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. A control group with 80 singleton term pregnancies was selected on the basis of equal sample-storage time. A combination of only six microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p; AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut-off > 0.652) could predict preterm delivery before 37 gestational weeks in early stages of gestation in 52.83% of pregnancies with a 10.0% FPR. This predictive model for preterm birth based on aberrant microRNA expression profile was further improved via implementation of maternal clinical characteristics (maternal age and BMI at early stages of gestation, infertility treatment with assisted reproductive technology, occurrence of preterm delivery before 37 gestational weeks in previous pregnancy(ies), and presence of any kind of autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, type 1 diabetes mellitus, or other autoimmune disease)). With this model, 69.81% of pregnancies destined to deliver before 37 gestational weeks were identified with a 10.0% FPR at early stages of gestation. When other clinical variables as well as those mentioned above—such as positive first-trimester screening for early preeclampsia with onset before 34 gestational weeks and/or fetal growth restriction with onset before 37 gestational weeks using the Fetal Medicine Foundation algorithm, as well as positive first-trimester screening for spontaneous preterm birth with onset before 34 gestational weeks using the Fetal Medicine Foundation algorithm—were added to the predictive model for preterm birth, the predictive power was even slightly increased to 71.70% with a 10.0% FPR. Nevertheless, we prefer to keep the first-trimester screening for any type of preterm birth occurring before 37 gestational weeks in the absence of other pregnancy-related complications as simple as possible.

• Klíčová slova
• cardiovascular microRNAs, early gestation, expression, peripheral venous blood, prediction, preterm delivery, preterm prelabor rupture of membranes, screening, spontaneous preterm birth,
• Publikační typ
• časopisecké články MeSH

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 (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.

• Klíčová slova
• cardiovascular microRNAs, early pregnancy, gene expression, gestational diabetes mellitus, prediction, screening, whole peripheral venous blood,
• MeSH
• biologické markery MeSH
• gestační diabetes * diagnóza   genetika   MeSH
• kardiovaskulární nemoci * genetika   MeSH
• komplikace těhotenství * genetika   MeSH
• lidé MeSH
• mikro RNA * metabolismus   MeSH
• první trimestr těhotenství MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA * MeSH

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 (n = 37) or FGR (n = 82) without PE and 80 appropriate-for-gestational age (AGA) pregnancies selected with regard to equality of sample storage time. Gene expression of 29 cardiovascular disease-associated microRNAs was assessed using real-time RT-PCR. Upregulation of miR-16-5p, miR-20a-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, and miR-195-5p was observed in SGA or FGR pregnancies at 10.0% false positive rate (FPR). Upregulation of miR-1-3p, miR-20b-5p, miR-126-3p, miR-130b-3p, and miR-499a-5p was observed in SGA pregnancies only at 10.0% FPR. Upregulation of miR-145-5p, miR-342-3p, and miR-574-3p was detected in FGR pregnancies at 10.0% FPR. The combination of four microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) was able to identify 75.68% SGA pregnancies at 10.0% FPR in early stages of gestation. The detection rate of SGA pregnancies without PE increased 4.67-fold (75.68% vs. 16.22%) when compared with the routine first-trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation. The combination of seven microRNA biomarkers (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) was able to identify 42.68% FGR pregnancies at 10.0% FPR in early stages of gestation. The detection rate of FGR pregnancies without PE increased 1.52-fold (42.68% vs. 28.05%) when compared with the routine first-trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation. Cardiovascular disease-associated microRNAs represent promising early biomarkers with very suitable predictive potential for SGA or FGR without PE to be implemented into the routine screening programs.

• Klíčová slova
• cardiovascular microRNAs, early pregnancy, fetal growth restriction, gene expression, prediction, screening, small for gestational age, whole peripheral venous blood,
• Publikační typ
• časopisecké články MeSH

These Special Issue IJMS were dedicated to the major complications responsible for maternal and perinatal morbidity and mortality, such as gestational hypertension (GH), preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), preterm birth, and chronic venous disease [...].

• MeSH
• gestační diabetes * MeSH
• hypertenze indukovaná těhotenstvím * epidemiologie   etiologie   MeSH
• lidé MeSH
• novorozenec MeSH
• předčasný porod * MeSH
• preeklampsie * etiologie   MeSH
• růstová retardace plodu etiologie   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• úvodníky MeSH

(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. (3) Results: Nearly one-third of preterm-born children (32.43%) had valve problems and/or heart defects. The occurrence of systolic and diastolic prehypertension/hypertension was also inconsiderable in a group of preterm-born children (27.03% and 18.92%). The vast majority of children descending from either PPROM (85.45%) or PTB pregnancies (85.71%) had also significantly altered microRNA expression profiles at 90.0% specificity. (4) Conclusions: Postnatal microRNA expression profiles were significantly influenced by antenatal and early postnatal factors (gestational age at delivery, birth weight of newborns, and condition of newborns at the moment of birth). These findings may contribute to the explanation of increased cardiovascular risk in preterm-born children. These findings strongly support the belief that preterm-born children should be dispensarized for a long time to have access to specialized medical care.

• Klíčová slova
• birth weight of newborns, cardiovascular risk, children, condition of newborns at the moment of birth, expression, gestational age at delivery, microRNA, preterm prelabor rupture of membranes, spontaneous preterm birth, whole peripheral blood,
• Publikační typ
• časopisecké články MeSH

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 (n = 58), spontaneous preterm birth (n = 55), and term delivery (n = 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. Administration of tocolytic drugs in order to prolong pregnancy, used in order to administer and complete a full course of antenatal corticosteroids, was associated with alterations in postpartal microRNA expression profiles to a lesser extent than in women with imminent delivery, where there was insufficient time for administration of tocolytics and antenatal corticosteroids. Overall, mothers who did not receive tocolytic therapy (miR-24-3p and miR-146a-5p) and mothers who did not receive corticosteroid therapy (miR-1-3p, miR-100-5p, and miR-143-3p) had increased or showed a trend toward increased postpartal microRNA expression when compared with mothers given tocolytic and corticosteroid therapy. In addition, mothers with serum C-reactive protein levels above 20 mg/L, who experienced preterm labour, showed a trend toward increased postpartal expression profiles of miR-143-3p and miR-199a-5p when compared with mothers with normal serum C-reactive protein levels. On the other hand, the occurrence of maternal leukocytosis, the presence of intra-amniotic inflammation (higher levels of interleukin 6 in the amniotic fluid), and the administration of antibiotics at the time of preterm delivery had no impact on postpartal microRNA expression profiles in mothers with a history of preterm delivery. Likewise, the condition of the newborns at the moment of birth, determined by Apgar scores at 5 and 10 min and the pH of cord arterial blood, had no influence on the postpartal expression profiles of mothers with a history of preterm delivery. These findings may contribute to explaining the increased cardiovascular risk in mothers with anamnesis of preterm delivery, and the greater increase of maternal cardiovascular risk with the decrease of gestational age at delivery. Women with preterm delivery in their anamnesis represent a high-risk group with special needs on a long-term basis, with a need to apply preventive and therapeutic interventions as early as possible.

• Klíčová slova
• birth weight of newborns, cardiovascular risk, corticosteroids, expression, gestational age, microRNA, mothers, peripheral white blood cells, preterm prelabor rupture of membranes, spontaneous preterm birth, tocolytics,
• MeSH
• C-reaktivní protein metabolismus   MeSH
• cerebrovaskulární poruchy genetika   MeSH
• dospělí MeSH
• kardiovaskulární nemoci genetika   MeSH
• komplikace těhotenství krev   genetika   MeSH
• leukocyty metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matky MeSH
• mikro RNA krev   genetika   metabolismus   MeSH
• novorozenec MeSH
• pilotní projekty MeSH
• poporodní období genetika   MeSH
• porodní hmotnost MeSH
• předčasný odtok plodové vody genetika   MeSH
• předčasný porod genetika   MeSH
• regulace genové exprese * MeSH
• reprodukovatelnost výsledků MeSH
• signální transdukce genetika   MeSH
• stanovení celkové genové exprese * MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• vedení porodu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• mikro RNA MeSH

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 (52.42% at 90.0% specificity) had substantially altered microRNA expression profile, which might originate lifelong cardiovascular risk. 26 out of 29 tested microRNAs were up-regulated in mothers with a history of such complicated pregnancies. MicroRNA expression profiles were also able to differentiate between mothers with normal and abnormal clinical findings (BMI (body mass index), waist circumference, systolic blood pressure, on blood pressure treatment, history of infertility treatment, and the presence of trombophilic gene mutations) irrespective of previous course of gestation. The treatment of hypertension even intensified upregulation of some microRNAs (miR-24-3p, and miR-342-3p) already present in women after complicated pregnancies. Newly, the presence of overweight/obesity (miR-155-5p), systolic hypertension (miR-92a-3p, and miR-210-3p), treatment for infertility (miR-155-5p), and treatment for hypertension (miR-210-3p) induced upregulation of several microRNAs. In general, mothers after complicated pregnancies are at increased risk of development of cardiovascular complications. Especially those mothers indicated to have postpartally altered microRNA expression profiles might be considered as a highly risky group that would benefit from dispensarization and implementation of primary prevention strategies.

• Klíčová slova
• BMI, cardiovascular risk, central obesity, expression, fetal growth restriction, gestational diabetes mellitus, gestational hypertension, hypertension, hypertension on treatment, infertility treatment, microRNA, mothers, overweight/obesity, preeclampsia, preterm prelabor rupture of membranes, spontaneous preterm birth preterm birth, trombophilic gene mutations, whole peripheral blood,
• Publikační typ
• časopisecké články MeSH