Profiling of cardiovascular and cerebrovascular disease associated microRNA expression in umbilical cord blood in gestational hypertension, preeclampsia and fetal growth restriction

Background and methods: Gene expression of 29 cardiovascular and cerebrovascular disease associated microRNAs was assessed in whole umbilical cord blood, compared between groups [47 gestational hypertension (GH), 56 preeclampsia (PE), 37 fetal growth restriction (FGR) and 44 normal pregnancies] and correlated with the severity of the disease with respect to clinical signs (mild PE vs. severe PE), delivery date (before and after 34 weeks of gestation), and Doppler ultrasound parameters [pulsatility index (PI) in the umbilical artery, PI in the middle cerebral artery and the cerebroplacental ratio]. Results: GH showed a down-regulation of miR-195-5p (p = 0.025). The down-regulation of miR-26a-5p (p = 0.031, p = 0.05), miR-145-5p (p = 0.042, p = 0.015), and miR-574-3p (p = 0.002, p = 0.022) was observed in severe PE pregnancies requiring termination before 34 weeks of gestation. Severe PE occurring regardless of the delivery date was associated with downregulation of miR-195-5p (p = 0.01), miR-199a-5p (p = 0.048), and miR-221-3p (p = 0.028). On the other hand, mild PE showed upregulation of miR-92a-3p (p = 0.044). The centralization of fetal circulation tended to higher levels of miR-1-3p (rho= -0.302, p = 0.045) and miR-133a-3p (rho = -0.348, p = 0.020) in PE pregnancies. FGR pregnancies with abnormal values of flow rate in the umbilical artery (miR-221-3p: rho= -0.390, p = 0.017) and the middle cerebral artery (miR-143-3p:. = 0.350, p = 0.036) demonstrated down-regulation of relevant microRNAs. Conclusion: Epigenetic changes induced by pregnancy-related complications in umbilical cord blood may appear as a result of dysfunctional placenta and impaired maternal cardiovascular function (hidden cardiovascular and cerebrovascular diseases) and may cause later onset of cardiovascular and cerebrovascular diseases in offspring. (C) 2017 Elsevier B.V. All rights reserved.