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Novel Plasma Proteins in Nepalese School-aged Children are Associated with a Small Head Size at Birth
Sun Eun Lee1, Keith P West2, Robert N Cole3
1Center for Human Nutrition, Dept. of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. slee278@jhu.edu.
Insights
Suboptimal fetal growth, particularly small head circumference at birth, is linked to altered childhood plasma proteins. These proteins are involved in angiogenesis and cytoskeleton dynamics, suggesting potential long-term health implications.
Area of Science:
- Pediatric Health
- Proteomics
- Developmental Biology
Background:
- Fetal growth restriction (FGR) is associated with adverse childhood outcomes and adult chronic diseases.
- The biological pathways linking intrauterine growth to long-term health effects remain poorly understood.
- Understanding these pathways is crucial for early identification and intervention.
Purpose of the Study:
- To investigate the association between anthropometric indicators at birth and the plasma proteome in Nepalese children.
- To identify specific plasma proteins linked to head circumference at birth.
- To explore potential biological pathways mediating the effects of early growth on later health.
Main Methods:
- Analysis of plasma proteome in a cohort of 500 Nepalese children aged 6-8 years.
- Quantification of 982 proteins using proteomic techniques.
- Statistical analysis adjusted for potential confounders to identify differentially abundant proteins based on birth anthropometrics, specifically head circumference z-scores.
Main Results:
- No plasma proteins were associated with birth weight, length, or weight-for-length.
- Twenty-five plasma proteins were differentially abundant in children with small versus normal head circumference at birth.
- These proteins included Angiopoietin-like 6 (elevated) and a cluster of actin-related proteins, muscle contraction proteins, and glycolytic enzymes (reduced).
Conclusions:
- A small head circumference at birth is associated with a distinct plasma proteomic profile in childhood.
- This profile involves proteins related to angiogenesis and cytoskeleton dynamics.
- Further research is needed to determine the prognostic value of this altered proteomic phenotype.
Abstract:
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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