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Cord Blood Proteins Linked to Weight at Birth, Early Childhood

NEW YORK – With a proteomic approach focused on hundreds of proteins involved in inflammatory processes, a Belgian research team has tracked down a handful of cord blood proteins with ties to infants' weight at birth as well as their weight trajectory for years to come.

"We found robust cord blood proteomic signatures associated with birth weight, and most of these proteins were still associated with weight and growth early in life," first and corresponding author Thessa Van Pee, an environmental sciences researcher with Hasselt University in Belgium, and colleagues wrote in JAMA Network Open on Tuesday.

For their study, the researchers used Olink assays to quantify protein profiles in cord blood samples from 288 infant-mother pairs from individuals enrolled in the Environmental Influence on Early Aging (ENVIRONAGE) birth cohort in Belgium. The infants had an average gestational age of around 277 days at birth, they noted, and had follow-up exams when they were about 4 1/2 years old, on average.

For the analyses, the team focused on 368 inflammation-related proteins, searching for potential cord blood protein ties to traits such as birth weight, the ratio between their birth weight and a reference birth weight, and growth in the children's early years of life.

Together, the work "highlights the possible long-term predictive effect of the cord blood proteome on early-life growth trajectories," Van Pee said in an email.

In particular, the researchers flagged two proteins that were found at enhanced levels in cord blood in infants with higher birth weight measurements or birth weight ratios, as well as five cord blood proteins (CELSR2, EPHA4, SLITRK1, TCN1, and UNC5D) with reduced representation in the cord blood samples as these growth traits increased.

The investigators noted that two of these proteins — afamin (AFM) and SFRP4 — continued to track with growth in blood samples collected from 12-month-old toddlers, while afamin levels in blood samples from 4- to 6-year-old children was linked to lower-than-usual chances of children being overweight. Likewise, samples collected from the 4- to 6-year-old children highlighted proteins with negative ties to the children's weight.

"For a doubling in protein expression, the absolute changes in birth weight ranged from 209 to 366 grams," Van Pee explained. "In addition, we observed for the majority of the identified cord blood proteins an association with rapid growth at 12 months, or weight, [body mass index] z-score, waist circumference, and overweight risk at 4 to 6 years old."

Although Van Pee emphasized that the current discovery analyses will require more research before being applicable in a clinical setting, she noted that the new work pointed to potential molecular targets related to growth and development, while underscoring the potential long-term effects of prenatal processes and stressors that impact proteomic patterns in cord blood.

"Overall, our findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics and possibly even be associated with disease development later in life," she and her co-authors wrote.

Similarly, they suggested that further investigation will be needed to untangle the biological mechanisms behind the cord blood proteomic associations identified so far.

"Cord blood proteins associated with birth weight and growth in early life may be due to a variety of proposed mechanisms," the authors explained, "including growth hormone synthesis, metabolism and metabolic disorders, neurological pathways, and placental vascularization."