Fetal circulating protein biomarkers and their association with early child weight development

 

Pregnancy is accompanied by diverse changes in metabolic, endocrinological, vascular and immunogenic processes. Fluctuations of various cardiovascular biomarkers have been associated with pregnancy diseases such as gestational diabetes mellitus and preeclampsia, as well as neonatal outcomes such as birthweight and resulting child weight development. Even in healthy pregnancies, certain proteins such as TGFβ1 present in cord blood at birth have been found to be associated with child weight gain in the early years of life. Therefore, we investigated the association of circulating cardiovascular biomarkers in cord serum at birth with child weight development in the first year of life.

Serum samples from 87 mothers taken at the 36th gestational week as well as cord serum from their respective offspring at birth were collected through the LIFE Child cohort study. All mothers were healthy and had uncomplicated pregnancies. All offspring were healthy term births with appropriate-for-gestational-age birthweight. Serum samples were analyzed using Olink®​ Target 96 Cardiovascular III high-multiplex immunoassays targeting 92 biomarkers. Maternal and cord serum normal protein expression (NPX) values were compared using Mann-Whitney U-test. Spearman’s correlation of the assessed biomarkers with parameters of child growth measured at standardized U-checkups during the first year of life was performed. All statistical analyses were carried out with R.

Of the 92 biomarkers assessed in our study, 54 had significantly higher NPX values in cord serum when compared to maternal serum. Furthermore, the NPX values of 8 biomarkers in maternal serum and 19 biomarkers in cord serum correlated positively and significantly with child weight at 1 year of age. Both tyrosine-protein kinase receptor UFO (AXL) in maternal serum and scavenger receptor cysteine-rich type 1 protein M130 in cord serum correlated positively and significantly with birthweight as well as weight at 1 year of age. Nine biomarkers simultaneously had significantly higher NPX values in cord serum in comparison to maternal serum and correlated significantly and positively with weight at 1 year of age. These included AXL, complement component C1q receptor, cadherin-5, contactin-1, collagen alpha-1(I) chain, ephrin type B-receptor 4, TNF receptor superfamily member 3, neurogenic locus notch homolog protein 3, and TNF receptor superfamily member 1B.

Our study showed that 54 of the assessed biomarkers found in cord serum at birth appear to be predominantly of fetal or placental origin. Furthermore, we found associations between several biomarkers detected in cord serum with child weight development in the first year of life, suggesting their possible role in the programming of fetal metabolic processes.

Publication History

Article published online:
18 April 2024

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