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Background: The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life-threatening pregnancy complication that is increasing in incidence., Objective: We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD-10 and assess contributing factors to incorrect code assignments., Methods: We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD-10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard., Results: Among 22,345 patients, 104 (0.46%) had an ICD-10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD-10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD-10 codes for placenta accreta spectrum subtypes- accreta, increta and percreta-were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features., Conclusion: These findings from a quaternary obstetric centre suggest that ICD-10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases., (© 2024 John Wiley & Sons Ltd.)

Despite documented effects linking underlying placental diseases and neurological impairments in children, little is known about the long-term effects of placental pathology on children's neurocognitive outcomes. In addition, maternal responsivity, known to positively influence early postnatal cognitive development, may act to protect children from putative adverse effects of placental pathology. The current study is a follow up of medically healthy, term born, preschool age children, born with placental pathology. A sample of 118 children (45 comparison children with normal placental findings, 73 born with placental pathology) were followed when children were 3-4 years old. In comparison to children born to mothers with normal placentas, placental pathology was associated with poorer performance in the executive function involving cognitive flexibility, but not inhibitory control or receptive language. Maternal responsivity was observed to be marginally protective on the impact of placental pathology risk on cognitive flexibility, but this was not seen for either inhibitory control or receptive language.

The placenta and fetal heart undergo development concurrently during early pregnancy, and, while human studies have reported associations between placental abnormalities and congenital heart disease (CHD), the nature of this relationship remains incompletely understood. Evidence from animal studies suggests a plausible cause and effect connection between placental abnormalities and fetal CHD. Biomechanical models demonstrate the influence of mechanical forces on cardiac development, whereas genetic models highlight the role of confined placental mutations that can cause some forms of CHD. Similar definitive studies in humans are lacking; however, placental pathologies such as maternal and fetal vascular malperfusion and chronic deciduitis are frequently observed in pregnancies complicated by CHD. Moreover, maternal conditions such as diabetes and pre-eclampsia, which affect placental function, are associated with increased risk of CHD in offspring. Bridging the gap between animal models and human studies is crucial to understanding how placental abnormalities may contribute to human fetal CHD. The next steps will require new methodologies and multidisciplinary approaches combining innovative imaging modalities, comprehensive genomic testing, and histopathology. These studies may eventually lead to preventative strategies for some forms of CHD by targeting placental influences on fetal heart development., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: The term placenta accreta spectrum (PAS) is commonly used to describe abnormal trophoblastic invasion of the myometrium, serosa, or organs adjacent to the uterus. It is of great obstetric importance because of its high morbidity, risk of hemorrhage, admission to the intensive care unit, risk of hysterectomy, and high risk of iatrogenic pelvic lesions and even death. These risks are minimized when prenatal diagnosis is performed. Prenatal diagnosis of PAS is based on imaging findings suggestive of abnormal and pathologically adherent placentation, including placental lacunae (intraplacental sonolucent spaces), disruption of the bladder-uterine serosa interface, turbulent flow on color Doppler, and bridging vessels., Objective: In this article, we review the major prenatal imaging features of PAS using diagnostic modalities (first trimester, two-dimensional ultrasound, three-dimensional ultrasound, and magnetic resonance imaging) for the diagnosis of PAS., (© 2023 Wiley Periodicals LLC.)

Objective: The present study aims to compare prophylactic common iliac artery (CIA) temporary clamping and preoperative balloon occlusion for managing placenta accreta spectrum (PAS) disorders., Study Design: Between January 2019 and June 2020, 46 patients with PAS disorders were included. Of them, 26 patients were offered CIA balloon occlusion (Group A), while temporary CIA clamping was done for the other 20 patients (Group B). Primary outcomes were procedure-related complications, and secondary outcomes included intraoperative and postoperative complications, reoperation rates, total procedure time, blood loss, and amount of blood transfusion., Results: Blood loss was statistically non-significant higher in group B than in group A (p-value = 0.143). Only one patient in group A and three in group B needed reoperation. The bleeding continued for a mean of 1.6 days in group A and 1.7 days in group B, with non-significant statistical differences between both groups p value = 0.71. Nine patients in group A (34.6%) and four in group B (20%) required ICU admission. The mean Apgar score was 7 and 6.6 in babies of group A and group B patients, respectively. The median number of allogeneic blood transfusions performed was two in patients in group A and 1 in group B (p-value = 0.001)., Conclusion: Both techniques offer good choices for patients with PAS to decrease mortality and morbidity rates. The selection of a better technique depends on institutional references and physicians' experience., (© 2023 Japan Society of Obstetrics and Gynecology.)

Objectives: To evaluate the occurrence of retained products of conception (RPOC) after termination of pregnancy in the first trimester and to assess the vascular signals with transvaginal ultrasonography (TVUS) examination in the detection of retained products., Methods: A retrospective cohort study was performed using TVUS examination in patients following termination of pregnancy. In cases of RPOC, 3 scales of vascular signal were identified: type 1, no or small amount, spot flow signals; type 2, medium amount, strip-like flow signals; type 3, rich amount, circumferential-like flow signals. The correlation between vascular signals and placenta accreta spectrum (PAS) staging was proposed by sonography and histopathology findings., Results: The 3 vascular patterns were differently distributed within non-RPOC as well as RPOC patients with and without PAS: type 1 vascular signal detection rates of non-RPOC and RPOC were 97.8% (262/268) and 28.1% (18/64), respectively. Of 64 cases of RPOC, 48.4% (31/64) of the patients had type 2 vascular signals. Vascular signals were enhanced in RPOC with PAS patients whose diagnosis was confirmed by histopathology., Conclusions: The vascularity (amount of flow), vascular pattern (spot, strip- or circumferential-like flow), and the flow penetrating myometrium were significant findings for distinguishing concomitant RPOC with and without PAS. Additionally, RPOC may contribute to PAS progression, or PAS and RPOC in coordination strengthen the observed vascular signals., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. All rights reserved.)

Background: Placenta accreta spectrum disorders are associated with substantial maternal morbidity and mortality. Despite a preoperative diagnosis, the rate of complications remains high, and the condition is generally associated with the need for a hysterectomy., Objective: This study aimed to evaluate the outcomes of a new uterine-preserving technique (called the combined approach, including surgical hemostasis, bilateral ligation of the descending branches of the uterine arteries, and hemostatic external supraplacental stitch with the use of the Zhukovsky double-balloon tamponade in patients with placenta accreta spectrum disorders) during cesarean delivery in women with placenta accreta spectrum disorders vs the surgical technique used until 2014., Study Design: This retrospective cohort study included 147 patients with placenta accreta spectrum disorders who were divided into 2 groups: the study group (n=95) is to undergo cesarean delivery using the combined approach, and the control group (n=52) is to undergo the surgical technique used until 2014, which included bilateral uterine artery ligation, which is the transfusion of plasma, red blood cells, platelets, and protease inhibitors., Results: The volume of blood loss was 1.5-fold lower (P=.0010), the number of blood transfusions was 5.1-fold lower (P=.026), and the rate of bladder injuries was 19-fold lower (P=.012) in the study group than that in the control group. The duration of hospital stay after delivery was 4 days lesser (P=.001) and the number of hysterectomies was 4.5-fold lower in the study group than in the control group (P=.023). The study groups did not differ in terms of placenta accreta spectrum type., Conclusion: The combined approach during cesarean delivery proved to be more effective than the surgical technique used until 2014 in reducing the number of hysterectomies, blood loss volume, number of blood transfusions, and duration of hospital stay in patients with placenta accreta spectrum disorders., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diagnostic performance of placenta accreta spectrum (PAS) by prenatal MRI is unsatisfactory. Deep learning radiomics (DLR) has the potential to quantify the MRI features of PAS., Purpose: To explore whether DLR from MRI can be used to identify pregnancies with PAS., Study Type: Retrospective., Population: 324 pregnant women (mean age, 33.3 years) suspected PAS (170 training and 72 validation from institution 1, 82 external validation from institution 2) with clinicopathologically proved PAS (206 PAS, 118 non-PAS)., Field Strength/sequence: 3-T, turbo spin-echo T2-weighted images., Assessment: The DLR features were extracted using the MedicalNet. An MRI-based DLR model incorporating DLR signature, clinical model (different clinical characteristics between PAS and non-PAS groups), and MRI morphologic model (radiologists' binary assessment for the PAS diagnosis) was developed. These models were constructed in the training dataset and then validated in the validation datasets., Statistical Tests: The Student t-test or Mann-Whitney U, χ 2 or Fisher exact test, Kappa, dice similarity coefficient, intraclass correlation coefficients, least absolute shrinkage and selection operator logistic regression, multivariate logistic regression, receiver operating characteristic (ROC) curve, DeLong test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI), calibration curve with Hosmer-Lemeshow test, decision curve analysis (DCA). P < 0.05 indicated a significant difference., Results: The MRI-based DLR model had a higher area under the curve than the clinical model in three datasets (0.880 vs. 0.741, 0.861 vs. 0.772, 0.852 vs. 0.675, respectively) or MRI morphologic model in training and independent validation datasets (0.880 vs. 0.760, 0.861, vs. 0.781, respectively). The NRI and IDI were 0.123 and 0.104, respectively. The Hosmer-Lemeshow test had nonsignificant statistics (P = 0.296 to 0.590). The DCA offered a net benefit at any threshold probability., Data Conclusion: An MRI-based DLR model may show better performance in diagnosing PAS than a clinical or MRI morphologic model., Level of Evidence: 3 TECHNICAL EFFICACY STAGE: 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Placentae collected from elective terminations during the first trimester are commonly used as control samples in research. However, it is widely acknowledged that many complications of pregnancies can occur or originate during the early stage of gestation. This raises the question that the placentae collected from the first trimester may not accurately reflect normal placental conditions. In this study, 95 placentae were collected from elective terminations and histology was performed. Out of these, 53 placentae (56 %) exhibited the typical structure of placental villi, indicating normal development. However, 42 placentae (44 %) showed placental hydrops, with varying degrees of severity (mild, moderate, or severe). Placental hydrops has been linked to several complicated pregnancies in the later stages of gestation. Our findings suggest that the development of pregnancy pathologies could start in the first trimester, as observed by the presence of hydrops. Placental researchers should be aware of when using first-trimester placentae from termination as controls in studies. However, it remains unclear whether pathological morphologies resolve or ameliorate as the pregnancy progression or whether such placentae continue to have such pathology, but clinical symptoms/signs do not manifest., Competing Interests: Declaration of competing interest None of the authors have a conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The success of in-utero or intrapartum treatment for congenital diaphragmatic hernia (CDH) can be impacted by poor placental function; however, this relationship has not yet been studied. To analyze placental histomorphology in CDH, the frequencies of 24 independent clinical and 48 placental phenotypes were compared. Slides from 103 CDH placentas (group 1) and 133 clinical umbilical cord (UC) compromise/anatomical UC abnormality placentas without CDH (group 2) were subjected to hematoxylin/eosin staining and CD34 immunostaining and then examined. CD34 immunostaining was performed to identify clustered distal villi with endothelial fragmentation of recent fetal vascular malperfusion (FVM). Cesarean delivery and ex utero intrapartum treatment were more common in group 1, but group 2 showed a higher frequency of statistically significant increases in other clinical phenotypes. The frequencies of large vessels and distal villous FVMs (clustered endothelial fragmentation by CD34 immunostaining, stromal vascular karyorrhexis, avascular, or mineralized villi) did not differ between the groups, but low-grade distal villous FVMs were statistically significantly more common in group 1 than in group 2, while high-grade distal villous FVMs were significantly more common in group 2 than group 1. Large vessel and distal villous FVMs were manyfold more common in both the CDH and UC compromise groups than in the general population. However, CDH placentas were more likely to show low-grade distal villous FVMs and less likely to show high-grade distal villous FVMs in UC compromise placentas. FVM of CDH may therefore be caused by a similar pathomechanism as that of UC compromise, resulting in impaired placental fetal blood outflow., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta. Early diagnosis of Type-III VP is important but technically challenging. The objective of this study was to gather the current available evidence on the perinatal diagnosis and outcome of Type-III VP., Methods: A systematic review of the literature on the perinatal diagnosis of atypical Type-III VP was carried out in PubMed, MEDLINE and EMBASE accordingto PRISMA guidelines from inception to March 2023. Data extraction and tabulation were performed by two operators and checked by a third senior author. The quality of the included studies was evaluated using the National Institutes of Health tool for the quality assessment of case-series studies. Our local ultrasound database was searched for previously unreported recent cases. Characteristics of prenatally and postnatally diagnosed Type-III VP, including clinical features and perinatal outcomes, were summarized using descriptive statistics., Results: Eighteen cases of Type-III VP were included, of which 16 were diagnosed prenatally (14 cases were retrieved from 10 publications and two were unpublished cases from our center) and two were diagnosed postnatally (retrieved from two publications). All prenatal cases were diagnosed on transvaginal ultrasound at a mean gestational age of 29 weeks (median, 31 weeks; range, 19-38 weeks). Conception was achieved with in-vitro fertilization in 4/16 (25.0%) cases. There were no prenatal symptoms in 15/18 (83.3%) cases, while in two (11.1%) cases there was vaginal bleeding and in one (5.6%) preterm labor occurred. In 15/18 (83.3%) cases, at least one placental abnormality was observed, including low-lying insertion (9/17), succenturiate or accessory lobe (1/17), velamentous cord insertion (3/18) and marginal insertion (9/18). All prenatally diagnosed cases were liveborn and were delivered by Cesarean section before rupture of membranes at a median gestational age of 35 weeks (range, 32-38 weeks) without neonatal complications. Emergency Cesarean section was performed in 2/16 (12.5%) cases with a prenatal diagnosis and 1/2 (50.0%) cases with a postnatal diagnosis (P = 0.179). Among those with data available, an Apgar score of ≤ 7 was observed in the prenatally vs postnatally diagnosed group in 5/13 vs 1/1 cases, respectively, at the 1-min evaluation and 3/13 vs 1/1 cases, respectively, at the 5-min evaluation., Conclusions: The prenatal diagnosis of Type-III VP is challenging, with few cases reported in the literature; however, it is crucial for minimizing the risk of adverse outcome by enabling early-term elective Cesarean delivery prior to rupture of membranes. Given that clinical manifestations and risk factors are non-specific, and that Type-III VP cannot be excluded when there is a normal cord insertion or a singular placental mass, systematic screening by transvaginal ultrasound in the general pregnant population is recommended, particularly in those with a low-lying or morphologically abnormal placenta and those who conceived using assisted reproductive technology. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Placenta accreta spectrum is a life-threatening complication of pregnancy that is underdiagnosed and can result in massive hemorrhage, disseminated intravascular coagulation, massive transfusion, surgical injury, multisystem organ failure, and even death. Given the rarity and complexity, most obstetrical hospitals and providers do not have comprehensive expertise in the diagnosis and management of placenta accreta spectrum. Emergency management, antenatal interdisciplinary planning, and system preparedness are key pillars of care for this life-threatening disorder. We present an updated sample checklist for emergent and unplanned cases, an antenatal planning worksheet for known or suspected cases, and a bundle of activities to improve system and team preparedness for placenta accreta spectrum., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To evaluate the risk of recurrence of severe placenta-mediated pregnancy complications and compare the efficacy of two different anti-thrombotic regimens in women with a history of late fetal loss without thrombophilia., Patients and Methods: We performed a 10-year retrospective observational study (2008-2018) analyzing a cohort of 128 women who suffered from pregnancy fetal loss (>20 weeks of gestational age) with histological evidence of placental infarction. All the women tested negative for congenital and/or acquired thrombophilia. In their subsequent pregnancies, 55 received prophylaxis with acetylsalicylic acid (ASA) only and 73 received ASA plus low molecular weight heparin (LMWH)., Results: Overall, one-third of all pregnancies (31%) had adverse outcomes related to placental dysfunction: pre-term births (25% <37 weeks, 5.6% <34 weeks), newborns with birth weight <2500 g (17%), and newborns small for gestational age (5%). The prevalence of placental abruption, early and/or severe preeclampsia, and fetal loss >20 weeks were 6%, 5%, and 4% respectively. We found a risk reduction for combination therapy (ASA plus LMWH) compared with ASA alone for delivery <34 weeks (RR 0.11, 95% CI: 0.01-0.95 p  = 0.045) and a trend for the prevention of early/severe preeclampsia (RR 0.14, 95% CI: 0.01-1.18, p  = 0.0715), while no statistically significant difference was observed for composite outcomes (RR 0.51, 95%CI: 0.22-1.19, p  = 0.1242). An absolute risk reduction of 5.31% was observed for the ASA plus LMWH group. Multivariate analysis confirmed a risk reduction for delivery <34 weeks (RR 0.32, 95% CI 0.16-0.96 p  = 0.041)., Conclusion: In our study population, the risk of recurrence of placenta-mediated pregnancy complications is substantial, even in the absence of maternal thrombophilic conditions. A reduction of the risk of delivery <34 weeks was detected in the ASA plus LMWH group.

Introduction: Inflammation and acidosis are two stress stimuli that correspond to pathophysiological processes occurring in placental-mediated vascular disorders. We aimed to investigate the effects of these stimuli on placental chorionic blood vessels reactivity using the ex-vivo placental perfusion model., Methods: Term placentas were obtained immediately after cesarean deliveries, and selected cotyledons were cannulated and dually perfused ex-vivo. Placentas were perfused with three different protocols: culture medium (M199-controls, n = 5), culture medium with lipopolysaccharide (inflammatory stimuli) (LPS,1 μg/ml, n = 7), and acidotic culture medium (M - 199, pH: 6.9-7, n = 6). Each perfusion experiment was maintained for 180 min. Fetal perfusion pressure was continuously measured. Measurements in response to angiotensin II (AT II) at the end of the perfusion were compared between the treatment groups, including amplitude of the contraction response, relaxation factor, time to maximal constriction and the area under the pressure curve (AUC)., Results: In response to ATII there was a significant difference in the amplitude of the contraction and the AUC between the treatment groups, (p = 0.049, p = 0.015, respectively). As compared with control perfused cotyledon, the inflammatory stimuli significantly increased the vasoconstriction response to ATII in fetal placental blood vessels, as expressed by increased AUC - median (IQR): 555 (235-1184) vs. 133 (118-207), respectively, p = 0.017. The time to maximal constriction and the relaxation factor did not differ between the groups., Discussion: Inflammatory stimuli but not acidosis impact fetal-placental vasculature in response to ATII, suggesting that inflammation can compromise vascular function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown., Aim: We present this original paper where we analyzed 60 parturients, at term, 30 without associated infection (C-) and 30 with associated infection (C+), present at birth., Methods: We analyzed the blood count and placental microscopic structure through classical and immunohistochemical staining and observed the placental areas affected by the presence of SARS-CoV-2., Results: SARS-CoV-2 infection was accompanied by a decrease in the number of lymphocytes, the number of platelets and the presence of placental structural changes, identifying extensive areas of amyloid deposits, placental infarcts, vascular thrombosis, syncytial knots, with a decrease in placental vascular density and the presence of infection in the cells located at decidual level, at syncytiotrophoblast level and at the level of the cells of the chorionic plate, still without overcoming this barrier and without causing any fetal infection in the analyzed cases., Conclusions: This study shows that the invasion of SARS-CoV-2 in the placenta can produce significant structural changes, with a decrease in placental vascular density that can have significant implications on proper fetal perfusion. Also, the presence of immunoreactivity at the level of decidua, the placental villi, as well as the chorionic plate proves that the virus can overcome the maternal-fetal barrier. However, in the analyzed cases there were no fetal infections at birth, which may show that local placental factors can be a protective filter for the fetus.

The placenta plays a critical role in fetal development. It serves as a multi-functional organ that protects and nurtures the fetus during pregnancy. However, despite its importance, the intricacies of placental structure and function in normal and diseased states have remained largely unexplored. Thus, in 2014, the National Institute of Child Health and Human Development launched the Human Placenta Project (HPP). As of May 2023, the HPP has awarded over $101 million in research funds, resulting in 41 funded studies and 459 publications. We conducted a comprehensive review of these studies and publications to identify areas of funded research, advances in those areas, limitations of current research, and continued areas of need. This paper will specifically review the funded studies by the HPP, followed by an in-depth discussion on advances and gaps within placental-focused imaging. We highlight the progress within magnetic reasonance imaging and ultrasound, including development of tools for the assessment of placental function and structure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The placenta provides the vital nutrients and removal of waste products required for fetal growth and development. Understanding and quantifying the differences in structure and function between a normally functioning placenta compared to an abnormal placenta is vital to provide insights into the aetiology and treatment options for fetal growth restriction and other placental disorders. Computational modelling of blood flow in the placenta allows a new understanding of the placental circulation to be obtained. This structured review discusses multiple recent methods for placental vascular model development including analysis of the appearance of the placental vasculature and how placental haemodynamics may be simulated at multiple length scales., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Congenital heart defects (CHD) remain the most common class of birth defect worldwide, affecting 1 in every 110 live births. A host of clinical and morphological indicators of placental dysfunction are observed in pregnancies complicated by fetal CHD and, with the recent emergence of single-cell sequencing capabilities, the molecular and physiological associations between the embryonic heart and developing placenta are increasingly evident. In CHD pregnancies, a hostile intrauterine environment may negatively influence and alter fetal development. Placental maldevelopment and dysfunction creates this hostile in-utero environment and may manifest in the development of various subtypes of CHD, with downstream perfusion and flow-related alterations leading to yet further disruption in placental structure and function. The adverse in-utero environment of CHD-complicated pregnancies is well studied, however the specific etiological role that the placenta plays in CHD development remains unclear. Many mouse and rat models have been used to characterize the relationship between CHD and placental dysfunction, but these paradigms present substantial limitations in the assessment of both the heart and placenta. Improvements in non-invasive placental assessment can mitigate these limitations and drive human-specific investigation in relation to fetal and placental development. Here, we review the clinical, structural, and molecular relationships between CHD and placental dysfunction, the CHD subtype-dependence of these changes, and the future of Placenta-Heart axis modeling and investigation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fetal microchimerism (FMc) arises during pregnancy as fetal cells enter maternal circulation and remain decades postpartum. Circulating FMc is increased in preeclampsia, fetal growth restriction, and as we recently showed, is associated with biomarkers of placental dysfunction in normotensive term pregnancies. Diabetes mellitus (DM) also correlates with placental dysfunction. We hypothesize that poor glucose control and markers of placental dysfunction are associated with increased circulating FMc in diabetic pregnancies. We included 122 pregnancies preceding active labor (pregestational DM, n = 77, gestational DM (GDM), n = 45) between 2001 and 2017. Maternal and fetal samples were genotyped for various human leukocyte antigen (HLA) loci, and other polymorphisms to identify fetus-specific alleles. We used validated polymerase chain reaction (PCR) assays to quantify FMc in maternal peripheral blood buffy coat. Negative binomial regression with adjustment for confounders was used to assess FMc quantity. In pregestational DM, increased circulating FMc correlated with elevation of HbA1c (≥ 6.0 %) (detection rate ratio (DRR) = 4.9, p = 0.010) and a 1000 pg/mL rise in the anti-angiogenic biomarker soluble fms-like tyrosine kinase-1 (sFlt-1) (DRR = 1.1, p = 0.011). In GDM, increased FMc correlated with elevated 2-hour oral glucose tolerance test results (DRR = 2.3, p = 0.046) and birthweight < 10th or > 90th percentile (DRR = 4.2, p = 0.049). These findings support our novel hypothesis that FMc correlates with poor glucose control and various aspects of placental dysfunction in DM. Whether increased FMc in pregnancies with poor glucose control and placental dysfunction contributes to the risk of preeclampsia in diabetic pregnancies and to the increased risk of chronic cardiovascular disease later in life remains to be investigated., Competing Interests: Declaration of Competing Interest Roche Diagnostics donated in-kind reagents for analysis of the placenta-related biomarkers (sFlt-1 and PlGF). Chimerocyte Inc., of which Sami B. Kanaan is founder, generated some of the microchimerism data in a blinded fashion. Neither Roche Diagnostics nor Chimerocyte had any further involvement in collection or interpretation of data, writing of the manuscript, or the decision to submit the article for publication. The remaining authors declare no other conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Early preeclampsia is associated with significant placental hypoperfusion. We explore the diagnostic value of placental diffusion-derived vessel density (DDVD), a biomarker derived from diffusion-weighted magnetic resonance imaging, which measures in vivo vessel microperfusion, in the differential diagnosis of normal and early preeclampsia pregnancies., Methods: This was a prospective study involving 29 controls and 17 singleton pregnancies affected by early preeclampsia. Nineteen pregnancies from 28 to 34 weeks of gestational age were included from the normal group for a comparison with the early preeclampsia group. Using a 3.0 T magnetic resonance imaging scanner, diffusion-weighted images were obtained with the diffusion weighting b values of 0, 20, and 40 s/mm 2 . DDVD mean was the mean of DDVD b0b20 and DDVD b0b40 , while DDVD b0b20 and DDVD b0b40 refer to the diffusion-derived vessel density values computed from b =0 and 20 s/mm 2 images, and from b =0 and 40 s/mm 2 images, respectively. The correlation between DDVD mean and gestational age was examined using a linear regression model. The area under the curve of the DDVD mean for early preeclampsia pregnancies detection was calculated by the receiver operating characteristic analysis., Results: As gestational age increased, DDVD mean linearly decreased. DDVD mean was significantly decreased in the early preeclampsia pregnancies compared with the normal pregnancies (52.72±46.73 versus 213.34±93.50 au/pixel; P <0.001). The area under the curve (DDVD mean ) for discriminating between normal and early preeclampsia pregnancies regardless of fetal growth restriction was 0.954, and the area under the curve was 1.000 when early preeclampsia pregnancies without fetal growth restriction were excluded., Conclusions: DDVD mean , an in vivo vessel microperfusion measure, allowed total separation of normal and early preeclampsia pregnancies., Competing Interests: Disclosures None.

The purpose of this study is to compare the levels of maternal serum pregnancy-associated plasma protein-A at the first trimester in pregnancies complicated by impaired placental diseases, such as preeclampsia (PE), intrauterine fetal growth restriction (IUGR), and gestational hypertension (GH), with those in pregnancies without the development of any of these outcomes to expand the knowledge of how this protein behaves in the different impaired placental diseases. This current work is an observational study based on a prospective cohort. Pregnancy-associated plasma protein-A was measured in 422 patients who had completed maternal-perinatal outcomes. Comparisons of pregnancy characteristics and the biomarker between outcome groups (PE, IUGR, gestational hypertension, and not impaired placental outcomes) were analyzed. PAPP-A MoM in the IUGR (0.8 IQR: 0.6-0.9) and GH groups (0.5 IQR: 0.3-1.4) compared to the PE group (1.06 IQR: 0.66-1.52) was significantly lower (p < 0.005). Pregnant women who developed early-onset PE (1.11 IQR 1.08-1.18) presented significant differences with the IUGR group (0.83 IQR: 0.59-0.98; p = 0.002) and those who developed preterm-PE (1.19 IQR: 0.66-1.58; p = 0.045). The results demonstrate that the levels of PAPP-A at first trimester in the sample of women who developed PE, and specially term-PE, were higher than those in women who developed GH or IUGR. The GH group had the lowest PAPP-A values in this sample of pregnant women. Research in a population with a high prevalence of preeclampsia is still lacking and deserves more extended studies to define if these patients could have different rates of PAPP-A., (© 2023. The Author(s).)

Objectives: To evaluate surgical outcomes of using a double uterine segment tourniquet in obstetric hysterectomy for bleeding control in patients with placenta accreta spectrum., Methods: Retrospective case-control study conducted at the Central Hospital of San Luis Potosi, Mexico. Patients with the diagnosis of placenta accreta spectrum who underwent obstetric hysterectomy were included. Two groups were formed: in the first, a double uterine segment tourniquet was used; and in the second, the hysterectomy was performed without a tourniquet. Primary surgical outcomes were compared., Results: Forty patients in each group were included. The use of a double uterine segment tourniquet had lower total blood loss compared with the non-tourniquet group (1054.00 ± 467.02 vs. 1528.75 ± 347.12 mL, P = 0.0171) and a lower drop in hemoglobin (1.74 ± 1.10 vs. 2.60 ± 1.25 mg/dL, P = 0.0486). Ten patients (23.80%) in the double tourniquet group required blood transfusion, compared with 26 (65.00%) in the non-tourniquet group (P = 0.0003). Surgical time did not show a statistical difference between groups., Conclusion: The use of a uterine segment tourniquet in obstetric hysterectomy may improve surgical outcomes in patients with placenta accreta spectrum with no difference in surgical time and urinary tract lesions., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Up to 20% of all stillbirths and 45% of term stillbirths are currently classified as unexplained. Many of these stillbirths do not undergo currently recommended investigations. This may leave questions unanswered and not identify stillbirths with a recurrence risk in subsequent pregnancies., Aims: To validate a new tool (Stillbirth Investigation Utility Tool) to identify the clinical utility of investigations in stillbirth and the inter-rater agreement on cause of stillbirth using the Perinatal Society of Australia and New Zealand-Perinatal Death Classification (PSANZ-PDC)., Materials and Methods: Thirty-four stillbirths were randomly selected for inclusion, each assessed independently by five blinded assessors. The investigations were grouped into three categories: clinical and laboratory; placental pathology; and autopsy examination. The cause of death was assigned at the end of each group. Outcome measures were clinical utility of investigations measured by assessor rated usefulness and inter-rater agreement on the assigned cause of death., Results: Comprehensive maternal history, maternal full blood count, maternal blood group and screen and placenta histopathology were useful in all cases. Clinical photographs were not performed and should have been performed in 50% of cases. The inter-rater agreement on cause of death assigned after all investigation results was 0.93 (95% CI 0.87-1.0)., Conclusions: The new Stillbirth Investigation Utility Tool showed very good agreement in assigning the cause of death using PSANZ-PDC. Four investigations were useful in all cases. Minor refinements will be made based on feedback to enhance usability for wider implementation in research studies to assess the yield of investigations in stillbirths., (© 2023 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To evaluate angiographic findings and outcomes of repeat uterine artery embolization (UAE) for recurrent postpartum hemorrhage (PPH) in patients who previously underwent UAE for PPH after a previous delivery., Materials and Methods: Among 1805 patients who underwent UAE for PPH from 2007 to 2020 at four participating hospitals, the data of 21 (1.16%) patients who underwent UAE for PPH after subsequent delivery were collected and analyzed retrospectively. The rate of placental abnormalities, causes of PPH, angiographic findings, and clinical success rate were evaluated., Results: The technical success rates were 100% and 95.2%, and clinical success rates were 85.7% and 95.2% in association with first and second UAEs, respectively. The time intervals between first and second UAEs ranged from 15.6 to 103.3 months (46.5 ± 25.0 months). The rate of placental abnormalities was significantly higher in association with second UAEs than with first UAEs (71.4% vs. 42.8%, p = 0.034). The causes of PPH were different between first and second UAEs with borderline significance (p = 0.049); uterine atony (81.0%) and placenta accreta spectrum (57.1%) were most common in association with first and second UAEs, respectively. During second UAEs, obliterated arteries were observed in 27 uterine arteries (27/42, 64.3%) of 16 patients (16/21, 76.2%), with partial obliteration predominating over total obliteration. Collateral arteries were observed in 15 patients during second UAEs., Conclusion: Repeat UAE is safe and effective for recurrent PPH after subsequent delivery in patients with prior UAE. Obliteration of UAs and formation of collateral arteries are common at the second UAEs., Key Points: • The rate of placental abnormalities was significantly higher in association with second UAEs than with first UAEs (71.4% vs. 42.8%, p = 0.034). • Obliteration of UAs and formation of collateral arteries are common at the second UAEs. • Repeat UAE is safe and effective for recurrent PPH after subsequent delivery in patients with prior UAE., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Complex congenital heart disease (CCHD) is associated with impaired neurodevelopmental outcomes. Peri- and post-operative factors are known contributors while the impact of the prenatal environment is not yet delineated. Variations in fetal circulation, seen in transposition of the great arteries (TGA) and single ventricular physiology (SVP), are associated with placenta abnormalities. These abnormalities may be associated with placental insufficiency, a risk factor for poor neurodevelopmental outcomes. We hypothesized there is a correlation between placental pathology and impaired neurodevelopmental outcomes in patients with CCHD. We performed a single center retrospective cohort study with patients with TGA and SVP from 2010 to 2017 at Children's Wisconsin. Patient variables were obtained from the medical record. Bayley Scales of Infant Development Third Edition standard scores for cognitive, motor, and language performance were collected from neurodevelopmental visits. Placenta pathology reports were reviewed with tabulation of predetermined anatomical and pathological characteristics. We identified 79 patients in our cohort and 61 (77.2%) had abnormal placentas. There was no significant difference between the two groups in any demographic or clinical variables. For cognitive and motor performance, without adjusting for the covariates, infants with placental abnormalities had significantly lower scores compared to infants without (p = 0.026, p = 0.045 respectively). Conversely, there was no significant difference in language scores between the two groups (p = 0.12). Placenta abnormalities are common in patients with CCHD, and placenta abnormalities are associated with impaired neurodevelopmental outcomes. These results underscore the complex causal pathways of neurodevelopmental impairment in infants with CCHD and offer opportunities for targeted postnatal developmental interventions after discharge., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

No abstract available.

Background: Placental related disorders, including preeclampsia and fetal growth restriction (FGR) are among the main determinants of adverse maternal and perinatal outcomes in both singleton and twin pregnancies. In view of its relevance, aspirin administration is commonly recommended to women at high risk for preeclampsia or FGR by the various national and international guidelines., Objectives: To establish the clinical heterogeneity among the clinical practice guidelines (CPGs) on aspirin use in pregnancy and to investigate the quality of these CPGs., Methods: We performed a systematic review of Clinical practice guidelines on main databases searching for all peer-reviewed guidelines into the literature, analyzing the following aspects related to use of aspirin in pregnancy: indications for aspirin administration, dosage, starting of therapy, ending of therapy, safety and side effects. The assessment of risk of bias and quality assessment of the included CPGs were performed using "The Appraisal of Guidelines for REsearch and Evaluation (AGREE II)" tool., Results: 16 CPGs were included. There was an overall general agreement among the published CPGs as regards to the indication for aspirin intake in pregnancy, with prior preeclampsia, chronic hypertension, autoimmune disease, and diabetes mellitus type 1 or 2 recognized as solitary major risk factors for Aspirin administration in 93.7% (15/16) of CPGs. There was heterogeneity in the recommendations provided by the different CPGs as regards the gestational age at which aspirin should be commenced., Conclusion: There is general agreement in the reported indications for aspirin intake in pregnancy, with prior preeclampsia and maternal medical co-morbidity associated with increased risk of preeclampsia being the major indications for aspirin intake. Conversely, there was heterogeneity in the recommended dose, gestational age at initiation and discontinuation of therapy among the different CPGs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Accumulating evidence indicates that maternal hypothalamic-pituitary-adrenal (HPA) axis activity over pregnancy differs according to maternal history of childhood maltreatment. DNA methylation of the placental 11-beta-hydroxysteroid dehydrogenase (BHSD) type 2 enzyme regulates fetal exposure to maternal cortisol, yet the association between maternal history of childhood maltreatment and methylation of placental 11BHSD type 2 has not been previously studied., Methods: We examined if maternal cortisol production at 11 and 32 weeks' gestation (n = 89) and placental methylation of the 11BHSD type 2 gene (n = 19) differed among pregnant women with and without histories of childhood maltreatment. Twenty-nine percent of participants reported a history of childhood maltreatment (physical/sexual abuse)., Results: Women with histories of childhood maltreatment displayed lower cortisol in early gestation, hypo-methylation of placental 11BHSD type 2, and lower levels of cord blood cortisol., Conclusion: Preliminary results suggest alterations in cortisol regulation over pregnancy according to maternal history of childhood maltreatment., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Conditions such as small for gestational age (SGA), which is defined as birthweight less than 10 th percentile for gestational age can predispose to neurodevelopmental abnormalities compared to babies with normal birthweight. Fetal growth and birthweight depend on placental function, as this organ transports substrates to the developing fetus and it acts as a source of endocrine factors, including steroids and prolactins that are required for fetal development and pregnancy maintenance. To advance our knowledge on the aetiology of fetal growth disorders, the vast majority of the research has been focused on studying the transport function of the placenta, leaving practically unexplored the contribution of placental hormones in the regulation of fetal growth. Here, using mice and natural variability in fetal growth within the litter, we compared fetuses that fell on or below the 10 th percentile (classified as SGA) with those that had adequate weight for their gestational age (AGA). In particular, we compared placental endocrine metabolism and hormone production, as well as fetal brain weight and expression of developmental, growth and metabolic genes between SGA and AGA fetuses. We found that compared to AGA fetuses, SGA fetuses had lower placental efficiency and reduced capacity for placental production of hormones (e.g. steroidogenic gene Cyp17a1 , prolactin Prl3a1 , and pregnancy-specific glycoproteins Psg21 ). Brain weight was reduced in SGA fetuses, although this was proportional to the reduction in overall fetal size. The expression of glucose transporter 3 ( Slc2a3 ) was reduced despite the abundance of AKT, FOXO and ERK proteins were similar. Developmental ( Sv2b and Gabrg1 ) and microglia genes ( Ier3 ), as well as the pregnancy-specific glycoprotein receptor ( Cd9) were lower in the brain of SGA versus AGA fetuses. In this mouse model of SGA, our results therefore demonstrate that placental endocrine dysfunction is associated with changes in fetal growth and fetal brain development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lopez-Tello and Sferruzzi-Perri.)

Objectives: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of stillbirth and assess whether IMD contributes to the prediction of stillbirth provided by the combination of maternal demographic characteristics and elements of medical history., Methods: This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criterion was delivery at ≥ 24 weeks' gestation of a fetus without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to its level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. Logistic regression analysis was used to determine whether IMD provided a significant independent contribution to stillbirth after adjustment for known maternal risk factors., Results: The overall incidence of stillbirth was 0.35% (551/159 125), and this was significantly higher in the most deprived compared with the least deprived group (Quintile 1 vs Quintile 5). The odds ratio (OR) in Quintile 1 was 1.57 (95% CI, 1.16-2.14) for any stillbirth, 1.64 (95% CI, 1.20-2.28) for antenatal stillbirth and 1.89 (95% CI, 1.23-2.98) for placental dysfunction-related stillbirth. In Quintile 1 (vs Quintile 5), there was a higher incidence of factors that contribute to stillbirth, including black race, increased body mass index, smoking, chronic hypertension and previous stillbirth. The OR of black (vs white) race was 2.58 (95% CI, 2.14-3.10) for any stillbirth, 2.62 (95% CI, 2.16-3.17) for antenatal stillbirth and 3.34 (95% CI, 2.59-4.28) for placental dysfunction-related stillbirth. Multivariate analysis showed that IMD did not have a significant contribution to the prediction of stillbirth provided by maternal race and other maternal risk factors. In contrast, in black (vs white) women, the risk of any and antenatal stillbirth was 2.4-fold higher and the risk of placental dysfunction-related stillbirth was 2.9-fold higher after adjustment for other maternal risk factors., Conclusions: The incidence of stillbirth, particularly placental dysfunction-related stillbirth, is higher in women living in the most deprived areas in South East England. However, in screening for stillbirth, inclusion of IMD does not improve the prediction provided by race, other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

The purpose of this study was to evaluate serum levels of anti- and pro-angiogenic substances measured using enzyme-linked immunosorbent assays and their ratios in pregnancies complicated by different clinical subsets of placental ischemic syndrome: preeclampsia and/or fetal growth restriction. A prospective case-control study was performed consisting of 77 singleton pregnancies complicated by preeclampsia, preeclampsia with concurrent fetal growth restriction (FGR), and isolated normotensive FGR pairwise matched by gestational age with healthy pregnancies. The entire study cohort was analyzed with respect to adverse pregnancy outcomes that occurred. In all investigated subgroups, placental growth factor (PlGF) was lower and soluble endoglin (sEng), the soluble fms-like tyrosine kinase-1-sFlt-1/PlGF and sFlt-1*sEng/PlGF ratios were higher than in the control group. The differences were most strongly pronounced in the PE with concurrent FGR group and in the sFlt-1/PlGF ratio. The highest sFlt-1 values in preeclamptic patients suggest that this substance may be responsible for reaching the threshold needed for PE to develop as a maternal manifestation of ischemic placental disease. The FGR is characterized by an elevated maternal sFlt-1/PlGF ratio, which boosts at the moment of indicated delivery due to fetal risk. We concluded that angiogenic imbalance is reflective of placental disease regardless of its clinical manifestation in the mother, and may be used as support for the diagnosis and prognosis of FGR.

Introduction: Pregnancies conceived through assisted reproductive techniques (ARTs) are on the rise worldwide and have been associated with a higher risk of placental-related disease in the third trimester., Methods: A cohort was created of singleton pregnancies after assisted reproduction, admitted at our institution for delivery, between January 2020 and August 2022. Fetal growth velocity from the second trimester to delivery was compared against a gestational-age-matched group of pregnancies spontaneously conceived according to the origin of the selected oocyte (i.e., autologous vs. donated)., Results: 125 singleton pregnancies conceived through ART were compared to 315 singleton spontaneous conceptions. Overall, after adjusting for possible confounders, multivariate analysis demonstrated that ART pregnancies had a significantly lower estimated fetal weight (EFW) z-velocity from the second trimester to delivery (adjusted mean difference = -0.002; p = 0.035) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 2.32 [95% CI, 1.15-4.68]). Also, when ART pregnancies were compared according to the type of oocyte, those conceived with donated oocytes showed a significantly lower EFW z-velocity from the second trimester to delivery (adjusted mean difference = -0.008; p = 0.001) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 5.33 [95% CI, 1.34-21.5])., Conclusions: Pregnancies achieved through ART exhibit a pattern of lower growth velocity across the third trimester, especially those conceived with donated oocytes. The former represents a sub-group at the highest risk of placental dysfunction that may warrant closer follow-up., (© 2023 S. Karger AG, Basel.)

Objective: This study aims to compare the maternal and fetal outcomes in subsequent pregnancies of patients who underwent conservative surgery (fertility-sparing) for placenta accreta spectrum (PAS) and the current pregnancies of patients who had a previous cesarean section. It aims to evaluate the feasibility of conservative surgery., Methods: The study was carried out between January 2011 and September 2021 at the Gynecology and Obstetrics Clinic of Necmettin Erbakan University Meram Medical Faculty Hospital. The files of patients who underwent uterine segmental resection surgery with the diagnosis of PAS and then became pregnant again and who underwent cesarean section were retrospectively scanned from the hospital electronic registry system of patients without a PAS diagnosis but with a history of at least one previous cesarean section., Results: Gestational week, birth weight, intrauterine growth retardation, and APGAR values were compared regarding the fetal outcomes and no statistically significant difference was found between the two groups. Seven patients in the study group and one patient in the control group required postpartum transfusions (P = 0.026), and urinary system infections were more frequent in patients with a history of PAS (P = 0.038)., Conclusion: Although cesarean hysterectomy is the standard treatment method in cases of placental invasion anomaly, conservative (uterus-sparing) surgery seems to be applicable in fertile patients despite surgical difficulties. Acar-style conservative surgery is important in terms of both fertility preservation in PAS cases.

Introduction: Transverse relaxation time (T2*) is related to tissue oxygenation and morphology. We aimed to describe T2* weighted MRI in selected fetal organs in normal pregnancies, and to investigate the correlation between fetal organ T2* and placental T2*, birthweight (BW) deviation, and redistribution of fetal blood flow., Methods: T2*-weighted MRI was performed in 126 singleton pregnancies between 23+6- and 41+3-weeks' gestation. The T2* value was obtained from the placenta and fetal organs (brain, lungs, heart, liver, kidneys, and spleen). In normal BW pregnancies (BW > 10th centile), the correlation between the T2* value and gestational age (GA) at MRI was estimated by linear regression. The correlation between fetal organ Z-score and BW group was demonstrated by boxplots and investigated by analysis of variance (ANOVA) for each organ., Results: In normal BW pregnancies fetal organ T2* was negatively correlated with GA. We found a significant correlation between BW group and fetal organ T2* z-score in the fetal heart, kidney, lung and spleen. A positive linear correlation was demonstrated between fetal organ T2* and outcomes related to placental function such as BW deviation and placenta T2* in all investigated fetal organs except for the fetal liver. In the fetal heart, kidneys, and spleen the T2* value showed a significant correlation with fetal redistribution of blood flow (Middle cerebral artery Pulsatility Index) before delivery., Discussion: Fetal T2* is correlated with BW, placental function, and redistribution of fetal blood flow, suggesting that fetal organ T2* reflects fetal oxygenation and morphological changes related to placental dysfunction., Competing Interests: Declaration of competing interest We declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: The differential diagnosis for a uterine mass and vaginal bleeding after abortion or delivery is broad and includes both benign and malignant causes. A rare etiology for this condition is retained morbidly adherent placenta. Few cases of retained morbidly adherent placenta presenting as a myometrial mass in the setting of vaginal bleeding have been described in the medical literature. In this case series and review of the current literature, we describe the ultrasound features of 3 retained morbidly adherent placentae, along with correlative magnetic resonance imaging findings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Maternal folate deficiency was associated with preeclampsia (PE) and PE was associated with placental maternal vascular malperfusion (MVM). However, no study has examined the association of maternal folate status with placental MVM., Methods: We examined the association of maternal folate status and placental MVM in the Boston Birth Cohort. Primary exposure variables were maternal self-reported multivitamin supplement (<2, 3-5, >5 times/week) per trimester; and plasma folate levels (nmol/L) after birth. Primary outcome was presence/absence of placental MVM defined by the Amsterdam Placental Workshop Group standard classification. Covariates included demographics, chronic hypertension, clinically diagnosed PE, eclampsia and HELLP syndrome, gestational and pre-gestational diabetes, overweight/obesity, maternal cigarette smoking and alcohol use. Associations between folate and placental MVM were evaluated using multivariate logistic regressions., Results: Of 3001 mothers in this study, 18.8% of mothers had PE, 37.5% had MVM. Mothers with the lowest self-reported frequency of folate intake had the highest risk of MVM (OR 1.45, 95% CI 1.03-2.05), after adjusting for the covariates. Consistently, among a subset of 939 mothers with plasma folate levels, folate insufficiency was associated with increased risk of MVM (OR 1.65, 95% CI 1.03-2.63), after adjusting for the covariables. As expected, mothers with low folate and placental MVM had highest rates of PE compared to those of high folate and no MVM (p < 0.001)., Discussion: In this high-risk birth cohort, low maternal folate status was associated with increased risk of placental MVM. Further investigation should explore the association between folate status, placental findings and the great obstetrical syndrome., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Giant chorioangiomas are a potentially life-threatening condition that may require intrauterine therapy. We describe a case of a large chorioangioma (>4cm) diagnosed at 30 weeks of gestation causing severe fetal anemia and hydrops. An intrauterine blood transfusion was performed at 31 weeks with reversal of the anemia and hydrops. The neonate was born at 37 weeks showing respiratory distress syndrome that required neonatal intensive care unit admission but was discharged at 30 days of life. Further evaluation at two months of age showed no signs of abnormal neurodevelopment. When timely indicated, intrauterine transfusion of a hydropic fetus with anemia due to a giant chorioangioma is a potentially life-saving therapy that shows good neurodevelopment of the surviving fetus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Preeclampsia, a multisystem pregnancy-specific hypertensive disorder, results in significant maternal and perinatal morbidity and mortality. This condition is associated with placental histopathological abnormalities and particularly affects the decidual spiral arteries. Reportedly, aspirin prevents preeclampsia, specifically early-onset preeclampsia, although findings in decidual arteries in women treated with aspirin therapy remain unclear. We compared the clinical and histopathological placental findings between women with a history of preeclampsia, who did and did not receive low-dose aspirin therapy (LDA and non-LDA groups, respectively). We identified 26 women with a history of preeclampsia; 9 women received LDA (aspirin ≤ 100 mg/day, initiated at < 16 weeks, LDA group), and 17 women did not receive LDA (non-LDA group). The mean gestational age was higher (36.7 weeks vs. 32.3 weeks, P = 0.0221) and the incidence of preeclampsia was lower (11% vs. 59%, P = 0.0362) in the LDA than in the non-LDA group. Histopathologically, the incidence of decidual arteriopathy, particularly that of fibrinoid necrosis and thrombosis, was lower in the LDA than in the non-LDA group (44% vs. 88%, P = 0.0283). Immunohistologically, endothelial marker (CD31 and CD39) expression was stronger in the LDA than in the non-LDA group. Notably, we observed no significant intergroup differences in inflammatory changes (chronic perivasculitis, protease-activated receptor 1 expression, and CD3-positive cells). This study highlights that LDA inhibits hypertension-induced endothelial injury and thrombosis, and thereby protects maternal placental perfusion and prevents preeclampsia., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Placenta accreta spectrum (PAS) is a major cause of obstetric bleeding in third trimester of pregnancy., Objective: This study aimed to compare the outcomes of uterine preservation surgery vs. hysterectomy in women with PAS., Materials and Methods: In this retrospective cross-sectional study, the records of 68 women with PAS referred to the Imam Khomeini hospital in Ahvaz, Iran, between March 2015 and February 2020 were included. The women were divided into 2 groups according to surgical approach: hysterectomy vs. uterine preservation (including just removing the lower segment, removing the lower segment with uterine artery ligation, or removing the lower segment with hypogastric artery ligation during cesarean section). The need for blood components transfusion (whole blood, packed cells, and fresh frozen plasma), maternal mortality, duration of surgery, and length of hospitalization were compared between groups., Results: In total, we investigated 68 women between the ages of 24-45 yr (mean age of 32.88 ± 5.08 yr). All participants were multiparous and underwent cesarean section. Furthermore, 28 women (41.2%) had a history of curettage. In total, 24 women (35.3%) underwent a hysterectomy, and 44 (64.7%) underwent uterine preservative surgeries. There were no significant differences between groups of hysterectomy and uterine preservative surgeries in terms of the need for blood components transfusion, maternal mortality, duration of surgery, and length of hospitalization., Conclusion: The results of this study showed no significant difference between groups regarding the studied outcomes. Therefore, conservative surgeries could be used to preserve the uterus instead of hysterectomy in women with PAS., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Mohammad Jafari et al.)

Introduction Cocaine use during pregnancy can affect fetal brain development. A fetal brain injury could happen from the direct effect of cocaine on the developing brain or from the reduction of placental perfusion from vasoconstriction, which may lead to hypoxia-ischemia. A potential mechanism for brain injury could be due to a neurotransmitter imbalance within the brain, especially glutamate. In an immature rat brain synaptosome model, we explored the additive effect of cocaine alone on glutamate release and the effect of cocaine combined with simulated hypoxic depolarization using potassium as a surrogate. Method Rat pups' brains were dissected and placed on a chilled petri dish. They then entered the experimental protocol. The suspended synaptosomes were divided equally into four experimental groups (control, high potassium "surrogate to hypoxic stimulation," cocaine, and cocaine + high K). Reversed-phase high-performance liquid chromatography analyzed glutamate with fluorescent detection Results The glutamate level was lowest in the cocaine-only group, with a level of 1.96 × 10 4 , compared to the control and high potassium group. However, combining cocaine with high potassium seemed to generate a synergistic effect, achieving the highest glutamate level of all groups with a value of 5.31 × 10 4 . Post hoc Conover's test for multiple pairwise-comparison between groups was done. In comparing various solutions to control, we did not find a statistically significant difference with the cocaine-only solution with a p-value of 0.074. Also, on comparing various other solutions to each other, there was no statistically significant difference between cocaine vs. cocaine + high potassium a p-value of 0.074. Conclusion Our data support the conclusion that cocaine alone does not induce glutamate release from fetal rat brain synaptosomes. Exposure to high potassium does lead to glutamate release. However, cocaine greatly enhances glutamate release in the presence of high potassium levels. This could explain how cocaine affects brain maturation during pregnancy with a low oxygen tension environment in the placenta. This hypothesis should be tested in vivo., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Penning et al.)

Background: Understanding the causes of perinatal death can provide relevant information to couples, caregivers, and society. Classification systems play a crucial role in identifying the most relevant conditions suggesting preventive measures for decreasing stillbirth (SB). In 2016 the International Classification of Disease to Deaths during the Perinatal Period (ICD-PM) was released with the aim to suggest a universally accepted classification., Methods: This is a prospective cohort study that enrolled all SBs occurred in Emilia-Romagna, from 2014 to 2017. We prospectively applied ReCoDe classification and retrospectively used Simplified CODAC classification and ICD-PM. The aim of this study is to compare different classification systems on a cohort of SBs, undergoing a comprehensive workup, to establish what classification minimizes rates of unexplained SB., Results: We registered 443 SBs. According to ReCoDe the largest category of SB was "placental insufficiency/infarction" (16.9%), followed by "abruptio placentae" (14.2%). Unexplained cases are 16.7%. Gestational age <37 weeks is less frequent in the group of women with unclassified SB (OR 0.50, OR95%CI [0.3-0.8]) against women with classified SB. Considering CODAC the two largest categories are "infarctions or thrombi" (16.3%) and "abruption or retro-placental haematoma" (15.1%), instead only 17.2% of cases remained unexplained., Conclusions: Comparing ReCoDe and CODAC we found no real difference in any category. ReCoDe and CODAC better underlines the primary cause of death. ICD-PM reveals to be easily applicable to clinical practice. ICD-PM has the lowest rate of unexplained SBs (9.3%) due to the structure itself and not to a deeper comprehension of death.