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.
Highlights
There exists a progressive increase of data linking specific levels of risk factors in prenatal life with cardiovascular disease outcomes in children and adolescents
Recent epidemiologic and experimental data substantially indicate that children descending from pregnancies complicated by gestational hypertension (GH), preeclampsia (PE), or fetal growth restriction (FGR) have an unique, lifetime cardiovascular risk profile that is present from early life
Since we identified within the group of children descending from normal pregnancies those ones with cardiac findings who were already dispesarized in the department of pediatric cardiology, or those ones who were overweight/obese, had prehypertension/hypertension, and/or abnormal echocardiogram findings, we compared the microRNA profile of this group to that one consisting of children with normal anamnesis, normal blood pressures (BP), normal body mass index (BMI) and normal reference values of echocardiographic measurements
Summary
There exists a progressive increase of data linking specific levels of risk factors in prenatal life with cardiovascular disease outcomes in children and adolescents. Maternal central pulsatile BP components (systolic BP and pulse pressure) during pregnancy were associated with higher BP in the offspring of women with PE This positive correlation was already evident at 3 years old children [8]. These results suggested a possible association between maternal hypertensive disorders of pregnancy and offspring BP that may be driven by genetics or familial non-genetic risk factors particular to BP [5]. Pulmonary artery pressure was roughly 30% higher and flow-mediated dilation was 30% smaller in children of PE-affected mothers than in controls This alteration predisposes children to exaggerated hypoxic pulmonary hypertension already during childhood and may cause premature cardiovascular disease in the systemic circulation at some time in the future [9]
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