Abstract
The goal was to assess how a history of any kind of pregnancy-related complication altered expression profile of microRNAs played a role in the pathogenesis of diabetes, cardiovascular and cerebrovascular diseases in the peripheral blood leukocytes of children at the age of 3–11 years. The prior exposure to gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes or spontaneous preterm birth causes that a significant proportion of children (57.42% to 90.0% specifically) had a substantially altered microRNA expression profile, which might be the origin of a lifelong cardiovascular risk. A total of 23 out of 29 tested microRNAs were upregulated in children born from such complicated gestation. The occurrence of overweight, obesity, valve problems and heart defects even intensified upregulation of microRNAs already present in children exposed to such pregnancy complications. The occurrence of overweight/obesity (miR-92a-3p, and miR-210-3p) and valve problems or heart defects (miR-342-3p) induced microRNA upregulation in children affected with pregnancy complications. Overall, 42.86% overweight/obese children and 27.36% children with valve problems or heart defects had even higher microRNA levels than children with normal clinical findings after complicated pregnancies. In addition, the microRNA expression profile was also able to differentiate between children descending from normal gestation in relation to the occurrence of overweight and obesity. Screening on the base of the combination of 19 microRNAs identified 70.0% overweight/obese children at 90.0% specificity. In general, children after complicated pregnancies, just as children after normal pregnancies, with abnormal findings are at a higher risk of the onset of cardiovascular complications, and their dispensarization, with the aim to implement primary prevention strategies, would be beneficial.
Highlights
The subject of our interest was extended to explore the impact of the actual occurrence of individual abnormal findings on already present abnormal microRNA expression profiles in children born from complicated gestation
With regard to a high number of outliers in children with normal body mass index (BMI) values and in children with normal values of echocardiographic measurements, and with regard to a large impact of the course of gestation of mothers on postnatal microRNA expression profile, we decided to evaluate microRNA expression data within the equal groups of children
In view of the fact that the prenatal and perinatal exposure to any pregnancy-related complication led to substantial alterations of postnatal microRNA expression profile in a proportion of children, we compared microRNA expression profile between equal groups of children with respect to actual findings
Summary
The increasing worldwide prevalence of pregnancy-related complications generates an increasing number of children with a lifelong cardiovascular risk [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51].Lifelong cardiovascular risk of children descending from pregnancy-related complications is based on the presence of overweight/obesity (increased body mass index and/or wider waist circumference) [1,2,3,4,5,6,7,8,9,10,11], higher systolic and/or diastolic blood pressures [1,2,6,7,8,12,13,14,15,16,17,18,19,20,21,22], higher nocturnal systolic and diastolic blood pressures [16], altered lipid profiles [6,21], altered metabolite pattern [23], impaired glucose tolerance [3,5,6,7,24], alteration in the systemic and the pulmonary circulation [25], altered cardiac geometry and function [26,27,28,29] and the acceleration of pubertal timing [30].Some children born from complicated pregnancies have already been suffering from severe diseases, such as asthma [31,32], pulmonary hypertension [33,34,35], diabetes mellitus [36], cardiorenal metabolic syndrome [37], chronic kidney diseases [38,39], cardiovascular diseases [40], ophthalmic disorders [41], neurodevelopmental and neuropsychiatric disorders [42,43,44,45,46,47,48,49,50,51], most likely as a result of abnormal fetal programming.Recently, we reported that a proportion of children affected with gestational hypertension (GH), preeclampsia (PE), fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) had altered microRNA expression profiles that may contribute to the predisposition of these children to later onset of diabetes mellitus, cardiovascular and cerebrovascular diseases [52,53].Prenatal exposure to maternal complications (GH, PE and GDM) or fetal complication (FGR) was associated in a proportion of children with deregulation of miR-1–3p, miR-17-5p, miR-20a-5p, miR-20b-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, miR-210-3p and miR-342-3p [52,53].In addition, a prior exposure to GDM induced postnatal deregulation of miR-16-5p, miR-92a-3p, miR-100-5p, miR-143-3p, miR-155-5p, miR-221-3p, miR-499a-5p and miR-574-3p [53]. Lifelong cardiovascular risk of children descending from pregnancy-related complications is based on the presence of overweight/obesity (increased body mass index and/or wider waist circumference) [1,2,3,4,5,6,7,8,9,10,11], higher systolic and/or diastolic blood pressures [1,2,6,7,8,12,13,14,15,16,17,18,19,20,21,22], higher nocturnal systolic and diastolic blood pressures [16], altered lipid profiles [6,21], altered metabolite pattern [23], impaired glucose tolerance [3,5,6,7,24], alteration in the systemic and the pulmonary circulation [25], altered cardiac geometry and function [26,27,28,29] and the acceleration of pubertal timing [30].
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