First-trimester predictive models for adverse pregnancy outcomes-a base for implementation of strategies to prevent cardiovascular disease development.

Introduction: This study aimed to establish efficient, cost-effective, and early predictive models for adverse pregnancy outcomes based on the combinations of a minimum number of miRNA biomarkers, whose altered expression was observed in specific pregnancy-related complications and selected maternal clinical characteristics.

Methods: This retrospective study included singleton pregnancies with gestational hypertension (GH, n = 83), preeclampsia (PE, n = 66), HELLP syndrome (n = 14), fetal growth restriction (FGR, n = 82), small for gestational age (SGA, n = 37), gestational diabetes mellitus (GDM, n = 121), preterm birth in the absence of other complications (n = 106), late miscarriage (n = 34), stillbirth (n = 24), and 80 normal term pregnancies. MiRNA gene expression profiling was performed on the whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time reverse transcription polymerase chain reaction RT-PCR).

First trimester prediction models for small-for- gestational age and fetal growth restricted fetuses without the presence of preeclampsia.

We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012-3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic.

First-Trimester Screening for Miscarriage or Stillbirth-Prediction Model Based on MicroRNA Biomarkers.

We evaluated the potential of cardiovascular-disease-associated microRNAs to predict in the early stages of gestation (from 10 to 13 gestational weeks) the occurrence of a miscarriage or stillbirth. The gene expressions of 29 microRNAs were studied retrospectively in peripheral venous blood samples derived from singleton Caucasian pregnancies diagnosed with miscarriage ( = 77 cases; early onset, = 43 cases; late onset, = 34 cases) or stillbirth ( = 24 cases; early onset, = 13 cases; late onset, = 8 cases; term onset, = 3 cases) and 80 selected gestational-age-matched controls (normal term pregnancies) using real-time RT-PCR. Altered expressions of nine microRNAs (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-342-3p, and miR-574-3p) were observed in pregnancies with the occurrence of a miscarriage or stillbirth.

First-Trimester Screening for HELLP Syndrome-Prediction Model Based on MicroRNA Biomarkers and Maternal Clinical Characteristics.

We evaluated the potential of cardiovascular-disease-associated microRNAs for early prediction of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Gene expression profiling of 29 microRNAs was performed on whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time RT-PCR. The retrospective study involved singleton pregnancies of Caucasian descent only diagnosed with HELLP syndrome ( = 14) and 80 normal-term pregnancies.

Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics.

The goal of the study was to establish an efficient first-trimester predictive model for any type of preterm birth before 37 gestational weeks (spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM)) in the absence of other pregnancy-related complications, such as gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age. The retrospective study was performed in the period from 11/2012 to 3/2020. Peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies.

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications.

We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM ( = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time.

First Trimester Prediction of Preterm Delivery in the Absence of Other Pregnancy-Related Complications Using Cardiovascular-Disease Associated MicroRNA Biomarkers.

The aim of the study was to determine if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict within 10 to 13 weeks of gestation preterm delivery such as spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM) in the absence of other pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age). In addition, we assessed if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict preterm delivery before and after 34 weeks of gestation. The retrospective study was performed within the period November 2012 to March 2020.

First-Trimester Screening for Fetal Growth Restriction and Small-for-Gestational-Age Pregnancies without Preeclampsia Using Cardiovascular Disease-Associated MicroRNA Biomarkers.

The goal of the study was to determine the early diagnostical potential of cardiovascular disease-associated microRNAs for prediction of small-for-gestational-age (SGA) and fetal growth restriction (FGR) without preeclampsia (PE). The whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case-control retrospective study, nested in a cohort, involved all pregnancies diagnosed with SGA ( = 37) or FGR ( = 82) without PE and 80 appropriate-for-gestational age (AGA) pregnancies selected with regard to equality of sample storage time.

Cardiovascular Disease-Associated MicroRNA Dysregulation during the First Trimester of Gestation in Women with Chronic Hypertension and Normotensive Women Subsequently Developing Gestational Hypertension or Preeclampsia with or without Fetal Growth Restriction.

The aim of the study was to assess if cardiovascular disease-associated microRNAs would be able to predict during the early stages of gestation (within 10 to 13 weeks) subsequent onset of hypertensive pregnancy-related complications: gestational hypertension (GH) or preeclampsia (PE). Secondly, the goal of the study was to assess if cardiovascular disease-associated microRNAs would be able to detect the presence of chronic hypertension in early pregnancies. The retrospective study was performed on whole peripheral blood samples collected from singleton Caucasian pregnancies within the period November 2012 to March 2020.

Postnatal Expression Profile of MicroRNAs Associated with Cardiovascular Diseases in 3- to 11-Year-Old Preterm-Born Children.

(1) Background: Preterm-born children have an increased cardiovascular risk with the first clinical manifestation during childhood and/or adolescence. (2) Methods: The occurrence of overweight/obesity, prehypertension/hypertension, valve problems or heart defects, and postnatal microRNA expression profiles were examined in preterm-born children at the age of 3 to 11 years descending from preterm prelabor rupture of membranes (PPROM) and spontaneous preterm birth (PTB) pregnancies. The whole peripheral blood gene expression of 29 selected microRNAs associated with cardiovascular diseases was the subject of our interest.

A History of Preterm Delivery Is Associated with Aberrant Postpartal MicroRNA Expression Profiles in Mothers with an Absence of Other Pregnancy-Related Complications.

This prospective cross-sectional case-control study investigated the postpartal gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases in the peripheral white blood cells of women with anamnesis of preterm prelabor rupture of membranes ( = 58), spontaneous preterm birth ( = 55), and term delivery ( = 89) by a quantitative reverse transcription polymerase chain reaction. After pregnancies complicated by preterm prelabor rupture of membranes or spontaneous preterm birth, mothers showed diverse expression profiles for 25 out of 29 tested microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-499a-5p, and miR-574-3p). The earliest gestational ages at delivery and the lowest birth weights of newborns were associated with the highest postpartal levels of the previously mentioned microRNAs in maternal peripheral white blood cells.

Association Analysis in Young and Middle-Aged Mothers-Relation between Expression of Cardiovascular Disease Associated MicroRNAs and Abnormal Clinical Findings.

The principal goal of the study was to map common postpartal alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases induced by most frequently occurring pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes, or spontaneous preterm birth). In addition, the association analyses between individual abnormal clinical findings (overweight/obesity, central obesity, hypertension, on blood pressure treatment, history of infertility treatment, actual hormonal contraceptive use, the presence of trombophilic gene mutations, actual smoking status, increased serum levels of total cholesterol, HDL (high density lipoprotein) cholesterol, LDL (low density lipoprotein) cholesterol, triglycerides, lipoprotein A, CRP (C-reactive protein), and uric acid, and increased plasma levels of homocysteine) and microRNA expression levels were performed in mothers with respect/regardless to previous course of gestation. The prior exposure to gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes, or spontaneous preterm birth caused that a significant proportion of mothers (52.

Association Analysis in Children Born from Normal and Complicated Pregnancies-Cardiovascular Disease Associated microRNAs and the Incidence of Prehypertension/Hypertension, Overweight/Obesity, Valve Problems and Heart Defects.

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.

Substantially Altered Expression Profile of Diabetes/Cardiovascular/Cerebrovascular Disease Associated microRNAs in Children Descending from Pregnancy Complicated by Gestational Diabetes Mellitus-One of Several Possible Reasons for an Increased Cardiovascular Risk.

Gestational diabetes mellitus (GDM), one of the major pregnancy-related complications, characterized as a transitory form of diabetes induced by insulin resistance accompanied by a low/absent pancreatic beta-cell compensatory adaptation to the increased insulin demand, causes the acute, long-term, and transgenerational health complications. The aim of the study was to assess if alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases are present in whole peripheral blood of children aged 3-11 years descending from GDM complicated pregnancies. A substantially altered microRNA expression profile was found in children descending from GDM complicated pregnancies.

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases.

Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3-11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases.

Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics.

The aim of the study was to examine the effect of previous pregnancies and classical cardiovascular risk factors on vascular endothelial function in a group of 264 young and middle-aged women 3 to 11 years postpartum. We examined microvascular functions by peripheral arterial tonometry and EndoPAT 2000 device with respect to a history of gestational hypertension, preeclampsia, fetal growth restriction, the severity of the disease with regard to the degree of clinical signs and delivery date. Besides, we compared Reactive Hyperemia Index (RHI) values and the prevalence of vascular endothelial dysfunction among the groups of women with normal and abnormal values of BMI, waist circumference, systolic and diastolic blood pressures, heart rate, total serum cholesterol levels, serum high-density lipoprotein cholesterol levels, serum low-density lipoprotein cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum C-reactive protein levels, serum uric acid levels, and plasma homocysteine levels.

The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs.

The aim of the study was to verify if quantification of placental specific C19MC microRNAs in plasma exosomes would be able to differentiate during the early stages of gestation between patients subsequently developing pregnancy-related complications and women with the normal course of gestation and if this differentiation would lead to the improvement of the diagnostical potential. The retrospective study on singleton Caucasian pregnancies was performed within 6/2011-2/2019. The case control study, nested in a cohort, involved women that later developed GH ( = 57), PE ( = 43), FGR ( = 63), and 102 controls.

Postpartum profiling of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases in women exposed to pregnancy-related complications.

Background And Methods: Gestational hypertension (GH), preeclampsia (PE) and fetal growth restriction (FGR) may predispose to later onset of cardiovascular/cerebrovascular diseases. We examined if pregnancy complications induce postpartum alterations in gene expression of cardiovascular/cerebrovascular disease associated microRNAs. 29 microRNAs were tested in peripheral blood of women, compared between groups with a history of GH, PE, FGR and controls, and correlated with the severity of the disease regarding clinical signs, delivery date, and Doppler parameters.

Maternal Cardiovascular Risk Assessment 3-to-11 Years Postpartum in Relation to Previous Occurrence of Pregnancy-Related Complications.

The aim of the present study was to assess the long-term outcomes of women 3-to-11 years postpartum in relation to the previous occurrence of pregnancy-related complications such as gestational hypertension (GH), preeclampsia (PE) and fetal growth restriction (FGR). Body mass index (BMI), waist circumference values, the average values of systolic (SBP) and diastolic (DBP) blood pressures and heart rate, total serum cholesterol levels, serum HDL (high-density lipoprotein) cholesterol levels, serum LDL (low-density lipoprotein) cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum CRP (C-reactive protein) levels, plasma homocysteine levels, serum uric acid levels, individual and relative risks of having a heart attack or stroke over the next ten years were compared between groups (50 GH, 102 PE, 34 FGR and 90 normal pregnancies) and correlated with the severity of the disease with regard to clinical signs (25 PE without severe features, 77 PE with severe features), and delivery date (36 early PE, 66 late PE). The adjustment for potential covariates was made, where appropriate.

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.

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.

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 34weeks 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.

Expression profile of C19MC microRNAs in placental tissue of patients with preterm prelabor rupture of membranes and spontaneous preterm birth.

The aim of the study was to demonstrate that preterm birth (PTB) is associated with altered C19MC microRNA expression profile in placental tissues. Gene expression of 15 placental specific microRNAs (miR‑512‑5p, miR‑515‑5p, miR‑516‑5p, miR‑517‑5p, miR‑518b, miR‑518f‑5p, miR‑519a, miR‑519d, miR‑519e‑5p, miR‑520a‑5p, miR‑520h, miR‑524‑5p, miR‑525‑5p, miR‑526a and miR‑526b‑5p) was compared between groups: 34 spontaneous PTB, 108 preterm prelabor rupture of membranes (PPROM) and 20 term in labor pregnancies. Correlation between variables including relative microRNA quantification in placental tissues and the gestational age at delivery, white blood cell (WBC) count at admission and serum levels of C‑reactive protein at admission in patients with PPROM and PTB was determined.

Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated RASSF1A, and SRY sequences.

The aim of the study was to evaluate the effectiveness of placental-specific markers, extracellular fetal DNA (sex-determining region Y and hypermethylated RASSF1A sequences) and circulating C19MC microRNAs (miR-516-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, miR-525, and miR-526a) for the diagnosis and consecutive follow-up of gestational trophoblastic disease/neoplasia. Increased levels of extracellular fetal DNA and C19MC microRNAs were detected in patients with active disease when compared with the period when the patients reached remission of the disease. The positive correlation between plasma levels of hypermethylated RASSF1A sequence, C19MC microRNAs, and human chorionic gonadotropin serum levels was found.

First trimester screening of circulating C19MC microRNAs and the evaluation of their potential to predict the onset of preeclampsia and IUGR.

Objectives: A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy.

Methods: The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39).

Results: Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.