Placenta-mediated Complications Research Articles

Antiphospholipid Syndrom and Its Association with Reproductive Losses and Placenta-Mediated Complications: A Comprehensive Study

Данное исследование посвящено антифосфолипидному синдрому (АФС), аутоиммунному заболеванию, характеризующемуся наличием антифосфолипидных антител (АФА) и связанному с различными осложнениями беременности и тромботическими событиями. Исследование охватывает историческую перспективу АФС, освещая его эволюцию с начала XX века до настоящего времени, как значительного системного патологического процесса, влияющего на исходы беременности и тромбофилии. С использованием ретроспективного дизайна исследования были проанализированы истории болезни 15 беременных женщин, перенесших ранние и поздние репродуктивные потери и плацента-ассоциированные осложнения. Проспективное рандомизированное контролируемое исследование оценивало эффективность антитромботической профилактики у беременных женщин с диагностированной тромбофилией. Исследование подчеркивает комплексные осмотры, включая клиническую оценку, лабораторные тесты и инструментальные критерии, для определения влияния АФА на исходы беременности. Результаты подчеркивают распространенность АФА среди 75% участников исследования, с наиболее частыми осложнениями, такими как ранние репродуктивные потери, хроническая плацентарная недостаточность с развитием гипотрофии плода, преэклампсия, преждевременная отслойка нормально расположенной плаценты. Այս հետազոտությունը նվիրված է հակաֆոսֆոլիպիդային համախ-տանիշին (APS), որն աուտոիմուն հիվանդություն է, բնութագրվում է հակաֆոսֆոլիպիդային հակամարմինների (APA) առկայությամբ և նրա հետ կապված հղիության տարբեր բարդությունների և թրոմբոզային պատահարների առաջացմամբ: Հետազոտությունը ներկայացնում է APS-ի պատմությունը ՝ ընդգրկելով նրա էվոլյուցիան 20-րդ դարի սկզբից մինչև մեր օրերը և համարվելով նշանակալի համակարգային հիվանդություն՝ ցույց է տալիս, թե ինչպես է ազդում հղիության ելքերի վրա։ Ռետրոսպեկտիվ ուսումնասիրության նախագծման միջոցով վերլուծվել են 15 հղի կանանց բժշկական պատմություններ, ովքեր ունեցել են վաղ և ուշ վերարտադրողական կորուստներ և պլացենտազուգորդված բարդություններ: Պրոսպեկտիվ պատահականացված վերահսկվող հետազոտությունը գնահատել է թրոմբոֆիլիա ախտորոշված հղի կանանց մոտ հակաթրոմբոզային պրոֆիլակտիկայի արդյունավետությունը։ Հետազոտության մեջ շեշտը դրվել է համապարփակ գնահատումների վրա՝ ներառյալ կլինիկական գնահատումը, լաբորատոր թեստերը և գործիքային չափորոշիչները, որպեսզի որոշվի APA-ի ազդեցությամբ հղիության ելքը:

Chronic Hypertension in Pregnancy and Placenta-Mediated Complications Regardless of Preeclampsia.

The prevalence of chronic hypertension in women of reproductive age is on the rise mainly due to delayed childbearing. Maternal chronic hypertension, prevailing prior to conception or manifesting within the early gestational period, poses a substantial risk for the development of preeclampsia with adverse maternal and fetal outcomes, specifically as a result of placental dysfunction. We aimed to investigate whether chronic hypertension is associated with placenta-mediated complications regardless of the development of preeclampsia in pregnancy. This was a population-based, retrospective cohort study from 'Soroka' university medical center (SUMC) in Israel, of women who gave birth between 1991 and 2021, comparing placenta-mediated complications (including fetal growth restriction (FGR), placental abruption, preterm delivery, and perinatal mortality) in women with and without chronic hypertension. Generalized estimating equation (GEE) models were used for each outcome to control for possible confounding factors. A total of 356,356 deliveries met the study's inclusion criteria. Of them, 3949 (1.1%) deliveries were of mothers with chronic hypertension. Women with chronic hypertension had significantly higher rates of all placenta-mediated complications investigated in this study. The GEE models adjusting for preeclampsia and other confounding factors affirmed that chronic hypertension is independently associated with all the studied placental complications except placental abruption. Chronic hypertension in pregnancy is associated with placenta-mediated complications, regardless of preeclampsia. Therefore, early diagnosis of chronic hypertension is warranted in order to provide adequate pregnancy follow-up and close monitoring for placental complications, especially in an era of advanced maternal age.

Impact of COVID-19 and Vaccination During Pregnancy on Placenta-Mediated Complications (COVIGRO Study)

ObjectivesCOVID-19 has been associated with preterm birth (PTB) and placental-mediated complications, including fetal growth restriction and preeclampsia (PE). This study aimed to estimate the impact of COVID-19 and vaccination on adverse pregnancy outcomes and markers of placental function. MethodsWe performed a study on a prospective cohort of women recruited in the first trimester of pregnancy during the early COVID-19 pandemic period (December 2020 to December 2021). At each trimester of pregnancy, the assessment included a questionnaire on COVID-19 and vaccination status; serological tests for COVID-19 (for asymptomatic infection); measurement of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal blood; measurement of mean uterine artery pulsatility index (UtA-PI); and pregnancy outcomes (PTB, PE, birth weight below the fifth and the tenth percentile). ResultsAmong 788 patients with complete data, we observed 101 (13%) cases of symptomatic infection and 74 (9%) cases of asymptomatic infection with SARS-CoV-2. Most cases (73%) of infection were among women with previous vaccination or COVID-19 infection before pregnancy. COVID-19 infection was not associated with adverse pregnancy outcomes, abnormal fetal growth, sFlt-1/PlGF ratio, or mean UtA-PI. Vaccination during pregnancy did not influence these outcomes either. We observed no case of severe COVID-19 infection requiring respiratory support. ConclusionMild symptomatic or asymptomatic COVID-19 during pregnancy did not influence the risk of adverse pregnancy outcomes and the markers of placental function in predominantly vaccinated women. Fetal growth monitoring is unlikely to be mandatory in women with mild symptoms of COVID-19.

EG-VEGF maternal levels predict spontaneous preterm birth in the second and third trimesters in pregnant women with risk factors for placenta-mediated complications

Prediction of spontaneous preterm birth in asymptomatic women remains a great challenge for the public health system. The aim of the study was to determine the informational value of EG-VEGF circulating levels for prediction of spontaneous preterm birth in the second and third trimesters in pregnant women at high risk for placenta-mediated complications. A prospective multicenter cohort study including 200 pregnant patients with five-serum sampling per patient. Women with spontaneous preterm birth have higher concentrations of serum EG-VEGF than uncomplicated patients at 24 weeks, 28 weeks and 32 weeks (p = 0.03, 0.02 and < 0.001). The areas under the curve reached 0.9 with 100% sensitivity at 32 weeks for the prediction of spontaneous preterm birth. Serum EG-VEGF concentrations could be considered as a reliable biomarker of spontaneous preterm birth in high-risk for placenta-mediated complications pregnant women.

Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications.

Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.

OP09_3. Relationship between vitamin D status and the risk for placenta-mediated complications in pregnancy at high risk: ANGIOPRED VITAD study

OP09_3. Relationship between vitamin D status and the risk for placenta-mediated complications in pregnancy at high risk: ANGIOPRED VITAD study

Impact of antibiotic cured chronic endometritis on perinatal outcomes: Re-evaluation of a cohort study with a detailed follow-up.

The impact of antibiotic-cured chronic endometritis (CE) on perinatal outcomes of patients conceived with frozen embryo transfer (FET) was unclear. This study was to re-evaluate the perinatal outcomes of a cohort of infertile patients who had undergone endometrial biopsy for CE detection from February 2018 to December 2019 and successfully delivered babies after FET. The study population was divided into two groups: the non-CE (NCE) group (0-4/HPF CD138) and the cured-CE (CCE) group (CD138+/HPF≥5 and has been cured after one or two rounds of antibiotic treatment). For subgroup analysis, the NCE group was further divided into subgroup 1 (CD138+/HPF=0), subgroup 2 (CD138+/HPF=1-4 with antibiotic treatment), and subgroup 3 (CD138+/HPF=1-4 without antibiotic treatment) RESULTS: A total of 321 live births, including 210 in the NCE group and 111 in the CCE group were analyzed. The prevalence rates of premature rupture of the membrane and preterm birth were comparable between NCE and CCE (6.2%vs. 7.1% and 10.8%vs. 10.1%, respectively) groups. In addition, no differences were detected in the rates of placenta-mediated complications, such as preeclampsia, placenta abruption, or low birthweight. Multiple logistic analyses confirmed that CCE was not associated with an increased risk of any adverse perinatal outcomes. Subgroup analysis in NCE failed to find any significant differences in the incidences of obstetrical and neonatal complications. CCE might not increase the risks of adverse perinatal outcomes after antibiotic treatment.

Anti-Phospholipid Antibodies in Women with Placenta-Mediated Complications Delivered at >34 Weeks of Gestation.

To determine the prevalence of positive antiphospholipid (aPL) antibodies among pregnant women with placenta-mediated complications delivered at >340/7 weeks of gestation. This was a single-center retrospective observational study conducted between 2017 and 2022. Inclusion criteria included pregnant or post-partum women, >18 years, diagnosed with any of the following placenta-mediated complications and delivered at >340/7 weeks of gestation: small-for-gestational-age neonate (SGA ≤ 5th percentile according to local birthweight charts), preeclampsia with severe features, and placental abruption. The primary outcome was the prevalence of positive aPL antibodies: Lupus anticoagulant, Anticardiolipin, or Anti-ß2glycoprotein1. Overall, 431 women met the inclusion criteria. Of them, 378(87.7%) had an SGA neonate, 30 had preeclampsia with severe features (7%), 23 had placental abruption (5.3%), and 21 patients had multiple diagnoses(4.9%). The prevalence of aPL antibodies in the cohort was 4.9% and was comparable between the three subgroups (SGA-3.9%; PET with severe features-3.3%; and placental abruption-13% (p = 0.17)). aPL antibodies prevalence in women with placenta-mediated complications > 34 weeks of gestation was 4.9%, with comparable prevalence rates among the three subgroups. Future prospective studies are needed to delineate the need for treatment in those who tested positive for aPL antibodies and do not meet Anti-Phospholipid Antibody Syndrome clinical criteria.

Winter, spring, summer or fall: temporal patterns in placenta-mediated pregnancy complications—an exploratory analysis

PurposePlacenta-mediated pregnancy complications, like growth restriction and hypertensive disorders, are leading causes of maternal, fetal and neonatal morbidity and mortality in high-income countries. The purpose was to investigate if there is a seasonal variation in placenta-mediated pregnancy complications (small for gestational age, intrauterine growth restriction, preeclampsia, preterm birth and intrauterine fetal death).MethodsThis is a Danish cohort study including all singleton deliveries at gestational week 22 up to and including week 41 conceived from December 2006 to November 2016 (N = 555,459). We used statistical process control charts to visualize data and to test for patterns of non-random variation in data over time for pregnancies with risk factors (BMI, diabetes, in vitro fertilization, maternal age > 40 years, primipara, previous caesarean and smoking) and each of the following outcome: fetal growth restriction, hypertensive disorders, preterm birth and intrauterine fetal death. The study was approved by the Danish Data Protection agency; REG-039-2019.ResultsWe found a seasonal pattern in hypertensive disorders during pregnancy with dips in pregnancies conceived in the fall season and highest risk by conception in the spring and summer season. We found no apparent seasonality in cases of preterm delivery, small for gestational age and intrauterine mortality. Individual risk factors (e.g. smoking and obesity) for placenta-mediated complicated over time were in consistency with the general trends.ConclusionsWe found a significant seasonal variation in the risk of hypertensive disorders of pregnancy with highest risk by conception in the spring and summer season. This study found no seasonal variation in other placenta-mediated complications.

Raised Maternal Homocysteine Levels in Antenatal Women at 10 to 14 Weeks of Gestation and Placenta-Mediated Complications: A Cohort Study.

Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and perinatal morbidity and mortality. Early detection and management of these conditions are crucial to ensuring optimal outcomes for both the mother and baby.However, there have been inconsistent correlations found between maternal homocysteine levels and placenta-related problems in various studies. Therefore, prospective research based on data pointing to a role for hyperhomocysteinemia in placenta-mediated complications will open doors for early detection and management of these complications. Thus, this study aims to determine if a higher risk of placenta-mediated problems is connected with a higher maternal plasma homocysteine content between 10 and 14 weeks of gestation. Methodology An observational prospective cohort study was conducted in the Department of Obstetrics and Gynecology, consisting of all the antenatal women between 10 and 14 weeks of gestation attending outpatient departments or inpatients admitted in labor rooms or wards having singleton pregnancies. Along with socio-demographic information and detailed history, a clinical examination was performed, and blood samples were collected to determine plasma homocysteine levels. Results As per thereceiver operating characteristic curve (ROC curve), the cut-off value taken was <5 for the low level of serum homocysteine, 5 to 15 micromol/L for the normal value, and >15 micromol/L for a raised serum homocysteine level. The cutoff value for our study was 45 micromol/L with a sensitivity of 78.33%, a specificity of 91.67%, a positive predictive value of 90.38%, and a negative predictive value of 80.88% with a diagnostic accuracy of 85%. This means that, for most of the women included in the present study, those who developed placenta-mediated complications had serum blood homocysteine levels of 45 micromol/L or more at 10-14 weeks of gestation. Conclusion Women with high homocysteine levels in the late first trimester had more placenta-mediated complications, such as abruption, pre-eclampsia, restricted fetal growth, and recurrent pregnancy losses, compared to women with a normal level of homocysteine in the late first trimester. Therefore, measuring blood homocysteine levels in pregnancy may be helpful as a diagnostic test for the early detection of high-risk individuals for placenta-mediated complications.

Assessment-based management of placenta-mediated pregnancy complications: Pragmatism until a precision medicine approach evolves.

The management of pregnant women with thrombophilia and a history of gestational vascular complications remains debatable. Treatment of the latter is often based on clinical outcome rather than disease mechanism. While the use of venous thromboembolism prophylaxis in pregnancy is recommended for those at increased risk, the ability of anticoagulant and/or antiplatelet agents to lower the risk of placenta-mediated complications in this clinical setting remains controversial. The available guidelines are inconsistent in some situations, which reflects the limited evidence base. This review critically discusses risk assessment models (RAMs) and management strategies of women with thrombophilia and pregnancy complications, using clinical vignettes. RAMs, taking into account obstetric and thrombotic history as well as thrombophilia status, could drive a precision medicine approach, based on disease mechanism, and guide individual therapeutic interventions in high-risk clinical settings.

High Homocysteine Levels During Pregnancy and Its Association With Placenta-Mediated Complications: A Scoping Review.

There is already abundant corroboration indicating that elevated serum homocysteine levels may be related to the risk of coronary, cerebral, and peripheral arterial diseases. High homocysteine levels have often been associated with placental vasculopathies and complications related to the placenta, such as fetal growth restriction, Abruption, hypertensive disorders of pregnancy, and recurrent abortions. This scoping review aims to integrate the currently available scientific literature and fill the gaps in our understanding of homocysteine metabolism during pregnancy and its relationship to placenta-mediated complications. Moreover, to summarize the existing literature on the correlation between raised maternal homocysteine levels in early gestation and its association with placenta-mediated complications. We developed this scoping review article by performing a literature review as per the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelinesand the search was conducted using PRISMA-S (an extension to PRISMA focusing on reporting the search components of systematic reviews) guidelines. The research question was clarified and modified using keywords with important literature published online between 2010 and 2022, which were included from PubMed, and Google Scholar databases with recognized titles and abstracts were examined and cross-checked for case overlap to choose the original reports. A summary of the descriptive data was organized according to the clinical manifestations (symptoms, imaging, and laboratory results) and outcomes (maternal and perinatal). In conclusion, a review of research papers from 2010 to 2022 showed that homocysteine levels during pregnancy fluctuate and are probably influenced by a population's regional, cultural, and socioeconomic status. According to the data, there is an association between elevated homocysteine levels and complications of pregnancies, such as early spontaneous abortions, pre-eclampsia, fetal development restriction, and abruption, as well as in certain cases of maternal and fetal mortality.

Serum D-dimer is not predictive of placenta-mediated complications in pregnancy at high risk: The multicentric prospective cohort AngioPred study.

Background: The theory that D-dimer level might has a predictive or diagnostic role in preeclampsia needs to be explored. Aim of the study was to evaluate the association between serum D-dimer level and the occurrence of placenta-mediated complications (PMC) in a pregnant population at high risk. Methods: A prospective multicenter cohort study including 200 pregnant women was conducted. Results: Serum D-dimer increases throughout pregnancy, with the highest levels at the end of gestation. Serum D-dimer level was similar for women with PMC and with no complication. Serum D-dimer level was not different in women with preeclampsia versus uncomplicated women. Serum D-dimer level was not different in women with early or late preeclampsia versus uncomplicated women. Conclusion: This result suggests that serum D-dimer level was not predictive of the PMC occurrence. This corroborates the fact that the origin of PMC based more on immunity than in hemostasis.

Short communication: Is there any benefit of initiating aspirin before the 11th week of gestation?

Aspirin initiated between 11 and 14weeks of gestation reduces the risk of preterm preeclampsia and other placenta-mediated complications in screen-positive women. Most of these adverse outcomes are associated with maternal vascular malperfusion of the placenta, a disease that begins during the early first trimester. Assuming that aspirin has direct beneficial actions on the developing placenta, tempts clinicians to believe in the maxim that "the earlier the better", however neither the safety nor the effectiveness of aspirin started before 11th week of gestation has been demonstrated. Therefore, outside of research protocols, aspirin should not be started before the 11th week of pregnancy for the prevention of preeclampsia.

A decrease in endometrial thickness before embryo transfer is not associated with preterm birth and placenta-mediated pregnancy complications

Research questionDoes a decrease in endometrial thickness (compaction ≥10%) before embryo transfer prognosticate the risk for preterm birth and placenta-mediated pregnancy complications among IVF pregnancies? DesignRetrospective cohort study at a large private fertility practice. Patients with a singleton live birth after a fresh or frozen embryo transfer between 2016 and 2019 were included. The primary outcome was preterm birth (delivery before 37 weeks gestational age). Secondary outcomes included gestational hypertension, pre-eclampsia, intrauterine growth restriction and placental abruption. ResultsOf the 252 patients that met the study criteria, 122 (48%) demonstrated endometrial compaction (≥10%) and 130 (52%) did not. Age, body mass index (BMI), parity, history of preterm birth or history of pre-existing maternal conditions between the compaction and no-compaction groups were not significantly different. The overall prevalence of placenta-mediated complications across all participants was 25% (n = 62). The number of preterm births between the compaction and no-compaction groups (13% and 6%, respectively, P = 0.09) as well as the prevalence of placenta-mediated complications (29.5% and 20%, respectively, P = 0.08) were not significantly different. Findings for the primary outcome (preterm birth) persisted even after adjustment for potential confounding variables, including maternal age, parity, BMI, embryo score and type of embryo transfer (fresh versus frozen) (adjusted OR 1.86, 95% CI 0.64 to 5.38). ConclusionsEndometrial compaction (or decrease in endometrial thickness) before embryo transfer is not associated with preterm birth or placenta-mediated pregnancy complications.

Contribution of Second Trimester Sonographic Placental Morphology to Uterine Artery Doppler in the Prediction of Placenta-Mediated Pregnancy Complications.

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. 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. 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 &lt; 3rd centile. 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%]). 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.

The Association Between Serum Homocysteine Levels and Placenta-Mediated Complications: A Narrative Review.

The most extremely unfavourable outcome of pregnancy is the death of the mother and newborn. Negative outcomes for mothers or babies can occur as a result of complications or issues during pregnancy, birthor the post-partum period. Early elevated maternal homocysteine (Hct) levels during pregnancy have been linked to altered placental development. There is evidence that suggests an elevated maternal blood Hct level is the new obstetrical risk factor, and the association between hyperhomocysteinemia (HHct) and numerous obstetrical problems was recently recognised. Hctis an essential amino acid, which contains sulphur and is formed from the metabolism of methionine. HHct has several known aetiologies, including genetic anomalies; a deficiency in folic acid, vitamin B6 and vitamin B12; hypothyroidism; old age; and renal illnesses. Vascular problems, coronary artery disease, atherosclerosis and embolic illnesses can all occur as a result of high blood levels of Hct. Hct levels are lower in normal pregnancies than it is in women who are not pregnant. Many pregnancy-related problems, including pre-eclampsia (PE), recurrent pregnancy loss (RPL), placental abruption, premature deliveryand foetal growth restriction (FGR) have been connected to HHct in recent research. We looked for pertinent literature using a thorough and systematic search from PubMed, Medline, Embase, Cochrane Library, Google, etc., and articles that were published before August 2022 based on serum Hct levels and various placenta-mediated complicationsfor this review. In this review,we describedthe synthesis andmetabolismof Hct in humans, Hct levels at various phases of normal pregnancyand the association between Hct and placenta-mediated pregnancy complications. The outcomes discovered can help obstetricians increase the likelihood of a successful pregnancy in cases where placenta-mediated issues are present. Lowering Hct levels with a high dose of folic acid tablets during the subsequent pregnancy may be useful for women who experienced these difficulties in prior pregnancies as a result of HHct.

Risk of Thrombosis, Pregnancy Morbidity or Death in Antiphospholipid Syndrome.

The antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity. The manifestations are caused by antibodies targeting cell membrane phospholipids and/or associated proteins. The triggers leading to these antibodies' production are unknown but recent work suggests cross-reactivity between the autoantigens and peptides produced by the intestinal microbiome. Work on how the autoantibodies could cause clinical manifestations implicates different mechanisms. Binding to surface proteins of different cell types can induce intracellular signaling leading to cell activation and tissue factor expression. Complement activation and neutrophil extracellular-traps are also involved, and recent evidence implicates endothelial protein C receptor-lysobisphosphatidic acid complex. Pregnancy is a high-risk situation for antiphospholipid syndrome patients due to the increased risk of thrombosis and obstetric complications. Epidemiological and clinical research on APS is hampered by heterogeneity in populations, testing and treatment strategies. About one in 10 to one in fifty APS pregnancies is complicated by thrombosis, despite treatment. Pregnant patients with prior thrombosis are prescribed therapeutic dose heparins and low dose aspirin. Without prior thrombosis a prophylactic dose is used. The most frequent obstetrical manifestation is recurrent early pregnancy loss. The association of APS antibodies with late pregnancy loss is stronger, however. Prevention of recurrence is achieved with aspirin and prophylactic dose heparin, although the evidence is of low certainty. The third obstetrical classifying manifestation comprises preterm delivery due to placenta-mediated complications and is treated in subsequent pregnancies with aspirin with or without prophylactic dose heparin, again based on low quality evidence. New therapies are under investigation.

A new decade awaits sticky platelet syndrome: where are we now, how do we manage and what are the complications?

ABSTRACT Introduction Sticky platelet syndrome is a less known platelet function disorder with a familiar occurrence and likely genetic background. Clinically, it is characterized by an increased risk of venous and arterial thromboembolic events and obstetric placenta-mediated complications. The increased aggregation after low-dose ADP and/or epinephrine is its distinctive laboratory feature. Though described for almost 40 years, several issues regarding its etiology, involved pathomechanisms, genetic background, optimal diagnostic and treatment approach remain controversial. Areas covered The work aims to summarize published studies, the actual definition of the syndrome, and point out its drawbacks. A literature search on Medline, Embase, and archives from EHA congresses was performed (terms: ‘sticky platelet syndrome’ – ‘platelet hyperreactivity’ – ‘platelet hyperaggregability’). The authors added in their unpublished data. The introductory overview of the present understanding is followed by the discussion of the pathophysiologic, diagnostic, and therapeutic problems. Expert Opinion Despite the growing evidence provided by case reports and series, the lack of robust studies limits the decision-making on diagnostics and management. The diagnostic issues, particularly the standardization of light transmission aggregometry, represent the crucial problem for the broader acceptance of the syndrome.

Soluble CD146 is increased in preeclampsia and interacts with galectin-1 to regulate trophoblast migration through VEGFR2 receptor

To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1 (Gal1) in placenta-mediated complications of pregnancy. Prospective pilot and experimental studies. University-affiliated hospital and academic research laboratory. One hundred fifteen women divided into three groups: 30 healthy, nonpregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications. Wound-healing experiments were conducted to study trophoblast migration. Quantification of sCD146 and Gal1 by enzyme-linked immunosorbent assay. Analysis of trophoblast migration by wound closure. Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies compared with nonpregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. In contrast, in women with preeclampsia, we found significantly higher sCD146 concentrations compared with women with normal pregnancies and no modification of Gal1. We emphasize the opposing effects of sCD146 and Gal, since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated with the use of an anti-CD146 blocking antibody or the use of small interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146, further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and inhibited its secretion, suggesting that sCD146 acts as a ligand trap. Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target. NCT01736826.