Placenta-mediated Pregnancy Complications Research Articles

Pregnancy Complications Are Associated with Premature Coronary Artery Disease: Linking Three Cohorts.

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case-control study design. Cases (n = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21-5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22-4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05-11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD.

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.

Effects of anti-Xa activity monitoring on the outcome of high-risk pregnancies treated with a prophylactic dose of low-molecular-weight heparin.

To evaluate if anti-Xa level monitoring and dose adjustment in women using a prophylactic dose of enoxaparin can decrease placenta-mediated pregnancy complications. This retrospective observational cohort study included pregnant women receiving enoxaparin prophylaxis, who were followed at the Thrombosis and Hemostasis Outpatient clinic between 2010 and 2017. The dose was adjusted according to enoxaparin anti-Xa levels in the study group or the weight of individuals in the control group. Of 585 women surveyed, 110 met the inclusion criteria; 63 of them were included in the study group and 47 in the control group. Mean starting dose was 46 versus 43 mg (p = .25), mean final dose was 52 mg versus 45 mg (p = .03) and dose adjustment was required in 37% versus 11% (p = .002) in the study and control groups, respectively. Twenty-eight percent of anti-Xa measurements in the second trimester were beneath the prophylactic threshold, compared to 11% and 16% in the first and third trimesters, respectively (p = .02). Labors ended with live birth in 91% versus 94% of cases (p = .5), 85% versus 68% of pregnancies were term (p = .05), 11% versus 23% of newborns were low birth weight (p = .1) and placenta-mediated pregnancy complications were documented in 9% versus 19%, (p = .17) in the study group relative to controls, respectively. The most prominent decrease in anti-Xa levels was observed in the second trimester. Monitored women had significantly more term deliveries and demonstrated a trend toward higher birth weight and fewer placenta-mediated pregnancy complications. Larger studies are needed to confirm improved pregnancy outcome in monitored women.

Integrative profiling of extrachromosomal circular DNA in placenta and maternal plasma provides insights into the biology of fetal growth restriction and reveals potential biomarkers.

Introduction: Fetal growth restriction (FGR) is a placenta-mediated pregnancy complication that predisposes fetuses to perinatal complications. Maternal plasma cell-free DNA harbors DNA originating from placental trophoblasts, which is promising for the prenatal diagnosis and prediction of pregnancy complications. Extrachromosomal circular DNA (eccDNA) is emerging as an ideal biomarker and target for several diseases. Methods: We utilized eccDNA sequencing and bioinformatic pipeline to investigate the characteristics and associations of eccDNA in placenta and maternal plasma, the role of placental eccDNA in the pathogenesis of FGR, and potential plasma eccDNA biomarkers of FGR. Results: Using our bioinformatics pipelines, we identified multi-chromosomal-fragment and single-fragment eccDNA in placenta, but almost exclusively single-fragment eccDNA in maternal plasma. Relative to that in plasma, eccDNA in placenta was larger and substantially more abundant in exons, untranslated regions, promoters, repetitive elements [short interspersed nuclear elements (SINEs)/Alu, SINEs/mammalian-wide interspersed repeats, long terminal repeats/endogenous retrovirus-like elements, and single recognition particle RNA], and transcription factor binding motifs. Placental multi-chromosomal-fragment eccDNA was enriched in confident enhancer regions predicted to pertain to genes in apoptosis, energy, cell growth, and autophagy pathways. Placental eccDNA-associated genes whose abundance differed between the FGR and control groups were associated with immunity-related gene ontology (GO) terms. The combined analysis of plasma and placental eccDNA-associated genes in the FGR and control groups led to the identification of potential biomarkers that were assigned to the GO terms of the epigenetic regulation of gene expression and nutrient-related processes, respectively. Conclusion: Together, our results highlight links between placenta functions and multi-chromosomal-fragment and single-fragment eccDNA. The integrative analysis of placental and plasma eccDNA confirmed the potential of these molecules as disease-specific biomarkers of FGR.

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.

Programmed frozen embryo transfer cycles are associated with a higher risk of abnormal placental development: a retrospective cohort study of singleton live births.

Abnormal placental development can lead to adverse outcomes for both mother and fetus. The effect of different types of endometrium preparation regimens of frozen-thawed cycles on the placental development features associated with the perinatal outcomes remains unclear. Hence, we conducted a retrospective cohort study to assess the impact of specific endometrial preparation regimens on placenta-mediated pregnancy complications in singleton live births. A retrospective cohort study was conducted evaluating data of all singleton live births both conceived naturally or by in vitro fertilization (IVF) therapy from 2018 to 2020 at our hospital. Two exposed groups of frozen-thawed embryo transfer (FET) were created by the endometrium preparation regimen as the modified natural cycles (mNC) and the programmed cycles. The nonexposed group was the singleton pregnancies conceived naturally. The obstetrical and perinatal outcomes were compared among the three groups using multivariate analysis to adjust the results for determinants potentially associated with the abnormal placental development. A total of 2186 pregnant women with singleton live births were included in our final analysis and were divided into three groups as naturally conceived group (n=1334), mNC-FETs group (n=217) and programmed-FETs group(n=635). After adjusting for maternal age and parity, no significant difference was observed on the risk of placental disorders between mNC-FET cycles and natural conceived pregnancies (aOR 1.16; 95%CI 1.31-7.01), while programmed-FET cycles were associated with a higher occurrence of placental disorders (aOR 5.36; 95%CI 3.63-8.05). Using the mNC-FET group as a reference and adjusting for confounders such as maternal age, parity, endometrial thickness, and number of embryos transferred, we found that the main manifestation of abnormal placentation in programmed FET cycles was abnormal placental attachment, including placental adhesion and placenta increta (aOR 2.50, 95%CI 1.36-4.90). The dysfunction of placentation in programmed-FET cycles was independently associated with the type of infertility, the total dose of Femostone and thinner endometrium. Additionally, placental disorders in the programmed-FET group were associated with higher rate of preeclampsia, postpartum hemorrhage and Cesarean section. Our retrospective study revealed that the programmed-FET has a substantial impact on placental development, resulting in a higher incidence of preeclampsia, postpartum hemorrhage and Cesarean section. These findings have significant implications on clinical decision-making.

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.

Maternal Hyperhomocysteinemia as a Predictor of Placenta-Mediated Pregnancy Complications: A Two-Year Novel Study.

Background Placenta-mediated pregnancy complications (PMPCs) are a significant contributor to adverse maternal and fetal outcomes. Though the exact cause of the array of pregnancy-related vascular disorders is still unknown, increased maternal serum homocysteine (Hct) levels have been linked to the pathophysiology. Hyperhomocysteinemia (HHct) has been strongly linked with the risk of developing PMPCs such as preeclampsia (PE), fetal growth restriction (FGR), intrauterine fetal death (IUFD), preterm births and placental abruption. Methodology The present observational study was carried out on 810 low-risk antenatal women in their early second trimester (13-20 weeks gestation age) in the department of obstetrics and gynecology of a tertiary care rural hospital to identify the significance of abnormally raised maternal serum Hct level in developing PMPCs. Results Of the 810 participants studied, 224 (27.65%) had raised Hct levelswhereas the rest of the 586 (72.35%) participants had normal Hct levels. The mean Hct level of raised homocysteine group (18.59 ± 2.46 micromol/L) was substantially raised than the normal Hct group (8.64 ± 3.1 micromol/L). It was observedthat women with elevated serum Hct levels developed PMPCs significantly morethan women with normal serum Hct levels (p-value <0.05).Among HHct subjects, 65.18% developed PE, 34.38% had FGR, 28.13% had a preterm delivery, 4.02% had abruptio placentae and 3.57%had IUFD. Conclusions The focus of the current study is on an easy and quick intervention suchas assessing the often-ignored levels of Hct duringpregnancythat can help predict and prevent PMPCs. It also highlights the necessity for well-thought-out large-scale studies and trials to further examine the phenomena, as pregnancy may be the only time whenrural women willhave the opportunityto receive advice and tobe tested for HHct.

Placenta-mediated pregnancy complications in women with a history of late fetal loss and placental infarction without thrombophilia: risk of recurrence and efficacy of pharmacological prophylactic interventions. A 10-year retrospective study

Purpose To evaluate the risk of recurrence of severe placenta-mediated pregnancy complications and compare the efficacy of two different anti-thrombotic regimens in women with a history of late fetal loss without thrombophilia. Patients and methods We performed a 10-year retrospective observational study (2008–2018) analyzing a cohort of 128 women who suffered from pregnancy fetal loss (>20 weeks of gestational age) with histological evidence of placental infarction. All the women tested negative for congenital and/or acquired thrombophilia. In their subsequent pregnancies, 55 received prophylaxis with acetylsalicylic acid (ASA) only and 73 received ASA plus low molecular weight heparin (LMWH). Results Overall, one-third of all pregnancies (31%) had adverse outcomes related to placental dysfunction: pre-term births (25% <37 weeks, 5.6% <34 weeks), newborns with birth weight <2500 g (17%), and newborns small for gestational age (5%). The prevalence of placental abruption, early and/or severe preeclampsia, and fetal loss >20 weeks were 6%, 5%, and 4% respectively. We found a risk reduction for combination therapy (ASA plus LMWH) compared with ASA alone for delivery <34 weeks (RR 0.11, 95% CI: 0.01–0.95 p = 0.045) and a trend for the prevention of early/severe preeclampsia (RR 0.14, 95% CI: 0.01–1.18, p = 0.0715), while no statistically significant difference was observed for composite outcomes (RR 0.51, 95%CI: 0.22–1.19, p = 0.1242). An absolute risk reduction of 5.31% was observed for the ASA plus LMWH group. Multivariate analysis confirmed a risk reduction for delivery <34 weeks (RR 0.32, 95% CI 0.16–0.96 p = 0.041). Conclusion In our study population, the risk of recurrence of placenta-mediated pregnancy complications is substantial, even in the absence of maternal thrombophilic conditions. A reduction of the risk of delivery <34 weeks was detected in the ASA plus LMWH group.

Effects of Salvia miltiorrhiza active compounds on placenta-mediated pregnancy complications.

Placenta-mediated pregnancy complications (PMPCs), including preeclampsia (PE), fetal growth restriction (FGR), and recurrent spontaneous abortion (RSA), occur in approximately 5% of pregnancies and are caused by abnormal placenta development. The development of effective therapies for PMPCs is still challenging due to the complicated pathogenesis, such as disrupted vascular homeostasis and subsequent abnormal placentation. Synthetic drugs have been recommended for treating PMPCs; however, they tend to cause adverse reactions in the mother and fetus. Salvia miltiorrhiza (S. miltiorrhiza) has potential effects on PMPCs owing to its advantages in treating cardiovascular disorders. S. miltiorrhiza and its active compounds could attenuate the symptoms of PMPCs through anticoagulation, vasodilation, antioxidation, and endothelial protection. Thus, in this review, we summarize the literature and provide comprehensive insights on S. miltiorrhiza and its phytochemical constituents, pharmacological activities, and on PMPCs, which would be valuable to explore promising drugs.

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.

Abstract 10005: Pregnancy Complications Are Associated With Premature Coronary Artery Disease - Linking Three South Australian Cohorts

Introduction: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are more likely to develop coronary artery disease (CAD) at a younger age. This is the first study to assess the relationship between pregnancy complications and premature coronary artery disease (PCAD) in Australian women. Hypothesis: We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM and risk of CAD prior to 60 years of age. Methods: The research project involved a data linkage approach merging three databases of South Australian cohorts by employing a retrospective, age-matched case-control study design. Cases (n=721) were ascertained from Coronary Angiogram Database of South Australia (CADOSA). Women &lt;60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to determine their pregnancy outcomes. Controls (n=194) were ascertained from North West Adelaide Health Study (NWAHS) and comprised of women who were healthy or had health conditions other than CAD, age-matched to CADOSA (+/- 5 years) and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as &gt; 50% stenosis in one or more coronary arteries at coronary angiography. Results: Women who were diagnosed with PCAD were more likely to have experienced a placenta-mediated pregnancy complication, previous miscarriage, asthma or anaemia and/or have risk factors for CAD including pre-existing diabetes (I &amp; II), active smoking and obesity during pregnancy compared to women without a history of CAD as shown in the table below (p &lt; 0.05). GDM was not associated with PCAD in these cohorts. Conclusion: Women diagnosed with PCAD have conventional CVD risk factors and some that are uniquely related to their pregnancy. These clinical events may be considered novel risk factors for future PCAD and require attention in contemporary preventative cardiology practice.

Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing the release of microparticles.

Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

Preconception ovarian reserve and placenta-mediated pregnancy complications among infertile women.

Are preconception ovarian reserve markers, such as Anti-Mullerian hormone and antral follicle count, associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation? This is a secondary analysis of women with unexplained infertility who had a singleton live birth after enrollment in the Analysis of Multiple Intrauterine Gestations after Ovarian Stimulation (AMIGOS) trial that randomized couples to superovulation with letrozole, clomiphene, or gonadotropins with insemination for up to 4 cycles. Compared to controls (N=156), women who developed preeclampsia (N=17) had lower Anti-Mullerian hormone levels (2.24±1.20 vs. 2.89±2.32, p=0.07) and lower antral follicle count (18±7.67 vs. 21±11.43, p=0.16); though these differences were not statistically significant. There was no relationship between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.76-1.25) or antral follicle count (OR: 0.98, 95% CI 0.93-1.04) with preeclampsia and between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.83-1.17) and antral follicle count (OR: 1.00, 95% CI: 0.97-1.04) with placenta medicated pregnancy complications after adjusting for age, BMI and race. Preconception ovarian reserve markers are not associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation with insemination.

The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review.

Plasminogen activator inhibitor type 1 (PAI-1) is a main inhibitor of fibrinolysis. The PAI-1 gene (SERPINE1) harbors genetic variants with the potential of modifying plasma levels of PAI-1. A delicate balance exists between the coagulation and fibrinolytic system, and changes in PAI-1 have been suggested to compromise establishment of a successful pregnancy. Therefore, this systematic review investigated the association between genetic variants and/or plasma levels of PAI-1 and placenta-mediated pregnancy complications. An extensive literature search was conducted in PubMed, Embase, and Web of Science on the 29th of April 2021. All studies underwent quality rating according to The Study Quality Assessment Tools checklist provided by National Heart, Lung and Blood Institute. A total of 71 studies were included, among which 60 studies investigated PAI-1 genotypes and 11 studies measured PAI-1 plasma levels. In 32 out of 59 studies, no association was found between the PAI-1 4G/5G polymorphism (rs1799768) and placenta-mediated pregnancy complications, which was stated as no significant difference in the genotype distribution comparing women with and without placenta-mediated pregnancy complications or no significantly increased odds of placenta-mediated pregnancy complications carrying the 4G/4G or 4G/5G genotype. Eight out of 11 studies reported significantly higher PAI-1 plasma levels in preeclamptic women than in women without preeclampsia. In conclusion, no clear evidence indicates that PAI-1 polymorphisms are associated with placenta-mediated pregnancy complications, and the possible association between high PAI-1 plasma levels and preeclampsia needs further investigations. Thus, investigation of PAI-1 genotypes and PAI-1 plasma levels does not currently seem to have a place in daily clinical practice managing placenta-mediated pregnancy complications.

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.

Hereditary thrombophilia and adverse pregnancy outcomes

Background: Multiple studies have found a relatively increased risk of placenta-mediated pregnancy complications in women with congenital thrombophilia, especially early recurrent pregnancy loss, fetal loss, early-onset preeclampsia, intrauterine growth restriction, and premature abruption of normally positioned placenta. However, the extent of the association and the absolute risk are very modest, but they significantly increase in pregnant women with severe obstetric complications. Conclusions: There is convincing evidence that deficiency of natural anticoagulants (antithrombin, protein C, protein S) is a risk factor for late fetal loss. Factor V Leiden G1691A gene mutation and prothrombin G20210A gene mutation are associated with a double risk for early and unexplained recurrent pregnancy loss and for non-recurrent late fetal loss. The association of congenital thrombophilia with preeclampsia is much more uncertain, being probably limited factor V Leiden G1691A gene mutation and more severe cases of preeclampsia. Fewer data are available on intrauterine growth restriction (IUGR) and premature abruption of the normally positioned placenta. There is insufficient evidence to suggest an association of other forms of congenital thrombophilia with adverse pregnancy outcomes. In addition, genetic and epidemiological research suggests that placenta-mediated pregnancy complications are of polygenic multifactorial etiology, with a risk determined by the interaction of multiple genetic variants and other risk factors.

Exposure to chemical components of fine particulate matter and ozone, and placenta-mediated pregnancy complications in Tokyo: a register-based study

BackgroundMaternal exposure to fine particulate matter (PM2.5) was associated with pregnancy complications. However, we still lack comprehensive evidence regarding which specific chemical components of PM2.5 are more harmful for maternal and foetal health.ObjectiveWe focused on exposure over the first trimester (0–13 weeks of gestation), which includes the early placentation period, and investigated whether PM2.5 and its components were associated with placenta-mediated pregnancy complications (combined outcome of small for gestational age, preeclampsia, placental abruption, and stillbirth).MethodsFrom 2013 to 2015, we obtained information, from the Japan Perinatal Registry Network database, on 83,454 women who delivered singleton infants within 23 Tokyo wards (≈627 km2). Using daily filter sampling of PM2.5 at one monitoring location, we analysed carbon and ion components, and assigned the first trimester average of the respective pollutant concentrations to each woman.ResultsThe ORs of placenta-mediated pregnancy complications were 1.14 (95% CI = 1.08–1.22) per 0.51 μg/m3 (interquartile range) increase of organic carbon and 1.11 (1.03–1.18) per 0.06 μg/m3 increase of sodium. Organic carbon was also associated with four individual complications. There was no association between ozone and outcome.SignificanceThere were specific components of PM2.5 that have adverse effects on maternal and foetal health.