Vaginal miR-210-3p as a potential biomarker for pregnancies complicated by early fetal growth restriction: A proof-of-concept case-control study

Introduction: Fetal growth restriction (FGR) is associated with increased risk of neonatal morbidity and mortality or long-term adverse outcomes. We investigated the ability of hypoxia and angiogenesis-related miR-210-3p and miR-126-5p to identify early FGR cases and their correlations with neonatal outcomes. Methods: Twenty-nine women with pregnancies complicated by early FGR diagnosis and 25 controls matched for gestational age (GA) were enrolled and their vaginal fluid (VF) and plasma were collected. MiR-210-3p and miR-126-5p were measured by RT-qPCR and their targets were identified by in-silico analysis limited only to those already experimentally validated in other contexts. Results: Overall, VF levels of miR-210-3p were lower in early FGR cases compared to controls (p < 0.05). miR-210-3p was lower in severe cases and in women who later developed preeclampsia (p < 0.05). VF miR-210-3p levels correlated with lower birth weight, premature birth and severe complications at birth (p < 0.05). miR-210-3p was not detected in plasma and no correlations were observed between miR-126-5p and FGR or neonatal outcomes. In silico analyses identified HIF-1α, HIF-3α, BDNF, IGFBP3, RAD52 and TWIST-1 as experimentally validated targets of miR-210-3p. Among the predicted biological pathways controlled by miR-210-3p, we found hypoxia-responsive signaling such as autophagy, oxidative stress and metabolic pathways. Discussion: Although validation is needed, these findings suggest that VF levels of miR-210-3p may potentially serve as biomarker for the diagnosis of early FGR; future mechanistic studies are also advisable to investigate whether pharmacological strategies based on miR-210-3p, or its downstream targets may be useful for FGR.