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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.)

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 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.)

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.)

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.)

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.)

The aim of this study is to verify the role of laminar necrosis (LN) in the diagnosis of hypoxic damage of the placenta. This is a retrospective case-control study in which 50 cases with laminar necrosis were compared with 100 gestational age-matched controls without laminar necrosis in a 1:2 ratio. The parameters analyzed were: the presence of other placental lesions, obstetric characteristics and neonatal outcome. For each of the 50 cases, the area affected by the lesion was detected, and the lesions were classified into three groups based on the morphology and time of onset of the lesion in order to understand whether these characteristics of the lesion had a clinical-pathology. The results showed that including the search for LN among placental lesions generally examined is useful to guide the pathologist in the diagnosis of placental dysfunction of hypoxic origin.

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29 +5 to 40 +4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

Background Determination of placentation and amnionicity is important for antenatal and intrapartum management in twin gestations. We present an typical monozygotic twin placenta and underscore the sonographic features and diagnostic pitfalls that may interfere with antenatal diagnosis. Case report: A 35-year-old G4P2 with a spontaneous pregnancy applied for routine second trimester anomaly screening. Upon prenatal ultrasonography at 20 weeks, an anatomically normal, same sex twin pregnancy was detected. A thin dividing membrane and a T-sign suggestive of a monochorionic diamniotic pregnancy were visualized. Antenatal follow-up was uneventful. Cesarean delivery was performed at 37 week. Postpartum examination revealed two distinct placental discs connected with each other through membranes. Microscopic examination of the membranes supported monochorionicity. Short Tandem Repeat Profile Analysis revealed identical pattern and confirmed monozygosity. Conclusion: Two separate placentas with a T-sign in same-sex twins should raise the suspicion of monozygosity, and should be followed accordingly.

Objective: This study aims to estimate the association between abnormal placental histopathology, fetal growth restriction (FGR), and preeclampsia (PEC) in twin pregnancies., Study Design: Retrospective cohort study of women with diamniotic twin pregnancies with live births at ≥24 weeks of gestation and available placental pathology. Findings were compared between women with and without FGR, which was defined as a birthweight <10th percentile, using singleton and twin growth curves, and those with and without PEC. The primary study outcome was a composite of abnormal placental histopathology. Chi-square, Fisher's exact, and Student's t -tests were used for analysis., Results: Among 859 patients with diamniotic twins, 806 (93.8%) had placental pathology. A total of 422 (52.4%) women had at least one twin with FGR, using a singleton growth curve. FGR affected 136 (16.9%) pregnancies when a twin growth curve was applied. There was no significant difference in composite outcome between groups, using either growth curve (45.5 vs. 44.8%, p  = 0.84; adjusted odds ratio (aOR): 1.06, 95% CI: 0.79-1.40 and 52.2 vs. 43.7%, p  = 0.07; aOR: 1.44, 95% CI: 0.90-2.10). A total of 122 of 789 (15.5%) patients developed PEC. There was no significant difference in composite outcome between patients with and without PEC (41.8 vs. 45.4%, p  = 0.46; aOR: 0.79, 95% CI: 0.53-1.18)., Conclusion: In twin pregnancies, FGR and PEC are not associated with abnormal placental histopathology. This suggests that the pathologic placental manifestations of these conditions may differ in twins and include factors other than those commonly described in singletons., Competing Interests: None declared., (Thieme. All rights reserved.)

Normal placental development and function is of key importance to fetal growth. Conversely aberrations of placental structure and function are evident in pregnancy complications including fetal growth restriction (FGR) and preeclampsia. Although trophoblast turnover and function is altered in these conditions, their underlying aetiologies and pathophysiology remains unclear, which hampers development of therapeutic interventions. Here we review evidence that supports a role for estrogen related receptor-gamma (ESRRG) in the development of placental dysfunction in FGR and preeclampsia. This relationship deserves particular consideration because ESRRG is highly expressed in normal placenta, is reduced in FGR and preeclampsia and its expression is altered by hypoxia, which is thought to result from deficient placentation seen in FGR and preeclampsia. Several studies have also found microRNA (miRNA) or other potential upstream regulators of ESRRG negatively influence trophoblast function which could contribute to placental dysfunction seen in FGR and preeclampsia. Interestingly, miRNAs regulate ESRRG expression in human trophoblast. Thus, if ESRRG is pivotally associated with the abnormal trophoblast turnover and function it may be targeted by microRNAs or other possible upstream regulators in the placenta. This review explores altered expression of ESRRG and upstream regulation of ESRRG-mediated pathways resulting in the trophoblast turnover, placental vascularisation, and placental metabolism underlying placental dysfunctions. This demonstrates that the ESRRG pathway merits further investigation as a potential therapeutic target in FGR and preeclampsia.

Objectives: This study was conducted in order to establish the joint Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) guidelines on placenta accreta spectrum (PAS) disorders and propose strategies to standardize image acquisition, interpretation, and reporting for this condition with MRI., Methods: The published evidence-based data and the opinion of experts were combined using the RAND-UCLA Appropriateness Method and formed the basis for these consensus guidelines. The responses of the experts to questions regarding the details of patient preparation, MRI protocol, image interpretation, and reporting were collected, analyzed, and classified as "recommended" versus "not recommended" (if at least 80% consensus among experts) or uncertain (if less than 80% consensus among experts)., Results: Consensus regarding image acquisition, interpretation, and reporting was determined using the RAND-UCLA Appropriateness Method. The use of a tailored MRI protocol and standardized report was recommended., Conclusions: A standardized imaging protocol and reporting system ensures recognition of the salient features of PAS disorders. These consensus recommendations should be used as a guide for the evaluation of PAS disorders with MRI., Key Points: • MRI is a powerful adjunct to ultrasound and provides valuable information on the topography and depth of placental invasion. • Consensus statement proposed a common lexicon to allow for uniformity in MRI acquisition, interpretation, and reporting of PAS disorders. • Seven MRI features, namely intraplacental dark T2 bands, uterine/placental bulge, loss of low T2 retroplacental line, myometrial thinning/disruption, bladder wall interruption, focal exophytic placental mass, and abnormal vasculature of the placental bed, reached consensus and are categorized as "recommended" for diagnosing PAS disorders.

Introduction: Chronic histiocytic intervillositis (CHI) is a placental disease that has been associated with unfavorable obstetric outcomes in small, noncomparative series. The objective was to measure the excess risk of adverse obstetric outcomes associated with the discovery of CHI after birth., Methods: Retrospective single-center case-control study from 2000 through 2016. The case patients had a CHI diagnosis after a pathology analysis of the placenta. Two types of controls were defined for each case: low-risk control women were those who gave birth in our hospital immediately before each case patient, and the high-risk controls were the next women after each case for whom microscopic examination of the placenta was indicated., Results: We observed 111 cases of CHI during the study period. Compared with the 111 low-risk controls, the cases had a significantly higher frequency of late miscarriages (5.4 vs 0.0%, p < .03), small for gestational age (SGA) babies <3rd centile (70.4 vs 0.9%, p < .001, OR 140, 95% CI, 19.9-2800), and in utero deaths (35.1 vs 0.9%, p < .001, OR 59.6, 95% CI 8.5-1192), with significantly fewer children surviving to discharge (54.9 vs 99.1%, p < .001, OR 0.01, 95% CI, 0.00-0.08). All of these factors also differed significantly compared with the high-risk women (severe SGA: OR 3.7, 95% CI 1.9-7.0; in utero death: OR 4.1, 95% CI 1.9-8.7; children surviving to discharge: OR 0.27, 95% CI, 0.14-0.52)., Discussion: Even compared with high-risk pregnancies, CHI is a severe placental disease associated with a substantial excess rate of late miscarriages, severe SGA and in utero death., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Placental abnormalities, therefore, can be an "early warning system" for fetal problems. A complete prenatal sonographic examination of the placenta is an essential component as its abnormalities can have a direct effect on fetal or maternal outcomes, obstetrical management and future fertility., Objective: To determine whether any association exists between the finding of an increased thickness of placenta, abnormal placenta shape, placental calcification, placental lake and abnormal cord insertion site at 20-22 and 30-32 weeks gestation with an increased risk of uteroplacental complications or a poor pregnancy outcome., Methodology: A real-time ultrasound was used at the time of detail scan (at 20-22 weeks gestation) and at 30-32 weeks gestation to look for placenta appearance, fetal growth and anomaly. The main outcome measures were risk of hypertension disease in pregnancy, fetal growth restriction and poor fetal outcomes such as low Apgar score and low cord pH., Result: The majority of the participants were Malay (77.9%). Abnormal placenta found at both gestations were placental lakes and thickness, and only one case had marginal cord insertion. Approximately 6% of the cases were confirmed placenta previa. No abnormal shape or abnormal calcification found at both gestations. About 10% patient developed hypertensive disease in pregnancy, 15% of the fetus was found to have growth restriction and another 16% have low umbilical cord pH. Majority of them delivered at term (90%) and via vaginal delivery (81%). There was no significance between presence of abnormal placental lake and thickness at both gestations with the maternal and fetal outcome., Conclusion: Presence of abnormal placental thickness and lakes at 30-32 weeks scan associated with maternal hypertensive disease, fetal growth restriction and low umbilical cord pH, however these were not statistically significant.

Placenta vascular lesions are a group of distinct yet related entities that include chorangiomas and diffuse multifocal chorangiomatosis. Chorangioma is an expansive nodular lesion with an incidence of about 1%. Diffuse multifocal chorangiomatosis is rare (0.2%) and mostly seen in placentas before the 32nd gestational week. The authors present a case of a monochorionic/biamniotic twin pregnancy, in which, at the 26th gestational week, one fetus developed intrauterine growth restriction (IUGR), hydrops, and anemia associated with a tumor of the placenta with increased vascularization in the Doppler study. Pathological examination of the placenta diagnosed diffuse multifocal chorangiomatosis. This rare case report of diffuse multifocal chorangiomatosis with prenatal manifestations resembling those of a chorangioma proves that prenatal ultrasound detection of a placenta tumor, with increased vascularization at Doppler study, must raise other diagnostic possibilities beside chorangioma.

Inadequate placental development results in a number of untoward pregnancy outcomes, including pre-eclampsia, placental abruption and infarction, and fetal growth restriction and stillbirth. Although it was once assumed that these pregnancy-related complications caused only upfront maternal and fetal morbidity and mortality, poor placental development and function is now a well-recognized female-specific risk factor for future vascular morbidity and mortality. The epidemiological, genetic, and physiological research linking placental development and cardiovascular disease is growing, and this knowledge will undoubtedly not only translate into improved pregnancy outcomes for at-risk women, but also help to identify which women who had a complicated pregnancy could benefit from long-term follow-up and risk modification for cardiovascular disease. This article reviews the literature and provides suggestions for future follow-up of this vulnerable population of women., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/purpose: The mechanisms of intrauterine vascular disruptions that result in the development of jejunoileal atresia (JIA) are not fully understood. Monochorionic twinning with fetal death of a cotwin is known to be correlated with the development of JIA in the survivor through placental communication. The aim of this study was to evaluate whether other placental vascular compromises might contribute to the development of JIA., Methods: Forty-five newborns (23 boys and 22 girls) who were treated for JIA at Tsukuba University Hospital from 1978 to 2003 were reviewed. Placental findings were informative in 23 cases., Results: No or slight abnormality of the placenta was found in 19 cases. Significant placental abnormalities were found in 4 patients who also had a low birth weight. One patient with apple peel atresia (APA) had excessive torsion of the umbilical cord (UC), which was inserted at the margin of the placenta, and there was an adjacent area of infarction. One patent with multiple atresia (MA) was a surviving monochorionic twin with intrauterine fetal death of the other. Another case of MA showed marginal insertion of the UC. Severe placental abnormalities including wide infarction, cyst formation, and marginal insertion of the UC were found in 1 case of MA. These 3 cases of MA were complicated with other anomalies including brain anomaly., Conclusions: Placental vascular compromises were involved infrequently in JIA but might possibly be responsible for the development of JIA as well as associated anomalies and a low birth weight as chronic insults since an early stage of gestation in some cases.

The purpose of the present study was to analyse correlation interactions between parameters of uterine-placental blood flow (UPF) and some enzymes of blood of 77 pregnant women with high risk of perinatal pathology, divided into 4 groups. Eleven correlation connections between parameters of blood flow and enzymes of blood were found in the first group of pregnant women without disturbance in UPF. In the pregnant women with a reduction in blood flow in the region of the large uterine-placental vessels there was dissociation of a large part of the aforementioned correlation connections as only 4 ware preserved (26.67%). New correlation connections occurred between oxytocinase and parameters of UPF. We found dissociation of all correlation connections between parameters of UPF and blood enzymes in the third group of pregnant women with a reduction of UPF in the whole uterine-placental blood flow. New correlation connections between alkaline and thermostable phosphatase in parameters of UPF were formed. Ten out of eleven correlation connections dissociated in the four group of pregnant women with a reduction of UPF only in the intervillous space. New correlation connections were formed between parameters of UPF and hydroxybutyrate dehydrogenase and lactate dehydrogenase. Having in mind the performed analysis of correlation interconnections between parameters of UPF and some blood enzymes we could assume that activation of various enzymic systems, forming links of adaptation-compensatory mechanisms of the placental system, occurs in the development of placental insufficiency.

The aim of the present study was to examine metabolic processes in pregnant women with high risk of perinatal pathology during disturbance in the uterine-placental blood flow (UPF). We determined the following parameters for evaluation of the metabolic disturbances: alanine aminotransferase, hydroxybutyrate dehydrogenase, lactate dehydrogenase, creatine phosphokinase, alkaline phosphatase, thermostable alkaline phosphatase, oxytocinase and lipid peroxidation. The analysis of the obtained data showed that reduction in UPF, limited only in the region of the large uterine-placental blood vessels, was accompanied by a reduction in the activity of HBDH, LDG, CPC, but moderate increase in the whole uterine-placental blood bed was accompanied by the intravillous space, was accompanied by a moderate increase in HBDH, ADG, CPC and AP in comparison with pregnant women without disturbance in UPF, which however occurred in smaller activity of these enzymes both in disturbance in blood flow of intervillous space and in the region of the large uterine-placental blood vessels. These changes as a whole characterized borderline state of energetic metabolism in the organism of the pregnant woman, which in the final analysis assured comparatively favourable outcome of the pregnancy for the fetus.