Beta Subunit Of Chorionic Gonadotropin Research Articles

Placental biomarkers in second trimester maternal serum are associated with postpartum hemorrhage: a secondary analysis of the NuMoM2b dataset.

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, which is often attributed to retained placenta (RP) after delivery. There are no biomarkers currently used to predict a risk of developing RP/PPH prior to labor. The objective of this study was to determine relationships between placental biomarkers measured in the first and second trimesters and proxy measures of postpartum blood loss relative to preeclampsia status in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) dataset. 2,192 participants had placental analytes drawn during the first and second trimesters (9-13 and 16-22 weeks gestation, respectively); the outcome was a composite of retained placenta and/or PPH requiring blood transfusion (RP/PPH). Using Kruskal-Wallis tests, median differences in levels of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), sFlt-1/PlGF ratio, soluble endoglin (sEng), beta subunit of human chorionic gonadotropin (β-hCG), inhibin A (INHA), and pregnancy-associated protein-A (PAPP-A) were assessed between women with (n=67) and without (n=2125) RP/PPH overall and stratified by preeclampsia status. Women with RP/PPH had significantly higher median levels of sEng, β-hCG, INHA, PAPP-A in the second trimester and sFlt-1was higher in both first and second trimesters, which was observed again when stratifying by preeclampsia status. Our findings indicate that biomarkers associated with angiogenesis, particularly when measured in the second trimester, are important targets for further study of RP and/or PPH pathophysiology and potential risk screening development.

Current and Evolving Biomarkers in the Diagnosis and Management of Testicular Germ Cell Tumors.

Testicular cancer is the most common cancer among young adult men and has favorable outcomes, with survival rates approaching 99% and over 80% for those with early and advanced stage disease, respectively. Biomarkers play a critical role in the diagnosis, pre-treatment risk stratification, surveillance, and assessment of post-treatment disease response in these men. Traditional serum tumor markers (STMs), which include alpha fetoprotein (AFP), beta subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are limited by low sensitivity (approximately 50%) during initial diagnosis; false-positive elevations as a result of other benign and malignant conditions; and negative levels in low-stage disease and in certain histologies such as teratoma and seminoma. As a result, novel biomarkers with potentially better performance characteristics, including microRNA (miRNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs), are being investigated. MicroRNAs are small noncoding RNA involved in transcription and translation and regulate the expression of almost one-third of human genes that regulate the cell cycle, differentiation, proliferation, and apoptosis. In germ cell tumor (GCT) patients, miR371a-3p has been identified as a promising biomarker with sensitivity and specificity of approximately 90-92% and 84-86%, respectively. The use of this new biomarker could aid in several clinical scenarios, such as predicting the presence of micrometastases in chemotherapy-naïve patients with clinical stage I-II disease, thereby guiding decisions on treatment versus surveillance and predicting the presence of viable GCT in patients with residual disease post chemotherapy. Clinical trials are ongoing to validate the use of miRNA 371 as a biomarker and to define its performance characteristics. Though promising, miRNAs are limited by their inability to detect teratoma. ctDNA and CTCs are two other emerging biomarkers, though further studies are needed to clarify their role in managing patients with GCT.

The Association and diagnostic value between Maternal Serum Placental Markers and Placenta Previa

ObjectiveThis study aims to evaluate the correlation and diagnostic value of maternal serum placental markers: pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (free β-hCG), and alpha fetoprotein (AFP) in relation to placenta previa. MethodsA retrospective case-control study was conducted to gather data on 137 pregnant women who were hospitalized for delivery at Hangzhou Obstetrics and Gynecology Hospital. These women participated in the late stage of early and mid-term maternal serum prenatal screening between January 2018 and December 2020. Of the 137 women, 45 were diagnosed with placenta previa, while 92 were selected at random as the control group, in a ratio of 1:2. Independent samples t-test or Mann-Whitney U test were utilized to compare the quantitative data of the two groups, and the Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of maternal serum placental marker levels for placenta previa. ResultsThe levels of first trimester and second trimester free beta subunit of human chorionic gonadotropin (FT-Free β-hCG; ST-Free β-hCG) in the placenta previa group were higher than those in the normal group [1.38 (0.55-6.03) MoM vs.1.08 (0.32-4.00) MoM, 1.38 (0.39-4.10) MoM vs.1.01 (0.29-4.12) MoM], and the differences between the groups were statistically significant (Z = 2.830, Z = 2.846, both P < 0.05). The AFP level was higher than the normal group [1.13 (0.65-2.15) MoM vs. 0.94 (0.51-2.02) MoM], and the difference was statistically significant (Z = 2.551, P < 0.05). There was no significant difference in PAPP-A between the placenta previa group and the normal group (Z = 1.396, P > 0.05). The ROC curve analysis results showed that the AUCs of FT-Free β-hCG and ST-Free β-hCG for placenta previa were 0.649 (95% CI: 0.551-0.747, P=0.005), 0.634 (95% CI: 0.539-0.730, P=0.011), and 0.650 (95% CI: 0.554-0.746, P=0.004). Using PPV, NPV, FPR, FNR, +LR, and -LR as evaluation indicators for the 5 models, the results showed that FT-Free β-hCG was the best performer in terms of PPV, FPR, and +LR, with values of 0.725, 0.600, and 2.632, respectively. The three-indicator combined detection model (AFP + ST-Free β-hCG + FT-Free β-hCG) had the best performance in terms of NPV and -LR, with values of 0.770 and 0.298, respectively. ConclusionThe elevated maternal serum levels of Free β-hCG and AFP may be associated with placenta previa. The combined detection of maternal serum markers in the early and mid-trimesters has better diagnostic value for predicting placenta previa than individual detection.

Brain metastases in testicular cancer: A single-institution experience in Guatemala.

e17019 Background: Brain metastases secondary to germ cell tumors develop in 2 to 3% of patients, in addition to implying a poor prognosis, its incidence in advanced stages increases to 10-15%. The European Urology Association guidelines recommend performing imaging studies using MRI or brain contrasted tomography to rule out metastases in patients with multiple lung metastases, or high beta subunit of human Chorionic Gonadotropin (β-HCG) values, or those in the poor-prognosis International Germ Cell Cancer Collaborative Group (IGCCCG) risk group. Methods: Retrospective descriptive study in patients with brain metastasis for testicular cancer at the Liga Nacional Contra el Cáncer – INCAN Guatemala, from 2018 to 2022. From medical records, we obtained: demographic, clinico-pathological and treatment data. Median was calculated for age, while frequencies and percentages were computed for the categorical variables. Results: Of the 238 patients diagnosed with testicular cancer, 22% (52) presented a β-HCG above 5,000 IU/L, of which 27% (14) developed brain metastases with a mean age of 28 years. Corresponding to 6% of the total cases studied. Among histological subtypes the most common was choriocarcinoma (43%), follow by mixed germ cell cancer (36%), embrionary carcinoma (14%) and classic seminoma (7%). All of the patients belonged to prognostic group S2. Most patients reported first symptom was headache (42%), followed by seizures (21%), cognitive dysfunction (15%), motor dysfunction (10%) and others (12%). Management of these patients included: orchidectomy in all of them, 57% (8) of patients died, of them 50% (4) of patients died before any other therapy. The rest of them, received chemotherapy and none received radiotherapy or surgery for the brain metastases. Conclusions: The presence of brain metastases in testicular cancer increases the mortality produced by the disease as previously reported in other regions of the world, reason why the early suspicion of it, should prompt the evaluation with a brain MRI or computed tomography.

Prediction of hypertensive disorders in pregnant women in the «gray» risk zone following combined first-trimester screening

Introduction. In obstetrics, hypertensive disorders of pregnancy (HDP) including preeclampsia (РЕ) are one of the primary causes resulting in critical cases and maternal mortality. HDP prediction is a milestone that allows preventing complications as well as reducing the number of most common relevant complications of pregnancy. Existing algorithms that predict PE risk distribute the risks in such a way that a considerable number of patients fall into the category of false negative results, and, consequently, receive no timely prevention and proper follow-up. In particular, this cohort usually consists of patients with borderline high risks, who may be designated as a medium risk group or located in a “gray” zone. Aim: to develop a prognostic model for risk stratification in female patients with borderline to high developing PE risk based on combined first-trimester screening. Materials and Methods. A prospective comparative study included 1089 female patients who underwent a combined screening at 11–14 weeks of gestation. Group 1 consisted of female patients at high РЕ risk (1:100 and greater), while female patients at moderate risk (1:101–1:250) and low risk (below 1:250) were included into Group 2 and Group 3, respectively. All pregnant women underwent examination including assessed anamnestic, general clinical and laboratory data, mean blood pressure (BP), uterine artery pulsatility index, serum level of human chorionic gonadotropin beta-subunits (β-hCG), placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A). Results. An impact of various factors on risk of developing hypertensive disorders in pregnancy was assessed by binary logistic regression by identifying most significant among them and generating a statistical prediction model – the prognostic index of hypertensive disorders in pregnancy. The latter included: obstetric history, body mass index, PlGF, mean ВР, and alanine aminotransferase level. The sensitivity and specificity comprised 91.2 and 53.6 %, respectively, and the method effectivenesswas 81.8 %. Conclusion. The method proposed for HDP prediction is a second-line approach that may be used in clinical practice to stratify patients with borderline high risk of developing PE.

A new contingent screening strategy increased detection rate of trisomy 21 in the first trimester

BackgroundAlthough the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21.MethodsThis was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care.ResultsWhen cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively.ConclusionsThe new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

Ovarian Masses in Children and Adolescents: A Review of the Literature with Emphasis on the Diagnostic Approach.

Most abdominal masses in the pediatric population derive from the ovaries. Ovarian masses can occur in all ages, although their incidence, clinical presentation and histological distribution vary among different age groups. Children and adolescents may develop non-neoplastic ovarian lesions, such as functional cysts, endometrioma, torsion, abscess and lymphangioma as well as neoplasms, which are divided into germ cell, epithelial, sex-cord stromal and miscellaneous tumors. Germ cell tumors account for the majority of ovarian neoplasms in the pediatric population, while adults most frequently present with epithelial tumors. Mature teratoma is the most common ovarian neoplasm in children and adolescents, whereas dysgerminoma constitutes the most frequent ovarian malignancy. Clinical manifestations generally include abdominal pain, palpable mass, nausea/vomiting and endocrine alterations, such as menstrual abnormalities, precocious puberty and virilization. During the investigation of pediatric ovarian masses, the most important objective is to evaluate the likelihood of malignancy since the management of benign and malignant lesions is fundamentally different. The presence of solid components, large size and heterogenous appearance on transabdominal ultrasonography, magnetic resonance imaging and computed tomography indicate an increased risk of malignancy. Useful tumor markers that raise concern for ovarian cancer in children and adolescents include alpha-fetoprotein, lactate dehydrogenase, beta subunit of human chorionic gonadotropin, cancer antigen 125 and inhibin. However, their serum levels can neither confirm nor exclude malignancy. Management of pediatric ovarian masses needs to be curative and, when feasible, function-preserving and minimally invasive. Children and adolescents with an ovarian mass should be treated in specialized centers to avoid unnecessary oophorectomies and ensure the best possible outcome.

Impact of COVID-19 and vaccination on first and second trimester screening results

COVID-19 has been shown to affect pregnant women. Since pregnant women are at risk of this infection, vaccination against COVID-19 has been suggested as an imperative way to diminish rate of COVID-19 in this population. In the current observational study, we have collected data of first and second trimester screening (FTS and STS) from pregnant women who were infected with SARS-CoV-2 and/or vaccinated against COVID-19 during their pregnancy, and compared this data with a group of control pregnant women. The cohort included 4612 and 2426 women referred for FTS and STS, respectively. There was no significant difference in median values of Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin-beta subunit (βHCG) between infected women and controls. Moreover, these levels were not different between “Infected + vaccinated” and “Only vaccinated” groups. However, median values of PAPP-A and βHCG were higher in “Infected + vaccinated” and “Only vaccinated” groups compared with “Infected” and “Control” groups (P < 0.001). Median values of unconjugated Estriol (uE3) and βHCG markers were not different between “Only vaccinated” and “Control” groups, yet both markers were elevated in “Infected” and “Infected + vaccinated” groups compared with other groups. AFP values were higher in “Infected” group (P = 0.012). However, multiple of the median (MoM) and risk of open spina bifida (OSB) were not affected. Finally, median of calculated risk of trisomy 18 was lower in “Infected” and “Vaccinated” groups compared with controls (P = 0.007). Moreover, AstraZeneca and Sinopharm vaccines were associated with elevation of the calculated risk values of trisomy 21 and trisomy 18 (P < 0.001). While Sinopharm did not affect nuchal translucency (NT) and NT MoM (P = 0.13), AstraZeneca and Barakat increased and decreased these values, respectively (P values = 0.0027 and 0.015, respectively). Taken together, COVID-19 during pregnancy might be associated with some adverse obstetric outcomes. Besides, vaccination against this infection might affect the results of STS or FTS.

Study on the Relationship and Predictive Value of First-Trimester Pregnancy-Associated Plasma Protein-A, Maternal Factors, and Biochemical Parameters in Gestational Diabetes Mellitus: A Large Case-Control Study in Southern China Mothers.

To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers. This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free β-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test. GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001). A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

Predicting fetal growth retardation: mathematical modeling

Introduction. Annually, more than 13 million neonates are born with fetal growth retardation (FGR) worldwide. FGR increases prenatal mortality and morbidity. Due to no effective treatments for FGR are available, its prevention and prognosis are of extreme relevance.Aim: development of prognostic clinical and anamnestic mathematical model for assessing a risk of developing FGR during pregnancy.Materials and Methods. A prospective, controlled, open, continuous study was performed. The main group (1) included 75 patients who had FGR during pregnancy; the control group (2) consisted of 414 women with favorable pregnancy outcome. All subjects underwent examination, including collecting medical history, a complex of prenatal diagnostics in the first trimester of pregnancy – ultrasound, Doppler uterine arteries, serum level of pregnancy-associated plasma protein-A (PAPP-A), free beta-subunit of human chorionic gonadotropin (β-hCG), placental growth factor (PlGF), and non-invasive prenatal test (NIPT).Results. To determine the relative contribution of each individual trait to the formation of FGR risk and develop a prognostic index, a discriminant analysis was carried out, on the basis of which a prognostic F-index was developed. The formula for calculating the F-index includes the age of pregnant woman, obstetric history data, method of conception, recorded nicotine addiction in pregnancy, detected uterine fibroids, body mass index, biochemical parameters (PAPP-A, β-hCG, PlGF), nuchal translucency of the fetus, the pulsation index of the uterine artery, the level of the fetal fraction and fetal gender (determined during NIPT). The parameters of sensitivity and specificity of the FGR prognosis were 90.1 and 82.18 % respectively, the method effectiveness was 83.97 %.Conclusion. The method developed for predicting FGR can be used in clinical practice to form risk groups for FGR development and choose tactics for pregnancy management.

Biochemical and ultrasonographic markers in fetal surveillance

Introduction/Objective. Fetal growth restriction (FGR) is associated with increased fetal and neonatal mortality and morbidity. The study objective was to investigate the correlation of maternal blood biochemical markers routinely determined in the first and second trimester screening and ultrasound fetal surveillance parameters in the prediction of fetal growth and condition in singleton pregnancies. Methods. In the first trimester we measured serum levels of beta subunit of human chorionic gonadotropin (?HCG) and pregnancy-associated plasma protein A (PAPP-A). In the second trimester we measured values of chorionic gonadotropin (HCG), alpha fetoprotein (AFP), unconjugated estriol (E3) and inhibin A, also examined ultrasonographic biometric fetal parameters, amniotic fluid index (AFI) and Doppler resistance indexes. FGR was defined as ultrasonographically determined fetal weight and growth parameters below the 10th percentile for the gestational age. Obtained biochemical and ultrasonographic parameters were correlated. Results. Study included 104 singleton pregnancies. ?HCG in the first trimester correlated negatively with fetal growth in the second and third trimester, and the second trimester AFI. Increased PAPP-A correlated positively with elevated resistance index in medial cerebral artery, lower biophysical profile scores, and intermediate type of non-stress test. Lower values of E3 were associated with FGR. Elevated serum AFP levels were linked to oligoamnion in the third trimester. There was no correlation of inhibin A levels with fetal condition. Conclusion. First and second trimester biochemical markers of pregnancy (?HCG, PAPP-A, HCG, AFP and E3) in combination with ultrasonographic biophysical parameters of fetus have predictive value for fetal growth and development.

Correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia

The aim of this study was to investigate the correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia (PE). In total, 32 normal pregnant women (the control group) and 58 subjects with PE were randomly selected from eligible case data. The serum levels of miR-146b-5p, pregnancy associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) were then detected. Next, we established predictive models of single or multiple markers for PE. The levels of miR-146b-5p in the mild pre-eclampsia (mPE) and severe pre-eclampsia (sPE) groups were higher than the control group and there were significant differences between the three groups (F = 3.424, P = 0.037). The statistical results of the model before and after 200 times 10-fold cross-validation were as follows: miR-146b-5p (AUC = 0.723 vs AUC = 0.710); miR-146b-5p + BMI + MAP + free β-hCG MoM + PAPP-A MoM (AUC = 0.929 vs AUC = 0.851). We found that expression levels of miR-146b-5p in the first trimester were significantly higher in the serum of pregnant women with PE than in the normal pregnancy group. A prediction model in combination with miR-146b-5p and other markers improved the early predictive value for PE. IMPACT STATEMENT What is already known on this subject? Pre-eclampsia is a complex systemic disease with hypertension as the main clinical manifestation and causes extensive damage to the body. Some existing maternal biochemical markers have limited value in predicting PE, and new biomarkers with high sensitivity and specificity are urgently needed in clinical practice. There are a variety of abnormal expression miRNAs in PE, however, the relationship between miR-146b-5p and PE has yet to be fully elucidated. What do the results of this study add? We first found that expression levels of serum miR-146b-5p in the first trimester were significantly higher in PE than in a normal pregnancy group. A prediction model a combination of miR-146b-5p and other maternal characteristics and biochemical markers can improve the early predictive value for PE. What are the implications of these findings for clinical practice and/or further research? PE progresses rapidly and has become a severe target organ complication when discovered. Therefore, the early prediction of a high risk of PE, along with early intervention and prevention measures, are of great significance. Compared to maternal biochemical markers, combination of miR-146b-5p and maternal characteristics and biochemical markers can improve the early predictive value for PE.

The findings about relationship between autoimmune thyroid disease and first-trimester aneuploidy results

Aim: The aim of this study was to investigate the relationship between thyroid autoantibody and first-trimester aneuploidy results. Thyroid autoimmunity (TAI) is the most common autoimmune disorder. Patients with TAI are usually euthyroid. Thyroid peroxidase (TPO-Ab) in patients with or without thyroid dysfunction is associated with infertility, recurrent embryo implantation failure, and early pregnancy loss. The impact of TPO-Ab on first-trimester aneuploidy test results needs to be studied.&#x0D; Material and Method: This retrospective case-control study was conducted between December 2019 and May 2022. Patients with thyroid autoantibody positivity (n=112) were included in the study as the case group. The control group was selected from age and body mass index (BMI)-matched patients (n=130). Nuchal translucency (NT), crown rump length (CRL), pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (β-hCG)) values were compared between the two groups.&#x0D; Results: This study included two hundred forty two age-matched (29.86±4.51) and BMI-matched (23.96±2.34) women. There was no statistically significant difference between groups in terms of free thyroxine (FT4), PAPP-A and free β-hCG (p&gt;0.05). NT as a marker for major chromosomal defects and CRL were comparable in case and control groups (p&gt;0.05).&#x0D; Conclusion: There is no statistically significant relationship between thyroid autoimmune diseases and the first-trimester aneuploidy results.

Prepubertal-Type Testicular Tumors in Postpubertal Patients: Epidermoid Cyst and Well-Differentiated Neuroendocrine Tumor

A man in his late 30s presented with testicular pain. On further evaluation, he was found to have a testicular mass, and serum tumor markers that are frequently elevated in germ cell tumors (beta subunit of human chorionic gonadotropin, lactate dehydrogenase, and alpha-fetoprotein) were within normal limits. He underwent radical orchiectomy, which revealed a 4.0 cm cystic mass.

Correlations between maternal hepatitis B virus carrier status and Down’s syndrome prenatal screening indicators and their effects on the screening results

The aim of this study was to determine the correlation between maternal hepatitis B virus (HBV) carrier status and pregnancy-associated serum screening indicators, as well as their implications on the prenatal screening results of Down’s syndrome (DS). This retrospective cohort study included two groups, namely the healthy gravidas group (n = 19804) and the maternal HBV carrier group (n = 792). Serum pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), and free beta subunit of human chorionic gonadotropin (free β-hCG) levels, as well as the foetal nuchal translucency (NT) thickness, were measured. Multivariatebinary logistic regression analysis was used to evaluate the association between the HBV carrier status and prenatal screening biomarkers. The PAPP-A multiple of the medium (MoM) and free β-hCG MoM in the first trimester were significantly higher in the HBV carrier group than in the control group (both P < .05). Multivariate binary logistic regression analysis showed that HBV carrier status was identified as a risk factor for PAPP-A and the intrahepatic cholestasis of pregnancy (ICP), with adjusted odds ratios (aOR) of 1.363 (1.216–1.527) and 3.255 (2.356–4.499), respectively. Pregnant women with HBV carrier status had higher influence on serum PAPP-A level and ICP, and the risk calculation algorithm for DS in HBV carriers should be corrected in the first trimester of pregnancy. IMPACT STATEMENT What is already known on this subject? The maternal serum levels of pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), and free beta subunit of human chorionic gonadotropin (free β-hCG), as well as the foetal nuchal translucency (NT) thickness, have been collectively used in the prenatal screening of Down’s syndrome (DS), Edward’s syndrome (ES), and open neural tube defects (ONTD). However, many factors, including the maternal age; maternal weight; gestational age; race; history of smoking and so on can affect those serum biomarker levels. Our aim is to know whether there is a difference for HBV status to pregnancy-associated serum screening indicators hoes. What the results of this study add? The PAPP-A multiple of the medium (MoM) and free β-hCG MoM in the first trimester were significantly higher in the HBV carrier group than in the control group (both p < .05). Multivariate binary logistic regression analysis showed that the PAPP-A and intrahepatic cholestasis of pregnancy (ICP) were risk factors for HBV carriers, with aORs of 1.363 (1.216–1.527) and 3.255 (2.356–4.499), respectively. What the implications are of these findings for clinical practice and/or further research? The PAPP-A MoM in maternal HBV carriers was significantly higher than that in healthy gravidas, and the risk calculation algorithm for DS in maternal HBV carriers should be corrected in the first trimester of pregnancy.

A retrospective cohort study on the effects of Down’s screening markers and maternal characteristics on pregnancy outcomes in preeclampsia

ABSTRACT Background To investigate the effects of down’s screening markers and maternal characteristics on preeclampsia (PE) pregnancy outcome during early and middle pregnancy. Methods A retrospective study of a cohort of 246 PE and 18,709 No-PE pregnant women who participated in Down’s screening during early and middle pregnancy was performed. Clinical data of pregnancy-related were collected. Multivariate binary logistic regression was used to analyze the adjusted odds ratio (aOR) and 95% confidence interval (CI) of Down’s screening markers, maternal characteristics, pregnancy outcome, and other related variables, and to evaluate the influencing factors of each indicator on PE. P < .05 was considered to be statistically significant. Results Compared with the non-PE group, the concentration and median multiple (MoM) of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) in PE group were both lower (P < .001). Multivariate binary logistic regression analysis showed that low birth weight, hydronephrosis, premature delivery, fetal growth retardation, cesarean section, live birth, hyperlipemia, infection, decreased free β-hCG and first trimester maternal weight were risk factors for PE (aOR were: 7.552, 6.684, 4.154, 3.762, 3.612, 2.454, 1.757, 1.562, 1.270, and 1.077, respectively), while uterine scar, premature rupture of membranes and elevated PAPP-A were protective factors of PE (aOR were: 0.222, 0.328 and 0.612, respectively). Conclusion Decreased maternal serum PAPP-A level, increased free β-hCG, hyperlipemia, premature delivery, cesarean section, live birth, hydronephrosis, fetal growth retardation, low birth weight, and infection are risk factors for PE, while uterine scar and premature rupture of membrane are protective factors for PE.

Progesterone limits the tumor-promoting effects of the beta-subunit of human chorionic gonadotropin via non-nuclear receptors

SummaryThe post-menopausal state in women is associated with increased cancer incidence, the reasons for which remain obscure. Curiously, increased circulating levels of beta-hCG (human chorionic gonadotropin) (a hormonal subunit linked with tumors of several lineages) are also often observed post-menopause. This study describes a previously unidentified interplay between beta-hCG and progesterone in tumorigenesis. Progesterone mediated apoptosis in beta-hCG responsive tumor cells via non-nuclear receptors. The transgenic expression of beta-hCG, particularly in the absence of the ovaries (a mimic of the post-menopausal state) constituted a potent pro-tumorigenic signal. Significantly, the administration of progesterone had significant anti-tumor effects. RNA-seq profiling identified molecular signatures associated with these processes. TCGA analysis revealed correlates between the expression of several newly identified genes and poor prognosis in post-menopausal patients of lung adenocarcinoma, colon adenocarcinoma, and glioblastoma. Specifically in these women, the detection of intra-tumoral/extra-tumoral beta-hCG may serve as a useful prognostic indicator, and treatment with progesterone on its detection may prove beneficial.

Clinical effect and influencing factors of focused ultrasound ablation surgery combined with suction curettage for the treatment of mass-type cesarean scar pregnancy

Objective: To investigate the clinical effect of focused ultrasound ablation surgery (FUAS) combined with suction curettage for mass-type cesarean scar pregnancy (CSP) and to analyze the influencing factors of vaginal bleeding and readmission. Methods: From January 2014 to December 2020, 88 patients with mass-type CSP were treated by FUAS combined with suction curettage in the Third Xiangya Hospital of Central South University. The clinical results and the influencing factors of bleeding and readmission for mass-type CSP were analyzed. Results: All the patients underwent one time FUAS treatment successfully. Immediately after FUAS treatment, color Doppler ultrasound showed obvious necrosis and no perfusion area in all lesions, and the blood flow in the mass-type CSP tissue significantly decreased. The median volume of blood loss in the procedure was 20 ml (range: 5-950 ml). Thirteen patients (15%, 13/88) had vaginal bleeding≥200 ml, and 15 patients (17%, 15/88) were hospitalized again. The average time for menstruation recovery was (28±8) days (range: 18-66 days). The average time needed for serum human chorionic gonadotropin-beta subunit to return to normal levels was (22±6) days (range: 7-59 days). The risk of large vaginal bleeding of patients were related to the blood supply of the mass (OR=5.280, 95%CI: 1.335-20.858, P=0.018) and the largest diameter of the mass (OR=1.060, 95%CI: 1.010-1.120, P=0.030). The risk of readmission were related to the largest diameter of the mass (OR=1.055, 95%CI: 1.005-1.108, P=0.030) and the depth of the uterus cavity (OR=1.583, 95%CI: 1.015-2.471, P=0.043). No serious complications such as intestinal and nerve injury occurred during and after FUAS treatment. Conclusions: FUAS combined with suction curettage is safe and effective in treating patients with mass-type CSP through this preliminary study. The volume of vaginal bleeding are associated with the blood supply of the mass and the largest diameter of the mass, the risk of readmission are related to the largest diameter of the mass and the depth of the uterus cavity.

First-trimester biomarkers and the risk of cerebral palsy

BackgroundCerebral palsy (CP) is the most common severe motor disability and a manifestation of early brain damage. AimsTo analyze if abnormal levels of first-trimester biomarkers were associated with CP. Furthermore, to investigate their clinical applicability in early predicting of CP. Study designNationwide cohort study. SubjectsWe included 258.057 singleton live births, born during 2008–2013 with completed first-trimester assessments. Outcome measuresData on beta subunit of human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency thickness, and biparietal diameter (BPD) were converted to multiple of the medians (MoM). Associations were analyzed by comparing mean and extreme levels between pregnancies with and without CP. All CP diagnoses were validated by trained neuropediatricians. Logistic regression was used to create an early prediction model. ResultsThe mean beta-hCG value was significantly lower in pregnancies with CP (0.96MoM [95% CI 0.91–1.02] vs 1.04MoM [1.04–1.04], p = 0.01) and the mean PAPP-A value tended to be lower (0.96MoM [0.91–1.01] vs 1.01MoM [1.00–1.01], p = 0.07). Moreover, fetuses that developed CP more likely had a BPD measurement below the fifth percentile (7.5% vs 5%, p = 0.045). The final prediction model had poor discrimination. ConclusionsPregnancies with CP tend to have lower values of beta-hCG and PAPP-A in the first trimester, however, the associations are mediated differently. Nonetheless, abnormal levels of the most common first-trimester biomarkers only have weak associations with CP; resulting in inadequate predictive abilities when included in an early prediction model.

The predictive value indicators of first trimester biochemical screening in assessing unfavorable factors of pregnancy course in women with HIV as well as hepatitis B and C

Aim: to find out the predictive value of blood serum biochemical parameters PAPP-A (pregnancy-associated plasma protein A) and β-hCG (beta subunit of human chorionic gonadotropin) in the assessment of unfavorable pregnancy outcomes in women infected by human immunodeficiency virus (HIV) as well as viral hepatitis B (HBV) and C (HCV).Materials and Methods. A retrospective study of the medical records from 52 women was carried out, including 19 HIV-infected women, 9 women with monoinfection HBV or HCV, 11 pregnant women who were co-infected (HIV/HBV or HIV/HCV) and 13 uninfected women. PAPP-A and β-hCG levels, expressed as MoM (multiple of median), were evaluated in all women.Results. Our study revealed that only PAPP-A was prognostically significant for developing chronic placental insufficiency in women with HIV infection and co-infection of HIV together hepatitis B and C. None of the parameters examined were significant in women with HBV or HCV monoinfection. PAPP-A and β-hCG in pregnant women without infections were effective in predicting development of chronic placental insufficiency.Conclusion. PAPP-A can be used as a diagnostic parameter of developing chronic placental insufficiency in pregnant women with monoinfection HIV and co-infection with HIV/HBV or HIV/HCV.