Fetal growth restriction increases the risk of poor childhood growth and development and chronic disease in adulthood. Yet, little is known about biological pathways that mediate the long-lasting effects of suboptimal intrauterine growth. We explored the plasma proteome in a cohort of 500 Nepalese children 6-8 years of age to identify plasma proteins associated with multiple anthropometric size indicators at birth. Among 982 proteins analyzed, no proteins differed by birth weight, length, or weight-for-length indicators. However, 25 proteins were differentially abundant in children with a small vs normal head circumference at birth (<-2 vs. ≥-2 z-scores of the WHO growth standards). Angiopoietin-like 6 was 19.4% more abundant and the other 24 proteins were 7-21% less abundant in children with a small vs normal head circumference at birth, adjusted for potential confounders. The less abundant proteins included actins, actin filament organizing proteins (α-actinin, talin, filamin, cofilin, profilin, and vinculin), proteins involved in muscle contraction, and glycolytic enzymes, which were all positively correlated with each other. A novel cluster of childhood plasma proteins involved in angiogenesis and cytoskeleton dynamics was associated with a small head size at birth. The prognostic value of an altered proteomic phenotype remains to be investigated.
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