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

  1. Raphael Goldman-Pham
  2. Matthew P. Alter
  3. Rebecca Bao
  4. Sophie É. Collins
  5. Catherine L. Debban
  6. James P. Allinson
  7. Antony Ambler
  8. Alain G. Bertoni
  9. Avshalom Caspi
  10. Stephanie Lovinsky-Desir
  11. Magnus P. Ekstrom
  12. James C. Engert
  13. David R. Jacobs
  14. Daniel Malinsky
  15. Ani Manichaikul
  16. Erin D. Michos
  17. Terrie E. Moffitt
  18. Elizabeth C. Oelsner
  19. Sandhya Ramrakha
  20. Stephen S. Rich
  21. Coralynn Sack
  22. Sanja Stanojevic
  23. Padmaja Subbarao
  24. Karen Sugden
  25. Reremoana Theodore
  26. Karol E. Watson
  27. Benjamin Williams
  28. Bin Yang
  29. Josée Dupuis
  30. Seif O. Shaheen
  31. R. Graham Barr
  32. Robert J. Hancox
  33. Benjamin M Smith
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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) and UKBiobank. 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 adjusted for age, sex, genotype-predicted height and genetic ancestry. Analyses were replicated in the Dunedin Multidisciplinary Health and Development Study (DMHDS) and the Multi-Ethnic Study of Atherosclerosis (MESA).

Findings

Among 4,582 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 were associated with larger adult height-GaP deficit (p<0.01). Among 483,385 UKBiobank participants (mean±SD age: 56±8 years at height-GaP assessment), height-GaP deficit was 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:1.33 95%CI:1.24-1.43) and coronary heart disease (aHR:1.68 95%CI:1.52-1.86). Early- and later-life height-GaP associations replicated in DMHDS and MESA.

Interpretation

This study introduces a simple index of early-life growth adversity deployable in adulthood to investigate the developmental origins of longevity and improve health equity across the life course.

Funding

Federal agencies and academic institutions.

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