Normal Pregnancy Research Articles

Evidence of kidney injury in preeclampsia: Increased maternal and urinary levels of NGAL and KIM-1 and their enhanced expression in proximal tubule epithelial cells.

Proteinuria and glomerular endotheliosis are characteristics of glomerular injury in preeclampsia, a hypertensive disorder in human pregnancy. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are biomarkers of acute/chronic renal tubule injury. To determine if tubule injury occurs in preeclampsia, we determined maternal plasma and urine NGAL and KIM-1 levels and evaluated NGAL and KIM-1 expression in kidney biopsy specimens from women with preeclampsia. Prenatal and postpartum maternal blood and urinary samples were collected from three groups of pregnant women: normal pregnancy (n = 100), preeclampsia (n = 83), and pregnancy complicated with chronic hypertension (n = 20). Plasma and urine levels of NGAL and KIM-1 were measured by ELISA. Kidney biopsy tissue sections from patients with preeclampsia (n = 5) were obtained from Pathology Archives and processed to determine NGAL and KIM-1 expression by immunostaining and high kidney solution images were assessed by electron microscopy (EM). Prenatal plasma and urine levels of NGAL and KIM-1 were significantly higher in preeclamptic than in normal controls, p < 0.01. In normal pregnancy, both plasma and urine levels of NGAL and KIM-1 at 24-48 h after delivery and 6-8 weeks postpartum were relatively comparable to that of antenatal levels. In preeclampsia, urine, but not plasma, NGAL levels were reduced at 6-8 weeks postpartum compared to the antenatal levels, p < 0.05. Although maternal and urine KIM-1 levels were reduced at 6-8 weeks postpartum compared to the antenatal levels in preeclampsia, the levels were still higher than those in normal pregnancy. Positive expression of NGAL and KIM-1 was detected in proximal tubule epithelial cells in kidney tissue specimens from preeclampsia but not in non-pregnancy controls. EM examination showed glomerular and tubular injury in preeclampsia. Our findings of increased maternal levels and urine secretion of NGAL and KIM-1, along with the upregulation of NGAL and KIM-1 expression in tubular epithelial cells in preeclampsia, provide plausible evidence that tubular injury exists in preeclampsia. The higher postpartum NGAL and KIM-1 levels in preeclamptic pregnancies indicate that tubular injury would not resolve within 2-3 months after delivery and suggest that proper follow-up and management of kidney function in women with preeclampsia would be necessary to reduce chronic kidney diseases in those women later in life.

Diagnostic potential of microRNAs Mi 517 and Mi 526 as biomarkers in the detection of hypertension and preeclampsia in the first trimester.

MicroRNAs have been observed to play a major role in various physiological processes, for instance, programmed cell death, cell division, pregnancy development, and proliferation. With the help of profiling of microRNAs in the serum of pregnant women, it is possible to link alterations in their concentration to the emergence of gestational problems. The aim of the study was to evaluate the diagnostic potential of MicroRNAs Mi 517 and Mi 526 as biomarkers in the detection of hypertension and preeclampsia. The study considered 53 patients who are in their first trimester of a singleton pregnancy. Participants have been divided into two study groups, one group with normal pregnancy and another group having the risk of developing preeclampsia or who developed hypertension or preeclampsia during follow-up constitute the study group. In order to collect data associated with circulating miRNAs in serum, blood samples have been collected from the participants of the study. Based on the univariate regression model, increased expression of Mi 517 and 526 and parity status (primapara/multipara) has been obtained. The multivariate logistic analysis shows that independent risk factors for hypertension or preeclampsia are the presence of an R527 and being a primipara. The study's findings have revealed that R517s and R526s act as major indicative biomarkers in the first trimester for the detection of hypertension and preeclampsia. The circulating C19MC MicroRNA was examined as a potential early indicator of preeclampsia and hypertension in pregnant individuals.

Organic Aciduria Disorders in Pregnancy: An Overview of Metabolic Considerations.

Organic acidurias are a heterogeneous group of rare inherited metabolic disorders (IMDs) caused by a deficiency of an enzyme or a transport protein involved in the intermediary metabolic pathways. These enzymatic defects lead to an accumulation of organic acids in different tissues and their subsequent excretion in urine. Organic acidurias include maple syrup urine disease, propionic aciduria, methylmalonic aciduria, isovaleric aciduria, and glutaric aciduria type 1. Clinical features vary between different organic acid disorders and may present with severe complications. An increasing number of women with rare IMDs are reporting successful pregnancy outcomes. Normal pregnancy causes profound anatomical, biochemical and physiological changes. Significant changes in metabolism and nutritional requirements take place during different stages of pregnancy in IMDs. Foetal demands increase with the progression of pregnancy, representing a challenging biological stressor in patients with organic acidurias as well as catabolic states post-delivery. In this work, we present an overview of metabolic considerations for pregnancy in patients with organic acidurias.

Ayurveda management of primary infertility associated with hypothyroidism and hyperprolactinemia: A case report

Abstract: Hypothyroidism and hyperprolactinemia adversely affect the fertility potential of women by impairing ovulatory function. There is a high prevalence of hypothyroid-associated hyperprolactinemia in infertility. Long-standing hypothyroidism promotes hyperprolactinemia which leads to irregular periods, and anovulation and ultimately results in infertility. This is a case report of the primary infertility of a couple married for seven years. The female partner had anovulatory cycles with elevated levels of Thyroid-Stimulating Hormone (TSH) and prolactin. Ayurveda treatment was planned in this case to evaluate its role to address hormonal imbalance, ensuring regular ovulation, and thereby helping to have a normal pregnancy. Based on the parameters of Ayurvedic Science, this case was diagnosed as Vandhyatva (~infertility), which was treated with both internal medicines and external therapies including Shodhana (~bio cleansing therapy) and Shamana chikitsa (~therapy which is aimed at mitigating the disease by pacifying Dosha). After the treatment, TSH was reduced from 14.99 to 4.0 μIU/mL and the prolactin level was reduced from 47.23 to 13 ng/mL. The intervention resulted in conception within three months, and she delivered a full-term female baby.

Use of rhPTH(1-84) for hypoparathyroidism during early pregnancy and lactation.

We present the first report of use of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) in a hypoparathyroid patient during early pregnancy and lactation. The patient developed postoperative hypoparathyroidism as a 28-year-old woman following total thyroidectomy for multinodular goiter. She was not well controlled with conventional therapy, and started rhPTH(1-84) in 2015 following its approval in the United States. She became pregnant in 2018 at age 40. She discontinued rhPTH(1-84) therapy at 5 weeks gestation but resumed in the postpartum period while breastfeeding. Her daughter's serum calcium was borderline elevated at 8 days postpartum but within the normal range at 8 weeks postpartum. The patient stopped nursing at around 6 months postpartum. Her daughter is now at 4 years and 5 months of age and is healthy and meeting developmental milestones. She was again pregnant at 8 months postpartum from her first pregnancy, and she made an informed decision to continue parathyroid hormone. At 15 weeks gestation, rhPTH(1-84) was recalled in the United States due to issues with the delivery device, and she discontinued rhPTH(1-84) treatment and resumed calcium and calcitriol supplements. She gave birth to a baby boy at 39 weeks in January 2020. At 3 years and 2 months of age, he is overall healthy. Further data are needed regarding the safety of rhPTH(1-84) in pregnancy and lactation. rhPTH(1-84) is approved for therapy of patients with hypoparathyroidism; however, there are no data regarding the safety of treatment during nursing and pregnancy. There are multiple alterations in mineral metabolism during normal pregnancy and lactation.

29. Measures of Arterial Stiffness and Subclinical Large Vessel Atherosclerosis After Preeclampsia: A Pooled Study-Level Meta-Analysis

Background: Preeclampsia has been suggested as the risk of subsequent cardiovascular disease, specifically sustained vascular dysfunction after delivery. Several vascular imaging modalities have been studied in the post-partum period. However, it remains unclear whether some degree of vascular dysfunction in form of increasing arterial stiffness and large vessel atherosclerosis persists in women after preeclampsia. Objective: This study aims to summarize evidence of increasing arterial stiffness and subclinical large vessel atherosclerosis after preeclampsia. Methods: A search for eligible studies was conducted until April 2022 on PubMed, ScienceDirect, Cochrane Library databases. Included studies were observational, with the preeclampsia as the main exposure, assessed at least 3 months post-partum. Arterial stifness and subclinical large vessel atherosclerosis are measured by augmentation index (AIx), carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) respectively. Review Manager (RevMan) 5.4 was utilized to compute mean differences (MD) and confidence intervals (CI). Results: We identified 22 studies that involve 1,954 patients. There was evidence of increasing arterial stiffness in women after preeclampsia compared with women with normal pregnancy when measured by AIx [MD 6.52% (95% CI 2.76, 10.28; p = 0.0007; I2 = 0.81)] and cfPWV [MD 0.64 m/s (95% CI 0.17, 1.11; p = 0.007; I2 = 0.81)]. Subclinical large vessel atherosclerosis via cIMT were more frequent in women after preeclampsia [MD 0.02 mm (95% CI 0.01, 0.04; p = 0.0007; I2 = 0.48)]. Conclusion: Pooled data from studies evaluating vascular imaging suggest that some vascular dysfunction in form of increasing arterial stiffness and subclinical large vessel atherosclerosis persists after preeclampsia as compared with women with prior normal pregnancy.

Risk Factors for Maternal Near Miss in Gaza Strip: A Case-Control Study

Background: Maternal near miss refers to pregnant women with severe life-threatening conditions who nearly die but, with good luck or good care, survive. This study aimed to determine the risk factors for maternal near-miss in Gaza Strip. Methods: A case-control study was used and 486 women who gave birth in 2020 were involved. The case group consisted of 243 identified near-miss cases, and the control group consisted of 243 women who had normal pregnancies and deliveries. The Maternal Near Miss Identification Checklist of the WHO Technical Working Group (2007) was used to collect data. Results: The total number of deliveries was 34,974, and the number of identified near-miss cases was 243, with a rate of 6.9/1000 delivery. The results showed that 70.8% of cases had severe hemorrhage, and 16% had hypertensive disorders at admission. Significant (p ˂0.05) risk factors associated with near miss included preterm labor ≤ 36 weeks [OR 25.081, 95% CI (7.736 – 81.315)], previous obstetric problems [OR 5.144, 95% CI (2.090 – 12.663)], previous cesarean section [OR 3.661, 95% CI (1.726 – 7.610)], history of abortion [OR 3.348, 95% CI (1.697 – 6.606)], previous medical problems [OR 2.317, 95% CI (1.490 – 3.603)], and prim parity [OR 1.770, 95% CI (1.071 – 2.923),]. Conclusion: The study concluded that more efforts are needed to improve maternal health services in Gaza and emphasized the imperative need to train obstetricians and midwives on emergency obstetric management.

Tert-butylhydroquinone Mitigates Renal Dysfunction in Pregnant Diabetic Rats via Attenuation of Oxidative Stress and Modulation of the iNOs/ NFkB/TNF Alpha Signalling Pathway.

The aim of the study was to determine the effect of tert-butylhydroquinone (tBHQ) supplementation on some biochemical parameters in pregnant diabetic rats and the foetus. The global incidence of gestational diabetes mellitus (GDM) has been on the increase despite current interventional therapies, underscoring the need for alternative or complementary therapeutic approaches. The objective is to determine the effect of tBHQ on blood glucose, insulin resistance, body weight, relative liver and kidney weights, serum lipid profile (total cholesterol, triacylglycerol, high-density lipoprotein cholesterol and very low-density lipoprotein cholesterol), liver function (albumin, aspartate and alanine amino transaminases) and kidney function markers (urea, creatinine and uric acid) in the sera, and study maternal and foetal renal levels of oxidative stress and inflammatory markers, foetal weights and histology of the kidney of streptozotocin (STZ)-induced GDM in rats. Twenty female pregnant rats were used, and they were divided into four groups of control (normal pregnancy), disease (diabetic untreated), metformin (received 200 mg/kg metformin dissolved in distilled water) and tBHQ groups (received 25 mg/kg tBHQ in 1% corn oil), respectively, with five rats in each group. GDM was induced in the disease and treated groups by intraperitoneal injection of STZ (45 mg/kg in sodium citrate buffer, pH 4.5). STZ induction in the disease group significantly increased their blood glucose levels (P<0.05), altered their body and foetal weights, relative liver and kidney weights, serum lipid profile, liver and kidney function markers in the sera (relative to the control), inducing oxidative stress and inflammation to the maternal and foetal kidneys and altering the maternal kidney histology, which was found to be improved following supplementation with tBHQ in a manner akin to or even better than metformin. tBHQ was found beneficial in protecting the foetal kidneys against oxidative stress and the foetus against mortality arising from maternal hyperglycaemia. Finally, the study showed the potential of tBHQ in mitigating histological changes in the maternal kidney arising from STZinduced hyperglycemia in rats.

Low-Grade Inflammation in Gestational Diabetes Mellitus and Its Correlation with Maternal Insulin Resistance and Fetal Growth Indices.

Chronic low-grade inflammation (LGI) plays a role in the pathogenesis of gestational diabetes mellitus (GDM). LGI, on the one hand, promotes insulin resistance and at the same time, affects fetal development. The study aimed to use clinically feasible means to evaluate the association between maternal LGI and maternal insulin resistance and fetal growth indices by ultrasound in the third trimester. A crossectional and descriptive study on 248 first-time diagnosed GDM in Vietnam. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) indices were significantly higher in GDM than in normal glucose-tolerant pregnancies (p = 0.048 and 0.016, respectively). GDM with LGI witnessed significantly higher systolic blood pressure, BMI, HbA1c, and significantly lower quantitative Insulin Sensitivity Check Index (QUICKI) than those without LGI. After adjusting for maternal BMI, fasting plasma glucose (FPG), age, and parity, C-reactive protein (CRP) was positively correlated with HOMA2-IR (B=0.13, p<0.01) and Mathews index (B=0.29, p<0.01). Regarding fetal characteristics, LGI was associated with fetal growth indices in the third trimester of GDM. NLR was negatively correlated with estimated fetal weight (EFW) (B=-64.4, p<0.05) after adjusting for maternal BMI and FPG. After adjusting for maternal BMI, FPG, age, and parity, PLR was negatively correlated with biparietal diameter (B=-0.02, p<0.01) and abdominal circumference (AC) (B=-0.16, p<0.05), and EFW (B=-1.1, p<0.01), and head circumference (HC) (B=-0.06, p<0.01); CRP was negatively correlated with AC (B=-0.16, p<0.001), EFW (B=-85.3, p<0.001), and HC (B=-5.0, p<0.001). In the third trimester, LGI was associated with maternal glucose and insulin resistance in GDM. Moreover, LGI was associated with fetal characteristics in ultrasonic images. There were negative correlations between LGI and fetal developmental characteristics.

Low-dose Aspirin may Prevent Preeclampsia by Inhibiting the Expression of ATF2.

To explore the ATF2 expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients. Preeclampsia is a severe pregnancy-related hypertension disorder and refers to hypertension. This study was designed to explore the activating transcription factor 2 (ATF2) expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients. Firstly, we collected the plasma of normal and preeclampsia pregnancies and quantified the expressions of ATF2 by ELISA. Then we quantified the expression of the three downstream target genes of ATF2 (IL-8, IL-6 and MMP-2). Finally, we collected and quantified the interventional and observational group plasma. All data were compared by t-test (p<0.05). ATF2 and its target genes (IL-6, IL-8 and MMP-2) were upregulated in preeclampsia patients. In addition, ATF2 and its target genes were downregulated in the interventional group (LDA-treated group). Our results indicated that LDA could inhibit ATF2 expression in preeclampsia. It suggests that ATF2 may be a potential target of LDA in the prevention of preeclampsia.

Circulatory and Placental Expression of Soluble Fms-like Tyrosine Kinase- 1 and Placental Growth Factor in HIV-infected Preeclampsia.

An imbalance between angiogenic and anti-angiogenic factors plays a fundamental role in the pathogenesis of preeclampsia (PE). Studies have shown a dysregulation of sFlt-1 and placental growth factor (PlGF) in PE. However, there are differing reports on the levels of these pro-/antiangiogenic factors in HIV-infected preeclamptic and normotensive pregnancies, possibly due to highly active antiretroviral therapy (HAART) and its immune reconstitution effect. The study aimed to investigate the effect of hypertension and ARVs on circulating and placental pro- and antiangiogenic factors in HIV-infected PE. The level of sFlt-1 expression is elevated in PE compared to normal pregnancies. PlGF was altered by placental dysfunction. Antiretroviral therapy does not impact the angiogenic shift in PE development. The angiogenic imbalance evident in the circulatory system by higher sFlt-1 compared to PlGF levels is replicated in the placenta by reduced expression of PlGF receptors in comparison to sFlt-1 receptors. However, there is a lack of data that explore the relationship between HAART and anti-angiogenic factors in the placenta and the circulation of PE comorbid with HIV infection.

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Fetal kidney measurement - additional biometric parameter for accurate gestational age assessment.

Ultrasound examination - recommended in the prenatal period - allows for an assessment of fetal anatomy and well-being and for monitoring its growth trend. Determining gestational age is important in monitoring the developing fetus. Research is increasingly being conducted in search of further biometric components that may improve ultrasound techniques in terms of predicting the gestational age. It should be noted that a fairly large number of publications focus on the accessibility of fetal kidneys to diagnostic imaging during routine ultrasound examination. The reported study was an attempt to answer the question whether fetal kidney dimensions correlated with gestational age. The obtained results are presented as fetal kidney normograms for particular weeks of gestation. The study covered by dissertation was conducted among patients hospitalized at the Provincial Specialist Hospital in Zgierz, Department of Gynecology, Obstetrics and Endoscopic Therapy, in the period from 1st April 2019 to 30th November 2019. The study group included patients in a single pregnancy. The control group was not included in the study. The ultrasound examinations, which are the basis of the study, were carried out using the PHILIPS Affiniti 70 ultrasound device, with a frequency of 3.5 MHz transabdominal transducer. All data were subjected to statistical analysis using the Statistica 13.1 program. Kidney dimensions strongly correlated with gestational age. Fetal kidney growth was a linear process in normal pregnancy. Fetal kidney measurements can provide additional biometric parameters for accurate gestational age assessment.

A biomarker for bacteremia in pregnant women with acute pyelonephritis: soluble suppressor of tumorigenicity 2 or sST2

Objective Sepsis is a leading cause of maternal death, and its diagnosis during the golden hour is critical to improve survival. Acute pyelonephritis in pregnancy is a risk factor for obstetrical and medical complications, and it is a major cause of sepsis, as bacteremia complicates 15–20% of pyelonephritis episodes in pregnancy. The diagnosis of bacteremia currently relies on blood cultures, whereas a rapid test could allow timely management and improved outcomes. Soluble suppression of tumorigenicity 2 (sST2) was previously proposed as a biomarker for sepsis in non-pregnant adults and children. This study was designed to determine whether maternal plasma concentrations of sST2 in pregnant patients with pyelonephritis can help to identify those at risk for bacteremia. Study design This cross-sectional study included women with normal pregnancy (n = 131) and pregnant women with acute pyelonephritis (n = 36). Acute pyelonephritis was diagnosed based on a combination of clinical findings and a positive urine culture. Patients were further classified according to the results of blood cultures into those with and without bacteremia. Plasma concentrations of sST2 were determined by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results The maternal plasma sST2 concentration increased with gestational age in normal pregnancies. Pregnant patients with acute pyelonephritis had a higher median (interquartile range) plasma sST2 concentration than those with a normal pregnancy [85 (47–239) ng/mL vs. 31 (14–52) ng/mL, p < .001]. Among patients with pyelonephritis, those with a positive blood culture had a median plasma concentration of sST2 higher than that of patients with a negative blood culture [258 (IQR: 75–305) ng/mL vs. 83 (IQR: 46–153) ng/mL; p = .03]. An elevated plasma concentration of sST2 ≥ 215 ng/mL had a sensitivity of 73% and a specificity of 95% (area under the receiver operating characteristic curve, 0.74; p = .003) with a positive likelihood ratio of 13.8 and a negative likelihood ratio of 0.3 for the identification of patients who had a positive blood culture. Conclusion sST2 is a candidate biomarker to identify bacteremia in pregnant women with pyelonephritis. Rapid identification of these patients may optimize patient care.

Relationship Between Serum microRNA-372-3p and Glucose Transporter 4 Levels and Insulin Resistance in Gestational Diabetes Mellitus

Objective: To observe the changes in insulin resistance in patients with gestational diabetes mellitus (GDM) based on the detection of serum microRNA-372-3p and glucose transporter protein 4 (GLUT4) levels. Methods: We conducted a retrospective cohort study of 42 patients who were diagnosed with GDM and hospitalized in our hospital during the period from January 2017 to December 2021 and another 42 patients who had normal pregnancy during the same period by collecting their clinical data. We analyzed their serum microRNA expression profiles and miR-372-3p levels to study the relationship between GDM and insulin resistance. Results: The relative expression of miR-372-3p in the serum of patients in the GDM group was significantly higher than that of patients in the control group, but the GLUT 4 level of the GDM group was significantly lower than that of the control group (P &lt; 0.05). Compared with the control group, the GDM group had significantly higher levels of fasting blood glucose (FBG), fasting insulin (FINS), 2-hour postprandial blood glucose (2h-BG), total cholesterol (TC), triglyceride (TG), and homeostatic model assessment for insulin resistance (HOMA-IR) index but significantly lower homeostasis model assessment of ?-cell function (HOMA-?) index (P &lt; 0.05). The relative expression of miR-372-3p in serum was independently and positively correlated with HOMA-IR, while the level of GLUT4 was independently and negatively correlated with HOMA-IR (P &lt; 0.05). Conclusion: Glycosylated hemoglobin test in the early stages of pregnancy (12–13 weeks of gestation) is important to ensure the health of pregnant women and fetuses. The screening and intervention for elevated glucose in pregnant women act as a guideline for the treatment of GDM. Patients with insulin resistance and related complications such as hyperinsulinemia and hypoglycemia should be given priority.

Expression of the serotonergic system components in the placenta in various types of preeclampsia

BACKGROUND: The serotonergic system plays an important role in the formation and development of the feto-placental complex. The study of the expression of the serotonin system components, including placental 5-HT2A (serotonin receptor) and SERT (serotonin transporter), in preeclampsia will create prerequisites for discovering new ways to correct hypertensive pregnancy complications and methods of influencing pregnancy outcomes.&#x0D; AIM: The aim of this study was to compare the expressions of 5-HT2A and SERT in placental tissue in pure preeclampsia and its combinations with other complications of pregnancy.&#x0D; MATERIALS AND METHODS: A comparative cohort study was conducted among patients with different preeclampsia phenotypes: preeclampsia (n = 6), preeclampsia and gestational diabetes mellitus (n = 6), gestational diabetes mellitus and superimposed preeclampsia (preeclampsia + chronic arterial hypertension) (n = 6), and normal pregnancy without pregnancy complications (n = 6). The expression of 5-HT2A (Abcam, USA) and SERT (BiossAntibodies, USA) was studied in placenta samples from all study groups by immunohistochemical method. Morphometric analysis was performed using the VideoTest-Morphology 5.2 program (Videotest Ltd., Russia). The database was constructed and statistical processing was performed using Microsoft Excel 2007 (Microsoft Corporation, USA) and the StatTech program v. 2.6.4 (Stattech Ltd., Russia).&#x0D; RESULTS: The expression of SERT and 5-HT2A is higher in the studied pregnancy complications when compared to the normal one. The relative 5-HT2A expression area in the placenta among the studied nosologies is higher in preeclampsia without gestational diabetes mellitus or in superimposed preeclampsia in combination with chronic arterial hypertension compared to expression in placentas in preeclampsia in combination with gestational diabetes mellitus or in preeclampsia in combination with gestational diabetes mellitus and chronic arterial hypertension (p = 0.02 and p = 0.017, respectively). The relative area of SERT expression is higher in preeclampsia without gestational diabetes mellitus or chronic arterial hypertension and in preeclampsia in combination with gestational diabetes mellitus compared to preeclampsia in combination with gestational diabetes mellitus and chronic arterial hypertension (p = 0.002 and p = 0.012, respectively).&#x0D; CONCLUSIONS: The highest expressions of 5-HT2A and SERT among the studied preeclampsia phenotypes were found in placentas in preeclampsia without gestational diabetes mellitus or chronic arterial hypertension.

Особливості функціонування імунологічної толерантності під час вагітності (огляд літератури)

Pregnancy is a special state in a woman’s life, which can definitely be considered an «immunological paradox», because the growth of a genetically «alien» fetus takes place in a woman’s body. Despite the direct contact between cells of fetal origin (syncytiotrophoblast) and cells of the maternal immune system, which are in excess in the decidual membrane of the uterus, rejection of the semi-allogeneic fetus does not occur. A state of permanent natural immunological tolerance, during which the body does not respond to certain antigens expressed by trophoblast cells, while maintaining the ability to respond immunologically to other immunogens is the opposite phenomenon of the immune response, it is acquired by the body during its development and is not genetically determined. Purpose - to analyze the phasing of immunological changes in the mother’s body, which are aimed at the development and preservation of pregnancy, to specify their role in the correct flow of placental waves, prevention of the development of placental dysfunction and obstetric complications associated with it. A review of modern medical literature on the processes of immunological changes during trophoblast invasion and placentation in early pregnancy is given. For a more detailed understanding, the influence of each link of the immune response in the process of developing immune tolerance was analyzed. It has been established that for the development of a normal pregnancy there is a genetically programmed immune mechanism that ensures a decrease in the local and systemic immune response to the semi-alien implanted blastocyst, embryo and fetus. This is achieved through the step-by-step course of three phases of immunological shifts: the unfolded immune conflict; suppression of the immune response and intense immune conflict. The physiological course of gestation and the development of the placenta, in which the balance between the processes of neoangiogenesis and apoptosis is maintained, is ensured by adequate expression of HLA-G locus molecules by trophoblast cells, inhibition of Th1-type cytotoxic reactions against placenta cells by the mother's body. Analyzed changes in the cytokine balance, which shifts towards immunosuppressive cytokines, which suppress cellular immune reactions and stimulate the production of blocking antibodies, the quantitative composition of which can be considered decisive when carrying a genetically foreign fetus. Consequently, a relative secondary cellular immunodeficiency is formed, which is mainly due to a deficiency of circulating T-helper/inducers, a decrease in the CD4/CD8 immunoregulatory index and suppression of the functional activity of the T-cell immune system. It has been proven that impaired immunological tolerance, trophoblast invasion and vascular remodelling processes controlled by the maternal immune system at the local and systemic levels lead to early reproductive losses, premature birth, placental dysfunction, and are associated with fetal growth retardation syndrome, pre-eclampsia and other complications. No conflict of interests was declared by the authors.

Effect of sterile vs clean gloves for cervical checks in labor on maternal infection at term: a randomized trial

Intrapartum infection usually warrants immediate delivery and impacts 5-12% of term pregnancies, with the most commonly identified pathogenic organism being of the Ureaplasma genus. When performing cervical examinations during labor, providers in the United States commonly use sterile gloves, although there are no data currently to support that this practice reduces rates of infection. Furthermore, in nearly all other settings of Gynecologic care, aside from surgery in an operating room, nonsterile gloves are used. Even though the uterus could be sterile in normal pregnancies, the provider performing the cervical examination must traverse the milieu of vaginal bacteria in order to reach the cervix to perform the exam, introducing vaginal microbiota into the uterus regardless of the type of glove used. This prospective randomized controlled study examines whether the type of glove used (sterile vs clean) impacts the rates of intrapartum infection in patients receiving cervical examinations during labor or induction of labor at term.. This study aimed to evaluate if the glove type (sterile vs clean) used for cervical examinations during labor affects the rates of intrapartum and postpartum infection. This randomized controlled trial assigned eligible and consenting participants to receive cervical examinations during labor with either sterile powder-free polyvinyl chloride examination gloves (current routine practice, control group) or clean powder-free nitrile examination gloves (nonsterile, experimental group). The primary outcome was rates of intrapartum infection (chorioamnionitis). Sample size calculations estimated that 300 participants would be needed with a rate of infection of 10% in the control group and 20% in the experimental group to demonstrate difference between the groups; however, the rates of infection were much lower than expected, at 5.4% and 4.4% in the sterile and clean glove group, respectively. At this point, it was determined futile to continue the study because a sample size of >29,000 participants would be needed, which would not be achievable at a single tertiary care referral center with approximately 3500 deliveries per year. The study was approved by the Eastern Virginia Medical School Institutional Review Board (IRB 21-09-FB-0206), and was registered at ClinicalTrials.gov (identifier NCT05603624; https://clinicaltrials.gov/ct2/show/NCT05603624). A total of 163 participants with singleton pregnancies completed the study; 74 (45%) were randomized to the sterile glove group, and 89 (55%) were randomized to the clean glove group. In the sterile glove group, 4 (5.4%) developed intrapartum infection (chorioamnionitis) and 1 (1.3%) developed postpartum infection (endometritis). In the clean glove group, 4 (4.4%) developed intrapartum infection and 2 (2.2%) developed postpartum infection. There was no significant difference in rates of intrapartum infection (P=1.0) or postpartum infection (P=1.0), or combined rates of infection (including both chorioamnionitis and endometritis; P=.99) between the sterile and the clean glove group. When comparing the participants from both groups who had any intrapartum or postpartum infection (n=11) with those who had no infection (n=152), the former were more likely to be nulliparous (P=.01), have lower gravidity (P<.01) and parity (P<.01), have longer times from first cervical examination to delivery (P=.02), have longer times from rupture of membranes to delivery (P=.0001), undergo cesarean delivery (P=.0002), and experience postpartum hemorrhage (P=.001). Although participants who were in labor for a longer time also likely had more cervical examinations, these data could suggest that duration of labor (P=.02) is more closely associated with infectious morbidity compared with the number of cervical examinations (P=.15). Using clean gloves for cervical examinations during labor is unlikely to increase risk of infection, and could reduce cost by up to 92.4% at our institution, saving over $25,000 annually.

The analysis of pesticides and fungicides in the inhibition of human and rat placental 3β-hydroxysteroid dehydrogenase activity: Mode of inhibition and mechanism

3β-Hydroxysteroid dehydrogenase/steroid Δ5,4-isomerase 1 (3β-HSD1) plays a critical role in the biosynthesis of progesterone from pregnenolone in the human placenta to maintain normal pregnancy. Whether they inhibit placental 3β-HSD1 and mode of inhibition remains unclear. In this study, we screened 21 pesticides and fungicides in five classes to inhibit human 3β-HSD1 and compared them to rat homolog 3β-HSD4. 3β-HSD activity was measured by catalyzing pregnenolone to progesterone in the presence of NAD+. Of the 21 chemicals, azoles (difenoconazole), thiocarbamates (thiram and ferbam) and organochlorine (hexachlorophene) significantly inhibited human 3β-HSD1 with half maximal inhibitory concentration (IC50) values of 2.77, 0.24, 0.68, and 17.96 μM, respectively. We also found that difenoconazole, ferbam and hexachlorophene are mixed/competitive inhibitors of 3β-HSD1 while thiram is a mixed/noncompetitive inhibitor. Docking analysis showed that difenoconazole and hexachlorophene bound steroid-binding site. Difenoconazole and hexachlorophene except thiram and ferbam also significantly inhibited rat 3β-HSD4 activity with IC50 of 1.12 and 2.28 µM, respectively. Thiram and ferbam significantly inhibited human 3β-HSD1 possibly by interfering with cysteine residues, while they had no effects on rat 3β-HSD4. In conclusion, some pesticides potently inhibit placental 3β-HSD, leading to the reduction of progesterone formation.

Cystic Fibrosis: Its Impact at Women’s Fertility and their Pregnancy. A Narrative Review

Women with cystic fibrosis (CF) leave more years than in the past. This is the reason why this population has increased expectations for a more “normal” life. We aimed to assess current maternal and fetal outcomes in women with CF with varied pre-pregnancy lung function, in addition with fertility outcome after artificial reproductive technology (ART). A review of relative literature was conducted, using the MEDLINE database, the ScienceDirect database and Google scholar and relevant keywords. Studies confirmed that more women with CF are considering pregnancy. Unplanned pregnancies also are happening, and women need the right guidance. Most women will have normal pregnancies, but preterm births are common. Optimization of treatment is recommended during family planning or pregnancy. Reduced fertility may be overcome with ART. With careful multidisciplinary antenatal and intrapartum management, successful outcomes have been obtained in women with CF.