Early Mid-pregnancy Blood-Based Proteins as Possible Biomarkers of Increased Infant Birth Size in Sex-Stratified Analyses

Abstract

The objective of this study was to evaluate the associations of 92 maternal blood-based proteins with increased infant birth size. The study was performed at the Uppsala University Hospital, Sweden, and included 857 mother and child dyads. The mean age of the women was 30.3 years, and 53.2% were nulliparous. Blood samples were collected at mean 18 + 2 weeks’ gestation, and the Olink cardiovascular II panel was used to measure 92 proteins, either known to be or suspected to be markers of cardiovascular and inflammatory disease in humans. Multiple linear regression models adjusted for maternal age, parity, pre-conception BMI, height, and smoking were performed to evaluate the association of each individual protein with infant birth size. We also performed sex-stratified analyses. Eight proteins (Matrix metalloproteinase-12 (MMP-12), Prostasin (PRSS8), Adrenomedullin (ADM), Pappalysin-1 (PAPP-A), Angiotensin-converting enzyme 2 (ACE2), Sortilin (SORT1), Lectin-like oxidized LDL receptor 1 (LOX-1), and Thrombomodulin (TM)) were associated with infant birth size after false discovery rate adjustment. In the analyses including only female infants, ten proteins (MMP-12, Growth/differentiation factor 2 (GDF-2), PRSS8, SORT1, ADM, Interleukin-1 receptor antagonist protein (IL-1ra), Leptin (LEP), ACE2, TM, and Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A)) were associated with infant birth size. Two proteins (PAPP-A and PRSS8) were associated with infant birth size among male infants. Our study suggests several proteins as potential biomarkers for increased birth weight, and our findings could act as a base for future research to identify new potential markers that could be added to improve screening for large infants.

Unveiling immune tolerance pathways in preeclampsia placenta: implications for molecular targets and discovery of potential biomarkers

“…In the hypoxic-ischemic environment of preeclampsia, a novel member of the CRH peptide family significantly increases Ucn2 and Ucn3, further promoting the response to oxidative stress in the placenta ( 31 ). LEP, as a pluripotent cytokine, is involved in promoting inflammation, suggesting it may have a crucial relationship with fetal pregnancy outcomes during pregnancy ( 32 ). Additionally, increased SIGLEC6 in trophoblast cells impairs vascular endothelial cell function by down-regulating Wnt6/β-catenin signal transduction in preeclampsia ( 33 ).…”

Maternal early mid-pregnancy adiponectin in relation to infant birth weight and the likelihood of being born large-for-gestational-age

“…To the best of our knowledge, this is the first study to evaluate the relation between maternal adiponectin levels and infant birth size in females and males separately. We have previously reported on sex-specific differences regarding maternal blood-based proteins measured in early mid-pregnancy in relation to infant birth size 30 . Hence, it seems that sex-specific adaptions to in-utero environmental changes occur, but the precise mechanisms behind are unknown.…”