Why do some babies born smaller than expected face higher risks of developing chronic diseases later in life? This question has puzzled researchers for years. Recent findings from a team at the University of Arizona may shed some light on this mystery by connecting certain proteins in umbilical cord blood to health outcomes in adulthood.
Researchers, by analyzing decades of blood sample data, discovered an overrepresentation of proteins linked to neuronal development in the umbilical cord blood of about one-third of babies classified as small for gestational age (SGA). This overabundance of proteins, notably axon guidance proteins, has been associated with poorer lung function as the children age.
Published in Nature Communications, these findings offer new perspectives on the roots of chronic illnesses and suggest potential areas for further research into how birth weight influences organ development.
“Low birth weight is one of the most important risk factors for the development of chronic diseases,” stated Dr. Fernando Martinez from the Asthma and Airway Disease Research Center. Dr. Martinez emphasized the known association between low birth weight and later lung dysfunction, while noting the lack of understanding of the biological mechanisms at play.
Utilizing data from the Children’s Allergy and Asthma Data Repository, or CADRE, the researchers followed individuals from birth into adulthood, measuring lung function and analyzing blood samples every five years. Their research revealed that SGA babies, particularly those with elevated axon guidance proteins, exhibited reduced lung function by age 40.
The study covered babies from five different U.S. cities, ensuring a diverse range of genetic backgrounds and environmental factors. The consistent presence of heightened axon guidance proteins across these varied demographics was unexpected, according to Anthony Bosco, a co-author of the study.
Further investigations into axon guidance proteins through genome-wide association studies (GWAS) found genetic variations linked to differences in lung development and function. Additional research using a sheep model confirmed the role of these proteins during fetal development in various organs, including the brain, heart, and lungs.
Co-author Bosco commented, “We have results from three studies providing a unified hypothesis to explain how low birth weight affects multiple organs through the axon guidance pathway and increases risk for multiple diseases.”
The research team aims to delve deeper into these genetic pathways, exploring their potential as therapeutic targets. Martinez noted, “This could be a fundamental biological system that may impact all body systems. We’re excited about the possibilities.”
Other contributors from the College of Medicine – Tucson include James F. Read, Debra A. Stern, Dr. Tara F. Carr, Amber L. Spangenberg, and Dr. Wayne J. Morgan. From the School of Animal and Comparative Biomedical Sciences, contributors included Rosa I. Luna-Ramirez and Sean W. Limesand, alongside Meiven Yang from the Department of Immunobiology.
This research was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institutes of Health (NIH), among other sources.
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