Researchers from The Institute develop a simple new way to assess how early-life experiences shape lifelong health
SOURCE: The Institute
December 14, 2025
A new international study led by Benjamin M. Smith, MD, M.Sc., at The Institute has developed a simple way to assess how early-life experiences influence health across the life course. Published in Communications Medicine, the study introduces "height-GaP," a measure comparing a person's actual adult height with the height predicted by their genetics.
Using international cohort data, the research team showed that height-GaP reflects the cumulative impact of early-life growth adversity and may help predict later-life health, including mortality risk.
"Height-GaP gives us a lens on early-life conditions that are otherwise very difficult to measure," said Dr. Smith. "It captures hidden developmental stresses that can shape health decades later."
A simple way to quantify early-life adversity
Across multiple cohorts, children exposed to adverse early-life conditions—such as maternal smoking, preterm birth, lower birthweight or length, reduced breastfeeding, household tobacco smoke or socioeconomic deprivation—were more likely to have a larger height-GaP deficit in adulthood. This deficit represents the difference between their achieved adult height and their genetically predicted potential.
These results were validated in two richly characterized birth cohorts, ALSPAC and the Dunedin Study, where height-GaP consistently reflected the cumulative burden of early-life growth adversity.
Predicting mortality in mid and later life
The researchers then examined whether the height-GaP measurement could predict adult health outcomes. In more than 480,000 adults from the UK Biobank and over 6,000 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a larger height-GaP deficit was strongly linked to a higher risk of:
- all-cause mortality
- death from atherosclerotic cardiovascular disease
- death from coronary heart disease
These associations remained robust even after accounting for age, sex, genetics and adult health factors. Notably, genetically predicted height alone did not predict mortality, underscoring that it is the deviation or "gap" from genetic potential rather than height itself, that carries information about early-life conditions.
Why this matters
Early-life conditions—from maternal health and nutrition to environmental pollutants—are increasingly recognized as powerful determinants of adult health and disease. But pinpointing which early factors matter most, and how to measure them, has been challenging.
Height-GaP offers a practical solution. It is simple to calculate, can be used in adulthood, and is validated across diverse international cohorts.
"This index can help detect new threats to healthy development, serve as a surrogate endpoint in early-life intervention studies and improve adult risk stratification for diseases with developmental origins," Dr. Smith added.
The study also provides the foundation for the research team's new lung health research program, which will investigate how early-life growth adversity influences respiratory health across the life course.
Supported by the Canadian Institutes of Health Research and multiple international partners, the work underscores the central role of early development in shaping lifelong health—and offers a new way to measure its impact at scale.
About the publication
The publication "Quantifying the impact of early life growth adversity on later life health" was written by Raphael Goldman-Pham, Matthew P. Alter, Rebecca Bao, Sophie É. Collins, Catherine L. Debban, James P. Allinson, Antony Ambler, Alain G. Bertoni, Avshalom Caspi, Stephanie Lovinsky-Desir, Magnus P. Ekstrom, James C. Engert, David R. Jacobs Jr, Daniel Malinsky, Ani Manichaikul, Erin D. Michos, Terrie E. Moffitt, Elizabeth C. Oelsner, Sandhya Ramrakha, Stephen S. Rich, Coralynn Sack, Sanja Stanojevic, Padmaja Subbarao, Karen Sugden, and Benjamin M. Smith. It was published in Communications Medicine, 5, 534 (2025).
DOI : 10.1038/s43856-025-01245-3
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