An adult proteomic signature associated with very low birth weight and chronic disease risk.

Authors

Cho-Yi Huang, David Seong, Jonathan Reiss, Chi-Hung Shu, Mohammad Amin Sadeghi, Philip Chung, Liu K Yang, Lei Xue, Yaxin Fang, Rui Xu, Xiruo Ding, Saber Sheybani, Lichy Han, Bernard C Mawuli, Marc Ghanem, Mehrdad Kiamari, Alan L Chang, Tomin James, Samson J Mataraso, Camilo Espinosa, Eloise Berson, Po-Nien Tsao, Martin S Angst, Brice Gaudiliere, Lawrence Prince, Gary Shaw, David Stevenson, Nima Aghaeepour

Published in

Med (New York, N.Y.). Pages 101297. Sep 16, 2026. Epub Sep 16, 2026.

Abstract

Adults born at very low birth weight (VLBW, <1.5 kg) have elevated risks of chronic disease, but it is unclear whether adult plasma proteomics contains a detectable signature associated with recalled VLBW.
We analyzed 2,923 plasma proteins in 26,061 UK Biobank participants (median sampling age 56.4 years) with recalled birth weight, including 368 with VLBW and 25,693 with normal birth weight. We derived a machine learning proteomic prematurity index (PPI) distinguishing these groups and evaluated associations with 425 adult diagnoses, discrimination relative to birth weight and electronic health record (EHR) information, incident diseases after proteomic sampling, and exploratory biological interpretation.
The PPI was associated with recalled VLBW (odds ratio [OR], 7.32; 95% confidence interval [95% CI], 4.01-13.42) and remained independently associated after adjustment for EHR-derived VLBW probability (OR, 5.82; 95% CI, 3.99-8.47). Recalled VLBW was associated with adult disease burden, and PPI showed higher discrimination than birth weight for 370 of 425 diseases. Incident-only analyses preserved the cross-disease hazard ratio patterns, while fewer events and adult factor adjustment attenuated some associations. Exploratory biological annotations paralleled the disease patterns. Among participants with normal birth weight, higher PPI was associated with disease burden and subsequent disease risk, indicating that PPI is not VLBW specific.
Adult plasma proteomics identifies a signature associated with recalled VLBW that provides information about adult disease risk beyond birth weight and EHR-derived measures. These findings are hypothesis generating and do not establish a direct molecular consequence of prematurity. External validation is required before clinical application.
The March of Dimes, the Alfred E. Mann Foundation, the Universe of Mind, and the Bill & Melinda Gates Foundation (INV-037517 and INV-076306).

PMID:
42748912
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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