Normal Pregnancy Research Articles

First trimester prediction models for small-for- gestational age and fetal growth restricted fetuses without the presence of preeclampsia

We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012–3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic. The study included all cases diagnosed with SGA (n = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm, were added to the prediction model for FGR, the detection power was even increased to 74.39 % cases and 78.05 % cases at 10.0 % FPR.

Umbilical cord variables in relation to gestational age by using ultrasonography in normal pregnancy and PIH women

To determine whether the antenatal assessment of CSA of umbilical cord variables is different in PIH compared with healthy pregnant women by using ultrasonography and to assess its relationship with gestational age.This study was conducted in the Department of Radio-diagnosis, Sri Siddhartha Medical College, among 600 (300 normal &300 PIH) pregnant women who underwent a routine prenatal gestational sonogram ranging from 28 to 39 weeks of age.There was a significant difference observed between two groups in all umbilical cord variables except umbilical artery area. Mean ± S.D of the CSA of the umbilical cord variables for each gestational age were studied in normal and PIH women.We found that the mean value of UCA and WJA was increased till 36 weeks then it decline sharply in the normal group whereas in PIH group, the mean value of UCA increases till 36 weeks then it attain plateau and the mean value of WJA increases even after 36 weeks. Our study was first of its kind to document the CSA of UC variables and their growth pattern according to gestation age, which can be used as an informational basis for both normal and PIH pregnant women.

Do elevated thyrotropin levels increase the risk of miscarriages: yes or no?

Background To examine correlation between elevated levels of thyrotropin with the frequency of miscarriages. Methods A cross-sectional study was conducted on the 380 respondents and it investigated TSH (thyrotropin), thyroid peroxidase antibody(anti-TPO) and free thyroxine (FT4) in pregnant women who had a miscarriage (N = 179) and pregnant women with normal pregnancies (N = 201). Results The incidence of subclinical hypothyroidism in the miscarriages group was higher than in control group (61.4% vrs 15.79% (p < 0.001). In the miscarriages group with hypothyroidism (first trimester) mean value of TSH was significantly higher 4.31 ± 2.55 mIU/L compared to the control group 1.95 ± 0.86mIU/L (p < 0.001). Logistic multivariate regression revealed that TSH and body mass index (BMI) have a significant influence on the miscarriage; TSH level has a higher odds ratio (OR) 1.47 CI (95% 1.22–1.78) than BMI (OR) 1.14 CI (95% 1.06–1.23)) (p < 0.001). The combination of thyroid autoimmunity and TSH > 2.5mIU/L increase the risk of miscarriage (65.75%) compared to positive anti-TPO antibodies and TSH < 2.5mIU/L(14.15%)(p < 0.001). Conclusions Higher TSH levels correspond with obesity during early pregnancy and may be a sign of maternal thyroid dysfunction. Physiological thyroid function in the first trimester of pregnancy is important for perinatal outcome.

Mesenchymal stem cell secretome ameliorates over-expression of soluble fms-like tyrosine kinase-1 (sFlt-1) and fetal growth restriction (FGR) in animal SLE model

Introduction In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a “by-product” of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. Materials and methods Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele’s Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. Results The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; p < 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; p = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 ± 80.76 mg vs. 550 ± 64.03 mg; p < 0.001 and birth length: 14.43 ± 1.27 mm vs. 19.00 ± 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 ± 75.47 mg and 18.14 ± 1.34 mm, p = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; p = 0.794). Conclusions Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.

Coronary vascular function in females with history of hypertensive disorders of pregnancy an oxygenation-sensitive cardiovascular magnetic resonance imaging study

Abstract Background Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, have been associated with increased risk for cardiovascular disease decades after HDP pregnancy. HDP is thought to unmask pre-existing cardiovascular risk in the mother; and in addition HDP triggers a cascade of inflammatory and oxidative stress which leads to vascular endothelial dysfunction and abnormalities in cardiac structure and function evident early post-partum that may persist sub-clinically. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) is an emerging approach that can identify dynamic changes of myocardial oxygenation as a marker for coronary vascular function. The objective of this study was to assess coronary vascular function in females with history of HDP using OS-CMR. Methods We analyzed data from two short axis OS-CMR slices in 20 females with history of HDP, including gestational hypertension, preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) and 20 healthy controls with history of normal pregnancy acquired on a 1.5T MRI scanner. Images were analyzed using a prototype tissue oxygenation module. The images were normalized for signal intensity to both ventricular blood pools. We used both traditional statistics and feature selection machine learning algorithms to select for predictive biomarkers in the dataset. Finally, we used a random forest classifier model for disease classification. We report area under the receiver operating curve (AUROC) as a metric for diagnostic accuracy. Results Global breathing-induced myocardial oxygenation reserve (B-MORE) of the mid left ventricular slice was significantly reduced in HDP females (-1.6 ± 14.8) when compared to healthy controls (11.3 ± 17.2, p=0.03), when normalized to ventricular blood pools (Figure 1A). Our feature selection algorithm selected the signal intensity during end-systole normalized to the series as the most predictive biomarker. Our model, which integrated data from &amp;gt;3,300 discrete data points per participant, correctly differentiated healthy controls from women with HDP history with a 90% ± 3% AUROC accuracy, indicating high sensitivity and specificity (Figure 1B). Conclusion Compared to healthy controls, females with history of HDP have abnormal coronary vascular function, as shown by reduced myocardial oxygenation on OS-CMR. Combining advanced machine learning approaches can further enhance the potential application of OS-CMR to risk stratify females with adverse pregnancy outcomes susceptible to future cardiovascular disease.

Long-term cardiovascular risk of pre-eclampsia

Abstract Background/introduction Pre-eclampsia is a complication of the second and third trimesters of pregnancy characterized by hypertension and endothelial dysfunction causing multiorgan damage. In 2017 few studies suggested an association between pre-eclampsia and long-term cardiovascular diseases. However, since those first studies, the literature has grown exponentially. Purpose To assess the association between a history of pre-eclampsia and subsequent cardiovascular diseases, including 1) cardiovascular death, 2) coronary heart disease, 3) heart failure, and 4) stroke. Methods Following PRISMA guidelines, from inception to September 2022, we performed a systematic review of PubMed, MEDLINE, Scopus, and EMBASE. Randomized, cohort or case-control studies in English were included if fulfilling the following criteria: 1) the association between pre-eclampsia and subsequent cardiovascular disease was adjusted for at least maternal age, smoking, and obesity; 2) the presence of a control group; 3) minimum one-year follow-up. Pooled Relative Risk (RRs) and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model. The primary endpoint was cardiovascular death. The secondary endpoints were coronary heart disease, heart failure, and stroke. Results Twenty-one studies met the inclusion criteria, including 478,708 women with a history of pre-eclampsia and 10,533,530 without. Pre-eclampsia was associated with a higher risk of cardiovascular disease death (RR 1.97, 95% CI 1.64-2.35, I2 60%, p&amp;lt;0.00001), coronary heart disease (RR 2.11, 95% CI 1.60-2.77, I2 85%, p&amp;lt;0.00001), heart failure (RR 2.47, 95% CI 1.70-3.59, I2 82%, p&amp;lt;0.00001), and stroke (RR 1.64, 95% CI 1.45-1.85, I2 43%, p&amp;lt;0.00001). Sensitivity analysis excluding those studies with a follow-up of less than 10 years evidenced similar results. Conclusions Compared to women who experienced a normal pregnancy, those suffering from pre-eclampsia have about double the risk of cardiovascular disease, including cardiovascular death, coronary heart disease, heart failure, and stroke. This risk becomes evident already in the first ten years after pregnancy. As such, obstetricians should counsel pre-eclamptic women on the importance of an early assessment and risk factors management in a multidisciplinary team with cardiologists.

A Comparative Study of Serum and Salivary Uric Acid Measurement in Pre-eclampsia and Normal Pregnancy in a Tertiary Care Hospital in Punjab: A Pilot Study

A Comparative Study of Serum and Salivary Uric Acid Measurement in Pre-eclampsia and Normal Pregnancy in a Tertiary Care Hospital in Punjab: A Pilot Study

Assessing awareness of long-term health risks among women with a history of preeclampsia: a cross-sectional study.

Pregnancy complications, such as hypertensive disorders, present a substantial global public health challenge, with significant long-term implications for maternal and offspring health. This cross-sectional study aims to determine the level of awareness regarding long-term health risks among women who experienced preeclampsia during pregnancy in Cyprus and Greece. The study participants included adult women with a history of preeclampsia, while women with normal pregnancies were used as the comparison group. Data collection took place between June 2021 and February 2022, utilizing an online, self-administered questionnaire. The study included 355 women, with 139 (39.2%) in the preeclampsia group and 216 (60.8%) in the comparison group. Findings revealed that more than half of the women with prior preeclampsia (55.4%) were not aware of hypertensive disorders that can occur during pregnancy before their diagnosis, and a similar percentage (45.2%) had not received information about the long-term health risks following their diagnosis. Remarkably, only 3 participants (4.7%) with a history of preeclampsia were aware of the risk of developing cardiovascular diseases. There were no statistically significant differences between the preeclampsia and the comparison group regarding their concerns about long-term health risks, frequency of health checks, perceptions of factors influencing cardiovascular disease development, and doctor communication about different health topics, except from hypertension or high blood pressure. The study underscores the low level of awareness of long-term health risks among women with prior preeclampsia in Cyprus and Greece. This emphasizes the importance of implementing public health programs aimed at promoting cardiovascular risk assessment and effective management, both for clinicians and women with have experienced preeclampsia.

Embryo Condition Media Collected from Polycystic Ovary Syndrome Patients with Abdominal Obesity Can Increase The Decidualization Potential of Healthy Endometrial Stromal Cells.

Polycystic ovary syndrome (PCOS) is a common endocrinological disorder associated with abdominal obesity (AO) and some reproductive complications including low pregnancy rate. Embryo-endometrium cross-talk has a key role in successful embryo implantation and subsequent normal pregnancy rate. The primary objective of this study is to evaluate the decidualization potential of endometrial stromal cells (ESCs) using the embryo condition media (ECM) collected from PCOS patients with AO, compared to ECM of those patients without AO. In this experimental study, we measured the capacity of ECM collected from PCOS patients with or without AO for decidualization induction in healthy ESCs after coculture. A total number of 53 embryos from 40 couples belonging to PCOS with AO, PCOS without AO, nonPCOS with AO, and nonPCOS without AO patients, were included in our study. The embryosof four groups were single-cultured up to the blastocyst stage. Their ECM (45λ/well) were pooled and added to healthy ESCs monolayer culture media to investigate their effects on decidualization potential via gene (PRL, IGFBP1, IL1-β, HOXA10, IL-6 and TNF-α) and protein (PRL, IGFBP1, IL1-β) expression analysis and ESCs migration assay. The morphological analysis, migration assay (P≤0.0321), protein (P≤0.0139) and gene expression analysis showed PCOS with AO accounted for the highest gene (PRL, IGFBP1, IL1-β, HOXA10, IL-6, TNF-α) and protein markers (PRL, IGFBP1, IL1-β) (P≤0.05). NonPCOS individuals without AO had the lowest level of both gene and protein decidualization markers (P≤0.05). Considering decidualization as an inflammatory process, a higher level of decidualization markers was associated with a higher inflammatory status created by AO and PCOS, separately. Inflammation may disrupt the process of inflammatory to anti-inflammatory phase required for prevention of pregnancy loss, this could explain the high rate of abortion in these cases.

Non-invasive mapping of human placenta microenvironments throughout pregnancy with diffusion-relaxation MRI

IntroductionIn-vivo measurements of placental structure and function have the potential to improve prediction, diagnosis, and treatment planning for a wide range of pregnancy complications, such as fetal growth restriction and pre-eclampsia, and hence inform clinical decision making, ultimately improving patient outcomes. MRI is emerging as a technique with increased sensitivity to placental structure and function compared to the current clinical standard, ultrasound. MethodsWe demonstrate and evaluate a combined diffusion-relaxation MRI acquisition and analysis pipeline on a sizable cohort of 78 normal pregnancies with gestational ages ranging from 15 + 5 to 38 + 4 weeks. Our acquisition comprises a combined T2*-diffusion MRI acquisition sequence - which is simultaneously sensitive to oxygenation, microstructure and microcirculation. We analyse our scans with a data-driven unsupervised machine learning technique, InSpect, that parsimoniously identifies distinct components in the data. ResultsWe identify and map seven potential placental microenvironments and reveal detailed insights into multiple microstructural and microcirculatory features of the placenta, and assess their trends across gestation. DiscussionBy demonstrating direct observation of micro-scale placental structure and function, and revealing clear trends across pregnancy, our work contributes towards the development of robust imaging biomarkers for pregnancy complications and the ultimate goal of a normative model of placental development.

Antepartum depression: The prevalence, associated factors and perinatal outcomes: A cross-sectional study

Objective: The current study aimed to track the prevalence of APD, its associated factors and perinatal outcomes among Egyptian pregnant women.&#x0D; Methodology: The current work included 122 pregnant women, with singleton normal pregnancy. They were evaluated for antepartum depression and perceived stress. In addition, demographics and obstetric data were collected and documented. The psychiatric status was assessed in the third trimester (preferably at 35 to 37 week of gestation). Then, the feto-maternal outcome was recorded. The primary outcome was the prevalence of APD and perceived stress. Neonatal outcome was document especially preterm birth and neonatal weight.&#x0D; Results: APD was recognized among 28 women (23.0%). The APD was significantly associated with employment (82.1% and 57.4%, in those with and without APD respectively). The unplanned pregnancy was significantly increase in women with than those without APD (35.7% vs 9.6%). Maternal obesity, low birth weight and preterm delivery were associated with APD. Finally, the perceived stress score was significantly higher among women with APD than those without APD (18.92±7.30 vs 14.75±9.07).&#x0D; Conclusion: APD was reported in nearly one of four women and significantly associated with maternal obesity, unplanned pregnancy and employment. In addition, preterm birth and low birth weight significantly increased with APD.

New aspects of the pathogenesis of placental insufficiency

Relevance. Placental insufficiency is a polycausal syndrome characterized by a violation of the molecular, cellular, tissue and organ adaptivehomeostatic reactions of the fetoplacental system. The active participation of the neutrophil component of the innate immune system in the development of endothelial dysfunction and thrombotic disorders, which underlie many complications of pregnancy, has been proven, which served as the reason for conducting exploratory studies to assess the level of neutrophil extracellular traps (NETs) in pregnant women at different stages of gestation.The purpose of the study is to identify the features of the formation of neutrophil extracellular traps in pregnant women with normal pregnancy and placental insufficiency associated with thrombophiliaMaterial and methods. 85 pregnant women in the second and third trimester were examined: 40 women with normal pregnancy (comparison group) and 45 (main group) with thrombophilia (protein S/protein C deficiency) and subcompensated placental insufficiency. The level of NVL was assessed in blood smears according to the monolayer type using an automatic microscopic system MECOS-C 2.Results. It was found that the level of DNA traps in normal pregnancy and in pregnant women with placental insufficiency at 21–24 weeks of gestation was 1.3 and almost 2 times higher than the level outside pregnancy (p &lt;0.05), with a predominance of phase IIa etosis. By 36–37 weeks, in a normal pregnancy, there was a slight increase in%NVL (16 %), while in the group of pregnant women with placental insufficiency,%NVL increased by 35.7 % compared to the initial data, maintaining a high content of extracellular structures in IIa phase of ethotic transformation (7.4 % versus 5.8 % at 21–24 weeks, p &gt;0.05).Conclusion. It is obvious that the presence of a high level of NIV indicates a failure of immune defense mechanisms and the development of an inadequate inflammatory response in the pathogenesis of fetoplacental insufficiency, which can be useful when carrying out intermediate dynamic monitoring of the condition of a pregnant woman.

Thrombodynamics and Quantitative phase imaging of platelets in the assessment of hemostasis in pregnant women with protein C / protein S deficiency

Relevance. A hypercoagulable state caused by hereditary or acquired deficiency of antithrombotic factors can contribute to disruption of the uteroplacental circulation with the development of serious pregnancy complications, which requires effective monitoring of hemostasis during the use of pathogenetic anticoagulant therapy.The purpose of the study is to improve methods for diagnosing and monitoring hemostatic disorders in pregnant women with thrombophilia (protein C/protein S deficiency) and complicated pregnancy based on the use of an integral thrombodynamic test and quantitative phase imaging of platelets.Material and methods. 45 pregnant women were examined in the first and second trimester: 20 women with normal pregnancy (comparison group) and 25 (main group) with thrombophilia (protein S/protein C deficiency). 16 pregnant women (subgroup 1A) received a full course of preconception preparation with the prescription of LMWH, 9 pregnant women (subgroup 1B) did not complete the course in full for various reasons. To study hemostasis, along with routine methods (determination of APTT, TT, PT, Fibrinogen, INR and D-dimer), an integral assessment of coagulation using the Thrombodynamics method and quantitative phase imaging (QPI) of platelets in real time were performed.Results. It was found that routine methods are not sufficiently informative; statistically significant changes against the background of thrombophilia and during treatment with LMWH were noted only based on the results of assessing the level of fibrinogen and D-dimer. In the complex of thrombodynamics indicators, the most sensitive parameters were the steady-state clot growth rate (Vst), clot size at 30 minutes of the study (CS) and clot density (D). The QPI method revealed features of the morphological structure of platelets with a predominance in pregnant women with protein S/protein C deficiency of the activated cell population with an increase in the median values of diameter and perimeter by 14 and 20 %, respectively (p &lt; 0.05). The effectiveness of LMWH therapy was assessed by normalization of the analyzed parameters.Conclusion. Timely and adequate correction of hemostasis disorders, carried out while monitoring coagulation and platelet parameters, taking into account all clinical data, can significantly reduce the risk of complications for the mother and fetus.

Alterations in the von Willebrand factor/ADAMTS-13 axis in preeclampsia

BackgroundPreeclampsia is a gestational hypertensive disorder characterized by maternal endothelial activation and increased ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) inhibitor to placental growth factor (PlGF). The von Willebrand factor (VWF)/ADAMTS-13 axis is of interest because of the underlying endothelial activation and clinical overlap with pregnancy-associated thrombotic thrombocytopenic purpura. ObjectivesTo assess VWF, ADAMTS-13, and VWF/ADAMTS-13 ratio in preeclampsia and look for associations with sFlt-1/PlGF ratio and clinical features. MethodsThirty-four preeclampsia cases and 48 normal pregnancies were assessed in a case-control study. Twelve normal pregnancies in women with a history of preeclampsia formed an additional comparator group. VWF antigen (VWF:Ag) and VWF activity (VWF:Ac [VWF:glycoprotein IbM]) were measured via automated immunoturbidimetric assay, ADAMTS-13 activity was measured via fluorescence resonance energy transfer–VWF73 assay, and sFlt-1 and PlGF were measured via enzyme-linked immunosorbent assay. ResultsVWF:Ag was higher in preeclampsia than in normal pregnancy (median, 3.07 vs 1.87 IU/mL; P < .0001). ADAMTS-13 activity was slightly lower (median, 89.6 vs 94.4 IU/dL; P = .02), with no severe deficiencies. Significant elevations in VWF:Ac were not observed in preeclampsia, resulting in reduced VWF:Ac/VWF:Ag ratios (median, 0.77 vs 0.97; P < .0001). VWF:Ag/ADAMTS-13 ratios were significantly higher in preeclampsia (median, 3.42 vs 2.06; P < .0001), with an adjusted odds ratio of 19.2 for a ratio of >2.7 (>75th centile of normal pregnancy). Those with a history of preeclampsia had similar ratios to normal pregnant controls. VWF:Ag/ADAMTS-13 and sFlt-1/PlGF were not correlated. However, percentage reduction in platelets correlated positively with VWF:Ac (P = .01), VWF:Ac/VWF:Ag ratio (P = .004), and sFlt-1/PlGF ratio (P = .01). ConclusionThe VWF/ADAMTS-13 axis is significantly altered in preeclampsia. Further investigation of potential clinical utility is warranted.

Comparison of Thrombocyte Indices and Immature Platelet between Preeclampsia and Normal Pregnancy

The primary pathophysiology of preeclampsia is abnormal trophoblast invasion, vasospasm, and endothelial dysfunction occurring, as well as platelet activation, increased platelet consumption, and the stimulation of the release of new platelets, which affects the platelet indices and immature platelets. This study compared the platelet indices (Mean Platelet Volume=MPV, Platelets Distribution Width=PDW, Platelet Large Cell Ratio=PLCR, and Immature Platelet Fraction (IPF) between preeclampsia and normal pregnancy. This research was an unpaired comparative analytic observational study with a cross-sectional design conducted in the Tangerang District General Hospital from February to August 2020. The platelet indices (MPV, PDW, PLCR) and IPF of preeclampsia subjects (n=33) at Tangerang District General Hospital and normal pregnant subjects (n=38) at Annisa Hospital Tangerang were examined using the Sysmex XN-1000 automatic hematology analyzer. Comparative platelet indices and IPF analysis were carried out by independent T-test or Man-Whitney test. Receiver Operating Characteristics (ROC) analysis was performed to obtain the cut-off value of the platelet indices and IPF to differentiate preeclampsia and normal pregnancy. The platelet indices and IPF were significantly higher in preeclampsia. The mean (SD) MPV was 10.86 (0.9) fL and 10. (0.89) fL, p&lt;0.001; PDW 12.7 (8.7-19.1) fL and 10.85 (8.5-15.7) fL, p&lt;0.001; PLCR 31.96 (7.02) % and 25.06 (6.92) %, p&lt;0.001; and IPF 8.50 (3.10-20.40)% and 2.75 (1.2-9.4)%, p&lt;0.001, respectively in preeclampsia and normal pregnancy. ROC analysis showed that an IPF with an AUC of 0.88 (95% confidence interval (CI) 0.78-0.95) with an IPF cut-off value of &gt;6.5% was a good marker, while the MPV cut-off &gt;10.2 fL, AUC 0.75(95% CI 0.63-0.84), PDW cut-off &gt;11.3fL, AUC 0.77 (95%CI 0.65-0.86) and PLCR cut-off &gt;26.1%, AUC 0.76 (95% CI 0.65-0.85) were good enough markers to differentiate preeclampsia from normal pregnancy. Platelet indices and IPF were statistically significantly higher in preeclampsia. The IPF parameter is a good marker, while the platelet indices can be a pretty good marker to distinguish preeclampsia and normal pregnancy. The IPF parameter and platelet indices can be proposed as a routine examination in pregnancy. Changes in IPF and platelet indices can be early signs of preeclampsia or the development of preeclampsia.

Effects of maternal pulmonary arterial hypertension on fetal hemodynamics and maternal-fetal outcome in late pregnancy.

The aim of this study was to investigate the effects of maternal pulmonary arterial hypertension (PAH) on fetal hemodynamics in the third trimester and to identify hemodynamic indicators associated with adverse maternal and fetal outcomes. We recruited 48 pregnant women with PAH in the third trimester and 32 women with normal pregnancies as controls matched for age and gestational week. Fetal growth and hemodynamic parameters were assessed by two-dimensional and color Doppler. All cases were followed up until delivery and maternal and fetal outcomes were collected. High throughput sequencing method was used to determine differential miRNA patterns in plasma exposed to pulmonary arterial hypertension (PAH) in pregnant women. We then performed the validated of key differentially expressed miRNAs by real-time PCR. Compared with the normal and mild PAH groups, resistance index (RI), pulsatility index (PI) of the fetal umbilical artery (UA) and quantitative ductus venosus (QDV) blood flow were increased in subjects with moderate to severe PAH, while PI and the ratio of peak systolic velocity (PSV) to end-diastolic velocity (EDV) (S/D) of the middle cerebral artery (MCA) were decreased. Compared with the normal group, subjects in the mild and moderate PAH groups had lower neonatal weight, shorter neonatal height, and higher preterm birth rates. In addition, miRNA sequencing data showed that PAH affected the levels of 23 miRNAs in plasma. At the same time, we showed that PAH significantly decreased the level of miR-1255a and increased the level of miR-548ar-3p by real-time PCR. In the group of pregnant women with moderate to severe pulmonary hypertension, there was a higher proportion of preterm births and low birth weight babies. Hemodynamic changes in the fetal UA, MCA, and ductus venosus (DV) during late pregnancy were associated with adverse fetal outcomes. At the same time, miRNA sequencing results showed that miR-1255a and miR-548ar-3p may play an important role in the development of PAH.

The Procoagulant Phospholipid Dependent Clotting Time and the Initiation Phase of Thrombin Generation Test Are Mandatory for the Evaluation of the Risk for Severe Early Onset Preeclampsia

Bakground: Preeclampsia occurs in up to 7% of pregnancies in Western Countries and is a leading cause of maternal and fetal morbidity and mortality. Classification of preeclampsia is based on the timing of symptoms' onset and the severity of the clinical status. Accordingly, early and late preeclampsia are characterized by symptom onset before or after 32-34 weeks of gestation respectively. Pathogenesis of preeclampsia is characterized by abnormal placental vascular development with impaired invasion of the uterine spiral arteries by trophoblasts, resulting in fetal complications and maternal endothelial dysfunction. Intact antithrombotic properties of the endothelial cells and efficient regulation of thrombin generation and platelet activation at the microenvironment of the uterus are necessary conditions for successful trophoblast invasion and development of feto-maternal circulation during normal pregnancy. , Prompt identification of pregnant women at risk of preeclampsia worsening could help to anticipated therapeutic intervention and improvement of the clinical outcome. Aim: The ROADMAP-Early Onset Preeclampsia study (ROADMAP-EOP) aiming to respond to this unmet need assessed the clinical relevance of biomarkers of hypercoagulability and endothelial activation for prompt identification of pregnant women at high risk of preeclampsia. Materials and Methods: An observational single center retrospective case-control study was conducted in pregnant women diagnosed with preeclampsia from July 2020 to July 2021. Pregnant women were retrospectively enrolled upon EOP diagnosis and stratified in mild EOP group (n=34) and severe EOP group (n=15 according to the criteria of the International Society for the Study of Hypertension in Pregnancy ). Eligible women were included in the study before initiation of any treatment for preeclampsia. The control group (n=35) consisted of women with uncomplicated pregnancy. All women were assessed with thromboelastometry, Calibrated Automated Thrombo-gram®, tissue factor activity (TFa), Procoagulant phospholipid dependent clotting time (Procoag-PPL), Proteins S, TFPI, D-dimer, antithrombin, thrombomodulin, fibrinogen prothrombin time and activated partial thromboplastin time. Primary and secondary end points were severe EOP and EOP respectively. Principal component analysis (PCA) was performed to check for associations among the biomarkers and the clinical out-come. Results: There were no significant differences regarding age, gravidity, gestational age and the body mass index (BMI) between EOP groups and normal pregnancy as well as within the EOP groups. Platelet counts were similar in healthy pregnant women, and mild EOP group, and significantly lower in severe EOP (p&amp;lt;0.05). No other statistically significant differences were found between-groups. The PCA showed that the repartition of data allowed to discriminate the patients with EOP from healthy pregnant women as well as patients with mild EPO from those with severe EOP. When biomarkers of hypercoagulability were considered according to the severity of EOP in PCA analysis the lag-time and PPL clotting time were independently associated with the risk of severe EOP (Table 1and Figure 1)). The increase of the lag-time by 1 min was associated with a 20.2-fold increase of the risk of severe EOP. The marginal effects curve shows that for a lag-time longer than 2.6 min, the probability of severe EOP was higher than 50% .Longer Procoag-PPL clotting time was associated with lower risk of severe EOP. The marginal effects curve, showed that for Procoag-PPL clotting time longer than 58.75 sec the probability of severe EOP decreased by 50%. These data suggest that a biological score composed of the Procoag-PPL® clotting time and thrombin generation (Throbmogram-Thrombinoscope® PPP-reagent 1 pM-TF as-say) could be a useful tool to identify pregnant women with high probability of EOP Conclusion: the Procoag-PPL® clotting time and thrombin generation assay reflect cellular derived hypercoagulability and allow accurate screening of pregnant women for the prompt identification of those at risk of EOP and the evaluation of its severity. This concept has to be validated in a large prospective cohort trial. . An external validation of the proposed methodology needs to be performed in a large prospective observational study.

Ultrasonographic correlation of placental thickness with some foetal biometry in seemingly normal singleton pregnancies in Taraba State, Nigeria

An accurate assessment of the gestational age (G.A) and evaluation of foetal growth is essential to antenatal care. GA prediction based on the sonographic foetal parameters may be the cornerstone in modern obstetrics and continues to remain an important component of the management of pregnancies. Placental thickness appears to be a promising parameter for the estimation of GA, for it tends to have a positive correlation with it. Ultrasonography helps in the assessment of the placenta and the detection of placental abnormalities using different parameters like placental thickness and volume. This study was conducted to sonographically measure the placental thickness and correlate it with some foetal biometry in apparently normal singleton pregnancies. A prospective cross-sectional design was employed for the study from March to July 2021 in Jalingo, Taraba State. A convenient sampling method was employed and included a total of 314 healthy pregnant women referred for obstetrics ultrasound scans in their 2nd and 3rd trimesters. Ultrasound scans were performed using an ultrasound system equipped with a 3.5 MHz curvilinear transducer. Findings from this study revealed an increasing trend in the values of the mean placental thickness with an increase in G.A, and the placental thickness in mm coincide almost exactly with the GA weeks, indicating there was a positive correlation between placental thickness and G.A from 14-35 weeks of gestation. However, placental thickness gradually declined from 36-40 weeks G. A, thereby, lagging behind the G.A marginally by 1-2 mm. Placental thickness cord insertion site can be used as an accurate sonographic parameter to determine the GA, especially from 14-35 weeks of gestation in apparently normal singleton pregnant women due to its statistically strong positive correlation with G.A.

Endostatin and Cystatin C as Potential Biomarkers for Early Prediction of Preeclampsia.

Preeclampsia (PE) is characterized by new onset hypertension and proteinuria. Undoubtedly, some individuals do not fit precisely into this description, and it could be challenging to spot newly developed PE in females who already have hypertension or renal illness. Monitoring the disease's progression enables the optimization of delivery time while minimizing premature births. The current study explores the diagnostic benefits of serum endostatin and cystatin C in addition to serum and urinary magnesium (Mg) and fractional excretion magnesium (FEMg) for early prediction of PE. The population sample included 82 pregnant women divided into 3 groups: normal pregnancy group served as a control (n = 26), nonpreeclampsia (NPE, n = 34) group included pregnant women with one or more risk factors but did not progress to PE, and pregnant women who developed preeclampsia (PE, n = 22) group. Blood samples were withdrawn at two sampling times: at 12th to 16th and 24th to 26th weeks of gestation. Compared to normal pregnancy, results (X̅ ± SD) indicated a significant increase in serum endostatin in NPE at the first sample (10.78 ± 3.63 ng/mL) and the second sample (28.03 ± 3.79 ng/mL), while cystatin C was at the first sample (0.68 ± 0.06 mg/dL) and the second sample (0.71 ± 0.07 mg/dL). In the PE group, the serum endostatin was 18.86 ± 4.37 ng/mL at the first sampling time and 53.56 ± 9.76 ng/mL for the second sample. Serum cystatin C was also elevated in PE with X̅ ± SD equivalent to 0.73 ± 0.08 and 0.89 ± 0.08 mg/dL at the first and second samples, respectively. On the other hand, serum and urinary Mg in addition to FEMg levels did not significantly differ across the groups under study. Receiver operating characteristic (ROC) curve analysis proved that both endostatin and cystatin C could be good indicators for PE. The findings imply that measuring endostatin and cystatin C at early pregnancy and before progression to PE may be effective in detecting the likelihood of PE. Endostatin could be more precise and sensitive in assessing the probability of PE than cystatin C; however, coupling of the two parameters may be promising.

Maternal and neonatal umbilical cord serum levels of 25-hydroxy vitamin D among Sudanese women with normal pregnancy: a cross-sectional study

Maternal and neonatal umbilical cord serum levels of 25-hydroxy vitamin D among Sudanese women with normal pregnancy: a cross-sectional study