Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

The prognostic role of CRL discordance in first trimester ultrasound.

OBJECTIVES: In the first trimester, intertwin crown-rump length (CRL) discordance has emerged as a notable factor linked to adverse perinatal health effects. It is frequently employed as a basis for counseling parents regarding potential adverse pregnancy outcomes. Despite its established association with adverse outcomes, the significance of CRL discordance in substantially predicting pregnancy problems and its efficacy in pregnancy screening remain subjects of ongoing discussion. The aim of this manuscript is to present current knowledge on CRL discordance. METHODS: PubMed was searched for related articles with terms "Crown-Rump length", "Prenatal Screening", "Twin pregnancy", "Discordance". RESULTS: Twenty-two studies were included in our study with six reporting data on monochorionic and 16 assessing the correlation between CRL discordance and adverse pregnancy outcomes. Fetal loss at the 20th and 24th week of the pregnancy, SGA neonates, pre-term delivery (32 weeks), perinatal death (24 weeks) are all reported adverse outcomes associated with CRL discordance. The reported cut-off for increased risk of adverse perinatal outcomes is a discordance of at least 10% or more. CONCLUSIONS: Increased CRL (>10 %) discordance is linked to a higher risk of sFGR in both monochorionic and dichorionic pregnancies, fetal loss, and preterm delivery.

Effect of acidic vaginal pH on the efficacy of dinoprostone (PGE2) vaginal tablet for labor induction in full term pregnant women: a randomized controlled trial.

OBJECTIVES: There is controversial evidence that acidification of vaginal pH may increase the efficacy of vaginal prostaglandins in labor induction, with research being mainly focused on misoprostol. This study aims to evaluate the impact of this intervention on the progress of labor induction with dinoprostone (PGE2) vaginal tablet. METHODS: This double-blind, parallel-group, randomized study was conducted between October 2021 and December 2022 at Alexandra General Hospital, Athens, Greece. A total of 230 women with singleton, full term pregnancy that were scheduled for labor induction were randomly divided into two groups: Group A, who received acidic vaginal wash (5 % acetic acid) and Group B, who received a normal saline vaginal wash. Afterwards, participants received a vaginal tablet of 3 mg dinoprostone every 6 h (maximum two doses). RESULTS: There were no statistically significant differences in mode of delivery, duration of different labor stages, Bishop score changes and possible complications. Participants in the acidification group needed less often labor augmentation with oxytocin and epidural anesthesia (p=0.03). CONCLUSIONS: Vaginal acidification seems to have no effect on the efficacy of the dinoprostone vaginal tablet. Even though it may reduce the need for oxytocin augmentation, there is no apparent benefit on clinical outcomes, such as reduction in cesarean section rates or shorter labor duration. Future research is necessary in order to validate these findings.

Cracking the Code: Investigating the Correlation between Aerobic Vaginitis and Preterm Labor.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which has a range of 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. An improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Efficacy and safety of oral and sublingual versus vaginal misoprostol for induction of labour: a systematic review and meta-analysis.

OBJECTIVE: Misoprostol is a synthetic PGE1 analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit maternal and neonatal adverse outcomes. The present meta-analysis investigates the efficacy and safety of oral compared to vaginally inserted misoprostol in terms of induction of labor and adverse peripartum outcomes. METHODS: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases from inception till April 2022. Randomized controlled trials that assessed the efficacy of oral misoprostol (per os or sublingual) compared to vaginally inserted misoprostol. Effect sizes were calculated in R. Sensitivity analysis was performed to evaluate the possibility of small study effects, p-hacking. Meta-regression and subgroup analysis according to the dose of misoprostol was also investigated. The methodological quality of the included studies was assessed by two independent reviewers using the risk of bias 2 tool. Quality of evidence for primary outcomes was evaluated under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, ranging from very low to high. RESULTS: Overall, 57 studies were included that involved 10,975 parturient. Their risk of bias ranged between low-moderate. There were no differences among the routes of intake in terms of successful vaginal delivery within 24 h (RR 0.90, 95% CI 0.80) and cesarean section rates (RR 0.92, 95% CI 0.82, 1.04). Sublingual misoprostol was superior compared to vaginal misoprostol in reducing the interval from induction to delivery (MD - 1.11 h, 95% CI - 2.06, - 0.17). On the other hand, per os misoprostol was inferior compared to vaginal misoprostol in terms of this outcome (MD 3.45 h, 95% CI 1.85, 5.06). Maternal and neonatal morbidity was not affected by the route or dose of misoprostol. CONCLUSION: The findings of our study suggest that oral misoprostol intake is equally safe to vaginal misoprostol in terms of inducing labor at term. Sublingual intake seems to outperform the per os and vaginal routes without increasing the accompanying morbidity. Increasing the dose of misoprostol does not seem to increase its efficacy. CLINICAL TRIAL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/V9JHF ).

The role of the PLGF in the prediction of the outcome in pregnancies with a small for gestational age fetus.

PURPOSE: To explore the value of measuring maternal serum PLGF in the prediction of the outcome of small for gestational age fetuses (SGA). METHODS: Singleton pregnancies referred with suspicion of SGA in the third trimester were included if they had: no indication for nor signs of imminent delivery, fetal abdominal circumference (AC) at or below the 10th centile and/or estimated fetal weight (EFW) at or below the 10th centile and/or umbilical artery pulsatility index (Umb-PI) at or above the 90th centile for gestation. Women with pre-eclampsia at presentation were excluded. Maternal blood was drawn at the first (index) visit and analyzed retrospectively. RESULTS: Fifty-one fetuses were examined. Multiple regression analysis showed that family history of microsomia, index EFW and PLGF were significant predictors of the birthweight centile; index femur length centile and PLGF were significant predictors of pre-eclampsia; PLGF and index systolic blood pressure were significant predictors of iatrogenic preterm delivery < 37 weeks, whereas PLGF and index EFW were significant predictors of birthweight ≤ 5th centile and admission to the neonatal intensive care unit. For all outcomes, the addition of maternal-fetal parameters did not improve the prediction compared to PLGF alone. Using a cutoff of 0.3 MoM for PLGF would identify 94.1% of the pregnancies with iatrogenic preterm delivery and/or intra-uterine death and all of the cases that developed pre-eclampsia, for a screen positive rate of 54.9%. Women with PLGF ≤ 0.3 MoM had a poor fetal/maternal outcome (iatrogenic preterm delivery, pre-eclampsia, intra-uterine death) in 61.5% of cases. CONCLUSION: In pregnancies complicated by SGA, PLGF identifies a very high-risk group that may benefit from intense surveillance.

Intrauterine Growth Restriction Due to Gestational Diabetes: From Pathophysiology to Diagnosis and Management.

Intrauterine growth restriction (IUGR) represents a condition where the fetal weight is less than the 10th percentile for gestational age, or the estimated fetal weight is lower than expected based on gestational age. IUGR can be caused by various factors such as maternal, placental or fetal factors and can lead to various complications for both the fetus and the mother, including fetal distress, stillbirth, preterm delivery, and maternal hypertension. Women with gestational diabetes are at an increased risk of developing IUGR. This article reviews the different aspects of gestational diabetes in addition to IUGR, the diagnostic methods available for IUGR detection, including ultrasound and Doppler studies, discusses the management strategies for women with IUGR and gestational diabetes and analyzes the importance of early detection and timely intervention to improve pregnancy outcomes.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

Healthcare workers' attitudes about vaccination of pregnant women and those wishing to become pregnant.

OBJECTIVES: We designed an electronic query that was distributed to healthcare workers in order to evaluate their attitudes towards COVID-19 vaccination of women that wish to conceive and those that are pregnant. METHODS: An electronic survey was designed and distributed through a network of 5.654 e-mails. The query was uploaded in Google Forms. RESULTS: Overall, 1,226 answers were retrieved. Ninety percent of respondents replied that they prescribe COVID-19 vaccination in women that wish to conceive, however, the rate falls to 80% for those that have schedules for imminent artificial reproductive techniques. Approximately 1 in 2 physicians (obstetricians and pediatricians) suggests that a delay in assisted reproduction following immunization is not recommended. At least 13% of women of reproductive age and 30% of women wishing to conceive with ART declined to do so according to respondents, report. Only 75% of respondents favored immunization during pregnancy and of those 48% responded that vaccination could be done in all trimesters of pregnancy. Approximately 40% of women decline; however, to receive vaccination. CONCLUSIONS: Despite the directions provided by international organizations; physician and patient hesitancy towards vaccination during pregnancy (and particularly the first trimester) remains an issue that deserves further attention.

First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth.

Spontaneous Preterm Delivery (sPTD) is one of the leading causes of perinatal mortality and morbidity worldwide. The present case−control study aims to detect miRNAs differentially expressed in the first trimester maternal plasma with the view to identify predictive biomarkers for sPTD, between 320/7 and 366/7 weeks, that will allow for timely interventions for this serious pregnancy complication. Small RNA sequencing (small RNA-seq) of five samples from women with a subsequent sPTD and their matched controls revealed significant down-regulation of miR-23b-5p and miR-125a-3p in sPTD cases compared to controls, whereas miR-4732-5p was significantly overexpressed. Results were confirmed by qRT-PCR in an independent cohort of 29 sPTD cases and 29 controls. Statistical analysis demonstrated that miR-125a is a promising early predictor for sPTL (AUC: 0.895; 95% CI: 0.814-0.972; p < 0.001), independent of the confounding factors tested, providing a useful basis for the development of a novel non-invasive predictive test to assist clinicians in estimating patient-specific risk.

The impact of vaginal pH on induction of labour outcomes: a meta-analysis of observational studies.

The present meta-analysis evaluates the impact of an acidic vaginal pH on the progress of labour induction with dinoprostone and misoprostol. We searched Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, Clinicaltrials.gov and Google Scholar databases for relevant studies. Meta-analysis was performed with Rstudio using the meta function and trial sequential analysis was used to evaluate the adequacy of sample size. Nine studies were retrieved that involved 809 patients. An acidic vaginal pH did not influence the efficacy of misoprostol or dinoprostone in terms of accomplishing a successful vaginal delivery (OR 0.62, 95% CI 0.29, 1.30). The interval to delivery was unaffected by the acidity of vaginal pH (Mean Difference 4.18 h, 95% CI -2.09, 10.45). In conclusion, vaginal pH does not seem to affect the potency of vaginally administered prostaglandins; therefore, moistening of vaginal tables with acetic acid does not seem reasonable until further evidence becomes available.

Myomectomy during pregnancy; diagnostical dilemmas: two case reports and a systematic review of the literature.

Myomectomy in pregnancy, until this day, remains very controversial. We present two cases of successful antepartum myomectomies performed in the second trimester of gestation. In both cases, the initial suspected origin of these tumours was the ovaries. However, as it was shortly after confirmed, since both women underwent laparotomy, the diagnosis of these masses was uterine fibroids. Both cases resulted on the live birth of two healthy infants via caesarean section. Secondarily, we conducted a thorough review of current data of myomectomies performed during pregnancy, including the characteristics and diagnosis of the myomas of pregnant women, the surgical details and complications, along with the outcomes of these gestations. Overall, the analysis of cases published in international literature, suggests that the surgical removal of myomas during pregnancy can be considered safe, given certain indications and considerations. Our review comprises of 71 women undergoing excision of fibroids during pregnancy. Only three cases ended in a miscarriage while the remaining 68 resulted in a second or third trimester delivery. However, the data concerning the safety of the procedure are scarce and originate mostly from case reports. Thus, conclusions on the exact maternal and obstetrical complication rates cannot be drawn.

Intraplacental Fetal Vessel Diameter May Help Predict for Placental Invasiveness in Pregnant Women at High Risk for Placenta Accreta Spectrum Disorders.

Background Prenatal identification of placenta accreta spectrum (PAS) disorder is essential for treatment planning. More objective means for predicting PAS and clinical outcome may be provided by MRI descriptors. Purpose To investigate the association of intraplacental fetal vessel (IFV) diameter at MRI with PAS and peripartum complications. Materials and Methods Between March 2016 and October 2019, 160 gravid women suspected of having PAS underwent placental MRI as part of a prospective trial. Secondary analysis was performed by two experienced genitourinary radiologists for presence and maximum diameter of IFVs. Relative risk ratios were computed to test the association of IFVs with presence and depth of PAS invasiveness. Receiver operating characteristic analysis was used to evaluate the ability of IFV diameter to help predict PAS, placenta percreta, and peripartum complications and for comparison of the area under the curve (AUC) versus that from other combined MRI predictors of PAS (eg, myometrial thinning, intraplacental T2-hypointense bands, uterine bulge, serosal hypervascularity, and signs of extrauterine placental spread). Intraoperative and histopathologic findings were the reference standard. Results A total of 155 women were evaluated (mean age, 35 years ± 5 [standard deviation]; mean gestational age, 32 weeks ± 3). PAS was diagnosed in 126 of 155 women (81%) (placental percreta in 68 of 126 [54%]). At delivery, 30 of 126 women (24%) experienced massive blood loss (>2000 mL). IFVs were detected at MRI in 109 of 126 women with PAS (86%) and in 67 of 68 women with placental percreta (98%). The relative risk ratio was 2.4 (95% CI: 1.6, 3.4; P < .001) for PAS and 10 (95% CI: 1.5, 70.4; P < .001) for placental percreta when IFVs were visible. IFVs of 2 mm or greater were associated with PAS (AUC, 0.81; 95% CI: 0.67, 0.95; P = .04). IVFs of 3 mm or greater were associated with placenta percreta (AUC, 0.81; 95% CI: 0.73, 0.89; P < .001) and with peripartum complications, including massive bleeding (AUC, 0.80; 95% CI: 0.71, 0.89; P < .001). Combining assessment of IFVs with other MRI descriptors improved the ability of MRI to predict PAS (AUC, 0.94 vs 0.89; P = .009). Conclusion Assessment of intraplacental fetal vessels with other MRI descriptors improved the ability of MRI to help predict PAS. Vessel diameter of 3 mm or greater was predictive of placenta percreta and peripartum complications. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Dighe in this issue.

Cephalad-caudad versus transverse blunt expansion of the low transverse hysterotomy during cesarean delivery decreases maternal morbidity: a meta-analysis.

OBJECTIVE: Cesarean delivery is the most prevalent surgical procedure worldwide, reaching approximately 29.7 million cases in 2015. It is directly associated with an increased risk of maternal and neonatal morbidity rates in the absence of malpresentation. Several techniques have been investigated, and there is evidence that cephalad-caudad expansion of the uterine incision might be associated with improved maternal outcomes compared with traditional transverse blunt expansion. The purpose of this meta-analysis was to evaluate the impact of cephalad-caudad expansion on adverse maternal outcomes, including intraoperative blood loss, risk of uterine vessel injury, and tearing of the lower uterine segment. DATA SOURCES: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials, Google Scholar, and Clinicaltrials.gov databases from inception to January 2021. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that assessed the impact of the cephalad-caudad blunt expansion of the low transverse uterine incision during cesarean delivery rather than those of transverse blunt expansion were selected for inclusion. METHODS: Effect sizes were calculated with the Hartung-Knapp-Sidik-Jonkman random-effects model in R. Trial sequential analysis was performed to evaluate the adequacy of sample sizes. RESULTS: Cephalad-caudad blunt expansion of the uterine incision was associated with a lower prevalence of unintended incision extension (relative risk, 0.62; 95% confidence interval, 0.45-0.86) and uterine vessel injury (relative risk, 0.55; 95% confidence interval 0.41-0.73). However, these complications were not accompanied by the increased need for additional suture placement (relative risk, 0.62; 95% confidence interval, 0.31-4.12) or transfusion rates (relative risk, 0.75; 95% confidence interval, 0.28-2.03). Similarly, the intraoperative duration was comparable with cases treated with transverse blunt expansion (mean difference = -0.45 minutes; 95% confidence interval -2.12 to 1.21) and the risk of intentional incision extension in the form of an inverted T (relative risk, 0.38; 95% confidence interval, 0.09-1.52). Trial sequential analysis revealed that the required sample size was reached in the unintended incision extension and uterine vessel injury outcomes. CONCLUSION: The findings of our study suggested that cephalad-caudad blunt expansion of the uterine incision is superior to transverse expansion in terms of reducing unintended incision extension and uterine vessel injury.

The Relevance of Notch Signaling in Cancer Progression.

The Notch signaling pathway controls normal embryonic development and tissue homeostasis of many cell types. It regulates cell proliferation, fate, differentiation, and cell death by short-range signaling between nearby cells that come in contact. The Notch pathway has also been critically involved in the pathobiology of a variety of malignancies, regulating cancer initiation and development, as well as early stages of cancer progression, by adjusting conserved cellular programs. Fibroblasts, an essential for tumor growth component of stroma, have also been affected by Notch regulation. Sequencing Notch gene mutations have been identified in a number of human tumors, revealing information on the progression of specific cancer types, such as ovarian cancer and melanoma, immune-associated tumors such as myeloid neoplasms, but especially in lymphocytic leukemia. Activation of the Notch can be either oncogenic or it may contain growth-suppressive functions, acting as a tumor suppressor in other hematopoietic cells, hepatocytes, skin, and pancreatic epithelium.

Covid-19 and pregnancy: the experience of a tertiary maternity hospital.

OBJECTIVES: The aim of our study is to present the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and evaluate its impact on maternal and neonatal outcomes. METHODS: We retrospectively reviewed the medical records of all COVID-19 positive pregnant women who were admitted to "Alexandra" maternity hospital from March to December 2020 (n=40). The infection status was determined via real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swab specimen. We documented the demographic features, clinical status, pregnancy characteristics and maternal and fetal outcomes. RESULTS: Forty COVID-19 positive pregnant women were admitted to our clinic during the study period. Mean maternal age was 27.6 years. Gestational age (GA) ranged from 10-42 weeks of pregnancy with mean GA calculated at 38+3 weeks. Associated comorbidities included hypertension, hypothyroidism, epilepsy, hepatitis B and asthma. Thirty-five out of 40 women delivered within the study period. Cesarean section was performed in 57.1% of the cases. Most of the cases (87.5%) were asymptomatic while ventilation was required for only one patient. All neonates tested negative for SARS-CoV-2. Neither maternal nor neonatal deaths occurred. CONCLUSIONS: In alignment to other studies, our data show that the course of coronavirus disease 2019 (COVID-19) during pregnancy in the majority of cases is mild and neonatal outcomes also appear favorable.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

Presence of amniotic fluid sludge and pregnancy outcomes: A systematic review.

INTRODUCTION: Several studies acknowledge that the presence of amniotic fluid sludge (AFS) is an independent predictive factor for preterm birth. In the present systematic review, we summarize research that focuses on the comparison of pregnancy outcomes among women with and without AFS. MATERIAL AND METHODS: Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were systematically searched from inception. Both observational and randomized controlled studies were considered eligible provided that they reported data on pregnancy outcomes among women with and without AFS. Outcomes were not meta-analyzed because of the high heterogeneity in terms of selected population and outcome reporting. RESULTS: Seventeen studies of 2432 women were included in this review. Six studies evaluated women at high risk for preterm birth. Pregnancies complicated by AFS had a lower gestational age at delivery and increased incidence of preterm delivery at <37 weeks. Neonatal death rates and admission to the Neonatal Intensive Care Unit were also increased. Evidence in low-risk women, those with signs of preterm labor, in those carrying twins, and in women with cervical cerclage or Arabin pessary was extremely limited. CONCLUSIONS: Women with AFS seem to deliver at an earlier gestational age, and preterm birth rates are also increased. Limited data seem to point to neonatal morbidity and mortality being increased. However, the presence of a direct association should not be assumed because the evidence is not adjusted for the presence of confounders.

First trimester neutrophil to lymphocyte ratio (NLR) and pregnancy outcome.

In early pregnancy, miscarriage is the most common complication. The early identification of women at high risk for miscarriage could improve pregnancy outcomes. We investigated whether the first trimester neutrophil to lymphocyte ratio (NLR) could be used as a prognostic marker for miscarriage, in pregnancies after spontaneous conception. We retrospectively identified 129 pregnant women who had a first trimester full blood count available and known pregnancy outcome. First trimester NLR was calculated for each woman and mean NLR values were compared between women with live births (group 1) with those with miscarriage (group 2). Mean NLR values were not significantly different between the two groups (2.5 ± 1.0 vs. 2.9 ± 1.5, p = .167) and were not associated with pregnancy outcomes. However, NLR values >5.8 were exclusively observed in the miscarriage group (p = .028).IMPACT STATEMENTWhat is already known on this subject? As a marker of inflammation, NLR has been found to be elevated in various diseases and complications that affect pregnancy outcome. Pregnancy complications, such as preeclampsia and gestational diabetes have been associated with an increased NLR, but little is known on their direct causal relationship. So far, there has been no evaluation of maternal NLR in regards to miscarriage in otherwise healthy women.What do the results of the study add? We found that NLR does not differ significantly between pregnant women with live birth and those whose pregnancy ended in miscarriage . However, NLR values >5.8 were solely found in the miscarriage group- an observation that was statistically significant.What are the implications of these findings for clinical practice and/or further research? The above finding supports high NLR values as a potential marker for the identification of the subset of miscarriages in otherwise healthy pregnant women. This may allow personalised approaches to prevent pregnancy loss.

MRI prognosticators for adverse maternal and neonatal clinical outcome in patients at high risk for placenta accreta spectrum (PAS) disorders.

BACKGROUND: Placenta accreta spectrum (PAS) disorders may be associated with significant mortality and morbidity for both mother and fetus. PURPOSE/HYPOTHESIS: To identify MRI risk factors for poor peripartum outcome in gravid patients at risk for PAS. STUDY TYPE: Prospective. POPULATION: One hundred gravid women (mean age: 34.9 years) at third trimester, with placenta previa. FIELD STRENGTH/SEQUENCE: T2 -SSTSE (single-shot turbo spin echo), T2 -TSE, T1 -TSEFS (TSE images with fat-suppression) at 1.5T. ASSESSMENT: Fifteen MRI features considered indicative of PAS were recorded by three radiologists and were tested for any association with the following adverse peripartum maternal and neonatal events: increased operation time, profound blood loss, hysterectomy, bladder repair, ICU admission, prematurity, low birthweight, and 5-minute APGAR score <7. STATISTICAL TESTS: Kappa (K) coefficients were computed as a measure of agreement between intraoperative information/histology and MRI results as well as for interobserver agreement; chi-square and Fisher's exact tests were used to explore the association of the MRI signs with clinical complications. A score was calculated by adding all recorded MRI signs and its predictive ability was tested using receiver operating characteristic (ROC) analysis, against all complications, separately; odds ratios (ORs) for optimal cutoffs were determined with logistic regression analysis. RESULTS: There was excellent agreement (K >0.75, P < 0.001) between MRI and intraoperative findings for invasive placenta, bladder and parametrial involvement. Intraplacental T2 dark bands, myometrial disruption, uterine bulge, and hypervascularity at the utero-placental interface or parametrium, showed significant association (P < 0.005) with poor clinical outcome for both mother and fetus. The MRI score showed significant predictive ability for each adverse maternal event (area under the curve [AUC]: 0.85-0.97, P < 0.001). The presence of ≥3 MRI signs was the cutoff point for a complicated delivery (OR: 19.08, 95% confidence interval [CI]: 6.05-60.13) and ≥6 MRI signs was the cutoff point for massive bleeding (OR: 90.93, 95% CI: 11.3-729.23), hysterectomy (OR: 72.5, 95% CI: 17.9-293.7), or extensive bladder repair (OR: 58.74, 95% CI: 7.35-469.32). The MRI score was not significant for predicting adverse neonatal events including preterm delivery (P = 0.558), low birthweight (P = 0.097), and 5-minute Apgar score (P = 0.078). DATA CONCLUSION: Preoperative identification of specific MRI features may predict peripartum course in high-risk patients for PAS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:602-618.