth at this time. Sex interactions were also absent. Conclusions: Our results suggest that the interplay between human milk-borne IGF-1 and cGP is similar to that reported in other mammals and may have an important role in defining infant growth trajectories beyond the first year of life. Further research should explore the determinants and origins of these milk-borne compounds and evaluate their effect on infant growth and metabolism.