Umbilical artery Thrombosis: A case report of prenatal diagnosis and systematic review of the literature.

Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still unclear but it is often associated with anatomical cord abnormalities that leads to blood stasis and thrombosis formation. Other possible risk factors are maternal thrombophilia, autoimmune disease, gestational diabetes, hypertension disorders of pregnancy and Rh-alloimmunization. The most common clinical symptom is the reduction of fetal movements. The diagnosis is histopathological, but it can be suspected by clinical and prenatal ultrasound findings. Generally, the first choice therapy is the immediate delivery with cesarean section. This study reported a case of a spontaneous intrauterine UAT in a low-risk pregnancy and a systematic review of the literature on clinical, ultrasound and histopathological findings of UAT, in order to help clinicians in the diagnostic process and management of this rare complication.

Early Fetal Growth Restriction with or Without Hypertensive Disorders: a Clinical Overview.

Early onset fetal growth restriction (FGR) is one of the main adverse pregnancy conditions, often associated with poor neonatal outcomes. Frequently, early onset FGR is associated with early onset hypertensive disorders of pregnancy (HDP), and in particular preeclampsia (PE). However, to date, it is still an open question whether pregnancies complicated by early FGR plus HDP (FGR-HDP) and those complicated by early onset FGR without HDP (normotensive-FGR (n-FGR)) show different prenatal and postnatal outcomes and, consequently, should benefit from different management and long-term follow-up. Recent data support the hypothesis that the presence of PE may have an additional impact on maternal hemodynamic impairment and placental lesions, increasing the risk of poor neonatal outcomes in pregnancy affected by early onset FGR-HDP compared to pregnancy affected by early onset n-FGR. This review aims to elucidate this poor studied topic, comparing the clinical characteristics, perinatal outcomes, and potential long-term sequelae of early onset FGR-HDP and early onset n-FGR.

Reconsideration of the Diagnostic Criteria for an Atypical Placental Site Nodule Comparing Typical Placental Site Nodule of the Uterus: A Report of Two Cases.

Placental site nodules (PSNs) are non-neoplastic remnants of chorionic-type intermediate trophoblastic cells from a previous gestation that form a well-defined single nodule or multiple nodules in the uterine and extrauterine sites. As the cases of PSNs transformed into gestational trophoblastic tumors were described in the literature, "atypical placental site nodules" (APSNs) have been considered as putative transitional lesions between PSNs and gestational trophoblastic tumors. Although histologic criteria and cutoff point of Ki-67 proliferation index for differentiating an APSN from a typical PSN have not been clearly defined, nodules larger than 5 mm with increased cellularity, a corded or nested appearance, marked nuclear atypia, increased mitotic activity, and an increased Ki-67 proliferation index (>5% or >8%) of intermediate trophoblastic cells seem to be accepted as diagnostic criteria for APSNs. However, some of the criteria, including lesion size and histologic features of the trophoblastic cells in the nodule are not only subjective but have features inherent of the intermediate trophoblastic cells of the fetal membrane and a typical PSN. We thought that it is not reasonable to consider them as diagnostic features of APSNs, if not associated with cellular proliferation. We present 2 cases of incidentally identified PSNs that were larger than 10 mm in size with a corded or nested arrangement of trophoblastic cells, which could have been categorized as APSNs according to the currently proposed criteria to discuss whether the currently proposed diagnostic criteria for APSNs are appropriate.

[Research progress on the effect of mitochondrial and endoplasmic reticulum stress caused by hypoxia during pregnancy on preeclampsia and intrauterine growth restriction].

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.

Pregnancy complicated with adrenal adenoma causing ACTH-independent Cushing's syndrome, accompanied by obstetric antiphospholipid syndrome and severe pre-eclampsia: case report and literature review.

This case report shares the management experience of a patient with pregnancy combined with adrenal adenoma causing ACTH-independent Cushing's syndrome (CS), accompanied by obstetric antiphospholipid syndrome (OAPS) and severe pre-eclampsia. The case was a 26-year-old that presented with typical clinical symptoms and signs of CS. The patient had a history of 4 spontaneous abortions in the last 4 years. The 24-hour urinary free cortisol was significantly increased, an abnormal cortisol circadian rhythm was demonstrated by a high late-night salivary cortisol, blood ACTH was suppressed (< 1ng/dL), anticardiolipin antibody was positive, and imaging examination showed an adrenal tumor. The patient underwent laparoscopic adrenal tumor resection under general anesthesia at 23 weeks of gestation. The tumor was pathologically confirmed to be an adrenocortical adenoma. The patient underwent a cesarean section at 39 weeks of gestation to give birth to a healthy baby girl with an Apgar score of 10. Pregnancy complicated by CS is clinically rare, easily masked by normal physiological changes of pregnancy, and is difficult to diagnose. The determination of 24-hour urinary free cortisol, the circadian rhythm of serum cortisol, ultrasound, and MRI can be helpful in the diagnosis of CS during pregnancy. Surgery is the first choice for the treatment of CS during pregnancy. As a subtype of antiphospholipid syndrome, patients with OAPS are prone to thrombotic events and recurrent miscarriages if not treated accordingly. To our knowledge no cases of CS with OAPS and severe pre-eclampsia have been reported. We summarize the experience of the treatment of this patient and review the literature to improve clinicians' awareness of this disease.

Influence of maternal psychological distress during COVID-19 pandemic on placental morphometry and texture.

The Coronavirus Disease 2019 (COVID-19) pandemic has been accompanied by increased prenatal maternal distress (PMD). PMD is associated with adverse pregnancy outcomes which may be mediated by the placenta. However, the potential impact of the pandemic on in vivo placental development remains unknown. To examine the impact of the pandemic and PMD on in vivo structural placental development using advanced magnetic resonance imaging (MRI), acquired anatomic images of the placenta from 63 pregnant women without known COVID-19 exposure during the pandemic and 165 pre-pandemic controls. Measures of placental morphometry and texture were extracted. PMD was determined from validated questionnaires. Generalized estimating equations were utilized to compare differences in PMD placental features between COVID-era and pre-pandemic cohorts. Maternal stress and depression scores were significantly higher in the pandemic cohort. Placental volume, thickness, gray level kurtosis, skewness and run length non-uniformity were increased in the pandemic cohort, while placental elongation, mean gray level and long run emphasis were decreased. PMD was a mediator of the association between pandemic status and placental features. Altered in vivo placental structure during the pandemic suggests an underappreciated link between disturbances in maternal environment and perturbed placental development. The long-term impact on offspring is currently under investigation.

Placental lesions associated with stillbirth by gestational age, according to feature importance: Results from the stillbirth collaborative research network.

INTRODUCTION: Previous studies have identified lesions commonly found in placentas associated with stillbirth but have not distinguished across a range of gestational ages (GAs). The objective of this study was to identify lesions associated with stillbirths at different GAs by adapting methods from the chemical machine learning field to assign lesion importance based on correlation with GA. METHODS: Placentas from the Stillbirth Collaborative Research Network were examined according to standard protocols. GAs at stillbirth were categorized as: <28 weeks (extreme preterm stillbirth [PTSB]), 28-33'6 weeks (early PTSB), 34-36'6 weeks (late PTSB), ≥37 weeks (term stillbirth). We identified and ranked the most discriminating placental features, as well as those that were similar across GA ranges, using Kernel Principal Covariates Regression (KPCovR). RESULTS: These analyses included 210 (47.2%) extreme PTSB, 85 (19.1%) early PTSB, 62 (13.9%) late PTSB, and 88 (19.8%) term stillbirths. When we compute the KPCovR, the first principal covariate indicates that there are four lesions (acute funisitis & nucleated fetal red blood cells found in extreme PTSB; multifocal reactive amniocytes & multifocal meconium found in term stillbirth) that distinguish GA ranges among all stillbirths. DISCUSSION: There are distinct placental lesions present across GA ranges in stillbirths; these lesions are identifiable using sophisticated feature selection. Further investigation may identify histologic changes across gestations that relate to fetal mortality.

Villitis of unknown etiology, chronic deciduitis, chronic chorioamnionitis and chronic histiocytic intervillositis in monozygotic and dizygotic twin pregnancies. A retrospective analysis of 16 cases.

INTRODUCTION: Villitis of unknown etiology (VUE), chronic chorioamnionitis (CC), chronic deciduitis (CD) and chronic histiocytic intervillositis (CHI) are most likely the result of a pathologic immune reaction caused by maternal anti-fetal rejection. We analyzed placentas of twin pregnancies with manifestation of these lesions in monozygotic and dizygotic instances. METHODS: Twin pregnancies from our archive with at least one chronic inflammatory lesion were selected for further analysis and assessed concerning zygosity (gender, chorionicity, short tandem repeat (STR)-analysis). RESULTS: The cohort comprised sixteen twin placentas, monozygotic in five cases and dizygotic in 11 cases, respectively. VUE (n = 4), CC (n = 1) and CHI (n = 3) manifested concordantly in both placentas of the monozygotic pregnancies and affected discordantly one of the twin placentas in the dizygotic instances. CD (n = 10) manifested concordantly in two and discordantly in one of the monozygotic placentas, and concordantly in three and discordantly in four of the dizygotic instances. Intrauterine fetal demise (n = 3), preterm birth (n = 9) and low birth weight (n = 2) were recognized. Discordant fetal growth in live born children was recognized in two dizygotic cases with discordant manifestation of VUE and CHI. DISCUSSION: The concordant manifestation of VUE, CC and CHI in monozygotic and the discordant pattern of inflammation in dizygotic pregnancies points to pathologic immune mechanisms against genetically determined fetal antigens being essential for the development of these entities. The heterogenous manifestation of CD could be a hint for diverse fetal or maternal etiologic factors that may contribute to this lesion.

Maternal Inflammatory Bowel Disease During Pregnancy and Infectious Disease in Offspring Younger Than 5 Years: A Population-Based Cohort Study.

INTRODUCTION: Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes. METHODS: This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis. RESULTS: Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection. DISCUSSION: Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD.

Association of intraplacental oxygenation patterns on dual-contrast MRI with placental abnormality and fetal brain oxygenation.

OBJECTIVES: Most human in-vivo placental imaging techniques are unable to distinguish and characterize various placental compartments, such as the intervillous space (IVS), placental vessels (PV) and placental tissue (PT), limiting their specificity. We describe a method that employs T2* and diffusion-weighted magnetic resonance imaging (MRI) data to differentiate automatically placental compartments, quantify their oxygenation properties and identify placental lesions (PL) in vivo. We also investigate the association between placental oxygenation patterns and fetal brain oxygenation. METHODS: This was a prospective study conducted between 2018 and 2021 in which dual-contrast clinical MRI data (T2* and diffusion-weighted MRI) were acquired from patients between 20 and 38 weeks' gestation. We trained a fuzzy clustering method to analyze T2* and diffusion-weighted MRI data and assign placental voxels to one of four clusters, based on their distinct imaging domain features. The new method divided automatically the placenta into IVS, PV, PT and PL compartments and characterized their oxygenation changes throughout pregnancy. RESULTS: A total of 27 patients were recruited, of whom five developed pregnancy complications. Total placental oxygenation level and T2* did not demonstrate a statistically significant temporal correlation with gestational age (GA) (R2 = 0.060, P = 0.27). In contrast, the oxygenation level reflected by T2* values in the placental IVS (R2 = 0.51, P = 0.0002) and PV (R2 = 0.76, P = 1.1 × 10-7 ) decreased significantly with advancing GA. Oxygenation levels in the PT did not show any temporal change during pregnancy (R2 = 0.00044, P = 0.93). A strong spatial-dependent correlation between PV oxygenation level and GA was observed. The strongest negative correlation between PV oxygenation and GA (R2 = 0.73, P = 4.5 × 10-7 ) was found at the fetal-vessel-dominated region close to the chorionic plate. The location and extent of the placental abnormality were automatically delineated and quantified in the five women with clinically confirmed placental pathology. Compared to the averaged total placental oxygenation, placental IVS oxygenation level best reflected fetal brain oxygenation level during fetal development. CONCLUSION: Based on clinically feasible dual-MRI, our method enables accurate spatiotemporal quantification of placental compartment and fetal brain oxygenation across different GAs. This information should improve our knowledge of human placenta development and its relationship with normal and abnormal pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Patterns of placental injury in various types of fetal congenital heart disease.

OBJECTIVES: Fetal blood circulation may be modified in congenital heart disease (CHD). This retrospective analysis was performed to study whether the type of CHD is associated with specific placental pathology. METHODS: Three types of CHD based on presumed proportion of placental and systemic blood distribution in fetal circulation were analyzed: Group 1: 89 cases with low placental blood content (hypoplastic left heart syndrome, transposition of great arteries, coarctation of aorta), Group 2: 71 placentas with intermediate placental and systemic blood content due to increased intracardiac blood mixing (tetralogy of Fallot, truncus arteriosus, double inlet/outlet ventricle), and Group 3: 24 placentas with high placental blood content (tricuspid or pulmonary atresia, Ebstein anomaly). Frequencies of 27 independent clinical and 47 placental phenotypes of 184 placentas in those three groups were statistically compared. RESULTS: The most advanced gestational age at delivery, and large vessel (global) fetal vascular malperfusion (FVM) were most common in Group 1, while macerated stillbirths, neonatal mortality, abnormal amniotic fluid volume (oligohydramnios or polyhydramnios), other congenital anomalies, distal villous lesions of FVM, placental edema and amnion nodosum were most common in Groups 2 and 3, although the frequencies of placental lesions were statistically not significant. CONCLUSIONS: Left heart obstructive lesions potentially associated with brain maldevelopment show increase in lesions of global FVM (in aggregate and individually fetal vascular ectasia, stem vessel obliteration and intramural fibrin deposition) as may be seen in umbilical cord compromise. CHD with increased intracardiac blood mixing or with right heart defects is associated with average preterm gestational age at delivery and placental lesions of distal villous FVM, villous edema and amnion nodosum.

Histopathological features of pemphigoid gestationis and polymorphic eruption of pregnancy: A blinded retrospective comparative study of 31 cases.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) are pregnancy-related dermatoses. Definitive diagnosis often relies upon histopathology and direct immunofluorescence (DIF). PG is associated with fetal and neonatal risks, while PEP confers minimal risk. OBJECTIVE: We aimed to compare histopathologic features to determine key differentiators. METHODS: A retrospective cohort study of PG and PEP cases, with accompanying DIF, conducted from 1995 to 2020. Skin biopsies were examined independently in a blinded fashion by two dermatopathologists for a list of histopathological features. RESULTS: Twenty-one cases of PG and 10 cases of PEP were identified. PG had significantly denser eosinophils than PEP (mean 155 vs. 48 cells/5 hpf; p < 0.018). PG was also noted to have eosinophilic spongiosis and eosinophils at the dermal-epidermal junction more frequently compared to PEP (80% PG vs. 10% PEP; p < 0.001). A mean cutoff value of 86 eosinophils and a mean optimal sensitivity and specificity of 81% and 83%, respectively, for eosinophils density's diagnostic power of PEP versus PG were achieved. Subepithelial separation was exclusively seen in PG (40% vs. 0%; p < 0.007). CONCLUSION: Eosinophilic spongiosis, eosinophilic epitheliotropism, and dense superficial dermal eosinophils were diagnostic of PG. Given overlapping clinicopathologic features, however, DIF results with clinicopathologic correlation, remain the gold standard.

Progress of oxidative stress in endometrium decidualization.

The difficulty in maintaining the balance between oxides and antioxidants causes a phenomenon named oxidative stress. Oxidative stress often leads to tissue damage and participates in the pathogenesis of a series of diseases. Decidua provides the 'soil' for embryo implantation, and the normal decidualization shows the characteristics of strong antioxidation. Once the mechanism of antioxidant stress goes awry, it will lead to a series of pregnancy-related diseases. In recent years, more and more studies have shown that oxidative stress is involved in pregnancy-related diseases caused by abnormal decidualization of the endometrium. In order to have a more comprehensive understanding of the role of oxidative stress in decidual defect diseases, this paper reviews the common decidual defect diseases in conjunction with relevant regulatory molecules, in order to arouse thinking about the importance of oxidative stress, and to provide more theoretical basis for the aetiology of decidual defects.

Analysis of the relationship between placental histopathological aspects of preterm and term birth.

OBJECTIVES: This study aims to establish a correlation between placental histopathological and immunohistochemical (IHC) changes and preterm birth with fetal growth restriction (FGR, formerly called intrauterine growth restriction - IUGR). PATIENTS, MATERIALS, AND METHODS: This prospective study was performed on a group of 30 parturients, with singleton gestation, of which 15 patients gave birth at term, and the other 15 patients gave birth prematurely. After the statistical correlation of the clinical and demographic data with premature birth (PB) and term birth (TB), we performed histological and IHC research on the respective placentae. To observe normal and pathological microscopic placental structures, we used the Hematoxylin-Eosin (HE) and Periodic Acid Schiff-Hematoxylin (PAS-H) classical stainings, but also special immunostaining with anti-cluster of differentiation 34 (CD34) and anti-vascular endothelial growth factor (VEGF) antibodies. RESULTS: We found a statistically significant difference between the TB∕PB categories and the age of the patients, their antepartum weight, the weight of the newborns, and the placenta according to the sex of the newborn. Histological analysis revealed in the case of TB, small areas of perivillous amyloid deposition, with the significant extension of these areas both intravillous and perivillous in the case of PB. Massive intravillous calcifications, syncytial knots, and intravillous vascular thrombosis were also frequently present in PB. With PAS-H staining were highlighted the intra∕extravillous vascular basement membranes, but especially the massive fibrin deposits rich in glycosaminoglycans. By the IHC technique with the anti-CD34 antibody, we noticed the numerical vascular density, higher in the case of TB, but in the case of PB, there were large areas of placental infarction, with a lack of immunostaining in these areas. Through the anti-VEGF antibody, we observed the presence of signal proteins that determined and stimulated the formation of neoformation vessels in the areas affected by the lack of post-infarction placental vascularization. We observed a highly significant difference between placental vascular density between TB∕PB and newborn weight, sex, or placental weight. CONCLUSIONS: Any direct proportional link between the clinical maternal-fetal and histological elements yet studied must be considered. Thus, establishing an antepartum risk group can prevent a poor pregnancy outcome.

Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on magnetic resonance imaging in very preterm infants.

BACKGROUND: The independent risk for neurodevelopmental impairments attributed to chorioamnionitis in premature infants remains controversial. Delayed brain maturation or injury identified on magnetic resonance imaging at term-equivalent age can be used as a surrogate measure of neurodevelopmental impairments that is less confounded by postdelivery neonatal intensive care unit environmental factors to investigate this relationship more clearly. OBJECTIVE: This study aimed to determine whether preterm infants born with moderate to severe acute histologic chorioamnionitis would have a higher magnetic resonance imaging-determined global brain abnormality score, independent of early premature birth, when compared with preterm infants with no or mild chorioamnionitis. STUDY DESIGN: This was a prospective, multicenter cohort study involving infants born very prematurely ≤32 weeks' gestational age with acute moderate to severe histologic chorioamnionitis, graded using standard histologic criteria. Brain abnormalities were diagnosed and scored using a well-characterized, standardized scoring system captured using a high-resolution 3 Tesla magnetic resonance imaging research magnet. In secondary analyses, total brain volume and 4 magnetic resonance imaging metrics of cortical maturation (cortical surface area, sulcal depth, gyral index, and inner cortical curvature) were calculated using an automated algorithm and correlated with chorioamnionitis. The association of funisitis (any grade) with brain abnormalities was also explored. We investigated if premature birth mediated the relationship between histologic chorioamnionitis and brain abnormality score using mediation analysis. RESULTS: Of 353 very preterm infants, 297 infants had mild or no chorioamnionitis (controls), and 56 were diagnosed with moderate to severe acute histologic chorioamnionitis. The primary outcome brain abnormality score was significantly higher in histologic chorioamnionitis-exposed infants than in the controls (median, 4 vs 7; P<.001). Infants with acute histologic chorioamnionitis had significantly lower brain tissue volume (P=.03) and sulcal depth (P=.04), whereas other morphometric indices did not differ statistically. In the multiple regression analysis, we observed persistent significant relationships between moderate to severe acute histologic chorioamnionitis and brain abnormality scores (ß=2.84; 1.51-4.16; P<.001), total brain volume (P=.03), and sulcal depth (P=.02). Funisitis was also significantly associated with brain abnormality score after adjustment for clinical confounders (P=.005). Mediation analyses demonstrated that 50% of brain abnormalities was an indirect consequence of premature birth, and the remaining 50% was a direct effect of moderate to severe acute histologic chorioamnionitis when compared with preterm infants with no or mild chorioamnionitis exposure. Examining gestational age as a mediator, funisitis did not exert a significant direct effect on brain abnormalities after the significant indirect effects of preterm birth were accounted for. CONCLUSION: Acute histologic chorioamnionitis increases the risk for brain injury and delayed maturation, both directly and indirectly, by inducing premature birth.

Reduced volumetric parameters of the placenta and extravillous trophoblastic cells in complicated pregnancies may lead to intrauterine growth restriction and small for gestational age birth.

AIM: We undertook this study to determine quantitative changes of the placenta, focusing on extravillous trophoblastic cells (EVTs) in pregnancies with intrauterine growth restriction (IUGR) and small for gestational age (SGA) compared to the control group. METHODS: Placentas from pregnancies complicated with SGA-IUGR (n = 10) and control group (n = 10) were obtained after cesarean surgery and evaluated using stereological assays after routine tissue processing and Masson's trichrome staining. Mann-Whitney U-test was employed, and the level of statistical significance was set at p <0.05. RESULTS: Our results showed that the volumetric parameters, including the total volume and volume density of chorionic villi, intervillous spaces, blood vessels in chorionic villi, and syncytiotrophoblast, decreased significantly in the SGA-IUGR group compared to control placentas (p <0.05). Also, total volume, number of EVTs, volume, the diameter of cytoplasm, and diameter of the nucleus in these cells were significantly lower in the SGA-IUGR group (p <0.05). In addition, the nucleus to cytoplasm ratio of EVTs was also higher in the SGA-IUGR group (p <0.05). CONCLUSIONS: There are several significant histological and stereological differences in the placenta, particularly its EVTs from the SGA-IUGR group compared to the control group. It seems that histological changes in the placental tissues could be helpful for the retrospective explanations of pregnancy complications.

Trophoblast inclusions and adverse birth outcomes.

OBJECTIVE: Trophoblast inclusions-cross sections of abnormal trophoblast bilayer infoldings-have previously been associated with aneuploidy, placenta accreta, and prematurity. This study was conducted to establish the relationship between trophoblast inclusions and a range of placental, pregnancy, and birth outcomes in a patient population with high smoking and alcohol exposure. Specifically, we sought to evaluate the association between the presence of trophoblast inclusions and 1) three primary birth outcomes: full-term birth, preterm birth, and stillbirth; 2) gestational age at delivery; and 3) specific placental pathologies. METHODS: Two slides containing chorionic villi were evaluated from 589 placentas that were collected from Stellenbosch University in Cape Town, South Africa as part of the prospective, multicenter cohort Safe Passage Study of the Prenatal Alcohol and SIDS and Stillbirth Network. The subsample included 307 full-term live births, 212 preterm live births, and 70 stillbirths. RESULTS: We found that the odds of identifying at least one trophoblast inclusion across two slides of chorionic villi was significantly higher for placentas from preterm compared to term liveborn deliveries (OR = 1.74; 95% CI: 1.22, 2.49, p = 0.002), with an even greater odds ratio for placentas from stillborn compared to term liveborn deliveries (OR = 4.95; 95% CI: 2.78, 8.80, p < 0.001). Gestational age at delivery was inversely associated with trophoblast inclusion frequency. Trophoblast inclusions were significantly associated with small for gestational age birthweight, induction of labor, villous edema, placental infarction, and inflammation of the chorionic plate. CONCLUSIONS: The novel associations that we report warrant further investigation in order to understand the complex network of biological mechanisms through which the factors that lead to trophoblast inclusions may influence or reflect the trajectory and health of a pregnancy. Ultimately, this line of research may provide critical insights that could inform both clinical and research applications.

Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway to induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy.

PURPOSE: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy complication. However, the pathogenesis of ICP is currently unclear. METHODS: We analyzed the placenta samples of 10 normal and 10 ICP pregnant women. the expressions of circ0060731, miR-21-5p, and their downstream target genes PDCD4, ESR1, and apoptotic protein cleaved-caspase3 were detected in the cell model. RESULTS: The expression of Circ_0060731, PDCD4, ESR1, and caspase-3 was higher in the ICP placenta tissue than in the control group, and the expression of miR-21-5p was lower in the ICP group than in the control group. In HTR8/Svneo cells treated with TCA, the expression/levels of Circ_0060731, PDCD4, ESR1, and caspase-3 were significantly higher in the ICP group than in the control group, and miR-21-5p was significantly lower in the ICP group than in the control group. Lentiviral knockdown of miR-21-5p significantly increased the expressions of its downstream genes of PDCD4 and ESR1, and also increased cell apoptosis. Overexpression of miR-21-5p significantly reduced the expression of PDCD4 and ESR1 and reduced cell apoptosis. The dual-luciferase experiment showed that both PDCD4 and ERS1 were the target genes of miR-21-5p. CONCLUSION: Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway could induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy.

Independent effect of gestational weight gain and prepregnancy obesity on pregnancy outcomes among Saudi women: A sub-cohort analysis from Riyadh mother and baby cohort study (RAHMA).

BACKGROUND: Gestational weight gain (GWG) and prepregnancy obesity are garnering more attention as determining factors of pregnancy outcomes when it comes to the wellbeing of both the mother and her baby. This study was conducted to describe the pattern of GWG among participants of Riyadh Mother and Baby Multicenter Cohort Study (RAHMA) and to investigate the detrimental effects of excessive GWG and prepregnancy obesity on pregnancy outcomes. METHODS: RAHMA is a multicentre cohort study conducted in three hospitals in Riyadh, Saudi Arabia. Participants were categorized according to the Institute of Medicine into inadequate, adequate, and excessive GWG, and stratified by body mass index (BMI) into under/normal weight, overweight, and obese. To examine the independent effect of maternal prepregnancy obesity and GWG, a multivariate regression model was used and adjusted odds ratio (AOR) and 95% Confidence Interval (CI) for each outcome were calculated. RESULTS: A total of 7029 participants were included in this study; 31.8% had adequate GWG, 25.9% had excessive GWG and 42.3% had inadequate GWG, while 29.7% had normal BMI, 33.3% were overweight, 34.8% were obese, and 2.2% were underweight. Excessive GWG was independently associated with increased risk of hypertensive events, (AOR = 1.77, 95% CI 1.20-2.63). Obesity was associated with higher risk of gestational diabetes (AOR 2.11, 95% CI 1.76-2.53), hypertensive events (AOR 2.06, 95% CI 1.48-3.01), and delivery by emergency caesarean section (AOR = 1.63, 95% CI 1.35-1.97). Infants of obese women had increased odds of macrosomia (AOR 3.11, 95% CI 1.94-4.99) and lower odds of low birth weight (AOR = 0.68, 95% CI 0.53-0.88). CONCLUSION: In comparison to excessive GWG, which increases the risk of hypertensive events during pregnancy, prepregnancy obesity is associated with more adverse outcomes including GDM, hypertensive events in pregnancy and emergency CS.

Recognition of asymptomatic hypercholanemia of pregnancy: Different clinical features, fetal outcomes and bile acids metabolism from intrahepatic cholestasis of pregnancy.

OBJECTIVE: To explore the clinical features, fetal outcomes and serum bile acids (BAs) metabolism in asymptomatic hypercholanemia of pregnancy (AHP), as well as the comparison with those in intrahepatic cholestasis of pregnancy (ICP) and normal pregnancies. METHODS: A study containing 676 pregnant women was performed to investigate the clinical informations, routine biochemical features and obstetric outcomes of AHP by the comparison with ICP and normal pregnancies. Within the study subjects, 203 pregnant women received prospective determination for 55 serum individual BAs based on a validated UPLC-QTOF-MS/MS method. The differences in clinical features and serum BAs metabolism among the three groups were then investigated. RESULTS: The risk of adverse fetal outcomes in AHP (28.3%) was significantly higher than that in normal pregnancies (8.9%, p < 0.001), but lower than that in ICP group (52.1%, p < 0.001). Multivariate statistics analysis indicated a distinctive serum BAs metabolic profiling among the three groups (PLS-DA, R2Y = 0.580, Q2 = 0.537). Levels of serum BAs especially for deoxycholic acid species were found remarkably elevated in AHP as compared to those in ICP. CONCLUSIONS: AHP group had distinguished clinical features and serum BAs metabolism as compared to ICP group and normal pregnancies.