Metabolic programming in early life in humans.

Area of Science:

• Developmental biology
• Public health
• Evolutionary medicine

Background:

• The developmental origins of health and disease (DOHaD) hypothesis posits that early-life exposures, including undernutrition and overnutrition, permanently program offspring metabolism, increasing later cardio-metabolic disease risk.
• Maternal gestational diabetes leading to high birth weight is linked to later diabetes, while low birth weight is associated with cardiovascular disease and diabetes.
• Postnatal factors like obesity and poor diet interact with fetal exposures to exacerbate disease risk.

Purpose of the Study:

• To explore the DOHaD hypothesis and its implications for cardio-metabolic disease prevention.
• To review the evidence for early-life programming of health and disease in humans and animal models.
• To highlight the potential of primordial prevention strategies targeting fetal and infant development.

Main Methods:

• Review of observational and quasi-experimental studies on maternal nutritional exposures and offspring health outcomes.
• Analysis of animal studies demonstrating permanent metabolic effects from altered maternal or early postnatal diets.
• Discussion of limitations in current human research, including observational data and short follow-up periods in randomized trials.

Main Results:

• Evidence suggests both fetal undernutrition and overnutrition can permanently alter offspring metabolism, increasing vulnerability to cardio-metabolic diseases.
• Animal studies confirm lasting metabolic programming from early dietary interventions.
• Human evidence is primarily observational, with limited data from randomized trials on long-term offspring outcomes.

Conclusions:

• DOHaD concepts offer a primordial prevention approach to reduce future generations' cardio-metabolic disease burden by optimizing early development.
• Interventions targeting pre-conception and early pregnancy are crucial for addressing critical developmental events like epigenetic changes and organogenesis.
• Future research, including trials with long-term offspring follow-up, is needed to fully elucidate and leverage DOHaD principles for public health.