Maternal plasma soluble neuropilin-1 is downregulated in fetal growth restriction complicated with abnormal umbilical artery doppler: a pilot study.

OBJECTIVE Fetal growth restriction constitutes a major complication of pregnancy. The efficacy of its prenatal identification remains challenging. Recently, placental expression of neuropilin-1 (NRP1) was discovered to be downregulated in fetal growth restriction (FGR) with abnormal umbilical artery (UA) Doppler. A member of the vascular endothelial growth factor receptor family, NRP1 has emerged as an important mediator of sprouting angiogenesis. Whereas NRP1 is proangiogenic, soluble NRP1 (sNRP1) is an antagonist to NRP1. However, little is known about sNRP1in normal or abnormal pregnancies. This study tested the hypotheses that sNRP1 would be detectable in maternal circulation, and its concentration would be upregulated in FGR pregnancies compared to those with normal fetal growth, and its upregulation would correlate with the severity of the disease process as assessed by UA Doppler. METHODS This was a prospective case-control pilot study involving 40 pregnancies (control 20, study 20) between 24 0/7 and 40 0/7weeks' gestation followed in an academic perinatal center from 1/2015 to 5/2017. Fetal ultrasound biometry and UA Doppler were performed using standard protocols. Plasma sNRP1 measurements were performed using a commercially available ELISA. RESULTS Maternal plasma sNRP1 levels were significantly decreased in FGR pregnancies as compared to those with normal fetal growth: 137.4±44.8pg/ml vs. 166.7±36.9pg/ml, respectively (p = 0.03). This contradicted the study hypothesis. Moreover, in comparison with FGR fetuses with normal UA Doppler studies, sNRP1 was downregulated in FGR with elevated UA S/D ratios (p = 0.023) and with UA absent/reversed end diastolic flow (p = 0.005). This also indicates that biometrically small fetuses without hemodynamic compromise are small for gestational age rather than FGR. CONCLUSION The study demonstrated a significant decrease in maternal plasma soluble NRP1 concentrations in growth restricted pregnancies with fetoplacental circulatory compromise. These findings suggest a possible role of sNRP1 in modulating fetal growth, and its potential as a biomarker for fetal growth restriction. This article is protected by copyright. All rights reserved.