Increase in transforming growth factor-ß didnot affect trombospondin1 in preeclampsia placentas.

Objective: The abnormalities of the placental growth process are a theory causing pre-eclampsia. Antiangiogenic factors contributed to it, such as thrombospondin-1 (TSp-1) that could stimulate transforming growth factor-beta (TGF-ß), or vice versa. Some research showed that an increase in TGF-ß did not always figurized its signaling. Therefore, we conducted a study to examine the TGF-ß signaling proteins through its receptors and TSp-1 expression in preeclampsia placentas. Materials and Methods: This observational study used 33 normal and 33 pre-eclampsia placental storaged samples, for examination of TGF-ß and TGF-ßR 1 and 2, SMAD2 using ELISA, and SMAD2 and TSp-1 mRNA using the reverse transcription polymerase chain reaction method. Data were analyzed using SPSS version 20.0, normality test by Kolmogorov-Smirnov, and significancy was analyzed using nonparametric Mann-Whitney test, or t-test for parametric, with confidence interval 95%. Spearman correlation was used for non-parametric data, besides the Pearson correlation for parametric data. Results: Results showed that there were significant differences between preeclampsia and normal placenta in TGF-ß, its receptors, SMAD2, and TSp-1 mRNA. Normal-TGF-ß=1.19 (0.713-2.051) pg/mg; preeclampsia-TGFB=2.69 (0.906-10.252) pg/mg; p=0.001; normal-TGFBR1=1.025 (0.622-1.402) ng/mg; preeclampsia-TGFBR1=1.223 (0.372-2.553) ng/mg; p=0.004; Normal-TGF-ßR2=0.959 (0.644-1.634) pg/mg; preeclampsia-TGFBR2=1.490 (0.775-3.645) pg/mg; p=0.0001; normal-SMAD2=2.087 (1.279-4.300) ng/mg; preeclampsia-SMAD2=3.508 (1.842-22.489) ng/mg; p=0.0001. The SMAD2 mRNA relative expression (Livax) in the normal placenta was=0.71 (0.03-7.25); pre-eclampsia placenta (PE)=0.49 (0.01-40.71); p=0.075, the normal TSp-1 mRNA expression=1.08 (0.09-5.31); PE=0.21 (0.002-24.06); p=0.002. The correlation test showed a strong correlation between TGF-ß with TGFBR1 and 2 in the normal placenta, conversely, there was no correlation in the preeclampsia placenta. There was also no correlation between SMAD2 and TSp-1 mRNA in both normal and pre-eclampsia. Conclusion: TGF-ß signaling in the preeclampsia placenta was changed due to the increased of the protein signaling it self without correlation between TGF-ß to its receptors and TSp-1 relative expression.

Perimortem caesarean section in COVID-19 era.

Cardiac arrest in pregnancy is very rare. Various methods have been proposed to return spontaneous circulation and prevent mortality, such as Perimortem Caesarean Section (PMCS). Since 2019, the COVID-19 pandemic has added to the difficulty in decision making and performing PMCS. Infection prevention being a priority due to the rapid spreading of the virus could cause hesitation upon initiating an emergency procedure, especially PMCS. We have reviewed the issues impacting on basic and advanced life support in adults with suspected or confirmed COVID-19.

Relationship of Placental Vascular Indices with Macroscopic, Histopathologic, and Intraoperative Blood Loss in Placenta Accreta Spectrum Disorders.

Introduction: Placenta accreta spectrum is an obstetrical complication with a high level of morbidity. The 3-dimensional (3D) power Doppler method has been widely used to improve the diagnosis. Therefore, this study aims to elucidate better the relationship of quantitative placental vascular indices towards macroscopic findings, histopathological grading, and intraoperative blood loss in the disorder. Methods: A preliminary study using a cross-sectional design was conducted on 34 clinically diagnosed women with PAS. The 3D power Doppler with the VOCAL II software was used to measure the level of vascularization index (VI), flow index (FI), and vascularization flow index (VFI). Gross anatomical appearance and histopathology results were categorized as accreta, increta, and percreta. In addition, the intraoperative blood loss level was measured, and 1500 mL was the cutoff for massive hemorrhage. Results: The vascularity indexes were VI = 44.2 (23.7-74.9), FI = 35.4 (24.9-57), and VFI = 15.3 (8.5-41.7). The FI value was significant in comparing gross pathological stages (p=0.015) and had a moderate positive correlation in relation to blood loss (r = 0.449). VI, FI, and VFI above the cutoff values were shown to be strongly associated with blood loss ≥ 1500 cc with aOR 7.00 (95% CI 1.23-39.56), aOR 10.00 (95% CI 1.58-63.09), and aOR 9.16 (95% CI 1.53-54.59), respectively. Conclusion: This preliminary study demonstrated an initial potential of the FI value from 3D USG power Doppler to predict the depth of PAS invasion before surgery and intraoperative blood loss level.

Ureter injury in obstetric hysterectomy with placenta accreta spectrum: Case report.

INTRODUCTION AND IMPORTANCE: Placenta accreta spectrum (PAS) is a state of abnormal attachment of the placenta, including placenta accreta, placenta increta, and placenta percreta. This condition can be life-threatening due to the placenta cannot spontaneously separated, resulting in continuous bleeding. Cesarean section followed by hysterectomy is one of the treatment options for PAS. There was a great liability for urinary tract injuries during the operation of PAS patient. CASE PRESENTATION: We present the case of ureter injury during subtotal hysterectomy in patient with PAS. A 30-years-old female patient was diagnosed with recurrent antepartum hemorrhage due to placenta previa accreta spectrum on G2P1 33 weeks of gestational age, singleton live breech presentation, previous c-section 1×. After uterine transverse incision, the baby was delivered. We decided to perform subtotal hysterectomy. There was severe adhesion. On the exploration after subtotal hysterectomy was performed, we found ruptured of the right ureter. CLINICAL DISCUSSION: Hysterectomy peripartum is one of the treatment of PAS, either to prevent or to control postpartum hemorrhage. In pregnant women with morbid placental adherence, there was a great liability for urinary tract injuries. Distal ureters are the most commonly injured while hysterectomy. Injuries to the ureters in this patient occurred due to severe adhesions and unclear visual organ. CONCLUSION: Although it is rare, ureter injury may occur during subtotal hysterectomy in patient with placenta accreta spectrum. To prevent that condition, inserting ureter stent can be perform before the operation. Multidisciplinary approach is carried out so that patient outcomes are good.

Relationship between Perineal Body Length and Degree of Perineal Tears in Primigravidas Undergoing Vaginal Delivery with Episiotomy.

BACKGROUND: Perineal tears are one of the most common complications of vaginal delivery. Severe perineal tears can cause various morbidities. There are many factors that affect the occurrence of perineal tears. One of the major factors related to the occurrence of perineal tears is the length of the perineal body. However, until now, no research in Indonesia has concluded that the length of perineal body can predict the perineal tears. OBJECTIVE: To find the relationship between perineal body length and perineal tears, so it can provide a reference on the use of perineal body length to predict severe perineal tears in vaginal delivery with episiotomy. METHODS: This nested case-control study was conducted at RSUD Tangerang and RSUD Karawang in Indonesia from February to September 2017. A total of 126 primigravida patients participated in the study consecutively. The length of the perineal body was then measured and followed until the start of the second stage of labor. Afterwards, the perineal length and degree of perineal tears were assessed using unpaired T-test for bivariate analysis, multivariate analysis, and scoring test to predict the occurrence of third- and fourth-degree of perineal tears with power calculation (ß) 80% and Zß 0.842. RESULTS: There was a significant difference in mean length of the perineal body between the group with first- and second-degree perineal tears and the group with third- and fourth-degree perineal tears (p < 0.001). From the multivariate analysis, adjusted OR was 5.26 (95% CI 1.52-18.17). Score test was performed to predict the occurrence of third- and fourth-grade perineal tears. Perineal body length and head circumference could be used as predicting factors of perineal tears. Perineum length ≤ 3.0 cm and head circumference ≥ 33.5 cm posed a risk of perineal tears of third and fourth degrees (70.52%). CONCLUSION: The length of the perineal body has a good ability to predict the occurrence of perineal tears.

Trans-arterial embolization of acquired uterine arteriovenous malformation after Cesarean section: A case series.

BACKGROUND: Acquired uterine arteriovenous malformation (AVM) is a rare condition due to traumatic episodes in cesarean section. The patient can suffer from life-threatening hemorrhage or recurrent vaginal bleeding. Establishing this diagnosis is difficult, often misdiagnosed due to lack of information and number of cases. Trans-Arterial Embolization (TAE) procedure is rarely performed in our center. All of the cases were found with history of massive bleeding and diagnosed lately after recurrent bleeding history. Even though promising, one of our cases failed to be managed with TAE. It is important to diagnose early symptoms of AVM in order to prevent the life threatening event. CASE PRESENTATION: In these case series, four cases of AVMs after cesarean procedures will be reviewed. One could be diagnosed in less than a month but the other three took several months. The symptom of vaginal bleeding might occur a few weeks after the procedure is done, and most patients need transfusion and hospitalization. Three out of four patients were initially sent to the hospital in order to recover from shock condition, and one patient was sent for a diagnostic procedure. AVMs diagnostic was established with ultrasound with or without angiography. Three of our cases were succeeded by performing TAE procedure without further severe vaginal bleeding. One case failed to be treated with embolization and had to proceed with hysterectomy. CONCLUSION: AVM should be considered early-on in patient with abnormal uterine bleeding and history of cesarean section. Embolization is still the first-choice treatment of AVMs, otherwise definitive treatment is hysterectomy in a patient without fertility need, or impossible to perform TAE.

Placenta accreta complicated with peripartum cardiomyopathy.

A 33-year-old G2P1 was referred to our hospital due to placenta accreta. During perioperative preparations, the patient was diagnosed with having a peripartum cardiomyopathy. The patient underwent caesarean hysterectomy at 36 weeks with an associated 2 L blood loss. Haemodynamic maintenance and stabilisation during the operation were challenging, with the combinations of fluid therapy, blood transfusions as well as vasoactive, antifibrinolytic and haemostatic drug. Postoperatively, the patient was managed in the intensive care unit and was subsequently transferred to intermediate care after less than 24 hours' observation. She was stable enough to be moved to the obstetrics ward the next day.

Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality worldwide. Vacuum-induced uterine tamponade is a possible alternative approach to balloon tamponade systems for the treatment of postpartum hemorrhage resulting from atony. METHOD: In a prospective proof-of-concept investigation of 10 women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage, tamponade was used. Vacuum-induced uterine tamponade was created through a device inserted transvaginally into the uterine cavity. An occlusion balloon built into the device shaft was inflated at the level of the external cervical os to create a uterine seal. Negative pressure was created by attaching a self-contained, mobile, electrically powered, pressure-regulated vacuum pump with a sterile graduated canister. EXPERIENCE: In all 10 cases, the suction created an immediate seal at the cervical os, 50-250 mL of residual blood was evacuated from the uterine cavity, the uterus collapsed and regained tone within minutes, and hemorrhaging was controlled. The device remained in place for a minimum of 1 hour and up to 6.5 hours in one case while vaginal and perineal lacerations were easily repaired. CONCLUSION: This preliminary investigation suggests that a device designed to create vacuum-induced uterine tamponade may be a reasonable alternative to other devices used to treat atonic postpartum hemorrhage.

Circulating mRNA for the PLAC1 gene as a second trimester marker (14-18 weeks' gestation) in the screening for late preeclampsia.

OBJECTIVE: To develop a model for prediction of late preeclampsia (PE; which develops at or after 34 weeks' gestation) based on maternal history and characteristics, mean arterial pressure (MAP), and circulating levels of mRNA for the placenta-specific 1 (PLAC1) gene in maternal plasma at 14-18 weeks' gestation. METHOD: This was a screening study of singleton pregnancies at 14-18 weeks' gestation including 43 women that subsequently developed PE and 200 that were unaffected by PE. A Gaussian model was fitted to the log distribution of the multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1 gene were used to combine the a priori risk from maternal characteristics with MAP to produce patient-specific risks for each case. RESULTS: Screening by maternal characteristics (including BMI, woman's mother's history of PE, previous PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at a fixed false-positive rate (FPR) of 10%. The addition of PLAC1 yielded a detection rate (DR) of 62.8% at the same level of FPR. PLAC1 alone yielded a DR of 30.2%. CONCLUSION: In late PE, molecular markers can be used to improve the DR of screening and can be a valid option for the biochemical approach.

Attitudes toward non-invasive prenatal diagnosis among pregnant women and health professionals in Japan.

OBJECTIVE: This study aims to assess the attitudes toward non-invasive prenatal diagnosis (NIPD) and NIPD problems in clinical practice in Japan. METHODS: A mail-in survey using a self-reported questionnaire was conducted among pregnant women and health professionals. The questionnaire enquired about attitudes, concerns, and expectations regarding NIPD. RESULTS: The responses from 252 respondents revealed that pregnant women have more positive attitudes toward NIPD than health professionals. In addition, there were wide discrepancies in concerns and expectations about NIPD, between medical professionals and pregnant women. The respondents with less NIPD knowledge had a more positive attitude toward the clinical application of NIPD. There was concern expressed by clinical geneticists whether an NIPD test should be performed or not when there is a lack of knowledge about the NIPD. All of the health professionals emphasized the importance of providing genetic counseling prior to and after the testing. CONCLUSION: Pregnant women place importance on the safety and non-invasiveness of the NIPD tests, whereas medical professionals consider the diagnostic accuracy and reliability of the test to be the most important. Health professionals pointed out that the tests might be frequently performed without the pregnant women having adequate knowledge or counseling.

Antioxidant supplementation in pregnant women with low antioxidant status.

AIM: The aim of this study was to investigate the benefit of antioxidant supplementation in a cohort of women with low antioxidant status and determine the changes in cell-free mRNA. MATERIAL AND METHODS: This study was a randomized, placebo-controlled trial of 8-12 weeks' pregnant women who had low antioxidant status treated with either antioxidants or control diets daily until 2 weeks' postpartum. The primary end-point was the risk of pre-eclampsia and the secondary end-point was the changes of angiogenic and anti-oxidant mRNA markers related to the outcome (ClinicalTrial.gov, number NCT01232205). RESULTS: There were 110 women enrolled in the study, randomly assigned to the supplementation (n = 52) and control group (n = 58). The overall rate of pre-eclampsia was 8.7% (nine subjects). There were significant differences (P = 0.034) between the supplementation and control group in the incidence of pre-eclampsia (2.0% [one case] and 14.5% [eight cases], respectively) and mRNA level of superoxide-dismutase, heme oxygenase-1, vascular endothelial growth factor receptor-1, endoglin and placental growth factor after supplementation. CONCLUSION: Supplementation of women with low antioxidant status with micronutrients containing antioxidants during early gestation might reduce the risk of pre-eclampsia.

Influence of early self-diagnosis and treatment of bacterial vaginosis on preterm birth rate.

OBJECTIVE: To assess whether early self-diagnosis and treatment of bacterial vaginosis (BV) could lower the preterm birth rate among a group of Indonesian women. METHODS: A randomized controlled trial of 331 pregnant women (14-18 weeks) was conducted. Participants were randomly assigned to either the active model group (n=176) or the control group (n=155). Women in the active model group were equipped with a kit to self-evaluate vaginal pH; those with a positive test result were treated with a twice daily dose of 500 mg of metronidazole for 7 days. The primary end point was preterm birth rate. RESULTS: There were 6 (3.8%) and 8 (5.4%) preterm births in the active model and control groups, respectively (P=0.468). No spontaneous abortions were recorded in either group. When compared with the gold standard (Gram staining), the vaginal acidity test had low ability to detect BV, with 88.7% specificity and 36.9% sensitivity. The positive predictive value of the test was 35.0% PPV, while the negative predictive value was 89.4%. CONCLUSION: Early self-diagnosis and treatment of BV did not reduce the preterm birth rate of the study group. ClinicalTrial.govnumber:NCT01232192.

Vitamin B6 supplementation in pregnant women with nausea and vomiting.

OBJECTIVE: To determine whether supplementation with vitamin B(6) improves nausea and/or vomiting in pregnancy. METHODS: This experimental study was conducted with 60 pregnant women experiencing nausea and/or vomiting prior to the 12th gestational week. Of these women, 30 were treated daily with 10mg and the remaining 30 with 1.28 mg of pyridoxine hydrochloride for 2 weeks. The primary outcome was the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score in each group at the end of treatment. RESULTS: The women experiencing nausea and/or vomiting in pregnancy had significantly lower levels of circulating vitamin B(6) (P=0.007) compared with those without this symptom. Vitamin B(6) supplementation significantly increased plasma vitamin B(6) concentration (P<0.05 in both groups). There were no significant differences in PUQE score or in plasma concentration levels of protein, dopamine, serotonin, unconjugated estriol, and ghrelin after supplementation between the 2 groups at baseline, but there was a significantly lesser decrease in PUQE score and a greater increase in vitamin B(6) level and vitamin B(6) concentration to plasma protein concentration ratios in group 1 than in group 2 after supplementation (P<0.05 for all). CONCLUSION: Although the high-supplementation group had a greater decrease in PUQE score in comparison to the low-supplementation group, the difference is unlikely to affect the severity of symptoms.

Quantitative RT-PCR gene expression analysis of a laser microdissected placenta: an approach to study preeclampsia.

Preeclampsia is still one of the leading causes of maternal and neonatal mortality and morbidity. Despite intensive research, the cause of preeclampsia has not yet been established. However, for a variety of reasons, the numerous aspects of normal and pathological pregnancies, particularly with regard to preeclampsia, remain difficult to study and are, therefore, poorly understood. The development of a laser-based microdissection system has provided rapid morphologically and phenotypically distinct types of cells in the placenta for molecular analysis. Alterations in gene expression in the cytotrophoblast and syncytiotrophoblast or other specific placental cell types from patients who later develop preeclampsia have been reported. Laser microdissection is an attractive method to study each specific placental cell type to characterize the development of preeclampsia or to study the pathophysiology of preeclampsia. This method may contribute to a better understanding of the pathophysiology of preeclampsia.

Gene expression in chorionic villous samples at 11 weeks of gestation in women who develop pre-eclampsia later in pregnancy: implications for screening.

OBJECTIVES: To determine the gene expression profile in chorionic villous samples (CVSs) of women destined to develop pre-eclampsia (PE). METHOD: Case-control study encompassing five women destined to develop PE [cases matched for gestational age with 30 controls]. We quantified mRNA expression on tissue samples from CVS of normal and PE patients. We then assessed mRNA expressions of cathepsin (CTSD), angiopoietin 2 (ANGPT2), interleukin 8, chemokine (C-X-C motif) ligand 10, neurokinin B (NKB), matrix metallopeptidase 9, major histocompatibility complex, class I, C (HLA-C)and human leukocyte antigen-G (HLA-G). Data were analyzed by nonparametric rank analysis. RESULTS: For all the mRNA species considered in this study, except CTSD and ANGPT2, all the mean observed ranks in the PE group were significantly altered compared with the rank expectation among controls. mRNA for NKB and HLA-C were the markers with the highest degree of aberration in PE, compared with those in controls. CONCLUSION: Our study has directly showed that gene expressions relating to trophoblastic cell invasion or utero-placental hemodynamic adaptation are altered in the first trimester trophoblasts that go on to develop PE later. These results posit the use of residual CVS as a possible screening method for PE.

Performance of messenger RNAs circulating in maternal blood in the prediction of preeclampsia at 10-14 weeks.

OBJECTIVE: The purpose of this study was to determine whether the combined distribution of a panel of cellular messenger RNA markers can detect preeclampsia long before onset. STUDY DESIGN: We compared blood at 10-14 weeks from 11 women who ultimately experienced preeclampsia with 88 matched control subjects. After multiples of the median conversion of all the markers, logistic regression was used to calculate the risk of the development of preeclampsia. RESULTS: Higher multiples of the median values than expected were found for endoglin, fms-related tyrosine kinase 1, and transforming growth factor-ß1. Lower multiples of the median values were found for placental growth factor and placental protein 13. Endoglin fms-related tyrosine kinase 1 and transforming growth factor-ß1 had the best discriminant power. Messenger RNA species provided independent contributions to the prediction of preeclampsia. In fact, 11 women with preeclampsia scored a median risk of 50% of experiencing preeclampsia. Control subjects scored a median risk of preeclampsia of 0.18%. The detection rate at a 5% false positive rate was 72.3%. CONCLUSION: The messenger RNA dosage in maternal blood would be a useful method for the calculation of the risk of the development of preeclampsia.

Genetics of endometrial cancers.

Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%-30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A beta-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.

PP13 mRNA expression in the cellular component of maternal blood as a marker for preeclampsia.

OBJECTIVE: To assess the PP13 expression in the cellular component of blood in both preeclamptic patients and asymptomatic pregnant women during the early second trimester. METHODS: In the case-control study, peripheral blood samples were obtained from pregnant women with preeclampsia (n = 24) and controls (n = 22). PP13 RNA expression was quantified in the cellular component of the blood by reverse transcription PCR assay. Next, as a cohort study of asymptomatic pregnant women at early gestation, cellular RNA from 41 cases who developed preeclampsia at later gestation and 123 cases of control were analysed, and the possibility of prediction of preeclampsia was assessed. RESULTS: In symptomatic patients, PP13 level in preeclampsia was significantly lower than that in controls (p < 0.001). In the asymptomatic pregnant women, the PP13 level in preeclampsia was significantly lower than that in the controls (p = 0.008). A receiver-operating characteristics (ROC) curve yielded a detection rate of 24 and 31% at a false positive rate of 5 and 10% respectively. CONCLUSION: An alteration in the cellular PP13 RNA expression would affect the placental pathophysiological change. The cellular PP13 expression level could therefore potentially be one of the key markers to predict the clinical onset of preeclampsia.

Gene expression in chorionic villous samples at 11 weeks of gestation in women who develop preeclampsia later in pregnancy: implications for screening.

OBJECTIVES: To determine the gene expression profile in chorionic villous samples (CVS) of women destined to develop preeclampsia. METHOD: cDNA microarray technology was employed. Ten singleton fetuses of women who subsequently developed preeclampsia where compared with a pool of 50 controls. The mRNA expression of some of the genes previously found to be up- or down-regulated were validated by RT-PCR in peripheral blood from 23 pregnant women at term affected with preeclampsia and 23 controls. RESULTS: Altered expression was found among several genes including those involved in invasion of human trophoblasts (Titin), in inflammatory stress (Lactotransferrin), endothelial aberration (Claudin 6), angiogenesis (Vasohibin 1), blood pressure control (Adducin 1). Also the peripheral blood from preeclampsia patients showed significant differences for all the genes studied. CONCLUSION: CVS show an aberrant gene profile prior to preeclampsia onset that may be predictive of the disease.