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Preeclampsia is a syndromic disease of the mother, fetus, and placenta. The main limitation in early and accurate diagnosis of preeclampsia is rooted in the heterogeneity of this syndrome as reflected by diverse molecular pathways, symptoms, and clinical outcomes. Gaps in our knowledge preclude successful early diagnosis, personalized treatment, and prevention. The advent of "omics" technologies and systems biology approaches addresses this problem by identifying the molecular pathways associated with the underlying mechanisms and clinical phenotypes of preeclampsia. Here, we provide a brief overview on how the field has progressed, focusing on studies utilizing state-of-the-art transcriptomics and proteomics methods. Moreover, we summarize our systems biology studies involving maternal blood proteomics and placental transcriptomics, which identified early maternal and placental disease pathways and showed that their interaction influences the clinical presentation of preeclampsia. We also present an analysis of maternal blood proteomics data which revealed distinct molecular subclasses of preeclampsia and their molecular mechanisms. Maternal and placental disease pathways behind these subclasses are similar to those recently reported in studies on the placental transcriptome. These findings may promote the development of novel diagnostic tools for the distinct subtypes of preeclampsia syndrome, enabling early detection and personalized follow-up and tailored care of patients. [ABSTRACT FROM AUTHOR]

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.

Introduction: Chronic intervillositis of unknown etiology (CIUE) is a placental inflammatory process associated with pregnancy loss and high recurrence risk. The pathogenesis is unclear but involves aberrant maternal inflammation. This study assesses expression of inflammatory mediators by placenta and intervillus macrophage using digital spatial profiling, which is applicable to formalin fixed paraffin embedded tissue and provides whole transcriptome expression analysis at cellular resolution.Methods: Ethics approval was obtained and all experiments were performed in accordance with applicable guidelines and regulations. Archival tissue from early spontaneous pregnancy loss with high grade CIUE (4 cases) was compared to non-inflamed control normal placenta (4 cases) and granulomatous lymphadenitis as a macrophage inflammation control (4 cases). Differential gene expression between CIUE and relevant controls was assessed using unpaired t-test with Benjamini-Hochberg false discovery correction. Gene Set Enrichment Analysis (GSEA) was used to characterize and compare pathways active in the CIUE and relevant control samples.Results: Principal component analysis of the gene expression data showed distinct clustering with relatively little intragroup variation in the control tissues whereas the CIUE cases are more variable. Gene expression analysis showed changes in CIUE; however, no genes remained statistically significant after correction for false discovery. GSEA revealed prominent activation of IFN-related signaling pathways in CIUE placenta, particularly IFNγ signaling.Discussion: This study demonstrates that CIUE is associated with a specific profile of inflammatory mediators expressed by placenta villi that is dominated by IFN signaling, suggesting that uncontrolled IFNγ signaling may play a primary role in the pathogenetic mechanism underlying CIUE. [ABSTRACT FROM AUTHOR]

Introduction: To clarify the perinatal outcome of retained products of conception (RPOC) after 22 weeks or more.Methods: The retrospective cohort study reviewed medical records of patients with RPOC without placenta previa at 186 Japanese perinatal centers.Results: Of the 323 patients with RPOC, pregnancies after assisted reproductive technology (ART) accounted for 43%. Transfusion at delivery was required in 33% of the patients. Logistic regression analyses revealed that transfusion was significantly required in the following situations: ART pregnancy (aOR: 6.0, 95%CI: 2.3-16, P < 0.001), and RPOC length ≥4 cm (aOR: 5.3, 95%CI: 2.1-13, P < 0.001). Transarterial embolization (TAE) and/or hysterectomy for subsequent RPOC-related bleeding was performed in 60 patients with RPOC. Logistic regression analysis revealed that additional interventions were significantly required in the following situations: multiparity (aOR: 6.1, 95%CI: 2.1-17.2, P < 0.001), and hypervascular RPOC (aOR: 12.8, 95%CI: 3.2-51.1, P < 0.001). TAE and/or hysterectomy was also frequently employed in ART pregnancy, although this was not significant (aOR: 2.8, 95%CI: 0.9-8.2, P = 0.063).Discussion: Patients with RPOC were significantly more likely to require transfusion at delivery in the presence of large RPOC and ART. They were also more likely to require hemostatic procedures for subsequent bleeding in the presence of hypervascular RPOC and ART. [ABSTRACT FROM AUTHOR]

We hypothesized isocaloric diets low in protein would decrease the sensitivity of caruncular (CAR) and cotyledonary (COT) arteries compared to placental arteries from ewes receiving adequate metabolizable protein (MP) requirements. Pregnant ewes were fed one of three isocaloric dietary treatments that provided 60% (MP60), 80% (MP80), or 100% (MP100) of the MP requirements. Diets were fed from day 100–130 of gestation. In vitro dose response curves to bradykinin (BK), sodium nitroprusside (SNP), potassium chloride (KCl), and phenylephrine (PE) in CAR and COT arteries were performed. As MP decreased, the sensitivity to a low dose of KCl increased (P = 0.05) in the COT arteries. There was an overall treatment effect in the CAR and COT arteries for the BK dose response curve, where CAR arteries of MP80 ewes were more sensitive (P = 0.05) to BK compared with MP60 and MP100 ewes, and COT arteries of MP60 and MP80 ewes were more sensitive (P = 0.01) to BK compared with MP100 ewes. There were no treatment effects (P ≥ 0.09) on the SNP or PE dose response curves in CAR or COT arteries. The mechanism of the BK induced vasodilation needs to be elucidated. Moreover, MP restriction appears to alter placental vascular function, which could help explain the differences in nutrient flux previously reported. [ABSTRACT FROM AUTHOR]

Among patients with placenta retention, the risk factors of massive blood loss remain unclear. In this study, a secondary data analysis was conducted to construct a predictive risk model for postpartum hemorrhage (PPH) in this particular population. A prediction model based on the data of 13 hospitals in the UK, Uganda, and Pakistan, from December 2004, to May 2008 was built. A total of 516 patients and 14 potential risk factors were analyzed. The least absolute shrinkage and selection operator regression (LASSO) model was used to optimize feature selection for the PPH risk model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the LASSO model. Discrimination and calibration were assessed using C-index and calibration plot. Among patients with placenta retention, the incidence of PPH was 62.98% (325/526). Risk factors in the model were country, number of past deliveries, previous manual removal of placenta, place of placenta delivery, and how the placenta was delivered. In these factors, patients in the low-income country (i.e., Uganda) (OR: 1.753, 95% CI=1.055–2.915), retained placentas delivered in the theater (OR: 2.028, 95% CI=1.016–4.050), and having placentas partially removed by controlled cord traction (cct), completely removed manually (OR: 4.722, 95% CI=1.280–17.417) were independent risk factors. The C-statistics was 0.702. By secondary data analysis, our study constructed a prediction model for PPH in patients with placenta retention, and identified the independent risk factors. [ABSTRACT FROM AUTHOR]

Objective: To explore the diagnostic efficacy of prenatal transabdominal gray scale combined with color flow ultrasound for placental implantation diseases. Methods: A total of 62 pregnant women with placenta previa diagnosed by prenatal ultrasound in our hospital from November 2019 -- December 2021, including 44 pregnant women with placenta implantation. All pregnant women underwent transabdominal gray-scale examination, transabdominal color ultrasound and their combination to detect placental implantation diseases. The screening efficiency of transabdominal gray-scale ultrasound combined with color blood flow ultrasound on placental implantation diseases was evaluated by analyzing the screening results of placental implantation diseases. Results: (1) The sensitivity and specificity of detecting placental implantation by gray-scale ultrasound were 73.42 % and 86.54 %; (2) the sensitivity and specificity of detecting placental implantation by color ultrasound were 76.89% and 89.07 %; (3) the sensitivity and specificity of detecting placental implantation by abdominal gray-scale combined with color blood flow ultrasound were 87.79 % and 90.36 %; (4) The positive rates of transabdominal gray scale examination, transabdominal color ultrasound examination and their combined examination in the screening of placental implantation diseases were 56.45 %, 62.90 % and 67.74 % respectively. The positive rates of the two combined examinations in the screening of prenatal placental implantation diseases were significantly higher than those of transabdominal gray scale examination and transabdominal color ultrasound examination (P<0.05). (5) The sensitivity was 72.26 %, the specificity was 90.54 %, the positive ratio was 95.55 %, and the diagnostic odds ratio was 78.89 %. Conclusion: Transabdominal gray scale combined with multi-parameter color flow ultrasound has high sensitivity and specificity in the diagnosis of prenatal placenta implantation diseases, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Background: A series of studies has shown that lipoprotein-associated phospholipase A2 (Lp-PLA2) is closely associated with abnormal lipid metabolism and vascular endothelial cell injury, but its role in hypertensive disorders of pregnancy (HDP) remains unclear. This study aims to determine the relationship between placental and serum LP-PLA2 levels and HDP, and to provide a feasible method for predicting HDP. Methods: The placental and serum Lp-PLA2 levels of 63 patients with HDP (20, 25, and 18 cases with gestational hypertension, mild preeclampsia, and severe preeclampsia, respectively) and 20 women with normal pregnancies (control group) were measured via a combination of tissue microarray and immunohistochemistry, real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA). Results: 1) The gene and protein expression levels of placental LP-PLA2: the HDP group had significantly higher levels than those of the control group (P < 0.05). The mild preeclampsia group had significantly higher levels than those of the control group (P < 0.05); the severe preeclampsia group had significantly higher levels than those of the mild preeclampsia group (P < 0.05). 2) Serum levels of Lp-PLA2: the HDP group had significantly higher levels than those of the control group (P < 0.05). The Lp-PLA2 levels increased gradually with the progression of the HDP; there were significant differences in the four groups using pair-wise comparisons (P < 0.05). 3) Serum levels of LP-PLA2 were positively correlated with placental LP-PLA2 levels in the HDP group (r = 0.435, P < 0.05). Conclusion: Elevated Lp-PLA2 levels may be associated with the occurrence of HDP, and changes of Lp-PLA2 levels in the maternal blood may be regarded as a monitoring indicator for this disease. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a common obstetric disease caused by placenta development abnormality, typically characterized as inadequate trophoblast invasion and spiral artery remodeling. In this study, we found that LMO2 level was decreased in both cytotrophoblast (CTB) and interstitial extravillous trophoblast (iEVT) in human PE placentas, and LMO2 selectively promoted cell migration in iEVT derived HTR-8/SVneo cells whereas increased proliferation in CTB derived JEG-3 cells. In mechanism, LMO2 interacted with NCKAP1, leading to destruction of WAVE regulatory complex and increased lamellipodia formation in HTR-8/SVneo cells, whereas interacted with β-catenin and up-regulated a number of core Wnt/Hippo pathway target genes in JEG-3 cells. This study revealed the differentially functional patterns of LMO2 in different trophoblast subtypes, and suggested LMO2 as a novel target for PE prediction, prevention and treatment in clinical. [Display omitted] • Compared with normal placenta, LMO2 showed decreased expression level in both CTBs and EVTs in preeclampsia placentas. • LMO2 increased cell migration in iEVT derived HTR-8/SVneo cells via targeting to NCKAP1. • LMO2 promoted cell proliferation in CTB derived JEG-3 cells via targeting to beta-Catenin. [ABSTRACT FROM AUTHOR]

β-thalassemia is a prevalent disease in Iran. The adverse effects of anemia on placental and neonatal outcomes have previously been shown. Women require additional iron during pregnancy and the anemia of women with β-thalassemia may adversely affect the neonatal outcome and increase placental abnormalities. In this study, we compared the placental histology and neonatal outcomes among pregnant women with and without β-thalassemia. In this population-based cross-sectional study, 144 pregnant women with β-thalassemia minor (case group) were compared to 142 women without β-thalassemia (control group). Women with singleton pregnancies over 20 weeks of gestation without pregnancy complications, anemia, collagen vascular diseases, or other hemoglobinopathies, all referred to hospitals affiliated to Shiraz University of Medical Sciences from March 2014 to February 2016, were included and maternal and neonatal data were extracted from medical records. After child birth, the placenta was evaluated for macroscopic and microscopic changes. The frequency of LBW was significantly higher in the case group than that in the control group (19.7 vs. 9.7%, respectively) (p =.019). Six in the case group had gross abnormalities of placenta, while none in the control group (p =.03) and the case group had a higher frequency of chorangiosis, calcification, syncytial knot, and umbilical cord position (p <.05). As β-thalassemia increases the chance of placental abnormalities, it is recommended to pay more attention to patients with β-thalassemia, especially during pregnancy, to prevent placental and neonatal adverse outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the association between placental pathologic features of maternal (MVM) or fetal (FVM) vascular malperfusion and clinical characteristics, sonographic findings and neonatal outcome in a cohort of pregnancies complicated by early-onset (diagnosed before 32 weeks of gestational age) fetal growth restriction (FGR). Methods: A prospective cohort study included 250 singleton early-onset FGR pregnancies diagnosed, followed up and delivered at a single center. Placental pathologic lesions were classified according to standard recommendations. Logistic regression and Cox analysis were used to evaluate outcomes adjusting for confounders. Results: Overall features of severe placental MVM and FVM were observed in 29.6% (74/250) and 12.8% (32/250) of the subjects, respectively. Severe placental MVM lesions were more common among subjects with umbilical artery Doppler Pulsatility Index >95th than ≤95th percentile (50/120 as opposed to 24/130, Adj odds ratio [OR] = 3, 95% CI = 1.6–5.4) and Cerebroplacental ratio <5th than ≥5th percentile (48/115 as opposed to 26/135, Adj OR = 2.7, 95% CI = 1.5–4.9). Mean time from FGR diagnosis to delivery was shorter among subjects with severe MVM (25.5 days, 95% CI = 20.6–30.2, Adj. OR = 1.9, 95% CI = 1.9, 95% CI = 1.4–2.5) when compared to both those with mild/moderate MVM (36.5 days [95% CI = 27.2–45, p = 0.04]) or no MVM (39.4, 95% CI = 35.4–43.4, p < 0.001). Finally, severe FVM was associated with an increased risk of perinatal/neonatal death or severe brain lesions (9/28 in subjects with perinatal/neonatal death/brain lesions as compared to 23/222 in controls, Adj OR = 3, 95% CI = 1.05–8.6) or severe adverse neonatal outcomes (13/46 in subjects with severe adverse outcome as compared to 19/204 among controls, Adj OR = 3.2, 95% CI = 1.2–8.5). Conclusions: In early-onset FGR, placental pathologic features of MVM and FVM are, in different regards, associated to severity of clinical picture, abnormal Doppler markers of placental and fetal circulation and of neonatal outcome, respectively. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive assessment of maternal cardiovascular potential and kinetic energy can be used to derive potential-to-kinetic-energy ratio (PKR) and Smith-Madigan inotropic index (SMII), which reflect the balance between blood pressure and blood flow. The aim of this study was to evaluate PKR and SMII in pregnancies complicated by hypertensive disorders of pregnancy (HDP) and/or small-for-gestational-age (SGA) birth.Methods: This was a prospective study that enrolled women with a singleton pregnancy between 5 and 41 weeks' gestation. Women who developed HDP and/or SGA underwent cardiovascular profiling from 20 weeks. To establish reference ranges for PKR and SMII, women without any pre-existing medical problems at the time of booking who did not develop HDP, SGA or other complications during pregnancy were also recruited for cardiovascular profiling. Measurements of cardiovascular parameters were obtained using a non-imaging ultrasound cardiac output monitor.Results: A total of 688 women completed the study, including 626 controls, 21 cases with HDP, 19 cases with SGA and 22 cases with HDP and SGA. PKR was significantly elevated in pregnancies with placental dysfunction compared with controls (HDP only, 29.81 ± 9.5; HDP and SGA, 44.33 ± 24.27; SGA only, 31.05 ± 13.14; vs controls, 22.30 ± 7.93; all P < 0.05). SMII values were significantly lower only in cases affected by SGA alone when compared with controls (1.47 ± 0.23 W/m2 vs 1.75 ± 0.40 W/m2 ; P < 0.005). These differences remained statistically significant when the analysis was undertaken using multiples of the median values corrected for gestational age.Conclusions: The findings of this study suggest that point-of-care non-invasive cardiovascular profiling using PKR and SMII may help distinguish between pregnancies affected by specific placental disorders and those exhibiting healthy cardiovascular adaptation to pregnancy. Women with HDP and/or SGA appear to have distinctive PKR and SMII profiles that reflect low kinetic energy in pregnancies with SGA and high potential energy in pregnancies affected by HDP. Finally, non-invasive assessment of potential and kinetic cardiovascular energy demonstrates physiological high-flow and low-resistance adaptation in uncomplicated pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?More than half of all pregnancies in the UK are exposed to adversity linked to increased problems in pregnancy for mothers and adverse outcomes for their children, but we do not know the mechanism(s) underpinning these relationships.What advances does it highlight?Studies in mice prove that placental endocrine insufficiency driven by genetic manipulation of imprinted genes in the offspring can concurrently drive fetal growth restriction, alterations in maternal caregiving and aberrant behaviour in wild‐type offspring exposed to an adverse environment. This suggests that placental endocrine insufficiency might contribute to the co‐morbidity of low birth weight, maternal depression and neurodevelopmental disorders observed in human populations. Prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and increases the chances of stillbirth, prematurity and infant mortality. Beyond these immediate and highly visible problems, infants that survive carry the invisible burden of increased risk of some of the most common and pervasive diseases that impact human populations. In utero exposure to depression and anxiety is one adversity that has been linked to these poorer outcomes, suggesting that maternal mood disorders drive the outcomes. However, recent studies in animal models suggest that both the maternal mood disorders and the detrimental outcomes for children could be the result of the same underlying placental pathology. In these studies, genetically wild‐type rodent mothers exposed to placental endocrine insufficiency engaged in less pup‐focused behaviours and less self‐care. Genetically wild‐type rodent offspring raised in this abnormal environment exhibited increased anxiety‐like behaviours, with male offspring additionally exhibiting deficits in cognition and atypical social behaviour, with some evidence of depressive‐like symptoms. This work establishes experimentally that placental endocrine insufficiency alone is sufficient to drive atypical behaviour in both mothers and their offspring. Although there are some data to suggest that this phenomenon is relevant to human pregnancy, considerably more work is required. [ABSTRACT FROM AUTHOR]

Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited. Using a cohort of pregnant women in the US nationwide Medicaid Analytic eXtract (2000–2014), we compared women with ≥2 opioid dispensings in pregnancy with unexposed women. Given an uncertain etiologically relevant window, we assessed exposure occurring in early pregnancy, late and not early pregnancy, and both early and late pregnancy. For placental abruption, preterm delivery, small for gestational age (SGA), and preeclampsia, we estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) using Cox proportional hazard models adjusting for demographic factors, indications/comorbidities, and medications. Among 1,833,871 eligible pregnancies, ≥2 opioid dispensings were filled in 6.5%. We observed an early exposure aHR of 1.34 (95% CI: 1.26, 1.43) for placental abruption, 1.21 (95% CI: 1.18, 1.23) for preterm delivery, 1.13 (95% CI: 1.09, 1.17) for SGA, and 0.95 (0.91, 0.98) for preeclampsia. Estimates for late exposure were attenuated. Early and late exposure was associated with higher aHRs for placental abruption, 1.62 (95% CI: 1.47, 1.78); preterm delivery, 1.37 (95% CI: 1.33, 1.42); and SGA, 1.26 (95% CI: 1.19, 1.33); but not preeclampsia, 0.99 (95% CI: 0.93, 1.05). Prescription opioids may modestly increase risk of placental abruption, preterm birth and SGA, but they do not appear to be associated with preeclampsia. [ABSTRACT FROM AUTHOR]

Discomfort and, to a lesser extent, pain are common complaints during pregnancy, and some patients may turn to opioids for pain relief. Esposito et al. (Am J Epidemiol. 2022;191(5):759–768) report associations between intermittent exposure to opioids during pregnancy and the risk of ischemic placental disease—a syndrome that includes preeclampsia, placental abruption, births that are small for gestational age, and preterm delivery. They found that early opioid exposure in pregnancy was associated with a modestly increased risk for abruption, births that are small for gestational age, and preterm delivery, and both early and late exposures were associated with the greatest risk for these outcomes. Surprisingly, preeclampsia was not associated with opioid use. Through quantitative bias analysis, the authors cleverly tackle a number of biases to assess their roles in explaining the associations, including unmeasured confounding, outcome misclassification, and residual confounding; none exerted strong influences on the associations. Although the findings appear fairly robust on the surface, the lack of association between intermittent opioid use and preeclampsia, and important differences in characteristics of patients in the opioid-exposed group compared with the unexposed group, suggest that further study is needed to clarify the relationship between intermittent opioid use, lifestyle factors, and ischemic placental disease risk. [ABSTRACT FROM AUTHOR]

* Context.--A severe third wave of COVID-19 disease affected Ireland in the first 3 months of 2021. In this wave, 1 second-trimester miscarriage and 6 stillbirths were observed in the Irish population because of placental insufficiency as a result of SARS-CoV-2 placentitis. This observation was at odds with the country's previous experience with COVID-19 disease in pregnant mothers. Objective.--To describe the clinical and pathologic features of these pregnancy losses. Design.--Retrospective review of clinical and pathologic data of cases of second-trimester miscarriage, stillbirth, or neonatal death identified by perinatal pathologists as being due to SARS-CoV-2 placentitis during the third wave of COVID-19 in Ireland. Results.--Clinical and pathologic data were available for review in 6 pregnancies. Sequencing or genotyping of the virus identified SARS-CoV-2 alpha (B.1.1.7) in all cases. Three of the 6 cases had maternal thrombocytopenia, and fetal growth restriction was not prominent, suggesting a rapidly progressive placental disease. Conclusions.--The identification of SARS-CoV-2 alpha in all these cases suggests that the emergence of the variant was associated with an increased risk of fetal death due to SARS-CoV-2 placentitis when compared with the original virus. Maternal thrombocytopenia may have potential as a clinical marker of placentitis, but other inflammatory markers need investigation. Three of the 6 women had been assessed for reduced fetal movements in hospital some days before the fetal deaths actually occurred; this could suggest that there may be a window for intervention in some cases. [ABSTRACT FROM AUTHOR]

Placenta accreta spectrum disorders are characterized by abnormal adhesion of the placenta that can be subdivided into three categories according to degree of invasion: placenta accreta (passing through the decidua basalis and adhering to the myometrium); placenta increta (penetrating the myometrium); and placenta percreta (invading the uterine serosa or adjacent tissues or organs). The incidence of placenta accreta has increased significantly in recent decades, mainly because of an increase in the rates of cesarean section, which is its main risk factor. Accurate prenatal identification makes it possible to institute the ideal treatment with a multidisciplinary team, significantly minimizing maternal morbidity and mortality. The examinations of choice are ultrasound and magnetic resonance imaging (MRI). When the ultrasound evaluation is inconclusive, as well as when the patient has risk factors for the condition or the placenta is in a posterior location, MRI is indicated. In cases of placental invasion of the adjacent pelvic organs, MRI is also preferable because it provides a broader field of view, which improves surgical planning. Numerous features of placenta accreta spectrum disorders are discernible on MRI, including dark intraplacental bands, uterine bulging, and heterogeneous placenta. Knowledge of these findings and the combination of two or more of them increase confidence in the diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Villitis of unknown etiology (VUE) is an inflammatory placental lesion with immune-mediated pathogenesis, diagnosed by histopathological examination. It is one of the three placental lesions which tend to recur in subsequent pregnancies, the other two being chronic histiocytic intervillositis and massive fibrin deposition. The frequency of VUE and its association with maternal, obstetric and neonatal complications are variability reported in the literature. The aim of this study is to determine the frequency of VUE in the population studied and to observe the association of specific subtypes of villitis with clinical features, placental morphometric and microscopic parameters.Methods: Placentas where villitis was observed, were obtained from the pathology database from January 2013 to June 2018. VUE was graded as low grade (LG), high grade (HG) and basal villitis (BV) and subcategorized based on extent and cell type. Its association with selected maternal, neonatal and placental parameters was evaluated.Results: A total of 1603 placentas were received and 163 singleton placentas with villitis (10%) were reported. LG and HG villitis was observed in 58% and 25% cases respectively. Basal villitis was seen in 24% and pure basal villitis without involvement of parenchymal villi was seen in 16.6%. While there was near equal distribution of focal (n = 45) and multifocal (n = 50) LG villitis, diffuse HG villitis (n = 32) was more common than patchy HG villitis (n = 9). Overall villitis was more common in preterm pregnancies (59.5%) with most of them being basal villitis and low-grade villitis (64.2%, p value .029). None of the other maternal and neonatal parameters had any significance. Placental dimensions (length and breadth) showed a significant negative association with VUE, especially high-grade and multifocal low-grade villitis.Conclusion: VUE was a common finding in preterm births and its novel association with placental size opens avenues for further research on alternative mechanisms involved in the association between villitis, placental function and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia. What is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity. What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia. What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: With the rise in Caesarean deliveries, complications related to the procedure are increasingly encountered. Sonography has an indispensable role in the assessment of these complications and is often the first-line investigation of choice. Topic Description: Part 1 of this pictorial review summarises the early complications unique to and associated with Caesarean deliveries. Discussion: Acute haemorrhagic complications include retained products of conception, subfascial and bladder flap haematomas and, rarely, postpartum uterine dehiscence or rupture and iatrogenic vascular complications. Infective complications include puerperal and wound infections. Key sonographic features of these conditions are illustrated. Pitfalls, mimics, limitations and indications for cross-sectional imaging are discussed. Conclusion: Sound knowledge of the sonographic features of common early complications of Caesarean delivery will facilitate accurate diagnosis, timely management and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Hofbauer cells (HBCs) are tissuemacrophages of the placenta thought to be important for fetoplacental vascular development and innate immune protection. The developmental origins of HBCs remain unresolved and could implicate functional diversity of HBCs in placenta development and disease. In this study, we used flow cytometry and paternally inherited reporters to phenotype placenta macrophages and to identify fetal-derived HBCs and placenta-associated maternal macrophages in the mouse. In vivo pulse-labeling traced the ontogeny of HBCs from yolk sac-derived erythro-myeloid progenitors, with a minor contribution from fetal hematopoietic stem cells later on. Single-cell RNA-sequencing revealed transcriptional similarities between placenta macrophages and erythro-myeloid progenitor-derived fetal liver macrophages and microglia. As with other fetal tissue macrophages, HBCs were dependent on the transcription factor Pu.1, the loss-of-function of which in embryos disrupted fetoplacental labyrinth morphology, supporting a role for HBC in labyrinth angiogenesis and/or remodeling. HBC were also sensitive to Pu.1 (Spi1) haploinsufficiency, which caused an initial deficiency in the numbers ofmacrophages in the early mouse placenta. These results provide groundwork for future investigation into the relationship between HBC ontogeny and function in placenta pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: To compare placental pathology from term singleton live births conceived with fresh embryo transfer vs. those conceived without assisted reproductive technology (ART).Design: Retrospective cohort study.Setting: Academic fertility center.Patient(s): Women with a term singleton live birth who conceived after fresh autologous in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles (ART group) and those who conceived without ART.Intervention(s): An experienced placental pathologist categorized placental pathology as anatomic, inflammatory, or vascular. Patient characteristics were compared by chi-squared tests, Student's t-test, or nonparametric tests. Multivariate logistic regression models were used to compare placental pathology between pregnancies conceived with and without ART.Main Outcome Measure(s): Incidence of anatomic, inflammatory, and vascular placental pathology.Result(s): There was a higher incidence of placental pathology in the ART group (n = 511) than in the non-ART group (n = 121), specifically anatomic (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.42-4.40) and vascular (aOR 2.00, 95% CI 1.13-3.53) pathology. These findings were driven primarily by the significantly higher odds of anatomic (aOR 2.97, 95% CI 1.55-5.66) and vascular (aOR 1.98, 95% CI 1.04-3.75) pathology observed in ICSI pregnancies. Single blastocyst transfers remained associated with increased anatomic pathology (ART: aOR 4.89, 95% CI 2.28-10.49; ICSI: aOR 3.38, 95% CI 1.49-7.71).Conclusion(s): Fresh embryo transfer is associated with increased anatomic and vascular placental pathology in term singleton live births compared with conception without ART. This finding should be investigated prospectively in a larger cohort of patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and safety of prophylactic intraoperative uterine artery embolization (UAE) performed immediately after fetal delivery during planned cesarean section or cesarean hysterectomy in patients with placenta accreta spectrum disorder or placenta previa. Methods: A systematic search was conducted on Ovid MEDLINE and Embase, PubMed, Web of Science, and Cochrane databases. Studies were selected using the Population/Intervention/Comparison/Outcomes (PICO) strategy. The intraoperative blood loss and the rate of emergent peripartum hysterectomy (EPH) were the primary outcomes, whereas the length of hospital stay and volume of blood transfused were the secondary outcomes. A random-effects model was employed to pool each effect size. The cumulative values of the primary outcomes were calculated using the generic inverse variance method. Results: Eleven retrospective cohort studies and five case series were included, recruiting 421 women who underwent prophylactic intraoperative UAE (UAE group) and 374 women who did not (control group). Compared with the control group, the UAE group had significantly reduced intraoperative blood loss (p = 0.020) during cesarean section or cesarean hysterectomy. Furthermore, the EPH rate was also significantly decreased (p = 0.020; cumulative rate: 19.65%), but not the length of hospital stay (p = 0.850) and volume of pRBC transfused (p = 0.140), after cesarean section in the UAE group. The incidence of major complications was low (3.33%), despite two patients with uterine necrosis. Conclusion: The currently available data provides encouraging evidence that prophylactic intraoperative UAE may contribute to hemorrhage control and fertility preservation in women with abnormal placentation. Registration: PROSPERO registration code: CRD42021230581. https://clinicaltrials.gov/ct2/show/CRD42021230581 Level of Evidence: Level 2a, systematic review of retrospective cohort studies. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of fetal gender on the maternal levels of first-trimester screening biochemical markers, such pregnancy-related plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG). Methods: In this retrospective study, we assessed 267 cases of singleton pregnancies, who underwent first trimester screening tests and delivered between January 2016 and January 2019 at our hospital. Multiple of median (MoM) levels of PAPP-A and free β-hCG, and the neonatal genders according to the birth records were compared and analyzed. Original Article Additionally, patients with small for gestational age (SGA) newborns, preeclampsia, and placental ablation, called ischemic placental diseases, were classified into a separate group and their PAPP-A and free β-hCG MoM values and fetal genders were compared. Results: There was no significant relationship between the mean values of PAPP-A (1.07±0.6) and free β-hCG (1.23±1.14) and the fetal gender (males: 137, 51.3%; females: 130, 48.7%), respectively (p=0.833; p=0.075). In 41 cases (15.4%) with ischemic placental disease, free β-hCG values was significantly higher in the fetal females (19 cases; 46.3%) than males (22 cases; 53.7%), (1.53±1.02 and 0.77±0.53, respectively), (p=0.004). Conclusion: Pregnancy-related plasma protein A and free β-hCG values were not affected by the fetal gender. However, the significant relationship observed between free β-hCG MoM levels and fetal gender in patients with ischemic placental diseases suggests the need for larger studies on this topic. [ABSTRACT FROM AUTHOR]

Abstract Bacterial placentitis in horses commonly results in abortion, premature birth or compromised neonatal foal health. Although mycobacterial infections are generally uncommon in horses, 10 equine abortion cases caused by Mycobacterium avium subsp. hominissuis (MAH) infections occurred between 2018 and 2019 in Japan. They occurred on seven Thoroughbred horse farms in the Hidaka district of Hokkaido, but direct contact among the mares on different farms was not recorded. Most cases were characterized by extensive pathological lesions of the placenta, which are not typical in cases of common pathogenic bacteria such as Streptococcus zooepidemicus and Escherichia coli. All abortions featured white–yellow exudates on the surface of the placenta. Mycobacterial granuloma formations were histologically found in the placenta and fetal organs, and acid‐fast bacteria were isolated from the placenta, fetal samples (heart, lung, liver, kidney, spleen and stomach contents) or uterine lavage fluid. The greatest number of bacteria was isolated from necrotic lesions on the placenta, which could be an important site for bacterial isolation in mycobacterial equine abortions. The isolates were identified as MAH based on internal genome sequences. In variable number tandem repeat analysis, all patterns of the strains were identical. Single nucleotide polymorphism analysis of the core genome grouped all strains in the II‐a/SC3 subcluster. Both results reveal that these strains share the same genetic background, suggesting that the horses had been infected by the same unknown contagious source.

While Malawi has made great strides increasing the number of facility-based births, maternal and neonatal mortality remains high. An intervention started in 2019 provided short-course training followed by year-long longitudinal bedside mentorship for nurse midwives at seven health facilities in Blantyre district. The intervention was initiated following invitation from the district to improve outcomes for patients during childbirth. This study examined the impact of the intervention on the reporting of obstetric and neonatal complications and related care. Patient level data were collected from the District Health Information System 2 database from intervention and non-intervention facilities. Bivariate analysis explored the impact of longitudinal bedside mentorship on select District Health Information System 2 variables at six-month intervals. Outcomes were then analyzed using nonlinear quantile mixed models to better account for the impact of time and clustering at the facility level. Significant changes were found in the reporting of obstetric and neonatal complications over time at intervention facilities compared to non-intervention facilities. Intervention facilities showed statistically significant increases in the reporting of prolonged labor, pre/eclampsia, fetal distress, retained placenta, and premature labor. There was also a statistically significant decrease in the reporting of no complications in the multivariate model (95%CI: − 0.8 to − 0.2). In both the bivariate and multivariate models, the reporting of 'None' significantly decreased (0.8 % median), while the reporting of prematurity (0.2 % median) and asphyxia (0.3 % median) both significantly increased. The missingness of data at intervention facilities decreased to almost zero compared to non-intervention facilities. The increase in reported maternal and neonatal complications suggests improved early identification of complications at the facility level. The improved accuracy of patient data from intervention facilities shows the impact mentorship has on data quality which is crucial for the allocation of resources. By highlighting the apparent dose–response relationship of longitudinal bedside mentorship, this study will inform the broader use of mentorship in training programs. Future research is needed to explore the impact of longitudinal mentorship on quality of care. [ABSTRACT FROM AUTHOR]

Infantile hemangiomas (IHs) are the most common vascular tumors in infants, appearing in early infancy and ultimately regressing with time. Clinical presentation may vary, with a minority of lesions causing impairment of vital function (e.g., respiratory or visual obstruction), permanent scarring, and/or disfigurement. The pathogenesis of IH is complex and poorly understood. Risk factors implicated in their development include preterm birth and placental anomalies. IH presents a myriad of clinical challenges, including correct diagnosis and whether or not to pursue treatment. This article is a review of the current literature regarding pathogenesis, clinical presentation, treatment, and prognosis of IH. Birth Defects Research 109:809-815, 2017. © 2017 Wiley Periodicals, Inc.

Editorial Heart disease is the leading cause of death globally for both sexes, affecting 1 in 5 women in the United States.[1] Although women have a lower prevalence of obstructive epicardial coronary artery disease compared with men of a similar age, they have higher rates of myocardial ischemia and associated cardiovascular morbidity and mortality.[2] While both sex-based differences due to biological factors such as the timing of menarche and menopause and gender-related differences related to social constructs (eg, delays in time to evaluation of chest pain for women vs men) contribute to these disparities, there is a growing recognition that traditional cardiovascular risk calculators fail to account for sex-specific risk factors such as adverse pregnancy outcomes, which are unique to birthing people who predominantly identify as women. Prevalence of subclinical coronary artery disease assessed by coronary computed tomography angiography in 45- to 55-year-old women with a history of preeclampsia. Association between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography. [Extracted from the article]

BackgroundThe Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal closure of myelomeningocele. The trial was stopped early at recommendation of the data and safety monitoring committee and outcome data for 158 of the 183 randomized women published.ObjectiveIn this report, pregnancy outcomes for the complete trial cohort are presented. We also sought to analyze risk factors for adverse pregnancy outcome among those women who underwent prenatal myelomeningocele repair.Study designPregnancy outcomes were compared between the 2 surgery groups. For women who underwent prenatal surgery, antecedent demographic, surgical, and pregnancy complication risk factors were evaluated for the following outcomes: premature spontaneous membrane rupture ≤34 weeks 0 days (preterm premature rupture of membranes), spontaneous membrane rupture at any gestational age, preterm delivery at ≤34 weeks 0 days, nonintact hysterotomy (minimal uterine wall tissue between fetal membranes and uterine serosa, or partial or complete dehiscence at delivery), and chorioamniotic membrane separation. Risk factors were evaluated using χ2 and Wilcoxon tests and multivariable logistic regression.ResultsA total of 183 women were randomized: 91 to prenatal and 92 to postnatal surgery groups. Analysis of the complete cohort confirmed initial findings: that prenatal surgery was associated with an increased risk for membrane separation, oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor, and earlier gestational age at birth. In multivariable logistic regression of the prenatal surgery group adjusting for clinical center, earlier gestational age at surgery and chorioamniotic membrane separation were associated with increased risk of spontaneous membrane rupture (odds ratio, 1.49; 95% confidence interval, 1.01-2.22; and odds ratio, 2.96, 95% confidence interval, 1.05-8.35, respectively). Oligohydramnios was associated with an increased risk of subsequent preterm delivery (odds ratio, 9.21; 95% confidence interval, 2.19-38.78). Nulliparity was a risk factor for nonintact hysterotomy (odds ratio, 3.68; 95% confidence interval, 1.35-10.05).ConclusionDespite the confirmed benefits of prenatal surgery, considerable maternal and fetal risk exists compared with postnatal repair. Early gestational age at surgery and development of chorioamniotic membrane separation are risk factors for ruptured membranes. Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk factor for nonintact hysterotomy at delivery.

BackgroundIn malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses.MethodsUsing cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes.ResultsCord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12-20 weeks of gestation; p = 0.048), but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP); p = 0.810). In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3-CD127+) were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035). This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p

We report an uncommon clinical presentation of a placental site trophoblastic tumor. The patient presented initially with abdominal pain with, fever, bleeding and pelvic mass on ultrasonography leading to the wrong diagnosis of a pelvic abscess. Dilation and curettage were performed and pathological examination confirmed the diagnosis. of placental site trophoblastic tumor. Therefore, she underwent abdominal hysterectomy. Four years after surgery, the patient is still disease free. Gestational trophoblastic diseases should be considered in every patient presenting abnormal uterine bleeding after delivery or pregnancy loss despite the associated symptoms being very unusual.

Objectives: To assess the association between advanced maternal age and adverse perinatal outcomes in single pregnancies. Materials and methods: A cohort study was conducted using data from 27,455 singleton births attended at our hospital between 2007 and 2018. Three maternal age groups were established, and perinatal outcomes were compared between-groups (40 years (n = 846; 3.1%). The data were compared using chi-square analysis and the results were adjusted using a logistic regression model. Decision trees were designed to examine the fetal mortality and caesarean section variables. We used the SPSS 23 statistical software program for the statistical analysis. Results: The mean age of the women was 31.21 years. No differences were found associated with age for neonatal acidosis, an Apgar score 35 years of age had worse perinatal outcomes, compared with younger women. This finding was more evident in patients >40 years of age, which highlighted the greater risk of fetal death and serious maternal complications in this group.