Severe Pregnancy Complications Research Articles

Downregulation of miR-92a in Decidual Stromal Cells Suppresses Migration Ability of Trophoblasts by Promoting Macrophage Polarization.

Preeclampsia (PE) is a severe pregnancy complication that accounts for about 14% of maternal deaths. Its clinical manifestations commonly include hypertension and proteinuria. However, it is largely limited in understanding its pathogenetic mechanism. In this study, we used bioinformatics to compare differential gene expressions in decidual stromal cells from PE patients and healthy donors. The result indicated that higher levels of CCL5 and CXCL2 were expressed in decidual stromal cells of PE patients compared with healthy pregnancy. The bioinformatics analysis confirmed that decidual stromal cells derived from PE patients expressed significantly lower miR-92a compared with those derived from healthy donors. Transfection of miR-92a inhibitors upregulated IL-6, CXCL2, CXCL3, CCL5, and CXCL8 expressions in decidual stromal cells. Luciferase activity assay confirmed that miR-92a directly targeted the mRNA of IRF3 whose overexpression could promote the secretion of cytokines. The flow cytometric analysis demonstrated that M1 macrophage infiltration was higher in the placentas of PE patients than in those of healthy donors. We also observed that after transfection of miR-92a inhibitor, condition medium (CM) derived from decidual stromal cells significantly promoted M1 polarization of macrophages. In addition, the transwell migration assay and flow cytometric analysis together showed that decidual stromal cell-derived CM induced macrophages to suppress the trophoblast migration and proliferation. Taken together, our result indicates that downregulation of miR-92a in decidual stromal cells promotes the macrophage polarization and suppresses the trophoblast migration and proliferation.

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway.

Pre-eclampsia (PE) is a severe pregnancy complication characterized by impaired trophoblast invasion and spiral artery remodeling and can have serious consequences for both mother and child. Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is involved in numerous tumor-related biological processes. However, the biological action and underlying mechanisms of PPP1R3G in PE progression remain unclear. We used western blotting and immunohistochemistry to investigate PPP1R3G expression in gestational age-matched pre-eclamptic and normal placental tissues. After lentivirus transfection, wound-healing, Transwell, cell-counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and TdT mediateddUTP Nick End Labeling (TUNEL) assays were used to assess trophoblast migration, invasion, proliferation, and apoptosis, respectively. The relative expression levels of PPP1R3G and the proteins involved in the Akt signaling pathway were determined using western blotting. The results showed that PPP1R3G levels were significantly lower in the placental tissues and GSE74341 microarray of the PE group than those of the healthy control group. We also found that neonatal weight and Apgar score were lower at birth, and peak systolic blood pressure and diastolic blood pressure were higher in the PE group than in the non-PE group. In addition, PPP1R3G knockdown decreased p-Akt/Akt expression and inhibited migration, invasion, and proliferation in HTR-8/SVneo trophoblasts but had no discernible effect on cell apoptosis. Furthermore, PPP1R3G positively regulated matrix metallopeptidase 9 (MMP-9), which was downregulated in placental tissues of pregnant women with PE. These results provided the first evidence that the reduced levels of PPP1R3G might contribute to PE by suppressing the invasion and migration of trophoblasts and targeting the Akt/MMP-9 signaling pathway.

Gestational Age-Dependent Regulation of Transthyretin in Mice during Pregnancy.

Our prior studies have shown that protein misfolding and aggregation in the placenta are linked to the development of preeclampsia, a severe pregnancy complication. We identified transthyretin (TTR) as a key component of the aggregated protein complex. However, the regulation of native TTR in normal pregnancy remains unclear. In this study, we found that pregnant mice exhibited a remarkable and progressive decline in serum TTR levels through gestational day (gd) 12-14, followed by an increase in late pregnancy and postpartum. Meanwhile, serum albumin levels showed a modest but statistically significant increase throughout gestation. TTR protein and mRNA levels in the liver, a primary source of circulating TTR, mirrored the changes observed in serum TTR levels during gestation. Intriguingly, a similar pattern of TTR alteration was also observed in the serum of pregnant women and pregnant interleukin-10-knockout (IL-10-/-) mice with high inflammation background. In non-pregnant IL-10-/- mice, serum TTR levels were significantly lower than those in age-matched wild-type mice. Administration of IL-10 to non-pregnant IL-10-/- mice restored their serum TTR levels. Notably, dysregulation of TTR resulted in fewer implantation units, lower fetal weight, and smaller litter sizes in human TTR-overexpressing transgenic mice. Thus, TTR may play a pivotal role as a crucial regulator in normal pregnancy, and inflammation during pregnancy may contribute to the downregulation of serum TTR presence.

Paternal Expressed Gene 10 (PEG10) is decreased in early-onset preeclampsia

BackgroundPreeclampsia is a severe complication of pregnancy which is attributed to placental dysfunction. The retrotransposon, Paternal Expressed Gene 10 (PEG10) harbours critical placental functions pertaining to placental trophoblast cells. Limited evidence exists on whether PEG10 is involved in preeclampsia pathogenesis. This study characterised the expression and regulation of PEG10 in placentas from patients with early-onset preeclampsia compared to gestation-matched controls.MethodsPEG10 expression was measured in plasma and placentas collected from patients with early-onset preeclampsia (< 34 weeks’) and gestation-matched controls using ELISA (protein) and RT-qPCR (mRNA). First-trimester human trophoblast stem cells (hTSCs) were used for in vitro studies. PEG10 expression was measured during hTSC differentiation and hTSC exposure to hypoxia (1% O2) and inflammatory cytokines (IL-6 and TNFα) using RT-qPCR. Functional studies used PEG10 siRNA to measure the effect of reduced PEG10 on canonical TGF-beta signalling and proliferation using luciferase and xCELLigence assays, respectively.ResultsPEG10 mRNA expression was significantly reduced in placentas from patients with early-onset preeclampsia (< 34 weeks’ gestation) relative to controls (p = 0.04, n = 78 vs n = 18 controls). PEG10 protein expression was also reduced in preeclamptic placentas (p = 0.03, n = 5 vs n = 5 controls, blinded assessment of immunohistochemical staining), but neither PEG10 mRNA nor protein could be detected in maternal circulation. PEG10 was most highly expressed in hTSCs, and its expression was reduced as hTSCs differentiated into syncytiotrophoblasts (p < 0.0001) and extravillous trophoblasts (p < 0.001). Trophoblast differentiation was not altered when hTSCs were treated with PEG10 siRNA (n = 5 vs n = 5 controls).PEG10 was significantly reduced in hTSCs exposed to hypoxia (p < 0.01). PEG10 was also reduced in hTSCs treated with the inflammatory cytokine TNF alpha (p < 0.01), but not IL-6. PEG10 knocked down (siRNA) in hTSCs showed reduced activation of the canonical TGF-β signalling effector, the SMAD binding element (p < 0.05) relative to controls. PEG10 knockdown in hTSCs however was not associated with any significant alterations in proliferation.ConclusionsPlacental PEG10 is reduced in patients with early-onset preeclampsia. In vitro studies suggest that hypoxia and inflammation may contribute to PEG10 downregulation. Reduced PEG10 alters canonical TGF-beta signalling, and thus may be involved in trophoblast dysfunction associated with this pathway.

Crosstalk between the Resident Microbiota and the Immune Cells Regulates Female Genital Tract Health.

The female genital tract (FGT) performs several functions related to reproduction, but due to its direct exposure to the external environment, it may suffer microbial infections. Both the upper (uterus and cervix) and lower (vagina) FGT are covered by an epithelium, and contain immune cells (macrophages, dendritic cells, T and B lymphocytes) that afford a robust protection to the host. Its upper and the lower part differ in terms of Lactobacillus spp., which are dominant in the vagina. An alteration of the physiological equilibrium between the local microbiota and immune cells leads to a condition of dysbiosis which, in turn, may account for the outcome of FGT infection. Aerobic vaginitis, bacterial vaginosis, and Chlamydia trachomatis are the most frequent infections, and can lead to severe complications in reproduction and pregnancy. The use of natural products, such as probiotics, polyphenols, and lactoferrin in the course of FGT infections is an issue of current investigation. In spite of positive results, more research is needed to define the most appropriate administration, according to the type of patient.

EP300 facilitates human trophoblast stem cell differentiation

Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective trophoblast development and function may result in severe pregnancy complications, including fetal growth restriction and pre-eclampsia. The incidence of these complications is increased in pregnancies of fetuses affected by Rubinstein-Taybi syndrome, a developmental disorder predominantly caused by heterozygous mutations in CREB-binding protein (CREBBP) or E1A-binding protein p300 (EP300). Although the acetyltransferases CREBBP and EP300 are paralogs with many overlapping functions, the increased incidence of pregnancy complications is specific for EP300 mutations. We hypothesized that these complications have their origin in early placentation and that EP300 is involved in that process. Therefore, we investigated the role of EP300 and CREBBP in trophoblast differentiation, using human trophoblast stem cells (TSCs) and trophoblast organoids. We found that pharmacological CREBBP/EP300 inhibition blocks differentiation of TSCs into both EVT and STB lineages, and results in an expansion of TSC-like cells under differentiation-inducing conditions. Specific targeting by RNA interference or CRISPR/Cas9-mediated mutagenesis demonstrated that knockdown of EP300 but not CREBBP, inhibits trophoblast differentiation, consistent with the complications seen in Rubinstein-Taybi syndrome pregnancies. By transcriptome sequencing, we identified transforming growth factor alpha (TGFA, encoding TGF-α) as being strongly upregulated upon EP300 knockdown. Moreover, supplementing differentiation medium with TGF-α, which is a ligand for the epidermal growth factor receptor (EGFR), likewise affected trophoblast differentiation and resulted in increased TSC-like cell proliferation. These findings suggest that EP300 facilitates trophoblast differentiation by interfering with at least EGFR signaling, pointing towards a crucial role for EP300 in early human placentation.

Blood transfusion for children in sub-Saharan Africa: 200 years on

In 1818, James Blundell completed the first successful human blood transfusion. This life-saving medical intervention has revolutionised patient care globally in the past two centuries. Nevertheless, many challenges remain in implementing safe blood transfusion procedures, particularly in sub-Saharan Africa 1 Ala F Allain JP Bates I et al. External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection. PLoS Med. 2012; 9e1001309 Crossref PubMed Scopus (53) Google Scholar where demand predominantly centres on acute paediatric severe anaemia and haemorrhagic complications of pregnancy and trauma. Severe anaemia, when the haemoglobin concentration drops below 6 g/dL, is very common in children admitted to hospital in sub-Saharan Africa. Infectious diseases, nutritional deficiencies, and sickle cell anaemia are the major underlying causes of anaemia. Outcomes remain unsatisfactory, with high mortality and high hospital readmission rates within 6 months of initial admission. 2 Phiri KS Calis JC Faragher B et al. Long term outcome of severe anaemia in Malawian children. PLoS One. 2008; 3e2903 Crossref PubMed Scopus (75) Google Scholar World Blood Donor Day on June 14, 2023, calls for donors to “Give blood, give plasma, share life, share often”. Not only is this a day to celebrate the charitable contributions of blood donors, it is an important opportunity to raise awareness that every pint of blood donated results in critically important life-sustaining therapy, especially for children in sub-Saharan Africa.

Comparison of Causes of Maternal Near Miss and Maternal Mortality in a Tertiary Care Hospital: A Prospective Study

The Maternal Near miss (MNM) concept has led to a more comprehensive and better assessment of the effect of care on maternal health. Investigating severe life-threatening pregnancy complications that women encounter and maternal morbidities (near misses) may help evaluate the quality of care in health facilities and recommend ways to improve maternal survival, especially in poor resource settings. Aim This study aimed to identify causes, classify, and determine the nature of complications in maternal near misses and in maternal death. Material and Methods The hospital-based prospective cohort study was conducted in the Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College, Aligarh Muslim University of Aligarh from 2020 to 2022. The study was approved by the Institutional Ethics Committee and informed written consent was obtained from the study participants. The outcome measures included causes, organ dysfunction, complications, maternal morbidities, and neonatal outcome. Results: Higher rate of unbooked referrals was observed in our study. Hemorrhage was 42.9%, followed by 39.1% hypertensive disorders, 8.6% sepsis in the maternal near miss group while in the maternal mortality group, 26.1% had hypertensive disorders followed by 23.8% women had hemorrhagic disorders, and 20.4% had sepsis. There was a significant difference in HDU, ICU Hospital stay and IUDs in the maternal mortality group compared to the maternal near-miss group. Conclusion The WHO near-miss approach was found to represent a feasible strategy in low-resource settings each Near Miss should be evaluated in detail to diagnose underlying pathology, correct and timely detection of complications, prompt referral and early institution of essential and comprehensive obstetrics care are important for maternal and infant survival.

РОЛЬ ИММУННОГО МЕХАНИЗМА В РАЗВИТИИ ДИСФУНКЦИИ ЭНДОТЕЛИЯ И АПОПТОЗА У БЕРЕМЕННЫХ ЖЕНЩИН С ТЯЖЕЛЫМИ ОСЛОЖНЕНИЯМИ

In order to identify the role of cellular and humoral immunity, nonspecific resistance, cytokine spec-trum in the development of endothelial dysfunction and apoptosis in the pathogenesis of obstetric complications, 40 women with severe pregnancy complications and critical conditions associated with thrombotic micro angiopathy and 30 patients with physiologically occurring pregnancy were exam-ined. The assessment of cellular elements of peripheral blood, indicators of cellular and humoral im-munity, the level of cytokines, a disintegrin and metalloprotease with thrombospondin-1-like domains, member 13 (ADAMTS – 13), Willebrand factor, apoptosis-inducing factor, CD95, progesterone and the number of endotheliocytes is given.&#x0D; The conducted study indicates the failure of the functional state of both innate and acquired immunity in women with complicated pregnancy. The leading role in the development of endothelial dysfunction and the mechanism of apoptosis in pregnant women with severe complications and criti-cal cases associated with thrombotic microangiopathy belongs to an insufficient reserve of nonspecific resistance, impaired cellular and humoral immunity with low background progesterone level and high cytokine activity

Cardiac Arrest Due to out-of-Hospital Pulmonary Embolism During Pregnancy: Successful Thrombolysis.

Pulmonary embolism (PE) is a rare, severe complication in pregnancy, in which case thrombolysis can be lifesaving but has risks. We aim to highlight actions specific to pregnant women. A 24-week pregnant woman developed shortness of breath and experienced sudden cardiac arrest. Cardiopulmonary resuscitation (CPR) was begun immediately in the ambulance and a perimortem caesarean section was performed upon arrival at hospital, but the new-born died. After 55 minutes of CPR, bedside echocardiography revealed right ventricular strain and thrombolysis was given. The uterus was bandaged to minimize blood loss. After massive transfusions and correction of haemostasis, a hysterectomy was performed due to inability of the uterus to contract. After 3 weeks, the patient was discharged in good health and placed on continuous anticoagulant treatment with warfarin. Approximately 3% of all out-of-hospital cardiac arrest cases are due to PE. Among the few patients who survive at the scene, thrombolysis can be lifesaving and should be considered in pregnant women with unstable PE. Prompt collaborative diagnostic work-up in the emergency room is necessary. In a pregnant woman with cardiac arrest, a perimortem caesarean section improves the chances of both maternal and fetal survival. Thrombolysis should be considered for patients with PE in pregnancy with the same indications as in a non-pregnant woman. In case of survival, there is profuse bleeding with need for massive transfusions and haemostasis correction. Despite being in very poor condition, the above patient survived and was fully restored to health. In a young person with a non-shockable rhythm, pulmonary embolism should be kept in mind, especially if they have risk factors for thromboembolism, and pregnant women should be thrombolysed on the same indication as non-pregnant women.In cardiac arrest, a perimortem caesarean section improves the chances of both maternal and fetal survival, but after major surgery one should be prepared for the need for massive transfusions after thrombolysis. Bandaging the uterus might minimize bleeding. Despite 1-hour cardiac arrest with CPR, the patient survived and made a complete recovery.Lifestyle advice with exercise and sun exposure might help avoid rethrombosis and depression in both the short and long term.

Diabetes and Hypertensive Disorders of Pregnancy and the Risk of Third- and Fourth-Degree Perineal Lacerations: A Large United States Cohort 2016–2020 [ID: 1377605

INTRODUCTION: The objective of this study was to assess the effect diabetes and hypertensive disorders of pregnancy have on the rate of third- and fourth-degree perineal laceration (3/4 PL). METHODS: This represents a retrospective cohort based on the Centers for Disease Control and Prevention Natality Live Birth database (2016–2020). We compared the rates of 3/4 PL in term, singleton vaginal births across the United States based on maternal gestational hypertension, preeclampsia, pregestational diabetes, and gestational diabetes. We used Pearson χ2 and multivariate logistic regression to control for confounding variables. Statistical significance was determined as P&lt;.05, and results were displayed as adjusted odds ratios (aORs) with 95% CI. RESULTS: Of the 11,677,671 who met inclusion criteria, 139,174 (1.2%) women experienced 3/4 PL. Gestational hypertension and preeclampsia were associated with increased rates of 3/4 PL (1.53% with aOR 1.28, 95% CI 1.25–1.30, and 1.61% with aOR 1.31, 95% CI 1.06–1.17, respectively). Additionally, both pregestational diabetes and gestational diabetes were associated with higher rates (1.44% with aOR 1.45, 95% CI 1.35–1.56, and 1.44% with aOR 1.27, 95% CI 1.25–1.30, respectively). CONCLUSION: Based on this current U.S. database, we identified several medical complications of pregnancy that are associated with an increased risk for 3/4 PL. Specifically, hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), pregestational as well as gestational diabetes were all associated with significantly increased risks. Understanding these associations may contribute to reduction in the rates of 3/4 PL in gravidas with these conditions.

Prediction of Early- and Late-Onset Pre-Eclampsia in the Preclinical Stage via Placenta-Specific Extracellular miRNA Profiling.

Pre-eclampsia (PE) is one of the severe complications of pregnancy in 3-8% of all cases and is one of the leading causes of maternal and perinatal mortality. The fundamental role in the pathogenesis of PE is assigned to maternal and/or placental factors, whereby the combination and manifestation of which determines the time of onset of the clinical symptoms of PE (before or after 34 weeks of gestation) and their severity. It is known that the expression level of miRNAs, the regulators of signaling cascades in the cell, depends on gestational age. In the present study, we focused on the identification of the placenta-specific miRNAs that differentiate between early- and late-onset pre-eclampsia (ePE and lPE) throughout pregnancy, from the first to the third trimester. A total of 67 patients were analyzed using small RNA deep sequencing and real-time quantitative PCR, which resulted in a core list of miRNAs (let-7b-5p, let-7d-3p, let-7f-5p, let-7i-5p, miR-22-5p, miR-451a, miR-1246, miR-30e-5p, miR-20a-5p, miR-1307-3p, and miR-320e), which in certain combinations can predict ePE or lPE with 100% sensitivity and 84-100% specificity in the 1st trimester of pregnancy. According to the literature data, these miRNA predictors of PE control trophoblast proliferation, invasion, migration, syncytialization, the endoplasmic reticulum unfolded protein response, immune tolerance, angiogenesis, and vascular integrity. The simultaneous detection of let-7d-3p, miR-451a, and miR-1307-3p, resistant to the repeated freezing/thawing of blood serum samples, in combination with biochemical (b-hCG and PAPP-A) and ultrasound (UAPI) parameters, allowed us to develop a universal model for the prediction of ePE and lPE onset (FPR = 15.7% and FNR = 9.5%), which was validated using a test cohort of 48 patients and demonstrated false-positive results in 26.7% of cases and false negatives in 5.6% of cases. For comparison, the use of the generally accepted Astraia program in the analysis of the test cohort of patients led to worse results: FPR = 62.1% and FNR = 33.3%.

Pregnancy complicated by iron deficiency anemia: does the problem have a solution?

Introduction. The problem of iron deficiency anemia by pregnant women remains relevant due to the wide spread of this complication (up to 40%) and requires the search for effective drugs with a minimum number of side effects.Aim. To improve perinatal outcomes in patients with iron deficiency anemia.Materials and methods. A retrospective analysis was done for 2020 of the medical records of patients, including an exchange card and birth histories. The patients were selected by a continuous sampling method. The study was conducted at the clinical base of the Department of Obstetrics and Gynecology with the course of perinatology of the Peoples’ Friendship University of Russia (Head of the Department, Corresponding Member of the Russian Academy of Sciences, Professor V.E. Radzinsky). All the patients (n = 114) were divided into three groups: the first group (n = 54) – a study group, which included pregnant women who had iron deficiency anemia in the II or III trimesters and received antianemic treatment; the second group (n = 30) – pregnant women with iron deficiency anemia (diagnosed in the 2nd trimester) who did not take iron supplements, the third group (n = 30) – a control group of women with normal hemoglobin levels during pregnancy and delivery.Results. The use of ferrous sulfate (Sorbifer durules) at a dose of 200 mg per day by pregnant women with IDA led to the fact that the weight-height parameters in newborns did not differ from those of children from healthy puerperas. At the same time, the volume of blood loss was greater in patients with IDA, however, there were no massive bleedings and moderate IDA in the postpartum period. The level of hemoglobin was significantly higher in women in labor who received ferrous sulfate (Sorbifer Durules) from the II trimester compared with pregnant women who had IDA in the III trimester. Thus, further research and the search for optimal dosages are required, as well as determining the most effective period for the use of iron supplements.Conclusions. Good tolerability and high efficacy of Sorbifer Durules in relation to a significant increase in hemoglobin and the absence of severe complications of pregnancy and childbirth associated with anemia allow us to recommend it for the treatment of IDA in pregnant women and puerperas.

Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002-2018; a case control study.

Stillbirth is a severe pregnancy complication. Maternal obesity is one of the most important modifiable risk factors of stillbirth, yet the biological mechanisms behind this association remain unclear. The adipose tissue is an endocrine organ which, in persons with obesity, causes a hyperinflammatory state. The aim of this study was to investigate inflammation as a contributing mechanism to the risk of stillbirth in women with obesity and if there are possible signs of different BMI phenotypes with different risk. This was a case control study based on all cases of term singleton stillbirth without major fetal malformation in Stockholm County between 2002-2018. Placentas have been examined according to a standardized protocol. Placental inflammatory lesions were compared both between placentas from pregnancies with live born and stillborn infants with different class of body mass index (BMI) as well as among women with stillborn and live born infants with different classes of BMI, respectively. All inflammatory placental lesions were more common in placentas from women with stillbirth compared to placentas from women with live born infants. Vasculitis, funisitis and chronic villitis as well as overall fetal and maternal inflammatory response were present with a significantly increased proportion with increasing BMI in placentas from women with term stillbirth however, there were no differences between placentas from women in different BMI classes with term live born infants. Both acute and chronic inflammatory placental lesions were more common in cases of stillbirth compared to pregnancies with live born infants. There were increased proportions of both acute and chronic placental inflammation (vasculitis, chronic villitis, funisitis and overall fetal and maternal inflammatory response) with increasing BMI among cases with term stillbirth, however no differences among controls with term live born infants.

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) is a severe pregnancy complication for both the woman and the child. Women who suffer from GDM have a greater risk of developing Type 2 diabetes mellitus (T2DM) later in life. Identification of any potential biomarkers for the early prediction of gestational diabetes can help prevent the disease in women with a high risk. Studies show microRNA (miRNA) as a potential biomarker for the early discovery of GDM, but there is a lack of clarity as to which miRNAs are consistently altered in GDM. This study aimed to perform a systematic review and meta-analysis to investigate miRNAs associated with GDM by comparing GDM cases with normoglycemic controls. The systematic review was performed according to PRISMA guidelines with searches in PubMed, Web of Science, and ScienceDirect. The primary search resulted in a total of 849 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 35 full-text articles, which were evaluated for risk of bias and estimates of quality, after which data were extracted and relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: MiR-29a, miR-330, miR-134, miR-132, miR-16, miR-223, miR-155, miR-122, miR-17, miR-103, miR-125, miR-210, and miR-222. While some miRNAs showed considerable between-study variability, miR-29a, miR-330, miR-134, miR-16, miR-223, and miR-17 showed significant overall upregulation in GDM, while circulating levels of miR-132 and miR-155 were decreased among GDM patients, suggesting further studies of these as biomarkers for early GDM discovery.

Circulating Chemerin Is Elevated in Women With Preeclampsia.

Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia. Maternal plasma and placenta were collected from women with early-onset preeclampsia (<34 weeks), with preeclampsia and eclampsia, or before preeclampsia diagnosis (36 weeks). Human trophoblast stem cells were differentiated into syncytiotrophoblast or extravillous trophoblasts across 96 hours. Cells were cultured in 1% O2 (hypoxia) or 5% O2 (normoxia). Chemerin was measured by enzyme-linked immunosorbent assay (ELISA) and RARRES2 (gene coding chemerin) by reverse transcription-quantitative polymerase chain reaction. Circulating chemerin was increased in 46 women with early-onset preeclampsia (<34 weeks) compared to 17 controls (P < .0006). Chemerin was increased in placenta from 43 women with early-onset preeclampsia compared to 24 controls (P < .0001). RARRES2 was reduced in placenta from 43 women with early-onset preeclampsia vs 24 controls (P < .0001). Chemerin was increased in plasma from 26 women with established preeclampsia (P = .006), vs 15 controls. Circulating chemerin was increased in 23 women who later developed preeclampsia vs 182 who did not (P = 3.23 × 10-6). RARRES2 was reduced in syncytiotrophoblast (P = .005) or extravillous trophoblasts (P < .0001). Hypoxia increased RARRES2 expression in syncytiotrophoblast (P = .01) but not cytotrophoblast cells. Circulating chemerin was elevated in women with early-onset preeclampsia, established preeclampsia, and preceding preeclampsia diagnosis of preeclampsia. RARRES2 was dysregulated in placenta complicated by preeclampsia and may be regulated through hypoxia. Chemerin may have potential as a biomarker for preeclampsia but would need to be combined with other biomarkers.

Von Willebrand factor antigen: a biomarker for severe pregnancy complications in women with hereditary thrombotic thrombocytopenic purpura?

BackgroundHereditary thrombotic thrombocytopenic purpura (hTTP) is associated with severe obstetric morbidity (SOM) during pregnancy. Treatment with fresh frozen plasma (FFP) mitigates the risk in some women, but others respond poorly and continue to suffer obstetric complications. ObjectivesTo determine a possible association between SOM and elevated nonpregnant von Willebrand factor (NPVWF) antigen levels in women with hTTP and whether the latter can predict the response to FFP transfusion. MethodsThis was a cohort-based study of women with hTTP due to homozygous c.3772delA mutation of ADAMTS-13 who had pregnancies both with and without FFP treatment. Occurrences of SOM were determined from medical records. Generalized estimated equation logistic regressions and receiver operating characteristic curve analysis determined the NPVWF antigen levels associated with the development of SOM. ResultsFourteen women with hTTP had 71 pregnancies; of which 17 (24%) culminated in pregnancy loss and 32 (45%) were complicated by SOM. FFP transfusions were administered in 32 (45%) of the pregnancies. Treated women had decreased SOM (28% vs 72%, p < .001) and preterm thrombotic thrombocytopenic purpura exacerbations (18% vs 82%, p < .001) and higher median NPVWF antigen levels than those of women with uncomplicated pregnancies (p = .018). Among the treated women, median NPVWF antigen levels were higher in those with SOM than in those without SOM (225% vs 165%, p = .047). Logistic regression models demonstrated a significant 2-way association between elevated NPVWF antigen levels (for SOM, odds ratio, 1.08; 95% CI, 1.001-1.165; p = .046) and SOM (for elevated NPVWF antigen levels, odds ratio, 1.6; 95% CI, 1.329-1.925; p < .001). The receiver operating characteristic curve analysis demonstrated that an NPVWF antigen level of 195% had 75% sensitivity and 72% specificity for SOM. ConclusionElevated NPVWF antigen levels are associated with SOM in women with hTTP. Women with levels >195% may benefit from increased surveillance and more intensive FFP treatment during pregnancy.

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.

Placenta Accreta Spectrum: We Can Do Better

(Aust N Z J Obstet Gynaecol. 2022;62:376–382) Placenta accreta spectrum (PAS) describes the range of placental disorders. Based on classifications by the International Federation for Gynecology and Obstetrics, Grade 1 PAS indicates an abnormal adherent placenta (accreta), Grade 2 PAS indicates an abnormal invasive placenta into the uterine muscle (increta), and Grade 3 PAS indicates an abnormal placenta that grows into the uterine wall and surrounding organs (percreta). Risk factors for PAS include increased maternal age, multiparity, previous cesarean delivery (CD) or uterine surgery, in vitro fertilization, and placenta previa. The incidence of PAS has been increasing from 0.4 per 1000 births in earlier studies to as high as 3.7 per 1000 births—a trend largely attributed to the worldwide increase in CD. Because PAS is associated with a number of severe pregnancy complications, such as maternal hemorrhage, hysterectomy, and mortality, its accurate diagnosis is important for the appropriate transfer of care and multidisciplinary team (MDT) management. The aim of this study was to determine the rate of antenatal detection of PAS and the impact of MDT management on pregnancy outcomes.

Cardiopulmonary Arrest During Pregnancy: A Review Article.

Massive pulmonary embolism (PE) is an uncommon but severe complication of pregnancy or during the first few weeks after giving birth. Our intention was to thoroughly analyze the information available to its management methods.Significant bleeding of mother survival and early deliveries in fetal survivals were having hemorrhage andwerehaving key outcomes. We found 127 severe PE cases that have had at least one form of treatment (at least 83% big; 23% with cardiac arrest). The 83 women who received thrombolysis had a 94% (95%) survival rate. Cardiac arrest in pregnancy is uncommon, although maintaining current competency can be challenging. While maternal mortality rates have decreased globally over the past 25 years, they have increased in the United States. The intricacy of the maternal mortality issue is a result of a number of clinical and socioeconomic problems such as unequal healthcare access, racial and ethnic disparities, maternal comorbidities, and bias in epidemiologic ascertainment. The importance of doctors being prepared to react to a potential maternal cardiac arrest in any situation where they are providing treatment for pregnant women is highlighted by the rise in maternal mortality. For the treatment of maternal cardiac arrest, an interdisciplinary team with expertise in both the maternal resuscitation procedure and the physiological changes that take place during pregnancy is necessary. Additionally offered are basic and advanced cardiac life support protocols. Techniques to remove obstacles like aortocaval compression that could impair the effectiveness of resuscitation should be used.