Maternal and fetal outcomes after planned cesarean or vaginal delivery in twin pregnancy: a comparison between 2 third level birth centers.

BACKGROUND: Twin pregnancy is associated with higher risks of adverse perinatal outcomes for both the mother and the babies. Among the many challenges in the follow-up of twin pregnancies, the mode of delivery is the last but not the least decision to be made, with the main influencing factors being amnionicity and fetal presentation. The aim of the study was to compare perinatal outcomes in two European centers using different protocols for twin birth in case of non-cephalic second twin; the Italian patients being delivered mainly by cesarean section with those in Belgium being routinely offered the choice of vaginal delivery (VD). METHODS: This was a dual center international retrospective observational study. The population included 843 women with a twin pregnancy ≥ 32 weeks (dichorionic or monochorionic diamniotic pregnancies) and a known pregnancy outcome. The population was stratified according to chorionicity. Demographic and pregnancy data were reported per pregnancy, whereas neonatal outcomes were reported per fetus. We used multiple logistic regression models to adjust for possible confounding variables and to compute the adjusted odds ratio (adjOR) for each maternal or neonatal outcome. RESULTS: The observed rate of cesarean delivery was significantly higher in the Italian cohort: 85% for dichorionic pregnancies and 94.4% for the monochorionic vs 45.2% and 54.4% respectively in the Belgian center (p-value < 0.001). We found that Belgian cohort showed significantly higher rates of NICU admission, respiratory distress at birth and Apgar score of < 7 after 5 min. Despite these differences, the composite severe adverse outcome was similar between the two groups. CONCLUSION: In this study, neither the presentation of the second twin nor the chorionicity affected maternal and severe neonatal outcomes, regardless of the mode of delivery in two tertiary care centers, but VD was associated to a poorer short-term neonatal outcome.

Effects of SARS-Cov-2 mRNA vaccine on placental histopathology: Comparison of a population of uncomplicated COVID-19 positive pregnant women.

1. INTRODUCTION: This study investigates the impact of SARS-CoV-2 infection on placental histopathology in pregnant women, comparing outcomes between vaccinated and non-vaccinated individuals. Despite known adverse pregnancy outcomes linked to SARS-CoV-2 infection, the specific effects on the placenta remain unclear. Although vaccination has demonstrated a substantial reduction in infection severity, its impact on placental health requires more insight. 2. METHODS: Between March 2021 and July 2022, 387 COVID-19-positive women were admitted for delivery. Of these, 98 with non-severe symptoms were analyzed: 35 vaccinated during pregnancy, and 63 non-vaccinated. Two independent pathologists evaluated all placental specimens. 3. RESULTS: The only differing obstetrical characteristic between groups was the mode of delivery (p 0.047), lacking clinical implications. Over 85% of placentas exhibited microscopic abnormalities, predominantly maternal vascular supply disorders (vaccinated 89.1%; unvaccinated 85.5%). Comparing vaccinated and unvaccinated groups revealed statistically significant differences, notably in increased focal perivillous fibrin deposits (IFPFD) [17.1% vs. 33.3% (p 0.04)] and avascular fibrotic villi (AFV) [0% vs. 11.1% (p 0.04)]. Binomial logistic regression confirmed the vaccine's protective role against IFPFD (aOR 0.36; 95%CI 013-0.99) and AVF (aOR 0.06, 95% CI 0.003-0.98). A sub-analysis in vaccinated women showed a positive correlation between the timing of the first dose and IFPFD presence (p 0.018). 4. DISCUSSION: The lower incidence of maternal and fetal vascular malperfusion placental features in vaccinated women, coupled with the timing correlation, supports the vaccine's protective effect on placental tissue in COVID-19-infected pregnant patients. Notably, no side effects were reported post-vaccination, emphasizing the vaccine's safety and advocating for its secure administration in pregnant populations.

Is the mental health of couples with twins more at risk? Results from an Italian cohort study.

Introduction: Our retrospective study aimed to investigate whether parents of twins encounter heightened psychological and emotional distress one year after childbirth, in comparison to parents of singletons within an Italian cohort. Methods: Exclusion criteria included multiparity, preterm birth, congenital anomalies, stillbirth, >2 fetus pregnancies, and pre-existing maternal mental health disorders. Out of the 300 couples (600 parents) invited to participate, 286 parents (158 mothers, 128 fathers) successfully completed a self-administered survey. We analyzed three scores separately for mothers and fathers, differentiating between singleton and twin pregnancies: the Edinburgh Postnatal Depression Scale (EPDS) score, the State and Trait Anxiety Inventory (STAI)-Y1 score, and the STAI-Y2 score. Results: Logistic models were used to assess the influence of age, BMI, marital status, education, and employment on the three binary scores (EPDS, STAI-Y1, and STAI-Y2), revealing no significant differences in absolute scores between parents of singletons and twins. Paired analysis revealed significantly higher EPDS (mean increase: 3.8, SD: 6.5), STAI-Y1 (mean increase: 5.4, SD: 12.5), and STAI-Y2 (mean increase: 4.5, SD: 12.4) scores for mothers (p < 0.0001). Approximately 10% of women and 8% of men reported suicidal thoughts. Discussion: Contrary to expectations, no substantial psychological differences emerged between parents of twins and singletons. Adjusting for confounders through univariate analysis maintained nonsignificant trends. Nevertheless, caution in interpretation is warranted due to strict inclusion criteria favoring twin pregnancies with better outcomes. Unintended bias could have resulted from routine psychological support offered to mothers of twins in our clinic. This presents an important framework for future research, including randomized controlled trials comparing parents of multiples with psychological support to those without.Finally, the elevated prevalence of depression symptoms and suicidal thoughts in our cohort underscores the importance of mental health during pregnancy and early parenting. We advocate for the screening of parents for postpartum depression and various psychological conditions, encompassing a spectrum of anxiety disorders. Those at elevated risk of mental distress should be proactively offered appropriate support.

The impact of placental anastomoses and umbilical cord insertions' sites on monochorionic twin pregnancy outcomes: Evidence from color-dye injection studies.

INTRODUCTION: Our knowledge of monochorionic pregnancies' complications is largely based on the extensive ongoing research on monochorionic placental structure. Previous studies on the concordance of umbilical cord insertions are limited. This study aimed to evaluate placental anastomoses and cord insertions as independent risk factors for neonatal adverse outcomes. METHODS: This was a prospective study conducted at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy from April 2021 to December 2022. Seventy-six women with a monochorionic pregnancy were enrolled at their first-trimester scan. After delivery, all placentas that were confirmed to be monochorionic were analyzed according to standard protocols, including those of complicated monochorionic twin pregnancies. The primary outcomes were a Composite Monochorionic Pregnancy Outcome (CMPO) and a Composite Neonatal Adverse Outcome (CNAO). The secondary outcome was the birth weight discordance between the neonates. RESULTS: The CMPO occurred in 15.8 % pregnancies, and the CNAO occurred in 67.1 % pregnancies. The analysis confirmed a significant association between velamentous cord insertions and neonatal adverse events (p = 0.003). Also, a significant positive association (p = 0.0326) between twin birth weight discordance and discordance in twins umbilical cord insertions' sites was found. No significant association between the number and type of the anastomoses and both the CMPO or CNAO was detected. DISCUSSION: Our data suggest that the routine sonographic assessment of umbilical cords' insertion sites during the first trimester could be helpful in predicting fetal and neonatal adverse events. We believe that this sonographic assessment should start to be implemented in our routine care of monochorionic pregnancies.

Risk factors associated with severe perineal lacerations during vaginal delivery: a 10-year propensity score-matched observational study.

BACKGROUND: Severe perineal lacerations are rare obstetrical complications in high-income countries. However, the prevention of obstetric anal sphincter injuries is crucial because of their long-term consequences on a woman's digestive function, sexual-mental health, and well-being. The probability of obstetric anal sphincter injuries can be predicted by assessing antenatal and intrapartum risk factors. OBJECTIVE: This study aimed to assess the incidence of obstetric anal sphincter injuries at a single institution for 10 years and to identify women more at risk by evaluating the relationship between antenatal and intrapartum risk factors and severe perineal tears. The main outcome measured in this study was the occurrence of obstetric anal sphincter injuries during vaginal delivery. STUDY DESIGN: This was an observational retrospective cohort study conducted at a University Teaching Hospital in Italy. The study was conducted from 2009 to 2019 using a prospectively maintained database. The study cohort included all women with singleton pregnancy at term who delivered via vaginal delivery in cephalic presentation. Of note, data analysis was performed in 2 stages: a propensity score matching to balance possible differences between patients with obstetric anal sphincter injuries and those without and a stepwise univariate and multivariate logistic regression. A secondary analysis was performed to further evaluate the effect of parity, epidural anesthesia, and duration of the second stage of labor by adjusting for potential confounders. RESULTS: Of 41,440 patients screened for eligibility, 22,156 met the inclusion criteria, and 15,992 were balanced after propensity score matching. Obstetric anal sphincter injuries occurred in 81 cases (0.4%), 67 (0.3%) after spontaneous delivery and 14 (0.8%) after vacuum delivery(P=.002). There was an increased odds of severe lacerations of nearly 2-fold for nulliparous women delivering by vacuum delivery (adjusted odds ratio, 2.85; 95% confidence interval, 1.19-6.81; P=.019), with a reciprocal reduction in women with spontaneous vaginal delivery (adjusted odds ratio, 0.35; 95% confidence interval, 0.15-0.84; P=.019) and at least 1 previous delivery (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.85; P=.005). Epidural anesthesia was associated with a lower incidence of obstetric anal sphincter injuries (adjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86; P=.011). The risk of severe lacerations was independent of the duration of the second stage of labor (adjusted odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P=.3), whereas the risk was reduced when mediolateral episiotomy was performed (adjusted odds ratio, 0.20; 95% confidence interval, 0.11-0.36; P<.001). Neonatal risk factors include head circumference (odds ratio, 1.50; 95% confidence interval, 1.18-1.90; P=.001) and vertex malpresentation (adjusted odds ratio, 2.71; 95% confidence interval, 1.08-6.78; P=.033). Induction of labor (adjusted odds ratio, 1.13; 95% confidence interval, 0.72-1.92; P=.6), frequent obstetrical examinations (adjusted odds ratio, 1.17; 95% confidence interval, 0.72-1.90), and women's supine position at birth (adjusted odds ratio, 1.25; 95% confidence interval, 0.61-2.55; P=.5) were further evaluated. Among severe obstetrical complications, shoulder dystocia increased the risk of obstetric anal sphincter injuries by nearly 4 times (adjusted odds ratio, 3.92; 95% confidence interval, 0.50-30.74; P=.2), whereas postpartum hemorrhage occurred 3 times more often in cases of delivery complicated by severe lacerations (adjusted odds ratio, 3.35; 95% confidence interval, 1.76-6.40; P<.001). The relationship among obstetric anal sphincter injuries, parity, and the use of epidural anesthesia was further confirmed in a secondary analysis. We found that primiparas who delivered without epidural anesthesia had the highest risk of obstetric anal sphincter injuries (adjusted odds ratio, 2.53; 95% confidence interval, 1.46-4.39; P=.001). CONCLUSION: Severe perineal lacerations were found to be a rare complication of vaginal delivery. By using a robust statistical model, such as propensity score matching, we were able to investigate a broad range of antenatal and intrapartum risk factors, including use of epidural anesthesia, number of obstetrics examinations, and patient position at birth, which are usually underreported. Moreover, we found that women who delivered for the first time without epidural anesthesia had the highest risk of obstetric anal sphincter injuries.

Multiple Pregnancy and the Risk of Postpartum Hemorrhage: Retrospective Analysis in a Tertiary Level Center of Care.

The aim of our study was to identify characteristics associated with postpartum hemorrhage (PPH defined as blood loss >1000 mL) in twin pregnancies in order to select patients at higher risk to be treated. This retrospective study includes multiple pregnancies between 2015 and 2020. The possible association between pregnancy characteristics and the primary endpoint (occurrence of PPH) was conducted using chi-square or Fisher exact test and Wilcoxon test. Then, univariate logistic models were performed considering as outcome the PPH, and the odds ratios with 95% CI were estimated. Finally, a multivariate logistic model was implemented, including all significant covariates. Seven hundred seven twin pregnancies giving birth beyond 32 weeks were included and of those, 120 (16.97%) had a PPH. The univariate analysis showed that factors significantly associated with PPH were: Preterm delivery, episiotomy, neonatal weight, and mode of delivery. The multivariate analysis showed that the most important factors were episiotomy and neonatal weight. The results show that the performance of episiotomy and the neonatal weight are the factors that most impact the risk of PPH in twin pregnancies. The correct identification of factors associated with PPH in twins could ideally allow to modify the clinical management and positively affect the rate of complications.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Pregnancy outcomes in breech presentation at term: a comparison between 2 third level birth center protocols.

BACKGROUND: Medical literature supports planned cesarean delivery for breech presentation at term because of observed reductions in neonatal morbidity and mortality compared with vaginal breech delivery. OBJECTIVE: This study aimed to compare perinatal outcomes of singleton pregnancies with breech presentation at term according to the different delivery protocols of 2 teaching hospitals, where vaginal breech delivery (protocol 1) or cesarean delivery (protocol 2) is routinely offered, respectively. STUDY DESIGN: A retrospective matched cohort study was conducted between January 2015 and May 2021. A total of 1079 women were eligible for analysis. After matching for possible confounding factors, the final analysis was performed on 257 patients in each group. The primary outcomes were a composite of adverse obstetrical outcomes and a composite of neonatal adverse outcomes. RESULTS: Overall, 1079 women were eligible for analysis. After matching for possible confounding factors, the final analysis was performed on 257 patients in each group. The composite of adverse obstetrical outcomes was similar in the 2 groups (24.1% vs 24.5%; P=1.000); however, the composite of neonatal adverse outcomes was significantly higher for protocol 1 (17.9% vs 1.2%; P<.001). No neonatal death or birth trauma was reported in either group. The rates of neonatal intensive care unit admission (4.3% vs 0.4%; P=.004), respiratory distress at birth (17.5% vs 1.2%; P<.001), and Apgar scores of <7 after 5 minutes (5.8% vs 0.4%; P<.001) were significantly higher for protocol 1. CONCLUSION: Short-term, nonsevere adverse neonatal outcomes were significantly increased in the protocol 1 group. These must be balanced against the possible negative effects of cesarean delivery on long-term infant and maternal health.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Case Report: Challenges of Non-Invasive Prenatal Testing (NIPT): A Case Report of Confined Placental Mosaicism and Clinical Considerations.

Since the introduction of cell-free (cf) DNA analysis, Non-Invasive Prenatal Testing (NIPT) underwent a deep revolution. Pregnancies at high risk for common fetal aneuploidies can now be easily identified through the analysis of chromosome-derived components found in maternal circulation, with the highest sensitivity and specificity currently available. Consequently, the last decade has witnessed a widespread growth in cfDNA-based NIPT use, enough to be often considered an alternative method to other screening modalities. Nevertheless, the use of NIPT in clinical practice is still not devoid of discordant results. Hereby, we report a case of confined placental mosaicism (CPM) in which a NIPT false-positive result for trisomy 13 required not only amniocentesis but also cordocentesis, to rule out the fetal aneuploidy, with the additional support of molecular cytogenetics on placental DNA at delivery. Relevant aspects allowing for precision genetic diagnosis and counselling, including the number of analysed metaphases on the different fetal cells compartments and a repeated multidisciplinary evaluation, are discussed.

Tissue engineered in-vitro vascular patch fabrication using hybrid 3D printing and electrospinning.

Three-dimensional (3D) engineered cardiovascular tissues have shown great promise to replace damaged structures. Specifically, tissue engineering vascular grafts (TEVG) have the potential to replace biological and synthetic grafts. We aimed to design an in-vitro patient-specific patch based on a hybrid 3D print combined with vascular smooth muscle cells (VSMC) differentiation. Based on the medical images of a 2 months-old girl with aortic arch hypoplasia and using computational modelling, we evaluated the most hemodynamically efficient aortic patch surgical repair. Using the designed 3D patch geometry, the scaffold was printed using a hybrid fused deposition modelling (FDM) and electrospinning techniques. The scaffold was seeded with multipotent mesenchymal stem cells (MSC) for later maturation to derived VSMC (dVSMC). The graft showed adequate resistance to physiological aortic pressure (burst pressure 101 â€‹± â€‹15 â€‹mmHg) and a porosity gradient ranging from 80 to 10 â€‹µm allowing cells to infiltrate through the entire thickness of the patch. The bio-scaffolds showed good cell viability at days 4 and 12 and adequate functional vasoactive response to endothelin-1. In summary, we have shown that our method of generating patient-specific patch shows adequate hemodynamic profile, mechanical properties, dVSMC infiltration, viability and functionality. This innovative 3D biotechnology has the potential for broad application in regenerative medicine and potentially in heart disease prevention.

Predicted Value of MicroRNAs, Vascular Endothelial Growth Factor, and Intermediate Monocytes in the Left Adverse Ventricular Remodeling in Revascularized ST-Segment Elevation Myocardial Infarction Patients.

Background: Primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) improves the survival of patients; nevertheless, some patients develop left ventricular adverse remodeling (LVAR) a few months after the intervention. The main objective of this study was to characterize the role of pro-inflammatory cell populations, related cytokines, and microRNAs (miRNAs) released after PPCI as reliable prognostic biomarkers for LVAR in patients with STEMI. Methods: We evaluated the level of pro-inflammatory subsets, before and after revascularization, 1 and 6 months after PPCI, using flow cytometry. We also performed a miRNA microarray in isolated peripheral blood mononuclear cells (PBMCs) and examined the levels of 27 cytokines in patients' serum of patients by multiplex ELISA. Results: We observed that the levels of classical and intermediate monocytes increased 6 h after PPCI in patients who developed LVAR later. Multivariate regression analysis and ROC curves indicated that intermediate monocytes, after PPCI, were the best monocyte subset that correlated with LVAR. Within the 27 evaluated cytokines evaluated, we found that the increase in the level of vascular endothelial growth factor (VEGF) correlated with LVAR. Furthermore, the microarray analysis of PBMCs determined that up to 1,209 miRNAs were differentially expressed 6 h after PPCI in LVAR patients, compared with those who did not develop LVAR. Using RT-qPCR we confirmed a significant increase in miR-16, miR-21-5p, and miR-29a-3p, suggested to modulate the expression of different cytokines, 6 h post-PPCI in LVAR patients. Interestingly, we determined that the combined analysis of the levels of the intermediate monocyte subpopulation, VEGF, and miRNAs gave a better association with LVAR appearance. Similarly, combined ROC analysis provided high accurate specificity and sensibility to identify STEMI patients who will develop LVAR. Conclusion: Our data suggest that the combined analysis of intermediate monocytes, VEGF, and miRNAs predicts LVAR in STEMI patients.

Evaluation of the new expert consensus-based definition of selective fetal growth restriction in monochorionic pregnancies.

OBJECTIVE: To compare the outcomes of a cohort of monochorionic pregnancies with selective fetal growth restriction (sFGR) diagnosed according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) definition published in 2015 with a cohort considered as sFGR according to new expert consensus-based diagnostic parameters published in 2019. METHODS: This was a retrospective study, conducted between January 1st 2010 and July 30th 2019. We reviewed the medical records of all the monochorionic pregnancies followed in our center including perinatal outcomes. Pregnancies complicated by fetal anomalies, infection, twin-twin transfusion syndrome, twin anaemia-polycythemia sequence and twin reversed arterial perfusion sequence were excluded. Patients were grouped according to the 2015 ISUOG definition into: normal (Group 1), sFGR (Group 2), and monochorionic pregnancies with abnormal growth that did not fulfill the full criteria for sFGR (Group 3). After the initial classifications were made, an additional group, was created, including all pregnancies reclassified as sFGR according to the 2019 expert consensus parameters (Group 4). RESULTS: During the study period, 291 monochorionic pregnancies were followed in our center, 132 of whom were eligible for inclusion in the final analysis. The prevalence of sFGR increased from 17.4% to 26.5% after applying the expert consensus-based parameters to the study population. Compared to group 1, group 2 had higher rates of emergency cesarean, neonatal intensive care admissions, invasive and noninvasive ventilation, surfactant use, metabolic disorders and lower gestational ages at birth. In contrast, the neonatal outcomes of Groups 1 and 4 were not significantly different. CONCLUSION: When the 2019 consensus-based diagnostic parameters for sFGR were applied to our study population, the number of sFGR cases increased by over 50%, without any improvements in perinatal outcomes. Larger prospective studies are needed to examine the potential clinical implications of these new parameters for sFGR in monochorionic pregnancies.

Prenatal prediction of postnatal survival in fetuses with congenital diaphragmatic hernia using MRI: lung volume measurement, signal intensity ratio, and effect of experience.

OBJECTIVE: To evaluate various signal intensity ratios in isolated congenital diaphragmatic hernia (CDH) and to compare their potential in predicting survival with that of the observed-to-expected (O/E) ratio of total fetal lung volume (TFLV) using magnetic resonance imaging (MRI) measurements. Our second objective was to evaluate the impact of operator's experience in comparing the prediction of postnatal survival by O/E-TFLV. METHODS: In 75 conservatively managed CDH fetuses and in 50 who underwent fetoscopic endoluminal tracheal occlusion (FETO), the fetal lung-to-amniotic fluid, lung-to-liver, lung-to-muscle, lung-to-spinal fluid signal intensity ratios, respectively LAFSIR, LLSIR, LMSIR, and LSFSIR, were measured, as was O/E-TFLV. Receiver operating characteristic (ROC) curves were constructed and used to compare the various signal intensity ratios with O/E-TFLV in the prediction of postnatal survival. In 72 MRI lung volumes assessed by the referring radiologists in Paris and Lille and secondarily by our expert radiologist in Brussels (M.M.C.) using the same MRI examinations, ROC curves were constructed and used to compare the value of O/E-TFLV determined by the two centers in the prediction of postnatal survival. RESULTS: In the total cohort of CDH fetuses, O/E-TFLV and LLSIR were predictive of postnatal survival whereas in the conservatively managed group O/E-TFLV, LLSIR, and LMSIR predicted postnatal survival. O/E-TFLV predicted postnatal survival far better than the signal intensity ratios: area under the ROC curve for prediction by O/E-TFLV in the total cohort was 0.866 (p < .001; standard error = 0.031). The area under the ROC curve for prediction of postnatal survival using O/E-TFLV by MRI evaluated at the referral centers was 0.640 (p = 102; standard error = 0.085), and with O/E-TFLV reevaluated by M.M.C., it was 0.872 (p < .001; standard error = 0.061). Pairwise comparison showed a significant difference between the areas under the ROC curves (difference = 0.187, p = .012; standard error = 0.075). CONCLUSION: In fetuses with CDH with/without FETO, LLSIR was significantly correlated with the prediction of postnatal survival. However, measurement of O/E-TFLV was far better in predicting postnatal outcome. Operator experience in measurement of lung volumes using MRI seem to play a role in the predictive value of the technique.

Fetal magnetic resonance imaging at 36 weeks predicts neonatal macrosomia: the PREMACRO study.

BACKGROUND: Large-for-gestational-age fetuses are at increased risk of perinatal morbidity and mortality. Magnetic resonance imaging seems to be more accurate than ultrasound in the prediction of macrosomia; however, there is no well-powered study comparing magnetic resonance imaging with ultrasound in routine pregnancies. OBJECTIVE: This study aimed to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound and magnetic resonance imaging with actual birthweights in routine pregnancies. STUDY DESIGN: From May 2016 to February 2019, women received counseling at the 36-week clinic. Written informed consent was obtained for this Ethics Committee-approved study. In this prospective, single-center, blinded study, pregnant women with singleton pregnancies between 36 0/7 and 36 6/7 weeks' gestation underwent both standard evaluation of estimated fetal weight with ultrasound according to Hadlock et al and magnetic resonance imaging according to the formula developed by Baker et al, based on the measurement of the fetal body volume. Participants and clinicians were aware of the results of the ultrasound but blinded to the magnetic resonance imaging estimates. Birthweight percentile was considered as the gold standard for the ultrasound and magnetic resonance imaging-derived percentiles. The primary outcome was the area under the receiver operating characteristic curve for the prediction of large-for-gestation-age neonates with birthweights of ≥95th percentile. Secondary outcomes included the comparative prediction of large-for-gestation-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles for gestational age and maternal and perinatal complications. RESULTS: Of 2914 women who were initially approached, results from 2378 were available for analysis. Total fetal body volume measurements were possible for all fetuses, and the time required to perform the planimetric measurements by magnetic resonance imaging was 3.0 minutes (range, 1.3-5.6). The area under the receiver operating characteristic curve for the prediction of a birthweight of ≥95th percentile was 0.985 using prenatal magnetic resonance imaging and 0.900 using ultrasound (difference=0.085, P<.001; standard error, 0.020). For a fixed false-positive rate of 5%, magnetic resonance imaging for the estimation of fetal weight detected 80.0% (71.1-87.2) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 59.1% (49.0-68.5) of birthweight of ≥95th percentile. The positive predictive value was 42.6% (37.8-47.7) for the estimation of fetal weight using magnetic resonance imaging and 35.4% (30.1-41.1) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.0% (98.6-99.3) for the estimation of fetal weight using magnetic resonance imaging and 98.0% (97.6-98.4) for the estimation of fetal weight using ultrasound. For a fixed false-positive rate of 10%, magnetic resonance imaging for the estimation of fetal weight detected 92.4% (85.5-96.7) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 76.2% (66.9-84.0) of birthweight of ≥95th percentile. The positive predictive value was 29.9% (27.2-32.8) for the estimation of fetal weight using magnetic resonance imaging and 26.2% (23.2-29.4) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.6 (99.2-99.8) for the estimation of fetal weight using magnetic resonance imaging and 98.8 (98.4-99.2) for the estimation of fetal weight using ultrasound. The area under the receiver operating characteristic curves for the prediction of large-for-gestational-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles was significantly larger in prenatal magnetic resonance imaging than in ultrasound (P<.05 for all). CONCLUSION: At 36 weeks' gestation, magnetic resonance imaging for the estimation of fetal weight performed significantly better than ultrasound for the estimation of fetal weight in the prediction of large-for-gestational-age neonates with birthweights of ≥95th percentile for gestational age and all other recognized cutoffs for large-for-gestational-age and small-for-gestational-age neonates (P<.05 for all).

Severe Acute Respiratory Syndrome Coronavirus 2 and Pregnancy Outcomes According to Gestational Age at Time of Infection.

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible.

Antenatal management and neonatal outcomes of monochorionic twin pregnancies in a tertiary teaching hospital: a 10-year review.

Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-to-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. In the current retrospective study, we determined the incidence of MC pregnancy complications in a tertiary care centre during a 10-year period. Single foetal death (FD) beyond 14 weeks' gestation was significantly higher when complicated by either TTTS, TAPS or selective foetal growth restriction (21.4%, 16.7% and 9.1% versus 1.6%, p<.001, p=.02 and p=.04, respectively). We also demonstrated that twins' weight discordance >20% is an independent risk factor for single or double FD after LPC. Consequently, prior to LPC, patients should be counselled that early diagnosis of TTTS, advanced Quintero stages and weight discordances >20% are potential risk factors for FD. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.Impact StatementWhat is already known on this subject? Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications.What the results of this study add? The results of the current study determined the incidence of MC pregnancy complications in a tertiary care centre in Brussels, and identified that twins' weight discordance >20% is an independent risk factor for single or double foetal death after LPC.What the implications are of these findings for clinical practice and/or further research? Prior to laser coagulation, patients should be counselled that early diagnosis of TTTS, Quintero stages 3 or 4 and weight discordances >20% are potential risk factors for foetal demise. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.

Impact of the delay between fetal death and delivery on the success of postmortem ultrasound following termination of pregnancy.

OBJECTIVE: To evaluate the impact of the delay between fetal death and delivery on the nondiagnostic rates of post-mortem ultrasound (PM-US), following the termination of pregnancy (TOP). METHODS: We reviewed 204 cases of fetal two-dimensional PM-US performed in our center as part of a post-mortem imaging research program, over the last 5 years. Informed consent was obtained from the parents for all cases. PM-US was performed and reported according to a prespecified template with operators blinded to the prenatal diagnosis. In order to calculate the precise delay between the fetal death and the delivery, we included 107 fetal TOP's ≥ 20 weeks of gestational age (GA), where feticide was performed using an injection of lidocaine 2% prior to induction of labor. Logistic regression analysis was conducted to analyze the impact of delay between fetal death and delivery (in hours), the GA at TOP (in weeks) and the method of feticide (intracardiac versus intraumbilical injection) on the PMUS nondiagnostic rates. RESULTS: The delay between fetal death and delivery increased the nondiagnostic rate of PM-US for cerebral examinations (OR: 1.04, IC 95%: 1.01-1.08, p < .05). For PM-US cardiac examination, the delay did not influence the nondiagnostic rate. However, GA (OR: 1.25, IC 95%: 1.10-1.46, p < .01) and feticide with intracardiac injection (OR: 4.29, IC 95%: 1.68-12.02, p < .01) were associated with higher nondiagnostic rates. For noncardiac thoracic and abdominal examinations, none of the studied variables influenced the nondiagnostic rate. CONCLUSION: The success rate of cerebral PM-US was influenced by the delay between fetal death and delivery, suggesting a possible advantage of performing the feticide closer to the delivery where the examination of the brain is planned. For cardiac abnormalities, feticide by intraumbilical, rather than intracardiac injection improves diagnostic rates of cardiac PM-US.