Developmental origins of health and disease (DOHaD).

DOHaD: understanding health through the history of development

Why are conditions experienced before birth and in infancy associated with diseases that may not appear for decades? This review introduces the developmental origins of health and disease, or DOHaD, as a way to connect early development with health across the life course.

Development is responsive to conditions. Organs, regulatory systems and patterns of gene activity develop within an environment. Nutrition, hormonal signals and other early exposures can influence that process. Human epidemiological studies and animal experiments described in the review linked such conditions with later risks including obesity, diabetes and cardiovascular disease.

The article sets out several related explanations. The thrifty phenotype hypothesis concerns metabolic adjustments associated with limited early resources. Developmental programming describes persistent effects of conditions encountered during sensitive periods. Predictive adaptive response models propose that early signals influence development in ways that may prepare an organism for later conditions. Match and mismatch refer to whether those later conditions resemble the environment to which development was adjusted.

These models are ways of organizing evidence and generating predictions; they are not interchangeable findings or proof that a developing organism literally anticipates the future.

How might an early influence persist? The review discusses changes in gene regulation through epigenetic processes, which affect how genes are used without changing their DNA sequence, as well as hormonal communication through the placenta and lactation. Different exposures may act through different mechanisms and at different sensitive periods.

The field’s contribution is a broader account of causation in chronic disease. Adult health can reflect the interaction of early development with later experience, so prevention may need to begin before the usual clinical risk factors become apparent. This 2007 review also addresses research methods and ethical considerations as the field was developing. It presents a framework for investigating risk, not a claim that an individual’s health is fixed at birth.