| Title: | Quantifying the impact of early life growth adversity on later life health |
| Journal: | Communications Medicine |
| Published: | 17 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41258496/ |
| DOI: | https://doi.org/10.1038/s43856-025-01245-3 |
| URL: | https://www.nature.com/articles/s43856-025-01245-3_reference.pdf |
Publication 18912
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BackgroundEarly-life growth adversity is important to later-life health, but precision assessment in adulthood is challenging. We evaluated whether the difference between attained and genotype-predicted adult height ("height-GaP") would associate with prospectively ascertained early-life growth adversity and later-life all-cause and cardiovascular mortality.MethodsData were first analyzed from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4582; 56/43% female/male) and UKBiobank (n = 483,385; 54/46% female/male). Genotype-predicted height was calculated using a multi-ancestry polygenic height score. Height-GaP was calculated as the difference between measured and genotype-predicted adult height. Early-life growth conditions were ascertained prospectively via standardized procedures (ALSPAC) and mortality via death register (UKBiobank). Regression models examined: (i) adult height-GaP as the outcome with early-life growth conditions as predictors; and (ii) mortality as the outcome with adult height-GaP as predictor. All models were adjusted for age, sex, genotype-predicted height and genetic ancestry. Analyses were replicated in the Dunedin Multidisciplinary Health and Development Study (DMHDS; n = 855; 49/51% female/male) and the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6352; 52/48% female/male).ResultsHere we show that among ALSPAC participants (median [IQR] age: 24 [18-25] years at height-GaP assessment), lower gestational age at birth, greater pre- and post-natal deprivation indices, tobacco smoke exposure and less breastfeeding are associated with larger adult height-GaP deficit (p < 0.01). Among UKBiobank participants (mean ± SD age: 56 ± 8 years at height-GaP assessment), height-GaP deficit is associated with death from all-causes (adjusted hazard ratio comparing highest-to-lowest height-GaP deficit quartile [aHR]: 1.25 95%CI: 1.21-1.29), atherosclerotic cardiovascular disease (aHR: 1.32 95%CI: 1.23-1.42) and coronary heart disease (aHR: 1.64 95%CI: 1.49-1.81). Early- and later-life height-GaP associations replicate in DMHDS and MESA.ConclusionsThis study introduces a precision index of early-life growth adversity deployable in adulthood to investigate the developmental origins of longevity and improve health equity across the life course.</p>
33 Authors
- 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
- 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
- Reremoana Theodore
- Karol E. Watson
- Benjamin Williams
- Bin Yang
- Josée Dupuis
- Seif O. Shaheen
- R. Graham Barr
- Robert J. Hancox
- Benjamin M. Smith
Enabling scientific discoveries that improve human health