The Impact of Platelet-Rich Plasma Application during Cesarean Section on Wound Healing and Postoperative Pain: A Single-Blind Placebo-Controlled Intervention Study.

Background/Objectives: The aim of this study was to evaluate if platelet-rich plasma (PRP) application into the wound during cesarean delivery improves wound healing and reduces pain in the postoperative period. Materials and Methods: A total of 46 patients undergoing cesarean section (CS) were included in this single-blind placebo-controlled intervention study: 23 women in the PRP group and 23 in the placebo group. Every patient was asked to evaluate pain by using the Visual Analogue Scale (VAS) immediately after surgery, as well as 6 and 12 h after the surgery. The use of analgetics was also recorded. The postoperative scar was assessed using the Patient and Observer Scar Assessment Scale (POSAS). Results: There was no case of wound dehiscence in either group. Significant differences between the groups in the scar quality assessment were detected in both patient and doctor POSAS results on days 8, 30 and 90 after surgery in the favor of the PRP group. There was no difference in the pain intensity assessment on the VAS recorded after surgery, but PRP patients required fewer paracetamol doses per day than the control group. Conclusions: PRP application during CS significantly improved wound healing in both short- and long-term assessment. Although it did not influence postoperative pain intensity, it may reduce the use of analgetics after surgery.

Understanding the Role of Chemerin in the Pathophysiology of Pre-Eclampsia.

Chemerin is a multifaceted adipokine that is involved in multiple biological processes, including inflammation, angiogenesis, adipogenesis, and energy metabolism, as well as oxidative stress. There is a vast body of evidence for a crucial role of chemerin in the development of different cardiovascular diseases. Blood chemerin levels, as well as its placental expression, are elevated in patients with pre-eclampsia (PE) and correlate positively with the severity of the disease. This narrative review summarizes the current knowledge about the potential role of chemerin during PE development, with a particular focus on its involvement in oxidative stress and endothelial dysfunction.

Gestational weight gain and blood pressure control in physiological pregnancy and pregnancy complicated by hypertension.

BACKGROUND: Obesity is a widely recognised risk factor for chronic and gestational hypertension. Influence of gestational weight gain on blood pressure control throughout the pregnancy is not well characterised. MATERIAL AND METHODS: Women in the third trimester of a singleton pregnancy were recruited to the study. Medical records were analysed and a special survey was conducted to obtain history on hypertensive disorders in pregnancy and weight changes during pregnancy. Blood pressure measurements were taken during the office visit in line with international guidelines. Relationships between gestational weight gain and maximal and office values of systolic and diastolic blood pressure values were analysed. RESULTS: Data of 90 women in normal pregnancy, 40 with gestational hypertension and 21 with chronic hypertension were analysed. Gestational weight gain was 11.9 ± 4.6 kg in the normal pregnancy group, 13.0 ± 5 kg in the gestational hypertension group and 10.6 ± 3.4 kg in the chronic hypertension group. Gestational weight gain positively correlated with both office (r = 0.48; p < 0.001) and maximal blood pressure values (r = 0.34; p = 0.004) in normal pregnancy and with maximal blood pressure values (r = 0.57; p = 0.02) in women with chronic hypertension. No correlation was observed between gestational weight gain and blood pressure values among women with gestational hypertension. CONCLUSION: In normal pregnancy and in women with chronic hypertension greater gestational weight gain is related to higher blood pressure values in the third trimester.

The Impact of Coexisting Gestational Diabetes Mellitus on the Course of Preeclampsia.

A strict correlation between gestational diabetes mellitus (GDM) and preeclampsia (PE) has been shown in previous studies. This case-control observational study evaluates the influence of concomitant GDM on the severity of PE. Ninety-nine patients were included: thirty-eight with PE without GDM (group 1), fourteen with PE and concomitant GDM (group 2), and forty-seven with uncomplicated pregnancies (group 3). Adverse maternal/fetal and neonatal outcomes were registered. Patients underwent blood sample analysis of serum PlGF, sFlt-1, creatinine levels, and platelet count (PLT). The incidence of preterm birth, FGR, HELLP syndrome, and NICU admission was significantly higher in group 1 in comparison to groups 2 and 3, whereas RDS was diagnosed most often in group 2 in comparison to groups 1 and 3. All studied biochemical parameters differed between the control group and both PE groups; however, there were no differences between patients with PE with and without GDM. The presented study indicates that the coexistence of GDM may mitigate the course of PE. The lack of differences between patients with PE with and without GDM in serum levels of studied biomarkers may also confirm its usefulness in the diagnosis and management of PE in patients with coexisting GDM.

Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy.

Endometriosis is a common inflammatory disease characterized by the presence of endometrial cells outside the uterine cavity. It is estimated that it affects 10% of women of reproductive age. Its pathogenesis covers a wide range of abnormalities, including adhesion, proliferation, and cell signaling disturbances. It is associated with a significant deterioration in quality of life as a result of chronic pelvic pain and may also lead to infertility. One of the most serious complications of endometriosis is an ectopic pregnancy (EP). Currently, the exact mechanism explaining this phenomenon is unknown; therefore, there are no effective methods of prevention. It is assumed that the pathogenesis of EP is influenced by abnormalities in the contraction of the fallopian tube muscles, the mobility of the cilia, and in the fallopian microenvironment. Endometriosis can disrupt function on all three levels and thus contribute to the implantation of the embryo beyond the physiological site. This review takes into account aspects of the molecular mechanisms involved in the pathophysiology of endometriosis and EP, with particular emphasis on the similarities between them.

The Role of Noncoding RNA in the Pathophysiology and Treatment of Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is defined as a loss of ovarian function before the age of 40 years, with a prevalence rate estimated at approximately 1%. It causes infertility and is related to serious long-term health consequences, including reduced life expectancy, increased cardiovascular risk, decreased bone mineral density and neurological disorders. There is currently no effective therapy for POI that is widely available in clinical practice; therefore, the treatment of patients with POI is based on hormone replacement therapy. One of the recent advances in the understanding of the pathophysiology of POI has been the role of microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) in the disease. Moreover, intensive research on human folliculogenesis and reproductive biology has led to the development of novel promising therapeutic strategies with the use of exosomal miRNAs derived from mesenchymal stem cells to restore ovarian function in POI patients. This narrative review focuses on the new studies concerning the role of ncRNAs in the pathogenesis of POI, together with their potential as biomarkers of the disease and targets for therapy.

Insight into the Key Points of Preeclampsia Pathophysiology: Uterine Artery Remodeling and the Role of MicroRNAs.

Preeclampsia affects about 3-8% of all pregnancies. It represents a complex and multifaceted syndrome with at least several potential pathways leading to the development of disease. The main dogma in preeclampsia is the two-stage model of disease. Stage 1 (placental stage) takes place in early pregnancy and is thought to be impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries that leads to reduced placental perfusion and release of numerous biological factors causing endothelial damage and development of acute maternal syndrome with systemic multiorgan failure (stage 2-the onset of maternal clinical symptoms, maternal stage). Recently, in the light of the vast body of evidence, two-stage model of preeclampsia has been updated with a few novel pathways leading to clinical manifestation in the second part of pregnancy. This paper reviews current state of knowledge about pathophysiology of preeclampsia and places particular focus on the recent advances in understanding of uterine artery remodeling alterations, as well as the role of microRNAs in preeclampsia.

The potential association between a new angiogenic marker fractalkine and a placental vascularization in preeclampsia.

PURPOSE: Impaired angiogenesis is one of the most common findings in preeclamptic placentas. A new angiogenetic role of fractalkine (CX3CL1) is recently recognized apart from inflammatory activity. In this study, a link between CX3CL1 and the development of placental vasculature in preeclampsia was examined. METHODS: The study comprised 52 women allocated to Group 1 (normotensive, n = 23) and Group 2 (preeclampsia, n = 29). In each group Doppler parameters, serum levels of CX3CL1, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) were assessed between 30 and 32 week of pregnancy. After the delivery, placental samples were taken and the vascularization and expression of CX3CR1 receptor were assessed after immunostaining. RESULTS: CX3CL1 and sFlt-1 serum levels were significantly higher levels in Group 2 vs Group 1, while PlGF serum levels was significantly lower in Group 2. Lower cerebroplacental ratio (CPR) was observed in Group 2. The vascular/extravascular tissue index (V/EVTI) was significantly lower in Group 2, while compared to Group 1, with the lowest value in the fetus growth restriction (FGR) subgroup (0.18 ± 0.02; 0.24 ± 0.03; 0.16 ± 0.02, respectively). The expression of examined CX3CR1 was higher in Group 2, while compared to Group 1, reaching the highest values in FGR subgroup. There was a moderate negative correlation between birth weight, V/EVTI and CX3CL1 serum level and CX3CR1 placental expression in the group of pregnancies complicated with preeclampsia. CONCLUSION: The significant underdevelopment of placental vascular network in preeclampsia is associated with the change in the CX3CL1/CX3CR1 system, especially in FGR complicated pregnancies.

Genetic Background of Fetal Growth Restriction.

Fetal growth restriction (FGR) is one of the most formidable challenges in present-day antenatal care. Pathological fetal growth is a well-known factor of not only in utero demise in the third trimester, but also postnatal morbidity and unfavorable developmental outcomes, including long-term sequalae such as metabolic diseases, diabetic mellitus or hypertension. In this review, the authors present the current state of knowledge about the genetic disturbances responsible for FGR diagnosis, divided into fetal, placental and maternal causes (including preeclampsia), as well as their impact on prenatal diagnostics, with particular attention on chromosomal microarray (CMA) and noninvasive prenatal testing technique (NIPT).

Downregulated expression of microRNAs associated with cardiac hypertrophy and fibrosis in physiological pregnancy and the association with echocardiographically-evaluated myocardial function.

The aim of the present study was to analyze the profiles of cardiac microRNAs (miRNAs/miRs) in healthy pregnant women and non-pregnant controls. A total of 61 healthy women >18 years of age with singleton pregnancies in the third trimester were compared with 19 non-pregnant controls. Specifically, expression of miRNAs associated with cardiac hypertrophy (miR-1, miR-17-5, miR-22, miR-34a, miR-124, miR-133a, miR-195, miR-199a-3p, miR-199b, miR-210, miR-222 and miR-1249) and miRNAs associated with cardiac hypertrophy and fibrosis (miR-15b, miR-21, miR-26a, miR-29-a, miR-29c, miR-30c, miR-101, miR-146a, miR-191, miR-208a-5p and miR-328) were analyzed and compared with echocardiographic examination results. Both groups had similar cardiac miRNA expression profiles, but differed in quantitative evaluation. Women in the third trimester of physiological pregnancy exhibited downregulation of certain profibrotic miRNAs (miR-21, miR-30c and miR-328), decreased expression of a hypertrophic and antimetabolic miRNAs (miR-146a), downregulation of an antifibrotic miRNA (miR-222), and downregulation of a hypertrophic miRNA (miR-195). In pregnant women, the indices of systolic function were associated with miR-195 expression, and an interplay between miR-17-5p and diastolic function was observed. While the profiles of cardiac miRNAs expressed in healthy pregnant women and healthy non-pregnant controls were similar, these two groups differed in terms of expression of specific miRNAs. In the third trimester of physiological pregnancy, a downregulation of miR-17-5p, miR-21, miR-30c, miR-146a, miR-195, miR-222 and miR-328 was observed. The differences in the association between echocardiographic indices with miRNAs in pregnant and non-pregnant women suggest that miRNAs regulate both the structure and function of the pregnant heart, influencing cardiac muscle thickness as well as systolic and diastolic function.

Non-obstetric complications in preeclampsia.

Preeclampsia is a multisystem disorder of pregnancy that remains a leading cause of maternal and foetal morbidity and mortality. It is still an underestimated risk factor for future cardiovascular, cerebrovascular, and kidney disease, developing often in the perimenopausal period of a woman's life. It remains unclear whether preeclampsia is an individual risk factor for future cardiovascular, cerebrovascular, and renal events or an early marker of women with high-risk profiles for these diseases. Risk factors for cardiovascular disorders and preeclampsia are very similar and include the following: obesity, dyslipidaemia, insulin resistance, pro-inflammatory and hypercoagulable state, and endothelial dysfunction. Thus, the pregnancy can only be a trigger for cardiovascular alterations that manifest in development of preeclampsia. On the other hand, there is strong evidence that changes in cardiovascular, endothelial, and metabolic systems occurring in the course of preeclampsia may not fully recover after delivery and can be a cause of future disease, especially in the presence of other metabolic risk factors regarding, for example, perimenopause. In this review the authors present current knowledge about short- and long-term maternal consequences of preeclampsia, such as: cardiovascular disease, cerebrovascular incidents (posterior reversible encephalopathy and stroke), kidney injury (including the risk of end-stage renal disease), liver failure, and coagulopathy (thrombocytopenia and disseminated intravascular coagulation).

Rise in antifibrotic and decrease in profibrotic microRNA protect the heart against fibrosis during pregnancy: A preliminary study.

BACKGROUND: Physiological pregnancy is associated with volume overload. Unlike cardiac pathologies linked with volume overload, such as mitral or aortic regurgitation, pregnancy is thought to be unrelated to fibrosis of the heart. However, changes in the cardiac extracellular matrix during pregnancy remain poorly understood. OBJECTIVES: The aim of the study was to examine the expression of 11 microRNAs associated with cardiac fibrosis (miR-21, miR-26a, miR-26b-5p, miR-29b-3p, miR-29c-3p, miR-101a, miR-146a, miR-208a, miR-223 and miR-328) during pregnancy and to compare them with a healthy control group. MATERIAL AND METHODS: Six women in singleton pregnancy (30-36 weeks) and 6 non-pregnant women as a control group were included in the study. Each woman underwent an echocardiographic examination, and had blood pressure on both arms measured and a blood sample taken. MicroRNAs expression was analyzed using Custom TaqMan® Array MicroRNA Cards (Applied Biosystems, Foster City, USA). RESULTS: Median age of the pregnant women was 34 years (range 25-39 years) and of the control group 32 years (range 29-43 years). Median week of pregnancy was 34 years (range 31-36 years). Most of the examined microRNAs had a lower expression in the pregnancy group (fold change 1.0). CONCLUSIONS: In the 3rd trimester of physiological pregnancy, there is a 244% increase in expression of miR-101a and a decrease by 73% in expression of miR-328. Both of these changes can protect against fibrosis during volume overload occurring in physiological pregnancy.

Strategies for overcoming oncological treatment-related ovarian dysfunction - literature review.

In the majority of developed countries, it is observed that the time for maternity is being postponed to over the 30th and even 40th year of life. A significant number of cancers are diagnosed during reproductive age, often before the first pregnancy. A fertility preservation is an important issue in oncological treatment, where there is a need for balancing between radicality and the preservation of function of reproductive organs. The authors discuss the problem of ovarian dysfunction after oncological treatment and present the possible strategies for saving the reproductive function of ovaries, including both invasive and pharmacological approaches.

Perinatal mortality and morbidity of growth restricted fetuses and newborns (own experience) - first report.

AIM: to evaluate the outcome of pregnancies complicated by fetal growth restriction with particular emphasis on the factors (fetal and maternal) related to perinatal mortality and morbidity of the fetus and newborn. MATERIAL AND METHODS: Retrospective analysis of the documentation of 53 women admitted with the diagnosis of fetal growth restriction based on ultrasound examination (fetal biometry and fetal vessel Doppler abnormalities). 38 (71.7%) patients were referred to our department with the diagnosis of fetal growth restriction, whereas 15 (28.3%) cases were diagnosed in our hospital. 32 (60.4%) women were referred to our department by their main obstetrician, 13 (24.5%) by other hospitals and 8 (15.1%) came to triage because of worrisome symptoms. The patients were divided into 2 groups according to the presence of fetal/neonatal complications: the first group (n=14) - with complications (defined as one or more of the following: stillbirth, neonatal death, respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH) Grade III or IV , necrotic enterocolitis (NEC), proven neonatal sepsis or bronchopulmonary dysplasia (BPD)) and the second one (n=39) - without severe complications. RESULTS: Gestational age at diagnosis and at delivery was lower in the first group (28.5 weeks vs. 32.15 weeks, p=0.003 and 29.2 weeks vs. 32.8 weeks, p=0.0004). Female fetuses predominated in the second group (64.1%), whereas male fetuses in the first group (64.3%). In both groups the majority of patients delivered by cesarean section (92.9% vs. 97.4% p=0.44). Birth weight was significantly lower in the first group (774g vs. 1416g, p<0.0001). Perinatal morbidity (severe neonatal complications) occurred in 14 (26.4%) cases. The fetal and newborn perinatal mortality rate in the studied group was 13.19% (in comparison to 0.6% for the entire population of pregnant women in Poland). CONCLUSIONS: 1. Gestational age (at diagnosis and at delivery) and birth weight are the most important prognostic factors related to the adverse outcome in the management of fetal growth restriction. 2.The most common mode of delivery for fetuses with growth restriction is the cesarean section. 3. Early detection of fetal growth restriction in routine perinatal care seems to be insufficient. 4. Fetal and newborn perinatal mortality and morbidity rates in fetal growth restriction are still high and the management of such pregnancies should take place in reference obstetric units, where detailed diagnostics, monitoring and treatment of fetal and neonatal complications can be performed.