Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial.

BACKGROUND: The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone. METHODS: RATIO37 was a randomised, open-label, multicentre, pragmatic trial, conducted in low-risk pregnant women, recruited from nine hospitals over six countries. The eligibility criteria were designed to be broad; participants were required to be 18 years or older, with an ultrasound-dated confirmed singleton pregnancy in the first trimester, an alive fetus with no congenital malformations at the routine second-trimester ultrasound, an absence of adverse medical or obstetric history, and the capacity to give informed consent. Women were randomly assigned in a 1:1 ratio (block size 100) using a web-based system to either the concealed group or revealed group. In the revealed group, the cerebroplacental ratio value was known by clinicians, and if below the fifth centile, a planned delivery after 37 weeks was recommended. In the concealed group, women and clinicians were blinded to the cerebroplacental ratio value. All participants underwent ultrasound at 36 + 0 to 37 + 6 weeks of gestation with growth assessment and Doppler evaluation. In both groups, planned delivery was recommended when the estimated fetal weight was below the tenth centile. The primary outcome was perinatal mortality from 24 weeks' gestation to infant discharge. The study is registered at ClinicalTrials.gov (NCT02907242) and is now closed. FINDINGS: Between July 29, 2016, and Aug 3, 2021, we enrolled 11 214 women, of whom 9492 (84·6%) completed the trial and were eligible for analysis (4774 in the concealed group and 4718 in the revealed group). Perinatal mortality occurred in 13 (0·3%) of 4774 pregnancies in the concealed group and 13 (0·3%) of 4718 in the revealed group (OR 1·45 [95% CI 0·76-2·76]; p=0·262). Overall, severe neonatal morbidity occurred in 35 (0·73%) newborns in the concealed group and 18 (0·38%) in the revealed group (OR 0·58 [95% CI 0·40-0·83]; p=0·003). Severe neurological morbidity occurred in 13 (0·27%) newborns in the concealed group and nine (0·19%) in the revealed group (OR 0·56 [95% CI 0·25-1·24]; p=0·153). Severe non-neurological morbidity occurred in 23 (0·48%) newborns in the concealed group and nine (0·19%) in the revealed group (0·58 [95% CI 0·39-0·87]; p=0·009). Maternal adverse events were not collected. INTERPRETATION: Planned delivery at term based on ultrasound fetal growth assessment and cerebroplacental ratio at term was not followed by a reduction of perinatal mortality although significantly reduced severe neonatal morbidity compared with fetal growth assessment alone. FUNDING: La Caixa foundation, Cerebra Foundation for the Brain Injured Child, Agència per la Gestió d'Ajuts Universitaris i de Recerca, and Instituto de Salud Carlos III.

Comparison of Cross-Sectional Area of Pubovisceral Muscle in Nulliparous and Primiparous Women.

INTRODUCTION AND HYPOTHESIS: The main risk factor for pelvic floor disorders is vaginal delivery, which may cause levator ani muscle (LAM) injury and denervation. LAM includes pubovisceral muscle (PVM, pubococcygeus), puborectalis muscle (PRM), and iliococcygeus muscle. We hypothesize that primiparous women with low pelvic floor muscle contraction have a reduced PVM cross-sectional area (CSA) compared to nulliparous women. METHODS (SAMPLE SIZE AND STATISTICAL APPROACHES): This single-centre prospective observational study compared healthy nulliparous (n = 40) to primiparous (n = 40) women after vaginal delivery without LAM avulsion and Oxford score ≤ 3. Demographics, questionnaires (ICIQ-UI-SF, OAB-Q-SF, PISQ-12), POP-Q, Oxford score, ultrasound measurements (minimal anteroposterior and lateral diameters, hiatal area, PRM thickness, levator-urethra gap) and magnetic resonance imaging (MRI)-PVM CSA were evaluated. Normality was tested, and an appropriate test was used to compare the groups. Power calculation suggested 40 participants per group. RESULTS: The primiparous group was older, had a higher BMI, and their hiatal area on ultrasound at contraction was larger compared to the nulliparous group. The CSA of the left-sided PVM (1.15 ± 0.50 cm2) was larger compared to the right side (1.03 ± 0.50 cm2), p = 0.02 in nulliparous women. The PVM CSA of primiparous women with low Oxford score was reduced compared to nulliparous (0.87 ± 0.30 versus 1.09 ± 0.50 cm2, p = 0.006). The intra-rater reliability for PVM CSA had an ICC of 0.90 and inter-rater ICC of 0.77. CONCLUSIONS: Primiparous women after vaginal delivery with low pelvic floor contraction force had reduced PVM CSA on MRI images compared to nulliparous women.

Dynamics of serum levels and reference ranges of copeptin in the 3rd trimester of pregnancy in healthy pregnant women with uncomplicated pregnancy and delivery.

OBJECTIVE: Copeptin is a stable fragment of vasopressin. Copeptin levels have been found to reflect the degree of endothelial stress in various conditions, including acute coronary syndrome. Copeptin may be a bio marker for endothelial stress during pregnancy. However, there is still a lack of understanding of its dynamics and levels throughout pregnancy. This study aims to describe intra-individual and longitudinal changes in copeptin levels at 30th and 36th gestational weeks in healthy pregnant women with uncomplicated pregnancy and delivery and to establish specific reference ranges. METHODS: A total of 125 pregnant women with uncomplicated pregnancy and delivery were included. These women were monitored throughout their pregnancy and gave birth at the Department of Obstetrics and Gynecology Olomouc University Hospital. The blood was taken at ~30 and ~36 gestational weeks. Serum copeptin levels were measured using a Kryptor Compact PLUS analyzer. For statistics, we used R software and the "referenceRanges" package. RESULTS: It was found that serum levels of copeptin were significantly higher in the 36th week group than in the 30th week group (P < 0.05). Cook's distance was used to eliminate outliers. The 30th week median was 3.377 pmol/l, reference range = 1.343-7.829 pmol/l, and the 36 week was median 4.735 pmol/l and reference range = 2.06-13.2 pmol/l. In the 36th week reference range, the median was higher than in healthy, non-pregnant women (P < 0.05). Copeptin values can exceed 10 pmol/l, particularly after the 36th week. In the 3rd trimester, this value may indicate cardiovascular and endothelial overload. CONCLUSION: Copeptin levels were found to vary significantly depending on gestational week. The proposed reference ranges take into account the increased secretion of vasopressin in pregnancy. The existence of specific upper reference limits represents a potential advantage in detecting pregnant women prone to hypertensive disease in the 3rd trimester.

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. The study included all cases diagnosed with SGA (n = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm, were added to the prediction model for FGR, the detection power was even increased to 74.39 % cases and 78.05 % cases at 10.0 % FPR.

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 (n = 77 cases; early onset, n = 43 cases; late onset, n = 34 cases) or stillbirth (n = 24 cases; early onset, n = 13 cases; late onset, n = 8 cases; term onset, n = 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. The screening based on the combination of these nine microRNA biomarkers revealed 99.01% cases at a 10.0% false positive rate (FPR). The predictive model for miscarriage only was based on the altered gene expressions of eight microRNA biomarkers (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 and miR-195-5p). It was able to identify 80.52% cases at a 10.0% FPR. Highly efficient early identification of later occurrences of stillbirth was achieved via the combination of eleven microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-145-5p, miR-210-3p, miR-342-3p, and miR-574-3p) or, alternatively, by the combination of just two upregulated microRNA biomarkers (miR-1-3p and miR-181a-5p). The predictive power achieved 95.83% cases at a 10.0% FPR and, alternatively, 91.67% cases at a 10.0% FPR. The models based on the combination of selected cardiovascular-disease-associated microRNAs had very high predictive potential for miscarriages or stillbirths and may be implemented in routine first-trimester screening programs.

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 (n = 14) and 80 normal-term pregnancies. Upregulation of six microRNAs (miR-1-3p, miR-17-5p, miR-143-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) was observed in pregnancies destined to develop HELLP syndrome. The combination of all six microRNAs showed a relatively high accuracy for the early identification of pregnancies destined to develop HELLP syndrome (AUC 0.903, p < 0.001, 78.57% sensitivity, 93.75% specificity, cut-off > 0.1622). It revealed 78.57% of HELLP pregnancies at a 10.0% false-positive rate (FPR). The predictive model for HELLP syndrome based on whole peripheral venous blood microRNA biomarkers was further extended to maternal clinical characteristics, most of which were identified as risk factors for the development of HELLP syndrome (maternal age and BMI values at early stages of gestation, the presence of any kind of autoimmune disease, the necessity to undergo an infertility treatment by assisted reproductive technology, a history of HELLP syndrome and/or pre-eclampsia in a previous gestation, and the presence of trombophilic gene mutations). Then, 85.71% of cases were identified at a 10.0% FPR. When another clinical variable (the positivity of the first-trimester screening for pre-eclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm) was implemented in the HELLP prediction model, the predictive power was increased further to 92.86% at a 10.0% FPR. The model based on the combination of selected cardiovascular-disease-associated microRNAs and maternal clinical characteristics has a very high predictive potential for HELLP syndrome and may be implemented in routine first-trimester screening programs.

Multilevel musculo-fascial defect magnetic resonance study of female pelvic floor: retrospective case control study in women with pelvic floor dysfunction after the first vaginal delivery.

INTRODUCTION: Magnetic resonance imaging (MRI) provides a detailed display of the pelvic floor structures responsible for normal pelvic floor anatomy. The aim of the study is to assess the appearance of musculo-fascial defects in women with pelvic floor dysfunction following first vaginal delivery. MATERIAL AND METHODS: Analysis of axial T3 (Tesla 3) MRI scans from a case control study of symptomatic (n = 149) and asymptomatic (n = 60) women after first vaginal delivery. Presence and severity of pelvic organ support and attachment system defects in three axial pelvic planes were assessed. RESULTS: In the symptomatic group, major muscular defects were found in 67.1% (for pubovisceral muscle complex) and 87.9% (for iliococcygeal muscle). Only 6.7% of major pubovisceral and 35.0% of major iliococcygeal defects were identified in the controls (p = 0.000). Prolapse patients had an odds ratio (OR) of 22.1 (95% CI 8.94-54.67) to have major pubovisceral muscle complex defect and OR of 4.9 (95% CI 1.51-15.71) to have major iliococcygeal muscle defect. Fascial defects were found in 60.4% and 83.2% the symptomatic group, respectively. Those with prolapse had an OR of 29.1 (95% CI 9.77-86.31) to have facial defect at the level of pubovisceral muscle complex and an OR of 16.9 (95% CI 7.62-37.69) to have fascial defect at the level of iliococcygeal muscle. Uterosacral ligaments detachment was associated with prolapse with an OR of 10.1 (95% CI 4.01-25.29). For the model based on combination on all MRI markers, the area under the receiver operating characteristic curve is 0.921. CONCLUSIONS: This study provides comprehensive data about first vaginal delivery-induced changes in the levator ani muscle and endopelvic fascial attachment system. These changes are seen also in asymptomatic controls, but they are significantly less expressed.

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. Whole peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group, 80 singleton term pregnancies, was selected on the base of equal sample storage time. Gene expression of 29 selected cardiovascular disease associated microRNAs was studied using real-time RT-PCR. Downregulation of miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-126-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, miR-221-3p and miR-342-3p was observed in pregnancies with preterm delivery before 37 (≤36 + 6/7) weeks of gestation. Majority of downregulated microRNAs (miR-16-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p) was associated with preterm delivery occurring before 37 (≤36 + 6/7) weeks of gestation. The only miR-210-3p was downregulated in pregnancies with preterm delivery before 34 (≤33 + 6/7) weeks of gestation. The type of preterm delivery also had impact on microRNA gene expression profile. Downregulation of miR-24-3p, miR-92a-3p, miR-155-5p, and miR-210-3p was a common feature of PTB and PPROM pregnancies. Downregulation of miR-16-5p, miR-20b-5p, miR-26a-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-221-3p, and miR-342-3p appeared just in PTB pregnancies. No microRNA was uniquely dysregulated in PPROM pregnancies. The combination of 12 microRNAs (miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p, AUC 0.818, p < 0.001, 74.53% sensitivity, 75.00% specificity, cut off > 0.634) equally as the combination of 6 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) can predict preterm delivery before 37 weeks of gestation in early stages of gestation in 52.83% pregnancies at 10.0% FPR. Cardiovascular disease associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current routine first trimester screening programme to predict preterm delivery.

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 (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.

Telemedicine in prenatal care.

Telemedicine, as a health service provided remotely, is increasingly becoming a common part of health care. Telemedicine is defined as "an umbrella term for health activities, services and systems operated remotely through information and communication technologies to promote global health, prevention and health care, as well as education, health management and health research". It also describes telemedicine as "the provision of services where distance is a critical factor, using information and communication technologies to exchange valid information for the diagnosis, treatment and prevention of disease and injury, for research and evaluation, and for the continuing education of healthcare providers to improve the health of individuals and communities". Both definitions imply that two of the hallmarks of telemedicine include the use of communication and information technologies to overcome distance as a critical factor, a factor that is well known to us, not least from the recent months of the COVID-19 pandemic. Distance medicine can thus act as a tool for improving access to health care and also complement health care itself in a very appropriate way.

Cesarean scar pregnancy.

OBJECTIVE: To summarize the current knowledge on pregnancy in a cesarean scar. METHODOLOGY: A literature review on the topic using the PubMed database. RESULTS: Gravidity in a cesarean scar is a relatively new type of ectopic pregnancy that will be an increasingly common problem in an era of increasing cesarean section rates. It is still a relatively rare event, occurring in about 6% of the population. Diagnosis is based primarily on ultrasound examination and is essential early on in pregnancy. The pathogenesis of the disease is due to a disorder of the basal layer of the endometrium and can lead to conditions that we refer to as placenta accreta spectrum. The management is completely individualized and depends on hCG values, ultrasound findings, fetal viability, the wishes of the pregnant woman and the experience of the gynecologist concerned. CONCLUSION: This is still a rare occurrence of ectopic pregnancy but with increasing potential. The solution is completely individualized based on a precise and early ultrasound diagnosis.

Relationship between urethrovesical junction mobility changes and postoperative progression of stress urinary incontinence following sacrospinous ligament fixation - a subanalysis of a multicentre randomized study.

OBJECTIVES: The study aimed to assess the relationship between urethrovesical junction (UVJ) descent and development of de novo stress urinary incontinence (SUI) and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse using the method of sacrospinal fixation (SSF). This was a secondary analysis of the SAME prospective randomized multicentre study (reg. no. NCT03053479) comparing three approaches to surgery for apical defects - sacropexy, SSF and transvaginal mesh. METHODS: The subanalysis included 81 patients with apical defects managed by SSF, either right-sided (N = 14, 17.3%) or bilateral (N = 67, 82.7%). Postoperative follow-up was assessed at 3 months (N = 59), 12 months (N = 47) and 24 months (N = 30). UVJ mobility at rest and with maximum effort, the Valsalva manoeuvre was determined using a standardized 3D/ 4D transperineal ultrasound protocol proposed by Dietz et al. De novo SUI and postoperative progression of preexisting SUI were ascertained from history. RESULTS: Preoperative demographic data (N = 81) were as follows: BMI 27.3 kg/ m2 (16.8-44.5), age 67.0 years (31-85), and parity 2 (1-6). Concomitant anterior repair was performed in 65.4%. Postoperative progression of SUI was 45.8% at 3 months, 21.3% at 12 months, and 23.3% at 24 months. There were significant differences between preoperative and postoperative UVJ descent values at 3, 12 and 24 months (P < 0.0001). Correlations between UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (P = 0.051-0.883). Correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively) and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (P = 0.691-0.779). CONCLUSIONS: The study showed significant changes in UVJ descent values preoperatively and at 3, 12 and 24 months after SSF. There were no significant correlations between UVJ descent and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up. There were no signifi cant correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up.

Cesarean scar pregnancy - a retrospective analysis of cases in the years 2012-2021.

INTRODUCTION: With the increasing number of caesarean sections, the number of cesarean scar pregnancies (CSP) is also increasing. This is a relatively new entity of an ectopic pregnancy, which is risky mainly because of its possible association with placenta accreta spectrum. CSP is thought to represent about 6% of the total number of ectopic pregnancies in all women who have a history of at least one caesarean section. The estimated incidence of CSP is about 1/1,688 of all pregnancies and about 1/2,000 of all caesarean sections. MATERIAL AND METHODS: Retrospective analysis of individual cases of cesarean scar pregnancies managed in our health care facility in the years 2012-2021. RESULTS: In total, we managed 16 cases of pregnancy in the caesarean scar in 15 women. In one woman, we recorded CSP twice. The mean age of the women was 36.6 years (27-41). The mean number of caesarean sections was 1.6 (1-3) and gestational week was 7 (4-10). The average time since the caesarean section was 3.6 years (2-11). The management was methotrexate administration once, hysteroscopic resection once and 11times primarily vacuum aspiration only, when in two cases we had to attach laparoscopic uterine artery ligation due to postoperative bleeding. We performed primary ligature of uterine arteries twice before performing vacuum aspiration. In pregnancies above 10 weeks of gestation, we observed more bleeding complications requiring surgical management. Bleeding complications were also related to the presence of fetal cardiac action. CONCLUSION: Early correct dia-gnosis is essential in the management of CSP. Pregnancies up to the 10th week of gestation are managed by simple vacuum aspirations under ultrasound guidance. If the pregnancy is over the 10th week of gestation and especially with cardiac activity, we add laparoscopic uterine artery ligation before vacuum aspiration. All patients are subsequently advised to undergo laparoscopic resuturing of the lower uterine segment.

Finite element modeling of maximum stress in pelvic floor structures during the head expulsion (FINESSE) study.

INTRODUCTION AND HYPOTHESIS: Several studies have assessed birth-related deformations of the levator ani muscle (LAM) and perineum on models that depicted these elements in isolation. The main aim of this study was to develop a complex female pelvic floor computational model using the finite element method to evaluate points and timing of maximum stress at the LAM and perineum in relation to the birth process. METHODS: A three-dimensional computational model of the female pelvic floor was created and used to simulate vaginal birth based on data from previously described real-life MRI scans. We developed three models: model A (LAM without perineum); model B (perineum without LAM); model C (a combined model with both structures). RESULTS: The maximum stress in the LAM was achieved when the vertex was 9 cm below the ischial spines and measured 37.3 MPa in model A and 88.7 MPa in model C. The maximum stress in the perineum occurred at the time of distension by the suboocipito-frontal diameter and reached 86.7 MPa and 119.6 MPa in models B and C, respectively, while the stress in the posterior fourchette caused by the suboccipito-bregmatic diameter measured 36.9 MPa for model B and 39.8 MPa for model C. CONCLUSIONS: Including perineal structures in a computational birth model simulation affects the level of stress at the LAM. The maximum stress at the LAM and perineum seems to occur when the head is lower than previously anticipated.

Effect of Maternal and Fetal Characteristics in Feto-Placental Doppler and Impact of Using Adjusted Standards in the Definition of Fetal Growth Restriction at Term.

INTRODUCTION: This study aimed to determine the effect and clinical impact of physiological characteristics on the 95th/5th centile of the umbilical artery (UA) Doppler and the cerebroplacental ratio (CPR), at 36+ weeks. METHODS: From the multicenter randomized trial "Ratio37," we selected 4,505 low-risk pregnant women between June 2016 and January 2020. We registered physiological characteristics and the pulsatility indexes (PI) of the UA and middle cerebral artery (36-39 weeks). The 95th/5th centile of the UA PI and CPR was modeled by quantile regression. To evaluate the clinical impact of adjusting Doppler, we retrospectively applied gestational age (GA) and fully adjusted standards to 682 small for gestational age (SGA)-suspected fetuses (37 weeks) from a cohort of consecutive patients obtained between January 2010 and January 2020. RESULTS: Several physiological characteristics significantly influenced the 95th/5th centile of the UA and CPR PI. The fully adjusted 95th centile of the UA was higher, and the 5th centile of the CPR was lower than GA-only-adjusted standards. Of the 682 SGA fetuses, 150 (22%) were classified as late fetal growth restricted only by GA and 112 (16.4%) when we adjusted Doppler. These 38 fetuses had similar perinatal outcome than the SGA group. DISCUSSION: The 95th/5th centile of the UA and CPR PI is significantly influenced by physiological characteristics. Adjusting Doppler standards could differentiate better between FGR and SGA.

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 (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.

Persistent occiput posterior position and stress distribution in levator ani muscle during vaginal delivery computed by a finite element model.

INTRODUCTION AND HYPOTHESIS: Objective of this study was to develop an MRI-based finite element model and simulate a childbirth considering the fetal head position in a persistent occiput posterior position. METHODS: The model involves the pelvis, fetal head and soft tissues including the levator ani and obturator muscles simulated by the hyperelastic nonlinear Ogden material model. The uniaxial test was measured using pig samples of the levator to determine the material constants. Vaginal deliveries considering two positions of the fetal head were simulated: persistent occiput posterior position and uncomplicated occiput anterior position. The von Mises stress distribution was analyzed. RESULTS: The material constants of the hyperelastic Ogden model were measured for the samples of pig levator ani. The mean values of Ogden parameters were calculated as: µ1 = 8.2 ± 8.9 GPa; µ2 = 21.6 ± 17.3 GPa; α1 = 0.1803 ± 0.1299; α2 = 15.112 ± 3.1704. The results show the significant increase of the von Mises stress in the levator muscle for the case of a persistent occiput posterior position. For the optimal head position, the maximum stress was found in the anteromedial levator portion at station +8 (mean: 44.53 MPa). For the persistent occiput posterior position, the maximum was detected in the distal posteromedial levator portion at station +6 (mean: 120.28 MPa). CONCLUSIONS: The fetal head position during vaginal delivery significantly affects the stress distribution in the levator muscle. Considering the persistent occiput posterior position, the stress increases evenly 3.6 times compared with the optimal head position.

Effects of non-ablative Er:YAG laser on the skin and the vaginal wall: systematic review of the clinical and experimental literature.

INTRODUCTION AND HYPOTHESIS: Er:YAG laser is frequently used in dermatology and gynecology. Clinical studies document high satisfaction rates; however, hard data on the effects at the structural and molecular levels are limited. The aim of this systematic review was to summarize current knowledge about the objective effects of non-ablative Er:YAG laser on the skin and vaginal wall. METHODS: We searched MEDLINE, Embase, Cochrane, and the Web of Science. Studies investigating objectively measured effects of non-ablative Er:YAG laser on the skin or vaginal wall were included. Studies of any design were included. Owing to the lack of methodological uniformity, no meta-analysis could be performed and therefore results are presented as a narrative review. RESULTS: We identified in vitro or ex vivo studies on human cells or tissues, studies in rats, and clinical studies. Most studies were on the skin (n = 11); the rest were on the vagina (n = 4). The quality of studies is limited and the settings of the laser were very diverse. Although the methods used were not comparable, there were demonstrable effects in all studies. Immediately after application the increase in superficial temperature, partial preservation of epithelium and subepithelial extracellular matrix coagulation were documented. Later, an increase in epithelial thickness, inflammatory response, fibroblast proliferation, an increase in the amount of collagen, and vascularization were described. CONCLUSIONS: Er:YAG laser energy may induce changes in the deeper skin or vaginal wall, without causing unwanted epithelial ablation. Laser energy initiates a process of cell activation, production of extracellular matrix, and tissue remodeling.

Ultrasound cesarean scar assessment one year postpartum in relation to one- or two-layer uterine suture closure.

INTRODUCTION: This study compared healing of the scars after cesarean section during the first postpartum year using a single- or double-layer suturing technique. Scarring was assessed by a transvaginal ultrasound. We explored the appearance and localization of uterine scars with regard to the obstetric history. Our aim was to compare the position of the scar or defect, if present, its dimensions, and any residual myometrium with respect to the suturing technique during the cesarean section. MATERIAL AND METHODS: Women with uncomplicated singleton pregnancies indicated for elective or acute cesarean section were randomly allocated to the uterine closure technique group. During the first postpartum year, their lower uterine segment was examined with a transvaginal ultrasound in three consecutive visits at 6 weeks, 6 months and 12 months. RESULTS: 324 women attended the 12-month visit; of these, 149 underwent single-layer closure of the uterine incision and 175 double-layer technique. A higher proportion of the defects is seen in the single-layer closure technique of suturing. Defects in the single-layer group were wider (0.002) and the residual myometrial thickness in the single-layer group were thinner (0.019). Women who underwent cesarean section at the stage of full cervical dilation had scars that were closer to the external cervical os (0.000). The position of the uterus varies greatly between controls (0.000). The combination of uterine position and scar defect presence changed significantly between controls (0.001), and was significantly dependent on the suturing method (0.003). Defects with or without contact with the uterine cavity changed statistically between controls (0.017). Both types of defects were more common in the single-layer closure technique group. CONCLUSIONS: The findings of this study demonstrate that double-layer technique with the first continuous nonlocking suture followed by a second continuous nonlocking suture is associated with better suture healing and greater residual myometrial thickness. No difference was observed between single- and double-layer closure for the presence of maternal infectious morbidity, wound infection or blood transfusion.

Prescriptive Reference Standards of Third-Trimester Cerebroplacental Ratio and Its Physiological Determinants.

OBJECTIVE: To construct valid reference standards reflecting optimal cerebroplacental ratio and to explore its physiological determinants. METHODS: A cohort of 391 low-risk pregnancies of singleton pregnancies of nonmalformed fetuses without maternal medical conditions and with normal perinatal outcomes was created. Doppler measurements of the middle cerebral artery and umbilical artery were performed at 24-42 weeks. Reference standards were produced, and the influence of physiological determinants was explored by nonparametric quantile regression. The derived standards were validated in a cohort of 200 low-risk pregnancies. RESULTS: Maternal body mass index was significantly associated with the 5th centile of the cerebroplacental ratio. For each additional unit of body mass index, the 5th centile was on average 0.014 lower. The derived 5th, 10th, and 50th centiles selected in the validation cohort were 5, 9.5, and 51% of the measurements. CONCLUSIONS: This study provides methodologically sound prescriptive standards and suggests that maternal body mass index is a determinant of a cutoff commonly used for decision-making.