Postnatal Expression Profile of microRNAs Associated with Cardiovascular and Cerebrovascular Diseases in Children at the Age of 3 to 11 Years in Relation to Previous Occurrence of Pregnancy-Related Complications

Abstract

Children descending from pregnancies complicated by gestational hypertension (GH), preeclampsia (PE) or fetal growth restriction (FGR) have a lifelong cardiovascular risk. The aim of the study was to verify if pregnancy complications induce postnatal alterations in gene expression of microRNAs associated with cardiovascular/cerebrovascular diseases. Twenty-nine microRNAs were assessed in peripheral blood, compared between groups, and analyzed in relation to both aspects, the current presence of cardiovascular risk factors and cardiovascular complications and the previous occurrence of pregnancy complications with regard to the clinical signs, dates of delivery, and Doppler ultrasound examination. The expression profile of miR-21-5p differed between controls and children with a history of uncomplicated pregnancies with abnormal clinical findings. Abnormal expression profile of multiple microRNAs was found in children affected with GH (miR-1-3p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, and miR-342-3p), PE (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-103a-3p, miR-133a-3p, miR-342-3p), and FGR (miR-17-5p, miR-126-3p, miR-133a-3p). The index of pulsatility in the ductus venosus showed a strong positive correlation with miR-210-3p gene expression in children exposed to PE and/or FGR. Any of changes in epigenome (up-regulation of miR-1-3p and miR-133a-3p) that were induced by pregnancy complications are long-acting and may predispose children affected with GH, PE, or FGR to later development of cardiovascular/cerebrovascular diseases. Novel epigenetic changes (aberrant expression profile of microRNAs) appeared in a proportion of children that were exposed to GH, PE, or FGR. Screening of particular microRNAs may stratify a highly risky group of children that might benefit from implementation of early primary prevention strategies.