Quantifying the impact of early life growth adversity on later life health

Raphael Goldman-Pham¹, Matthew P Alter¹, Rebecca Bao¹, Sophie É Collins¹, Catherine L Debban², James P Allinson³, Antony Ambler⁴, Alain G Bertoni⁵, Avshalom Caspi^{6

7}, Stephanie Lovinsky-Desir⁸, Magnus P Ekstrom⁹, James C Engert¹, David R Jacobs Jr¹⁰, Daniel Malinsky¹¹, Ani Manichaikul², Erin D Michos¹², Terrie E Moffitt^{6

7}, Elizabeth C Oelsner¹³, Sandhya Ramrakha⁴, Stephen S Rich², Coralynn Sack¹⁴, Sanja Stanojevic¹⁵, Padmaja Subbarao¹⁶, Karen Sugden⁶, Reremoana Theodore⁴, Karol E Watson¹⁷, Benjamin Williams⁶, Bin Yang¹¹, Josée Dupuis¹⁸, Seif O Shaheen^{19

20}, R Graham Barr¹³, Robert J Hancox²¹, Benjamin M Smith^{22

23

24}

Affiliations

¹ Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
² Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
³ Faculty of Medicine, Imperial College London National Heart and Lung Institute, London, UK.
⁴ Department of Psychology, University of Otago - Ōtākou Whakaihu Waka, Dunedin, New Zealand.
⁵ Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC, USA.
⁶ Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
⁷ Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
⁸ Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁹ Department of Clinical Sciences, Lund University, Lund, Sweden.
¹⁰ School of Public Health, University of Minnesota, Minneapolis, MN, USA.
¹¹ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹² Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹³ Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁴ Department of Medicine and Department of Environmental & Occupational Health Sciences, School of Medicine, University of Washington, Seattle, WA, USA.
¹⁵ Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
¹⁶ Department of Paediatrics and Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
¹⁷ Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁸ Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
¹⁹ Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²⁰ Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
²¹ Department of Preventive & Social Medicine, Dunedin School of Medicine, University of Otago - Ōtākou Whakaihu Waka, Dunedin, New Zealand.
²² Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. benjamin.m.smith@mcgill.ca.
²³ Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA. benjamin.m.smith@mcgill.ca.
²⁴ Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. benjamin.m.smith@mcgill.ca.

PMID: 41258496
DOI: 10.1038/s43856-025-01245-3

Free article

Quantifying the impact of early life growth adversity on later life health

Raphael Goldman-Pham et al. Commun Med (Lond). 2025.

Free article

. 2025 Nov 17.

doi: 10.1038/s43856-025-01245-3. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
² Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
³ Faculty of Medicine, Imperial College London National Heart and Lung Institute, London, UK.
⁴ Department of Psychology, University of Otago - Ōtākou Whakaihu Waka, Dunedin, New Zealand.
⁵ Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC, USA.
⁶ Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
⁷ Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
⁸ Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁹ Department of Clinical Sciences, Lund University, Lund, Sweden.
¹⁰ School of Public Health, University of Minnesota, Minneapolis, MN, USA.
¹¹ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹² Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹³ Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁴ Department of Medicine and Department of Environmental & Occupational Health Sciences, School of Medicine, University of Washington, Seattle, WA, USA.
¹⁵ Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
¹⁶ Department of Paediatrics and Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
¹⁷ Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁸ Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
¹⁹ Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²⁰ Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
²¹ Department of Preventive & Social Medicine, Dunedin School of Medicine, University of Otago - Ōtākou Whakaihu Waka, Dunedin, New Zealand.
²² Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. benjamin.m.smith@mcgill.ca.
²³ Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA. benjamin.m.smith@mcgill.ca.
²⁴ Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. benjamin.m.smith@mcgill.ca.

PMID: 41258496
DOI: 10.1038/s43856-025-01245-3

Abstract

Background: Early-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.

Methods: Data 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).

Results: Here 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.

Conclusions: This 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.

Plain language summary

Early-life exposures that adversely affect body growth have been implicated in later-life health, but assessment in adulthood is challenging. We tested whether the difference between one’s standing height in adulthood and one’s genetically predicted adult height (“height-GaP”) would be a suitable method for assessing cumulative exposure to early-life growth adversity and predicting later-life health. In two early-life studies that followed children into adulthood, pre-natal and post-natal exposure to tobacco smoke, poverty, less breast feeding and poor nutrition were associated with larger adult height-GaP deficit. In two adult studies, larger height-GaP deficit was associated with death from all-causes and from heart disease. This study introduces a precision measure of early-life growth adversity that can be deployed in adulthood to investigate the developmental origins of health and disease.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

Update of

Quantifying the impact of early-life growth adversity on later-life health.
Goldman-Pham R, Alter MP, Bao R, Collins SÉ, Debban CL, Allinson JP, Ambler A, Bertoni AG, Caspi A, Lovinsky-Desir S, Ekstrom MP, Engert JC, Jacobs DR Jr, Malinsky D, Manichaikul A, Michos ED, Moffitt TE, Oelsner EC, Ramrakha S, Rich SS, Sack C, Stanojevic S, Subbarao P, Sugden K, Theodore R, Watson KE, Williams B, Yang B, Dupuis J, Shaheen SO, Barr RG, Hancox RJ, Smith BM. Goldman-Pham R, et al. medRxiv [Preprint]. 2025 Jun 17:2025.06.16.25327714. doi: 10.1101/2025.06.16.25327714. medRxiv. 2025. Update in: Commun Med (Lond). 2025 Nov 17. doi: 10.1038/s43856-025-01245-3. PMID: 40585119 Free PMC article. Updated. Preprint.

References

1. Kuh, D., Susser, E., Blodgett, J. M. & Ben-Shlomo, Y. A Life Course Approach to the Epidemiology of Chronic Diseases and Ageing (Oxford University Press, 2025).
1. Wadsworth, M. E. J., Hardy, R. J., Paul, A. A., Marshall, S. F. & Cole, T. J. Leg and trunk length at 43 years in relation to childhood health, diet and family circumstances; evidence from the 1946 national birth cohort. Int. J. Epidemiol. 31, 383–390 (2002).
1. Li, L., Dangour, A. D. & Power, C. Early life influences on adult leg and trunk length in the 1958 British birth cohort. Am. J. Hum. Biol. 19, 836–843 (2007).
1. Denholm, R., Power, C. & Li, L. Adverse childhood experiences and child-to-adult height trajectories in the 1958 British birth cohort. Int. J. Epidemiol. 42, 1399–1409 (2013).
1. Gigante, D. P., Nazmi, A., Lima, R. C., Barros, F. C. & Victora, C. G. Epidemiology of early and late growth in height, leg and trunk length: findings from a birth cohort of Brazilian males. Eur. J. Clin. Nutr. 63, 375–381 (2009).

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Quantifying the impact of early life growth adversity on later life health

Affiliations

Quantifying the impact of early life growth adversity on later life health

Authors

Affiliations

Abstract

Plain language summary

Conflict of interest statement

Update of

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous