Normal Pregnancy Research Articles

Medical Diseases in Pregnancy: An Acute on Chronic Focus

In the last decade or so obstetric care has evolved and become more complex. This can be attributed to a combination of factors including rising obesity rates, maternal age and medical treatment advances. Clinicians are caring for more pregnant women with chronic medical disease in addition to any de novo presentations which may occur, emphasising the need for the general medicine body to feel confident and skilled in the management of medical problems before, during and after pregnancy. One of the difficulties faced by clinicians in the assessment and management of pregnant women is the differentiation between symptoms of a normal pregnancy vs symptoms of clinical significance which warrant further investigation, particularly in mothers with background medical disease. Careful consideration and knowledge of normal pregnancy physiology is required when assessing a pregnant women/birthing person to avoid closed thinking and adverse outcomes. Unfortunately, clinician inertia around the care of pregnant women is a common feature in maternal mortality reviews. The most recent maternal mortality report discusses common themes around cardiovascular disease in pregnancy, alongside management of acute and acute-on-chronic presentations in the context of common endocrine, gastrointestinal and neurological disease in pregnancy. This article discusses some of these themes and the management of common medical problems in pregnancy.

Cell-free pregnancy-associated microRNAs in blood plasma as potential biomarker in early diagnosis of ectopic pregnancy.

Ectopic pregnancy (EP) is one of the life-threatening disorders in early pregnancy and current strategies are inadequate in its clinical management. There is a need to identify more accurate biomarkers for early diagnosis of ectopic pregnancy. This case-control study was conducted in a group of 35 women diagnosed with ectopic pregnancy and 31 women with a normal singleton pregnancy. Patients' characteristics including the level of β-hCG, age, body mass index (BMI), and gestational age have been recorded. The plasma levels of cell-free hsa-miR-411, hsa-miR-433, and hsa-miR-524 were examined by qRT-PCR using specific primers. There was no statistically significant difference in maternal age, gestational age, and BMI between the two groups. β-hCG concentrations in EP were significantly lower than normal pregnancy group. Cell-free hsa-miR-411 and hsa-miR-433 had statistically significant differences in concentrations in women with EP and normal pregnancy. hsa-miR-411 and hsa-miR-433 had better diagnostic values for discriminating EP from normal pregnancy. Moreover, hsa-miR-411 and hsa-miR-433 showed a specificity of 61% and 53%, and a sensitivity of 72% and 79%, respectively. hsa-miR-411 and hsa-miR-433 microRNAs concentrations in plasma have potential as a predicting biomarker for early diagnosis of EP. However, further research is needed before using miRNAs in clinical practice for both diagnostic and therapeutic goals.

The Nuchal Cord Conundrum: Understanding and Addressing Umbilical Entanglement in the Third Trimester of Pregnancy

Background/Objectives: Better understanding of and addressing umbilical entanglement in the third trimester of pregnancy is necessary to estimate its impact on fetal circulation. An analysis of single physiological pregnancies wrapped with one or two coils of the umbilical cord around the neck makes it possible to understand the severity of the problem and distinguish it from perinatal umbilical strangulation. Methods: In an echocardiographic study performed at 32.1 weeks of pregnancy in fetuses with one and two coils of the umbilical cord around the neck, the pulsatility index (PI) and the Tei index for the left (Tei LV) and right ventricle (Tei RV) of the heart were measured to evaluate cardiac function. Results: The study showed significantly higher Tei RV and Tei LV for fetuses with one (93 cases) and two coils of the umbilical cord around the fetal neck (26 cases) with respect to the control group of fetuses (680 cases) with no umbilical cord around the fetal neck, whereas PI UMBA did not differ significantly. Conclusions: Wrapping of the umbilical cord around the fetal neck may affect the study of the fetal heart without any mechanically induced compression of the umbilical vessels in normal pregnancy.

Intravoxel incoherent motion MRI to assess feto-placental diffusion and perfusion properties in small fetuses.

To investigate the use of intravoxel incoherent motion (IVIM) to study microperfusion and microstructural characteristics of lungs, brain, and placenta in normal and small fetuses. We retrospectively enrolled 30 small fetuses and 82 normal pregnancies who underwent a 1.5-T MRI examination using an IVIM-DWI. Small fetuses were distinguished in small for gestational age (SGA) and "true" fetal growth restriction (FGR). ROIs were placed on the brain parenchyma, lungs, and fetal/maternal placental sides. Differences in perfusion fraction f, diffusion coefficient D, and pseudo-diffusion coefficient D* and their correlation with gestational age (GA) and birth weight (BW) were investigated. LUNG: f showed significantly lower values (p = 2·10-7) in small fetuses (SGA + FGR); f discriminates SGA and FGR from normal (p = 0.001; p = 1·10-6). f increases with GA (p < 0.0001) in the control group; a positive correlation was also obtained in small fetuses, although less significant. FGR showed lower f values than normal ones, in both the fetal (p = 1.4·10-7) and maternal side (p = 0.001); f discriminates between SGA and FGR (p = 0.03). In small fetuses (SGA + FGR), f correlates positively with BW. D values in supratentorial white matter (WM) were significantly higher compared to other regions, in both normal and small fetuses. Small fetuses showed higher D values in occipital WM and pons (p = 0.041; p = 0.027) than in normal. D correlates negatively with GA in the healthy group. No correlation between D and GA was found in SGA + FGR group. In our study, IVIM-MRI allowed us to detect microstructural and microperfusion changes in the placenta, brain, and lung of small fetuses, noninvasively.

Transcriptomic profiling with vascular tension analyses reveals molecular targets and phenotypes in preeclamptic placental vasculature

IntroductionThe placental vascular system plays an important role in the development of pregnancy hypertension in preeclampsia. The gene profiles of whole placental tissue (containing blood vessels and many other structural components) and pure vascular tissue should be very different. All previous reports using RNA-seq analysis in the placenta have tested its whole tissue or the villous part, and thus the gene profiles in the pure placental blood vessels are unknown.MethodsThis study was the first to address this point with RNA-seq in human placenta at the transcript level. Isolated placental micro-vessels from normal and preeclamptic pregnancies were used for RNA-seq analysis, real-time quantitative polymerase chain reaction (RT-qPCR) verification, and vascular function tests. Furthermore, a vascular function-centric core network was constructed to show the gene-gene interactions and gene-function associations in the placental vessel system.ResultsDifferential expression analysis identified a total of 486 significantly changed transcripts. Bioinformatics analysis further confirmed that multiple genes were highly related to blood vessel and placental phenotypes. Several hub genes, including ELMO1, YWHAE, and IL6ST, were significantly reduced in the placental vessels in preeclampsia. Vascular tension experiments showed that angiotensin II-mediated vasoconstriction and exogenous NO donor sodium nitroprusside-induced vasodilation were decreased, while phenylephrine-mediated vascular responses were unchanged in placental micro-vessels in preeclampsia.DiscussionThe results provide important insights into the pathological process in the placental vasculature in preeclampsia and offer great potential for further investigation of these molecular targets in the human placental vascular system.

Adverse maternal and fetal outcomes among tribal pregnant women suffering from sickle cell disease: A retrospective cohort study in a community-based hospital situated in a tribal block of Gujarat, India.

The study presents the risk of the maternal-fetal morbidity and mortality among one of the largest cohort of sickle cell disease (SCD) pregnancies in India and reports the epidemiology of the maternal morbidity. This was a retrospective cohort study conducted at Kasturba Maternity Hospital, SEWA Rural, in the tribal area of Gujarat, India. All pregnant women admitted to the Hospital between 2016 and 2021 were screened for SCD, and their maternal-fetal morbidities were recorded throughout the pregnancy. We quantified risk of maternal-fetal morbidity and mortality among SCD, trait and normal pregnancies after adjusting for potential confounders using Poisson and logistic regression. A total of 24 256 delivered during the study period, with 354 (1.5%) and 4216 (17.4%) suffering from SCD and trait, respectively. After adjusting for potential confounders, the women with SCD pregnancy had higher risk of maternal death (adjusted-odds-ratio [AOR] 13.7, 95% CI: 4.5-42.7), anemia (AOR 6.8, 95% CI: 4.5-10.2), severe anemia (AOR 4.3, 95% CI: 3.3-5.6), preterm delivery (AOR 4.5, 95% CI: 3.6-5.7), cesarean section (AOR 5.5, 95% CI: 4.7-7.0), stillbirth (AOR 3.4, 95% CI: 2.3-5.3), and low birth weight (AOR 3.1, 95% CI: 2.4-39) compared to normal pregnancies. Maternal morbidities occurred throughout the pregnancy; however, the risk was highest during the last month of pregnancy. Pregnant women who had severe manifestation of SCD before the pregnancy were at higher risk of developing maternal morbidities. We concluded that SCD might be an independent risk-factor for developing maternal-fetal morbidities. The SCD pregnancies with prior severe manifestations must be carefully managed during the last month of pregnancy when the risk is highest.

Serum Magnesium concentration in normal and preeclamptic pregnancy: A tertiary center experience

Preeclampsia and maternal mortality are more prevalent in underdeveloped nations. Preeclampsia has an estimated 16% incidence rate in Bangladesh, which is extremely high. One of the body's major macronutrients is magnesium. It also serves a multitude of enzymes as a cofactor. This cross-sectional study was done in the department of Biochemistry of Mymensingh Medical College, Mymensingh, from July 2016 to June 2017. This study involved a total of 100 individuals, where 50 preeclamptic patients and 50 healthy pregnant women served as the case and control groups, respectively. The results were shown as mean ±SD. For both the case and control groups, the mean ±SD of serum magnesium levels were 1.75 ±0.22 mg/dl and 1.63 ±0.21, respectively. Comparison of the mean ±SD of serum magnesium in the case and control groups revealed a highly significant difference (P&lt;0.001). Students' unpaired ‘t’ test was used to compute the statistical difference. Mediscope 2024;11(2): 73-76

Transuterine relocation of pregnant uterine horn segment in an exploratory rat model with implications for tubal ectopic pregnancy

Ectopic pregnancy affects ~ 2% of pregnancies annually in the United States, with no current treatments allowing for the continuation of the pregnancy. Thus, this study sought to initiate an investigation into the potential design of a surgical technique, in an animal model, that could serve as a foundation for future research into the potential of relocating an ectopic embryo into the uterus at the human level. Female Long-Evans rats were randomly assigned to one of two groups: Embryo Relocation (ER; n = 12; underwent embryo relocation surgery) and Normal Pregnancy (NP; n = 12; carried a normal pregnancy; no surgery). Eight rats/group were allowed to carry their pregnancy to term and deliver, while four had their uteri collected at the end of gestation. Briefly, for the ER group, a uterine horn containing 1–2 embryos was translocated to the contralateral horn, which had been incised and cleared of its contents, prior to being wrapped around the relocated horn. Rat weight, food consumption and vaginal impedance of the mothers were measured throughout the experiment. Ultrasounds were performed and fetal heart rates measured on day 20–21 of gestation. Additionally, rat weight of all offspring was measured at adulthood. Our findings indicate that, in the ER group, 15/15 (100%) of the relocated embryos had detectable heart rates at the end of gestation (within the normal range), 14/15 (93%) were delivered vaginally, and 12/14 (86%) survived until adulthood. A significant decrease in rat weight and food consumption was observed only on the day following surgery. Fertility, as measured by vaginal impedance, was minimally impacted by surgery. Moreover, there was no significant difference between groups in average body weight of offspring at adulthood. Histological analysis indicated a thicker placenta in the ER group, attributable to the fetal part of the placenta, potentially indicating compensatory mechanisms. Our findings reflect a successful transuterine embryo relocation followed by vaginal birth and survival of offspring to adulthood, in a rat model. Such findings lay the foundation for future preclinical research in higher animals, with potential implications on a procedure relevant to human ectopic embryo relocation.

Placental gene therapy in nonhuman primates: a pilot study of maternal, placental, and fetal response to non-viral, polymeric nanoparticle delivery of IGF1.

Currently, there are no placenta-targeted treatments to alter the in utero environment for administration to pregnant women who receive a diagnosis of fetal growth restriction (FGR). Water-soluble polymers have a distinguished record of clinical relevance outside of pregnancy. We have demonstrated the effective delivery of polymer-based nanoparticles containing a non-viral human insulin-like growth factor 1 (IGF1) transgene to correct placental insufficiency in small animal models of FGR. Our goals were to extend these studies to a proof-of-concept study in the pregnant macaque, establish feasibility of nanoparticle-mediated gene therapy delivery to trophoblasts, and investigate the acute maternal, placental, and fetal responses to treatment. Pregnant macaques underwent ultrasound-guided intraplacental injections of nanoparticles (GFP- or IGF1-expressing plasmid under the control of the trophoblast-specific PLAC1 promoter complexed with a HPMA-DMEAMA co-polymer) at approximately gestational day 100 (term = 165 days). Fetectomy was performed 24 h (GFP; n = 1), 48 h (IGF1; n = 3) or 10 days (IGF1; n = 3) after nanoparticle delivery. Routine pathological assessment was performed on biopsied maternal tissues and placental and fetal tissues. Maternal blood was analyzed for complete blood count (CBC), immunomodulatory proteins and growth factors, progesterone (P4), and estradiol (E2). Placental ERK/AKT/mTOR signaling was assessed using Western blot and qPCR. Fluorescent microscopy and in situ hybridization confirmed placental uptake and transient transgene expression in villous syncytiotrophoblast. No off-target expression was observed in either maternal or fetal tissues. Histopathological assessment of the placenta recorded observations not necessarily related to the IGF1 nanoparticle treatment. In maternal blood, CBCs, P4, and E2 remained within the normal range for pregnant macaques across the treatment period. Changes to placental ERK and AKT signaling at 48 h and 10 days after IGF1 nanoparticle treatment indicated an upregulation in placental homeostatic mechanisms to prevent overactivity in the normal pregnancy environment. The lack of adverse maternal reaction to nanoparticle-mediated IGF1 treatment, combined with changes in placental signaling to maintain homeostasis, indicates no deleterious impact of treatment during the acute phase of study.

β3-adrenergic agonist counters oxidative stress and Na+-K+ pump inhibitory S-glutathionylation of placental cells: Implications for preeclampsia.

Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na+-K+ pump inhibition and S-glutathionylation of its β1 subunit (GSS-β1), a modification that inhibits the pump. β3-adrenergic receptor (β3-AR) agonists can reverse GSS-β1. We examined effects of the agonist CL316,243 on GSS-β1 and sources of H/R-induced oxidative stress in immortalized first trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal term pregnancies. H/R increased GSS-β1 and, reflecting compromised α1/β1 subunit interaction, it reduced α1/β1 pump subunit co-immunoprecipitation. H/R increased p47phox/p22phox NADPH oxidase subunit co-immunoprecipitation reflecting membrane translocation of cytosolic p47phox that is needed to activate NADPH oxidase. Fluorescence of O2•--sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples NO synthesis towards synthesis of O2•- and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α (TNF-α) increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-β1 and decreases of α1/β1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release and restored trophoblast integration in endothelial cell networks. H/R induced GSS-β1, α1/β1 subunit co-immunoprecipitation and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a β3-AR agonist counters key pathophysiological features of preeclampsia in vitro. β3 agonists already in human use for another purpose are potential candidates for re-purposing to treat preeclampsia.

Complications in equine transvaginal ultrasound‒guided follicular aspiration

Transvaginal ultrasound-guided follicular aspiration has revolutionised equine assisted reproduction, particularly in in vitro embryo production. This literature review examines the complications associated with transvaginal ultrasound-guided follicular aspiration in mares and its potential impact on future fertility. While transvaginal ultrasound-guided follicular aspiration is generally safe, it has inherent risks, ranging from mild rectal bleeding to severe complications such as peritonitis and acute haemorrhage. Factors influencing complication rates include veterinarian experience, mare anatomy and procedural technique. Despite concerns, studies suggest that repeated transvaginal ultrasound-guided follicular aspiration does not significantly impair future fertility, with normal pregnancy rates observed in mares undergoing artificial insemination or embryo transfer after transvaginal ultrasound-guided follicular aspiration. However, further research is needed to fully understand the long-term effects on ovarian function and oocyte quality. Veterinary practitioners must prioritise appropriate training and procedural precautions to minimise the risk of complications and safeguard mare welfare and fertility in the expanding field of equine assisted reproduction.

Electrokinetic indices of erythrocytes as diagnostic criteria for preeclampsia

Objective. To evaluate the features of changes in the morphofunctional status of peripheral blood erythrocytes during normal pregnancy and in preeclampsia based on rapid analysis of biophysical parameters of cells.Materials and methods. A total of 136 pregnant women were examined at 22–24 and 34–35 weeks of gestation. The comparison groups included: 40 pregnant women with moderate preeclampsia (PE), 30 pregnant women with severe preeclampsia, 30 pregnant women with chronic arterial hypertension (CAH), 36 women with normal pregnancy who do not have signs of hypertensive disorders. Electrokinetic features of peripheral blood erythrocytes were studied using cellular microelectrophoresis, the average value of the amplitude of oscillations of mobile erythrocytes (μm) and the proportion of mobile cells (%) were analyzed.Results. At 22–24 weeks, the percentage of immobile erythrocytes in pregnant women with moderate PE increased by 2.8 times (p&lt;0.05), the amplitude of oscillations of mobile cells decreased by 21% (p&lt;0.05). In pregnant women with severe PE, the proportion of immobile erythrocytes increased by 3.2 times (p&lt;0.05), the amplitude decreased by 30% (p&lt;0.05). In pregnant women with CAH, a slight increase in the percentage of immobile cells (8.2 vs 6.8%) and a tendency to a decrease in the average amplitude (21.5 vs 23.2 μm) were noted. At 34–35 weeks in the group with moderate PE, the% of immobile erythrocytes exceeded the corresponding indicator in women with physiological pregnancy by 3.3 times (p&lt;0.05), the average amplitude decreased by 28% (p&lt;0.05), in pregnant women with severe PE, the% of immobile erythrocytes increased by 3.7 times (p&lt;0.05), the amplitude decreased by 36% (p&lt;0.05). In pregnant women with CAH, there was a tendency for a slight increase in the proportion of immobile erythrocytes.Conclusion. The functional and morphological usefulness of erythrocytes as active participants in the pathogenesis of preeclampsia can be objectively assessed using indicators of electrokinetic activity of cells, and erythrocytes can be considered as biomarkers of the disease and a promising tool for stratifying patients for early detection of high-risk pregnancies.

Gestational Diabetes Mellitus and Subsequent Risks of Diabetes and Cardiovascular Diseases: the Life Course Perspective and Implications of Racial Disparities.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research. Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.

Periovulatory PM2.5 constituent exposures and human clinically recognized early pregnancy loss: Susceptible exposure time windows and high–risk constituents

Evidence for effects of PM2.5 chemical constituent exposures during the periovulatory period on pregnancy complications was limited. We explored the associations of maternal PM2.5 and constituent exposures from the 12th week before to 4th week after ovulation with human clinically recognized early pregnancy loss (CREPL). From July 2017 to January 2024, 828 CREPL and 828 normal early pregnancy (NEP) participants were recruited in Tianjin, China. Daily residential exposures to PM2.5 and five main constituents of all participants were estimated using data of the Tracking Air Pollution in China platform. Nonlinear and linear associations between weekly pollutant exposures and CREPL were estimated using conditional logistic regression models combined with distributed lag nonlinear and distributed lag models, respectively. The risk of CREPL increased with per 10 μg/m³ increment in PM2.5 and per 1 μg/m³ increment in sulfate, nitrate, and ammonium exposures during specific weeks from the 5th week before to 2nd week after ovulation, with the largest OR (95% CI) of CREPL associated with PM2.5, sulfate, nitrate, and ammonium being 1.73 (1.07, 2.78), 1.71 (1.18, 2.46), 1.80 (1.12, 2.90), and 1.61 (1.01, 2.56), respectively. CREPL was positively associated with the 10th to 90th percentiles exposure to organic matter during the 2nd and 3rd week after ovulation. In analyses for constituent residuals, the five constituents were all independently related to CREPL, with organic matter being the highest risk constituent, and nitrate and ammonium affecting at the initial stage of preantral follicle development. In conclusion, periovulatory PM2.5 and constituent exposures were associated with increased risk of CREPL. Women planning a pregnancy are advised to take exposure precautions starting from the follicular development period.

CHORIOCARCINOME GESTATIONNEL DECOUVERT A J46 DUN ACCOUCHEMENT NORMAL

The choriocarcinoma is a rare and aggressive tumor that can grow quickly and spread easily to other parts of the body, sometimes occurring after spontaneous or elective abortion, tubal pregnancy or, more rarely, normal pregnancy. In our case, we reported abnormal uterine bleeding following vaginal delivery at day46. The post-partum period was unremarkable, and the diagnosis of gestational choriocarcinoma was evoked and retained in view of the clinical, biological and radiological picture, management was multidisciplinary and timely, and the prognosis was favorable.

Association of 25(OH)-Vitamin D3 Serum Concentrations and Vitamin D Receptor Gene Variants with the Risk of Idiopathic Spontaneous Preterm Birth in the Croatian Population.

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed.

Normal values and distribution of ventricular global longitudinal strain in 513 healthy fetuses measured by two-dimensional speckle-tracking echocardiography: a multi-institutional cohort study.

This study aimed to determine the normal reference values and distribution of global longitudinal strain (GLS) in the right and left ventricles of healthy Japanese fetuses during pregnancy. This multi-institutional cohort study included healthy Japanese fetuses during normal pregnancies without maternal or fetal complications between 18 and 40weeks of gestation. Two-dimensional fetal echocardiographic images of the four-chamber view with a high frame rate were acquired and stored as DICOM clips. Data were collected and analyzed in a central laboratory to measure the left ventricular (LV) and right ventricular (RV) GLS using two-dimensional speckle tracking. In total, 513 fetuses were enrolled. The mean LV-GLS and RV-GLS were - 24.3% ± 3.5% and - 23.5% ± 3.7%, respectively. The magnitude of the GLS, with normal limits in both ventricles, decreased with advancing gestation. LV values were r = 0.34 (95% confidence interval, 0.27-0.42) and p < 0.0001; RV values were r = 0.33 (95% confidence interval, 0.25-0.41) and p < 0.0001. The normal values of healthy Japanese fetuses in healthy pregnancies is the first to be established by the large-scale, multi-institutional cohort study as LV-GLS of 24.3% ± 3.5% and RV-GLS of - 23.5% ± 3.7%, respectively. This can serve as a basic reference for assessing the cardiac functions in Japanese fetuses with various heart diseases.

Trace elements exposure affects the outcomes of in vitro fertilization embryo transfer, a cohort study in Northern China.

With urbanization and industrialization process accelerated, humans are exposed more and more trace elements. This study aimed to explore the potential associations of trace elements with the outcomes of in vitro fertilization embryo transfer (IVF-ET). Total 181 women who underwent IVF-ET were enrolled, among which 89 women underwent fresh ET after IVF. Trace elements were measured in the serum and follicular fluid (FF) samples by inductively coupled plasma-mass spectroscopy. The associations of the levels of different trace elements with IVF-ET outcomes, including normal fertilization, high-quality embryos, and clinical pregnancy (fresh ET) were analyzed. Twenty-five out of twenty-eight trace elements showed higher concentrations in the serum than those in the FF. Normal fertilization was positively associated with Cu and Mn in the FF. High-quality embryos was positively associated with Cu in the serum and FF, and Zn in the serum. Clinical pregnancy was positively associated with Ge in the serum, and inversely associated with Al, Ba, and Pb in the serum. Additionally, poor outcomes of IVF-ET should be noticed in women with FF level of Cu < 955.38ng/mL, FF level of Mn < 3.42ng/mL, serum level of Ge < 6.11ng/mL, serum level of Al > 28.44ng/mL, and serum level of Pb > 0.90ng/mL. IVF-ET outcomes were positively associated with Cu, Mn, Zn, and Ge, and inversely associated with Al and Pb. Properly controlling the exposure of relevant trace elements is necessary for patients with the need of IVF-ET.

Cytokine balance in pregnant women with preeclampsia

Studies were conducted to study the levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory (IL-4) cytokines in the blood serum of pregnant women at different stages of gestation: 18-20, 28-30, and 33- 38 weeks. The study involved 76 patients at risk of developing preeclampsia. Of these, 34 women developed preeclampsia, making up the main group, and 42 pregnant women had no symptoms of preeclampsia and made up the comparison group. The control group consisted of 28 somatically healthy women with a physiologically normal pregnancy. The average age of the examined patients with preeclampsia was 26.2±4.3 years, and in the group of pregnant women with normal pregnancy it was 25.8±4.7 years. The purpose of the study was to study the levels of cytokines IL-4, IL-6, IL-17A, and IL-18 in women with uncomplicated pregnancy and preeclampsia. These cytokines play an important role in the immune response and may be associated with the development of preeclampsia. The results of the study may help further understand the mechanisms of the disease and develop strategies for its prevention and management. The levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10) were studied in blood serum by ELISA using test systems of Vector-best JSC (Novosibirsk, Russia) in accordance with the manufacturer’s recommendations. Statistical processing of research results was carried out using variation statistics methods. The results are presented as the sample mean (M) and standard error (m). The significance of the differences in the mean values (P) of the compared indicators was assessed using the Student t test (t). A study conducted by the authors found the following patterns in interleukin (IL) levels in pregnant women at risk of developing preeclampsia (PE). The levels of IL-6, IL-17A, and IL-18 were significantly increased in pregnant women with PE. There was a tendency to decrease the levels of IL-4, and IL-10 in women at risk of developing preeclampsia. These findings may help guide further research and development of strategies to prevent and manage preeclampsia in pregnant women.

Endothelin-1 potentiated constriction in preeclampsia placental veins: Role of ETAR/ETBR/CaV1.2/CALD1

BackgroundPlacenta plays a vital role in preeclampsia. The present study investigated the role of endothelin-1 (ET-1) and its receptors in preeclampsia placenta. MethodPlacenta samples were collected from normal and preeclampsia pregnancies, with one single fetus. Placental chorionic plate vessel tone was measured with DMT using vasoactive agents with or without antagonists. Role of L-type voltage-dependent calcium channels (CaV1.2) in single smooth muscle cell was detected using whole-cell patch clamp. PCR, Western blot, and ELISA was used to detect molecule expressions. Placental vessel explants and human umbilical vein smooth muscle cell (HUVSMC) were exposed to ET-1 treatment with or without antagonists. Human umbilical vein endothelial cell (HUVEC) and pregnant sheep was exposed to hypoxic condition, simulating preeclampsia. ResultsET-1 and IRL1620 mediated stronger contractions in preeclampsia placental veins, despite unchanged ETAR and decreased ETBR expression. Comparing with control, there was higher ET-1 in umbilical plasma, maternal plasma, and placental vessels from preeclampsia. In utero hypoxia increased plasma ET-1 in fetal lambs and ewes. Hypoxia promoted ET-1 production in HUVEC. Role and expression of CaV1.2 was decreased in preeclampsia placental vessels, while high-molecular-weight caldesmon (CALD1), the marker of contractile phenotype of smooth muscle cells, was significantly increased. ET-1 treatment increased CALD1 in placental explants and in HUVSMC via ETAR/ETBR. ConclusionThe present study firstly demonstrated ET-1 induced greater contraction in preeclampsia placental chorionic plate veins via ETAR/ETBR, instead of via weaker CaV1.2. In utero hypoxia promoted plasma ET-1 in fetal lambs and ewe, similar to that in preeclampsia. ET-1, binding with ETAR/ETBR increased CALD1, which was associated with stronger contraction in preeclampsia. The data provided important information in preeclampsia onset.