Low maternal plasma apelin in the second trimester is associated with adverse pregnancy outcome in severe, early-onset fetal growth restriction

Abstract

Context: Fetal growth restriction increases adverse pregnancy outcomes such as preterm birth and intrauterine fetal death. Apelin is a secreted peptide expressed in placental syncytiotrophoblast and downregulated in fetal growth restriction. Objectives: We tested the hypothesis that adverse pregnancy outcome is associated with low maternal plasma apelin at diagnosis of early-onset fetal growth restriction. Methods: Plasma samples and fetomaternal blood flow Doppler velocimetry measurements were obtained from pregnant women (n=59) at diagnosis of early-onset fetal growth restriction in the second trimester. Plasma apelin was determined by ELISA and pregnancy outcome was recorded. Placental gene expression was analysed after birth by qRT-PCR, compared to term placentas from women with late-onset fetal growth restriction or with appropriate-for-gestational age infants. Results: At diagnosis of early-onset fetal growth restriction, plasma apelin concentration was significantly lower in women who delivered extremely preterm (<28 weeks gestation) or had an intrauterine fetal death, compared to women who had a livebirth greater than or equal to 28 weeks (P<0.05). Plasma apelin correlated directly with uterine artery volume flow rate and inversely with pulsatility index. Placental gene expression of apelin, but not the apelin receptor or elabela, was lower in women with early-onset fetal growth restriction delivering preterm than in appropriate-for-gestational-age, term control women. Conclusion: Low maternal circulating apelin during the second trimester is associated with impaired uteroplacental perfusion and subsequent adverse pregnancy outcome in severe, early-onset fetal growth restriction. Placental apelin deficiency may contribute mechanistically to the pathogenesis of early-onset fetal growth restriction.