Search Results (8)

Background/Objectives: Although preeclampsia (PE) and small for gestational age (SGA) are known to come from impaired placentation during the first trimester, prior studies have focused mostly on Doppler findings in the second trimester. Methods: In this retrospective pilot study, we enrolled 628 singleton pregnant women who underwent ultrasound in both the first and second trimesters and blood test. For SGA correlation, we further excluded 12 subjects with PE because PE may be the cause of SGA. We first presented the reference range of parameters of uterine artery Doppler in the first trimester and then grouped the subjects according to the presence of SGA (presence = 104, absence = 512) or PE (presence = 12, absence = 616) and investigated the association of uterine artery Doppler findings and serum markers in the first trimester with the occurrence of SGA or PE. Results: The uterine artery pulsatility index and the resistance index and the proportion of uterine artery notch decreased progressively in the first trimester. A lower serum beta-hCG level in the first trimester predicted the occurrence of SGA (adjusted odds ratio [AOR] = 0.53, p = 0.019), while the presence of the uterine artery notch in the first trimester predicted the development of PE (notch at least on one side: AOR = 8.65, p = 0.045 and notch on both sides: AOR = 8.91, p = 0.047). Regardless of whether a notch was present in the second trimester, a uterine artery notch in the first trimester was associated with an excellent negative predictive value (99.6%) for PE. Conclusions: This study suggests the clinical importance of assessing serum beta-hCG and the uterine artery notch in the first trimester to predict SGA and PE. Full article

The placenta is a vital organ that supports fetal development by mediating nutrient and gas exchange, regulating immune tolerance, and maintaining hormonal balance. Its formation and function are tightly linked to the processes of embryo implantation and the establishment of a robust placental-uterine interface. Recent advances in molecular biology and histopathology have shed light on the key regulatory factors governing these processes, including trophoblast invasion, spiral artery remodeling, and the development of chorionic villi. This review integrates morphological and molecular perspectives on placental development, emphasizing the roles of cytokines, growth factors, and signaling pathways, such as VEGF and Notch signaling, in orchestrating implantation and placental formation. The intricate interplay between molecular regulation and morphological adaptations highlights the placenta’s critical role as a dynamic interface in pregnancy. This review synthesizes current findings to offer clinicians and researchers a comprehensive understanding of the placenta’s role in implantation, emphasizing its importance in maternal-fetal medicine. By integrating these insights, the review lays the groundwork for advancing diagnostic and therapeutic approaches that can enhance pregnancy outcomes and address related complications effectively. Full article

Regarding the hypertensive disorders of pregnancy, pre-eclampsia (PE) remains one of the leading causes of severe and life-threatening maternal and fetal complications. Screening of early-onset PE (<34 weeks of pregnancy), as well as late-onset PE (≥34 weeks), shows poor performance if based solely on clinical features. In recent years, biochemical markers from maternal blood—the pro-angiogenic protein placental growth factor (PlGF) and the antiangiogenic protein soluble FMS-like tyrosine kinase 1 (sFlt-1)—and Doppler velocimetry indices—primarily the mean uterine pulsatility index (PI), but also the uterine resistivity index (RI), the uterine systolic/diastolic ratio (S/D), uterine and umbilical peak systolic velocity (PSV), end-diastolic velocity (EDV), and uterine notching—have all shown improved screening performance. In this review, we summarize the current status of knowledge regarding the role of biochemical markers and Doppler velocimetry indices in early prediction of the onset and severity of PE and other placenta-related disorders, as well as their role in monitoring established PE and facilitating improved obstetrical surveillance of patients categorized as high-risk in order to prevent adverse outcomes. A sFlt-1/PlGF ratio ≤ 33 ruled out early-onset PE with 95% sensitivity and 94% specificity, whereas a sFlt-1/PlGF ≥88 predicted early-onset PE with 88.0% sensitivity and 99.5% specificity. Concerning the condition’s late-onset form, sFlt-1/PlGF ≤ 33 displayed 89.6% sensitivity and 73.1% specificity in ruling out the condition, whereas sFlt-1/PlGF ≥ 110 predicted the condition with 58.2% sensitivity and 95.5% specificity. The cut-off values of the sFlt-1/PlGF ratio for the screening of PE were established in the PROGNOSIS study: a sFlt-1/PlGF ratio equal to or lower than 38 ruled out the onset of PE within one week, regardless of the pregnancy’s gestational age. The negative predictive value in this study was 99.3%. In addition, sFlt-1/PlGF > 38 showed 66.2% sensitivity and 83.1% specificity in predicting the occurrence of PE within 4 weeks. Furthermore, 2018 ISUOG Practice Guidelines stated that a second-trimester mean uterine artery PI ≥ 1.44 increases the risk of later PE development. The implementation of a standard screening procedure based on the sFlt-1/PlGF ratio and uterine Doppler velocimetry may improve early detection of pre-eclampsia and other placenta-related disorders. Full article

Background: Second-trimester uterine artery Doppler is a well-established tool for the prediction of preeclampsia and fetal growth restriction. At delivery, placentas from affected pregnancies may have gross pathologic findings. Some of these features are detectable by ultrasound, but the relative importance of placental morphologic assessment and uterine artery Doppler in mid-pregnancy is presently unclear. Objective: To characterize the association of second-trimester sonographic placental morphology markers with placenta-mediated complications and determine whether these markers are predictive of placental dysfunction independent of uterine artery Doppler. Methods: This was a retrospective cohort study of patients with a singleton pregnancy at high risk of placental complications who underwent a sonographic placental study at mid-gestation (160/7−246/7 weeks’ gestation) in a single tertiary referral center between 2016–2019. The sonographic placental study included assessment of placental dimensions (length, width, and thickness), placental texture appearance, umbilical cord anatomy, and uterine artery Doppler (mean pulsatility index and early diastolic notching). Placental area and volume were calculated based on placental length, width, and thickness. Continuous placental markers were converted to multiples on medians (MoM). The primary outcome was a composite of early-onset preeclampsia and birthweight < 3rd centile. Results: A total of 429 eligible patients were identified during the study period, of whom 45 (10.5%) experienced the primary outcome. The rate of the primary outcome increased progressively with decreasing placental length, width, and area, and increased progressively with increasing mean uterine artery pulsatility index (PI). By contrast, placental thickness followed a U-shaped relationship with the primary outcome. Placental length, width, and area, mean uterine artery PI and bilateral uterine artery notching were all associated with the primary outcome. However, in the adjusted analysis, the association persisted only for placenta area (adjusted odds ratio [aOR] 0.21, 95%-confidence interval [CI] 0.06–0.73) and mean uterine artery PI (aOR 11.71, 95%-CI 3.84–35.72). The area under the ROC curve was highest for mean uterine artery PI (0.80, 95%-CI 0.71–0.89) and was significantly higher than that of placental area (0.67, 95%-CI 0.57–0.76, p = 0.44). A model that included both mean uterine artery PI and placental area did not significantly increase the area under the curve (0.82, 95%-CI 0.74–0.90, p = 0.255), and was associated with a relatively minor increase in specificity for the primary outcome compared with mean uterine artery PI alone (63% [95%-CI 58–68%] vs. 52% [95%-CI 47–57%]). Conclusion: Placental area is independently associated with the risk of placenta-mediated complications yet, when combined with uterine artery Doppler, did not further improve the prediction of such complications compared with uterine artery Doppler alone. Full article

Pregnancy-induced hypertension (PIH), especially when complicated with pre-eclampsia (PE), could be a life-threatening complication of pregnancy. Pre-eclampsia is one of the leading causes of perinatal morbidity and mortality in women. Pre-eclampsia is mainly characterized by hypertension and kidney damage with proteinuria. Abnormal placentation and altered structure of the placental barrier are believed to participate in the pathogenesis of pregnancy-induced hypertension, leading to PE. In the current study, we aimed to analyze the immunohistochemical expression pattern of E-cadherin and p120, two markers of epithelial–mesenchymal transition, in placental samples derived from a group of 55 patients with pregnancy-induced hypertension, including pre-eclampsia and 37 healthy pregnant controls. The results were correlated with the presence of an obtained early uterine artery flow notching during diastole on Doppler ultrasound. We observed a higher frequency of discontinuous E-cadherin staining in the basement membrane of syncytiotrophoblast in patients with PIH/PE compared to controls (p < 0.001, Fisher’s exact test). Moreover, the loss of continuity of E-cadherin expression correlated with the presence of a bilateral early diastolic notch on Doppler ultrasound (p < 0.001, Fisher’s exact test) and the presence of proteinuria (p = 0.013, Fisher’s exact test). These findings suggest that E-cadherin contributes to the integrity of the placental barrier, and its loss could be an immunohistochemical marker of PE. Full article

Maternal spiral arteries and newly formed decidual capillaries support embryonic development prior to placentation. Previous studies demonstrated that Notch signaling is active in endothelial cells of both decidual capillaries and spiral arteries, however the role of Notch signaling in physiologic decidual angiogenesis and maintenance of the decidual vasculature in early mouse pregnancy has not yet been fully elucidated. We used the Cdh5-Cre^ERT2;Jagged1(Jag1)^flox/flox (Jag1∆EC) mouse model to delete Notch ligand, Jag1, in maternal endothelial cells during post-implantation, pre-placentation mouse pregnancy. Loss of endothelial Jag1 leads to increased expression of Notch effectors, Hey2 and Nrarp, and increased endothelial Notch signaling activity in areas of the decidua with remodeling angiogenesis. This correlated with an increase in Dll4 expression in capillary endothelial cells, but not spiral artery endothelial cells. Consistent with increased Dll4/Notch signaling, we observed decreased VEGFR2 expression and endothelial cell proliferation in angiogenic decidual capillaries. Despite aberrant Dll4 expression and Notch activation in Jag1∆EC mutants, pregnancies were maintained and the decidual vasculature was not altered up to embryonic day 7.5. Thus, Jag1 functions in the newly formed decidual capillaries as an antagonist of endothelial Dll4/Notch signaling during angiogenesis, but Jag1 signaling is not necessary for early uterine angiogenesis. Full article

Background and objectives: The objective of this study was to evaluate the potential of first trimester uterine artery Doppler ultrasonography for the early prediction of preeclampsia (PE), in at-risk pregnant women. Materials and Methods: This was a prospective longitudinal study, including 120 Caucasian pregnant women with risk factors for PE. The potential of pulsatility indexes (PI) and notch was assessed as a tool for preeclampsia screening. Results: Doppler examination of the uterine artery performed early at 11–14 WA allows the detection of pregnancies that will develop PE with a sensitivity of 61.5% and a specificity of 63.8% based on PI analysis. Predictive power increases slightly by adding bilateral notch (sensitivity = 65.4%; specificity = 66%). Conclusions: Uterine artery Doppler examination is an effective non-invasive screening test for the development of PE in pregnancies at risk, particularly appropriate in health systems with limited means of evaluating other biomarkers. Full article

Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20–22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the combination of notching and PI of the uterine arteries to screen for preeclampsia. This was done in a cohort of 380 twin pregnancies. The results showed that the combination of notching and the highest PI above the 95th centile of the uterine arteries gives the best screening characteristics for preeclampsia in twin pregnancies. We calculated sensitivities for preeclampsia for notching, highest PI, and the combination of notching and the highest PI of 50%, 45% and 91%, with specificities of 96%, 96% and 93%, respectively. The present findings demonstrate that notching, increased highest PI, and the combination of notching and the highest PI of the uterine arteries is associated with an increased risk of preeclampsia in twin pregnancies. We observed the highest sensitivity and specificity by using the combination of notching and the highest PI of the uterine arteries. Full article