Pregnancy-associated Complications Research Articles

Relationship Between Recurrent Pregnancy Loss With Unknown Etiology and Endoplasmic Reticulum Stress.

Recurrent pregnancy loss (RPL) is characterized by consecutive pregnancy losses before 20 weeks of gestation, with evolving definitions necessitating adjustments to prevent delays in couples' evaluation. Limited etiological data on RPL prompts comprehensive evaluations, often yielding no pathological findings. Emerging research implicates endoplasmic reticulum (ER) stress in various reproductive processes, yet its association with RPL remains understudied. To evaluate ER stress in patients with RPL with unknown etiology by determining the plasma concentration of X-box binding protein-1 (XBP-1). A total of 45 patients aged 18 to 35 years with at least two pregnancy losses with unknown etiology before the completion of 20 weeks of gestation between March 2020 and September 2020 were included in the study group. The control group consisted of 45 healthy women with at least two previous live births, no pregnancy-associated complications, and no history of pregnancy loss or infertility. The XBP-1 levels were determined from serum samples. Statistical analyses assessed differences between groups, and receiver operating characteristic (ROC) curve analysis determined XBP-1's predictive value for RPL. The mean XBP-1 concentration in the RPL group was significantly higher than in the control group (p < 0.001). The mean values were 2243.65 ± 9425.27 pg/mL and 1196.32 ± 4378.81 pg/mL, respectively. The use of XBP-1 levels for the prediction of RPL was evaluated. In an ROC curve analysis, the area under the curve was found to be 87% (95% CI: 80% to 94.8%). The specificity was 78%, the sensitivity was 88%, the positive likelihood ratio (LR) was 4, the negative LR was 0.15, the positive predictive value was 80%, and the negative predictive value was 87% for the cut-off XBP-1 level at 1364.68 pg/mL. This study highlights the potential role of ER stress in RPL and proposes XBP-1 as a predictive biomarker for pregnancy loss. Understanding ER stress mechanisms in RPL could inform diagnostic and therapeutic strategies. Further research is essential to validate these findings and explore their clinical implications.

Concurrent spontaneous coronary dissection and reversible cerebral vasoconstriction syndrome during postnatal care.

Pregnancy-associated spontaneous coronary artery dissection (SCAD) and reversible cerebral vasoconstriction syndrome (RCVS) are rare conditions that may occur during pregnancy and the postpartum period. The coexistence of both diseases may pose a risk to patients, potentially resulting in a variety of complications and clinical manifestations. This is considered the first case of a patient who successfully recovered from a critical condition in the postpartum period, with contemporaneous SCAD and RCVS. A 33-year-old female with no known medical history was referred to the emergency department after experiencing cardiac arrest, which occurred 1 week after giving birth to her third child. She complained of sudden anterior squeezing chest pain, accompanied by a headache, and eventually collapsed due to ventricular fibrillation with seizure. She was successfully resuscitated after receiving basic life support. She showed an alert mentality and did not experience any further seizure events or additional neurological symptoms. Although vital sign remained stable, the level of highly sensitive troponin I was significantly elevated. Electrocardiography revealed sinus rhythm with T-wave inversion at V1-4, while chest computed tomography (CT) demonstrated severe aspiration pneumonia. The patient was admitted to the intensive care unit due to a high requirement of O2 supply. A consultation with the neurologic department and a brain magnetic resonance angiography (MRA) were conducted for the thunderclap headache. The brain MRA demonstrated stenosis in the basilar artery, the right M2 segment, and bilateral A1 segments, along with sulcal hyperintensity on post-contrast fluid-attenuated inversion recovery (FLAIR) suggesting blood-brain barrier breakdown due to vasoconstriction. Formal echocardiography showed regional wall motion abnormality in the left anterior descending artery (LAD) territory. After the improvement of pneumonia, a coronary angiography was performed, revealing diffuse luminal narrowing from the mid to distal LAD due to a long segmental, extensive dissection. We decided to maintain the medical therapy. A follow-up coronary CT angiography performed 6months later revealed complete remission of the dissected coronary vessel, and a brain MRA checked 3months later showed resolved vasoconstriction of the relevant cerebral vessels. The physicians must be aware of pregnancy-associated complications in certain patients. Clear diagnoses and proper treatments are required in pregnant patients who may be exposed to multiple acute conditions, in order to reduce complications and achieve favorable outcomes.

Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation.

Pregnancy is an extremely stressful period in a pregnant woman's life. Currently, women's awareness of the proper course of pregnancy and its possible complications is constantly growing. Therefore, a significant percentage of women increasingly reach for various dietary supplements during gestation. Some of the most popular substances included in multi-ingredient supplements are folic acid and choline. Those substances are associated with positive effects on fetal intrauterine development and fewer possible pregnancy-associated complications. Recently, more and more attention has been paid to the impacts of specific environmental factors, such as diet, stress, physical activity, etc., on epigenetic modifications, understood as changes occurring in gene expression without the direct alteration of DNA sequences. Substances such as folic acid and choline may participate in epigenetic modifications by acting via a one-carbon cycle, leading to the methyl-group donor formation. Those nutrients may indirectly impact genome phenotype by influencing the process of DNA methylation. This review article presents the current state of knowledge on the use of folic acid and choline supplementation during pregnancy, taking into account their impacts on the maternal-fetal unit and possible pregnancy outcomes, and determining possible mechanisms of action, with particular emphasis on their possible impacts on epigenetic modifications.

Design of a targeted blood transcriptional panel for monitoring immunological changes accompanying pregnancy.

Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm. Based on a de novo dataset from a resource-constrained setting and a dataset from a resource-rich area readily available in the public domain, whole blood gene expression profiles of uneventful pregnancies were captured at multiple time points during pregnancy. BloodGen3, a fixed blood transcriptional module repertoire, was employed to analyze and visualize gene expression patterns in the two datasets. Differentially expressed genes were identified by comparing their abundance to non-pregnant postpartum controls. The selection process for a targeted gene panel considered (i) transcript abundance in whole blood; (ii) degree of correlation with the BloodGen3 module; and (iii) pregnancy biology. We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, when compared to the postpartum controls. The gene panel presented here holds promise for the development of predictive, targeted, transcriptional profiling assays. Such assays might become useful for monitoring of pregnant women, specifically to detect potential adverse events early. Prospective validation of this targeted assay, in-depth investigation of functional annotations of differentially expressed genes, and assessment of common pregnancy-associated complications with the aim to identify these early in pregnancy to improve pregnancy outcomes are the next steps.

Addressing Reproductive Education Among Young Adults with Sickle Cell Disease (SCD): Sickle Cell Reproductive Outreach and Education (ROE) Project

Background: As children with sickle cell disease (SCD) survive into adulthood, it is important to address emerging reproductive health concerns. This population faces unique fertility challenges, including balancing the desire for biological parenthood, risk of pregnancy-associated complications, unintended pregnancy, and fertility concerns with the use of SCD modifying therapies (DMTs) (Smith-Whitley, Blood, 2014, Pecker, Br J Haematol, 2021) . Recent research identified knowledge gaps that impact reproductive care for adults with SCD (Carrithers, Frontiers, 2023). To overcome these gaps, we need to evaluate the baseline knowledge of young adults with SCD regarding reproduction to understand the complex implications of reproductive decision-making. This study was done to gauge young adults' knowledge of reproduction, understanding of fertility, and current reproductive behaviors in order to develop educational material to support young adults' with SCD reproductive decisions. Methods: This IRB-approved, cross-sectional study included young adults living with SCD (ages 18-35) from University of Alabama-Birmingham's Lifespan Comprehensive SCD Center. Patients were recruited during routine clinic visits to complete an electronic 33-question survey to evaluate reproductive health topics adapted from the Sisters Informing Sisters About AIDS (SISTA) questionnaire (CDC, 2008), including demographics (age separated into younger age (18-25) and older age (26-35), sexual health behaviors (contraception, sexually transmitted infection (STI) prevention), family planning, patient advocacy, and attitudes towards reproductive education. Responses were recorded as “Yes, No, Don't Know”, unless questions specifically asked for participants to choose an option. Attitudes toward reproductive education were graded on 5-point Likert scale (1= strongly disagree to 5=strongly agree). Data analysis includes averages to evaluate subgroup comparisons and independent student's t-test to compare subgroups with statistical significance set at p&amp;lt;0.05. Results: We enrolled 47 participants (55% women and 51% were of older age). In this cohort, 87% completed high school and 60% were sexually active. Among those who were sexually active, 86% had previously undergone STI testing and 36% had prior history of STI (22% men vs. 77% women, 22% younger age vs. 77% older age, p&amp;lt;0.05). Thirty-eight percent identified personal or partner contraceptive use. Regarding children, 19% had birthed/fathered a child(ren) (55% men vs. 45% women, 22% younger age vs. 77% older age, p&amp;gt;0.005) among whom 11% knew their child had SCD, 55% knew their child had sickle cell trait (SCT), and 33% did not know if their child had SCD/SCT. Only 26% were aware of contraceptive options for people with SCD (17% men vs. 83% women, p&amp;lt;0.05). Importantly, 89% recognized high risk sexual activity as a risk factor for STIs but no one in the cohort recognized the risk of infertility due to STIs. When asking about their partners, 32% knew if their partner had SCD/SCT (20% men vs. 80% women, p&amp;lt;0.05). Notably, 79% desired biologic children. Among those who desired children, 41% felt that their SCD changed their decision to have children and 26% were previously told they could not have children due to SCD (12% men vs. 88% women, 25% younger age vs. 75% older age, p&amp;lt;0.05). Notably, 57% were interested in conceiving if pregnancy was planned (41% men vs. 59% women, 37% younger age vs. 63% older age, p&amp;lt;0.05). When asked if patients wanted to discuss their reproductive health, 87% wanted to discuss this with their hematologist but only 51% would discuss this with PCPs. Conclusion: In this study, we identified evaluated 4 tenets of reproductive health knowledge: contraceptive use, STI prevention, family planning, and patient advocacy. We identified gaps in knowledge in these areas that can be addressed to improve reproductive education in young adults with SCD. Young adults with SCD in our cohort have low contraceptive use and were often not aware of contraceptive options for people with SCD or their partner's SCD/SCT status. Our cohort also reported a significant history of STI but was unaware of the associated increasing risk for infertility. Importantly. young adults are especially interested in discussing reproductive health with their hematologists, which provides an opportunity to improve reproductive education within this unique population.

Addressing Cardiovascular Risk Across the Arc of a Woman's Life: Sex-Specific Prevention and Treatment.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in womenin the United States of America. Despite this, women are underdiagnosed, less often receive preventive care, and are undertreated for CVD compared to men. There has been an increase in sex-specific risk factors and treatments over the past decade; however, sex-specific recommendations have not been included in the guidelines. We aim to highlight recent evidence behind thedifferential effect of traditional risk factors and underscore sex-specific risk factors with an intention to promote awareness, improve risk stratification, and early implementation of appropriate preventive therapies in women. Women are prescribed fewer antihypertensives and lipid-lowering agents and receive less cardiovascular care as compared to men. Additionally, pregnancy complications have been associated with increased cardiovascular mortality later in life. Findings from theARIC study suggest that there is a perception of lower risk of cardiovascular disease in women. The SWEDEHEART study which investigated sex differences in treatment, noted a lower prescription of guideline-directed therapy in women. Women are less likely to be prescribed statin medications by their providers in both primary and secondary prevention as they are considered lower risk than men, while also being more likely to decline and discontinue treatment. A woman's abnormal response to pregnancy may serve as her first physiological stress test which can have implications on her future cardiovascular health. This was supported by the CHAMPs study noting a higher premature cardiovascular risk after maternal complications. Adverse pregnancy outcomes have been associated with a 1.5-4.0 fold increase in future cardiovascular events in multiple studies. In this review, we highlight the differences in traditional risk factors and their impact on women. Furthermore, we address the sex-specific risk factors and pregnancy-associated complications that increase the risk of CVD in women. Adherence to GDMT may have implications on overall mortality in women. An effort to improve early recognition of CVD risk with implementation of aggressive risk factor control and lifestyle modification should be emphasized. Future studies should specifically report on differences in outcomes between males and females. Increased awareness and knowledge on sex-specific risks and prevention are likely to lower the prevalence and improve outcomes of CVD in women.

O-glycan structures in apo(a) subunit of human lipoprotein(a) suppresses the pro-angiogenic activity of galectin-1 on human umbilical vein endothelial cells.

Apolipoprotein(a) [apo(a)] is a highly polymorphic O-glycoprotein circulating in human plasma as lipoprotein(a) [Lp(a)]. The O-glycan structures of apo(a) subunit of Lp(a) serve as strong ligands of galectin-1, an O-glycan binding pro-angiogenic lectin abundantly expressed in placental vascular tissues. But the pathophysiological significance of apo(a)-galectin-1 binding is not yet been revealed. Carbohydrate-dependent binding of galectin-1 to another O-glycoprotein, neuropilin-1 (NRP-1) on endothelial cells activates vascular endothelial growth factor receptor 2 (VEGFR2) and mitogen-activated protein kinase (MAPK) signaling. Using apo(a), isolated from human plasma, we demonstrated the potential of the O-glycan structures of apo(a) in Lp(a) to inhibit angiogenic properties such as proliferation, migration, and tube-formation in human umbilical vein endothelial cells (HUVECs) as well as neovascularization in chick chorioallantoic membrane. Further, in vitro protein-protein interaction studies have confirmed apo(a) as a superior ligand to NRP-1 for galectin-1 binding. We also demonstrated that the protein levels of galectin-1, NRP-1, VEGFR2, and downstream proteins in MAPK signaling were reduced in HUVECs in the presence of apo(a) with intact O-glycan structures compared to that of de-O-glycosylated apo(a). In conclusion, our study shows that apo(a)-linked O-glycans prevent the binding of galectin-1 to NRP-1 leading to the inhibition of galectin-1/neuropilin-1/VEGFR2/MAPK-mediated angiogenic signaling pathway in endothelial cells. As higher plasma Lp(a) level in women is an independent risk factor for pre-eclamsia, a pregnancy-associated vascular complication, we propose that apo(a) O-glycans-mediated inhibition of the pro-angiogenic activity of galectin-1 may be one of the underlying molecular mechanism of pathogenesis of Lp(a) in pre-eclampsia.

Prospecting of exosomal-miRNA signatures as prognostic marker for gestational diabetes mellitus and other adverse pregnancy outcomes.

Exosomal microRNA (ExomiRs) serves as potential cargo molecules responsible for post-translation of gene expression and intracellular communication playing a vital role in acting as clinically relevant prognostic biomarkers for identifying pregnancy-associated complications in patients. ExomiRs are associated with Gestational Diabetes Mellitus (GDM) as potential targets for understanding the pathophysiology of beta-cell dysfunction. ExomiRs (ExomiR 122, ExomiR 16-5p, ExomiR 215-5p, ExomiR 450b-3p, ExomiR 122-5p) aid to act as biomarkers and regulate the progression of diabetes and its related complication. These ExomiRshave been reported to interfere with the regulation of various genes such as ZEB2, IRS1, IRS2, GLUT1, GLUT4, etc. and inhibition of several pathways like PI3K/AKT, Wnt, and mTOR signaling pathways leading to the modulation in the development of GDM affecting the clinical and pathological features of women. These ExomiRs have also been associated with other pregnancy-associated complications, including preeclampsia, hypothyroidism, pregnancy loss, and ectopic pregnancies. On the other hand, overexpression of certain ExomiRs such as Exomir-515-5p, ExomiR-221, and ExomiR-96 serve a regulatory role in overcoming insulin resistance. Taken together, the current review focuses on the prospective capabilities of ExomiRs for diagnosis and clinical prognosis of GDM women with respect to pregnancy outcomes.

Long COVID-A New Challenge in Medicine: Focus on Pregnancy and Breastfeeding

Long COVID (coronavirus disease) has been described as anew multi-organ disease, which appears to be more prevalent in women than in men. Pregnant and breastfeeding women are aspecial subgroup of patients to consider with long COVID, as only scarce data have been collected to date. Menstrual changes are commonly observed during or after COVID-19; some studies also attribute slight changes of cycle length to previous inoculation against the virus. Pregnant women who have asymptomatic infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are at ahigher risk for adverse outcomes and pregnancy-associated complications. Moreover, more and robust data are required to evaluate vertical transmission. COVID vaccines are the most effective tool against the pandemic, as they prevent infection, but also appear to be able to ease long COVID symptoms. Vaccines have been proven safe and effective in both pregnant and breastfeeding women. This article aims to present current data on long COVID in pregnant and breastfeeding women and elucidate risk factors and possible treatment options.

Generation of 3D Trophoblast Organoids from Human Naïve Pluripotent Stem Cells.

The human placenta is a transient organ that functions to support the needs of the fetus throughout gestation. Trophoblasts are the major epithelial cells found within the placenta and comprise a variety of distinct cell types with specialized roles in fetal-maternal communication. Our understanding of human trophoblast development remains limited due to ethical and legal restrictions on accessing first-trimester placental tissues, as well as the inability of common animal models to replicate primate placental development. It is therefore important to advance in vitro models of human trophoblast development as a basis for studying pregnancy-associated complications and diseases. In this chapter, we describe a protocol for generating 3D trophoblast organoids from naïve human pluripotent stem cells (hPSCs). The resulting stem-cell-derived trophoblast organoids (SC-TOs) contain distinct cytotrophoblast (CTB), syncytiotrophoblast (STB), and extravillous trophoblast (EVT) cell types, which closely correspond to trophoblast identities in the human post-implantation embryo. We discuss methods for characterizing SC-TOs by immunofluorescence, flow cytometry, mRNA and microRNA expression profiling, and placental hormone secretion. Furthermore, SC-TOs can undergo differentiation into specialized 3D EVT organoids, which display robust invasion when co-cultured with human endometrial cells. Thus, the protocol described herein offers an accessible 3D model system of human placental development and trophoblast invasion.

Estimation of malondialdehyde and catalase activity in pregnant women at IIMS&amp;R Hospital, Lucknow, India

Background: During pregnancy, the physiological production of reactive oxygen species (ROS) is associated with a variety of maternal, placental, and fetal developmental functions. These functions are disrupted by excessive amounts of ROS, resulting to pregnancy complications. Different stages of pregnancy require a balance between oxidant and antioxidant production.&#x0D; Objective: The aim of this study is to investigate the status of malondialdehyde (MDA) and catalase (CAT) activity in pregnant and age matched non-pregnant women.&#x0D; Methods: In this cross-sectional study, a total of 74 participants were enrolled, including 37 pregnant and 37 age-matched non-pregnant women. The age range of participants was 18 to 40 years. MDA and CAT levels were measured spectrophotometrically. A p-value 0.05 was statistically significant.&#x0D; Results: Compared to non-pregnant women, the mean plasma level of MDA was considerably elevated in pregnant women (p&lt;0.0001). However, the mean level of CAT activity in pregnant women was significantly lower than in non-pregnant women (p&lt;0.0001) In pregnant women, there is a significant strong negative correlation between MDA levels and CAT activity (p&lt;0.01).&#x0D; Conclusion: Pregnant women have high level of oxidative stress, indicating that the pregnant women are more susceptible to oxidative damage and may develop pregnancy-associated complications.&#x0D;

LDHA deficiency inhibits trophoblast proliferation via the PI3K/AKT/FOXO1/CyclinD1 signaling pathway in unexplained recurrent spontaneous abortion.

Dysregulated trophoblast proliferation, invasion, and apoptosis may cause several pregnancy-associated complications, such as unexplained recurrent spontaneous abortion (URSA). Recent studies have shown that metabolic abnormalities, including glycolysis inhibition, may dysregulate trophoblast function, leading to URSA. However, the underlying mechanisms remain unclear. Herein, we found that lactate dehydrogenase A (LDHA), a key enzyme in glycolysis, was significantly reduced in the placental villus of URSA patients. The human trophoblast cell line HTR-8/SVneo was used to investigate the possible LDHA-mediated regulation of trophoblast function. LDHA knockdown in HTR-8/SVneo cells induced G0/G1 phase arrest and increased apoptosis, whereas LDHA overexpression reversed these effects. Next, RNA sequencing combined with Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the PI3K/AKT signaling pathway is potentially affected by downstream genes of LDHA. Especially, we found that LDHA knockdown decreased the phosphorylation levels of PI3K, AKT, and FOXO1, resulting in a significant downregulation of CyclinD1. In addition, treatment with an AKT inhibitor or FOXO1 inhibitor also verified that the PI3K/AKT/FOXO1 signaling pathway influenced the gene expression of CyclinD1 in trophoblast. Moreover, p-AKT expression correlated positively with LDHA expression in syncytiotrophoblasts and extravillous trophoblasts in first-trimester villus. Collectively, this study revealed a new regulatory pathway for LDHA/PI3K/AKT/FOXO1/CyclinD1 in the trophoblast cell cycle and proliferation.

Pulmonary disorders in pregnancy: Bronchiectasis, cystic fibrosis, sarcoidosis and interstitial diseases.

This chapter aims to provide expert guidance to obstetricians, general practitioners, allied health staff and women with lung disease about the interactions between pregnancy and different lung diseases. This chapter will cover other airway diseases such as bronchiectasis and cystic fibrosis (CF) together with sarcoidosis and interstitial lung disease (ILD), noting that another chapter covers asthma. The physiological changes which occur in pregnancy, such as the changes in airway physiology, resting ventilation and sleep, are summarised in another chapter. This chapter extends the evidence-based approach and clinical expertise of the recent European Respiratory Society/Thoracic Society of Australia and New Zealand (ERS/TSANZ) taskforce. The papers selected were based on the population (pregnant women with lung disease other than asthma) and the effects of these diseases on risks of pregnancy-associated complications and miscarriages, breastfeeding, nutritional considerations, lung function, long-term maternal outcomes and management considerations during pregnancy. As there are very few randomised control trials in the area, the majority of the literature consists of observational studies (prospective or retrospective), cross-sectional surveys and case series. Other guidelines have also recently been published, which may be helpful to the reader.

Trends, Predictors and Outcomes of Cardiovascular Complications at Delivery Associated with Gestational Diabetes Mellitus-a National Inpatient Sample Analysis (2004-2019)

BACKGROUNDWomen with gestational diabetes mellitus (GDM) have an increased risk of pregnancy-associated complications and long-term risk of cardiovascular (CV) disease. However, data on in-hospital peripartum CV complications remain limited. Hence, we investigated trends, outcomes, and predictors of CV complications associated with GDM diagnosis during delivery hospitalizations in the United States. METHODS AND RESULTSWe used data from the National Inpatient Sample (2004-2019). ICD-9 or ICD-10 codes were used to identify delivery hospitalizations and GDM diagnosis. A total of 63,115,002 hospitalizations for deliveries were identified, of which 3.9% were among women with GDM (n=2,435,301). The prevalence of GDM, and of obesity increased during the study period (p-trend<0.01) (Figure A). Women with GDM were older (median 32 vs 28 years, p<0.01) and had higher prevalence of obesity, and dyslipidemia. After adjustment for age, race/ethnicity, comorbidities, and insurance/income, GDM remained an independent predictor of CV complications including preeclampsia [aOR 2.02 (95% CI 2.01-2.03), p<0.01], eclampsia [aOR 1.68 (1.64-1.72), p<0.01], peripartum cardiomyopathy [aOR 1.15 (1.08-1.22), p<0.01], acute kidney injury [aOR 1.16 (1.11-1.21), p<0.01], stroke [aOR 1.15 (1.09-1.23), p<0.01] and cardiac arrhythmias [aOR 1.48 (1.46-1.50), p<0.01], compared to no GDM (Figure B). Delivery hospitalizations among women with GDM were associated with increased length (3 vs 2 days, p<0.01) and cost of hospitalization ($4,909 vs $3,682, p<0.01). CONCLUSIONSWomen with GDM had higher risk of preeclampsia/eclampsia, peripartum cardiomyopathy, acute kidney injury, stroke, and cardiac arrhythmias during delivery hospitalizations. Moreover, delivery hospitalizations among women with GDM diagnosis were associated with increased length and cost of hospitalization.

Pregnancy in spina bifida patients: a comparative analysis of peripartum procedures and complications.

Spina bifida (SB) is caused by a failure in neural tube closure that can present with lower extremity sensory deficits, paralysis, and hydrocephalus. Medical advances have allowed increased pregnancies among SB patients, but management and pregnancy-associated complications have not been thoroughly investigated. The objective is to delineate peripartum procedures and complications in patients with SB. A national de-identified database, TriNetX, was retrospectively queried to evaluate pregnant SB patients and the general population. Procedures and complications were investigated using corresponding ICD-10 and CPT codes within 1year of pregnancy diagnosis. 11,405SB patients were identified and compared to 9,269,084 non-SB patients. SB patients were significantly more likely to undergo cesarean delivery (1.200; 95% CI [1.133-1.271]) and less likely to receive neuraxial analgesia (0.406; 95% CI [0.383-0.431]). Additionally, patients with SB had an increased risk of seizures (3.922; 95% CI [3.529-4.360]) and venous thromboembolism (VTE) (3.490; 95% CI [3.070-3.969]). Risks of preeclampsia and hemorrhage were comparable. SB patients with hydrocephalus and Chiari malformation type 1 (CM-1) or type 2 (CM-2) were compared to patients without these comorbid conditions. This sub-group analysis showed a significantly increased risk of having cesarean deliveries (SB with hydrocephalus: 12.55%, S.B. with CM-1 or CM-2: 12.81% vs. SB without hydrocephalus or CM, 6.16%) and VTE (3.74%, 2.43% vs. 0.81%). There were also increased risks of hemorrhage and seizures and decreased use of neuraxial analgesia, but the sample size was insufficient. SB patients were more likely to undergo cesarean section and exhibit peripartum complications compared to those without SB.

An old friend with a new face: YB-1 and its role in healthy pregnancy and pregnancy-associated complications.

By promoting tissue invasion, cell growth and angiogenesis, the Y-box binding protein (YB-1) became famous as multifunctional oncoprotein. However, this designation is telling only part of the story. There is one particular time in life when actual tumorigenic-like processes become undoubtedly welcome, namely pregnancy. It seems therefore reasonable that YB-1 plays also a crucial role in reproduction, and yet this biological aspect of the cold-shock protein has been overlooked for many years. To overcome this limitation, we would like to propose a new perspective on YB-1 and emphasize its pivotal functions in healthy pregnancy and pregnancy-related complications. Moreover, we will discuss findings obtained from cancer research in the light of reproductive events to elucidate the importance of YB-1 at the feto-maternal interface.

Preeclampsia and Fetal Growth Restriction as Risk Factors of Future Maternal Cardiovascular Disease-A Review.

Cardiovascular diseases (CVDs) remain the leading cause of death in women worldwide. Although traditional risk factors increase later-life CVD, pregnancy-associated complications additionally influence future CVD risk in women. Adverse pregnancy outcomes, including preeclampsia and fetal growth restriction (FGR), are interrelated disorders caused by placental dysfunction, maternal cardiovascular maladaptation to pregnancy, and maternal abnormalities such as endothelial dysfunction, inflammation, hypercoagulability, and vasospasm. The pathophysiologic pathways of some pregnancy complications and CVDs might be linked. This review aimed to highlight the associations between specific adverse pregnancy outcomes and future CVD and emphasize the importance of considering pregnancy history in assessing a woman’s CVD risk. Moreover, we wanted to underline the role of maternal cardiovascular maladaptation in the development of specific pregnancy complications such as FGR.

Nigericin Abrogates Maternal and Embryonic Oxidative Stress in the Streptozotocin-Induced Diabetic Pregnant Rats.

Hyperglycemic exposure in diabetic pregnancy can lead to many developmental changes, such as delayed development, fetal malformations, and fetal/embryo death. These detrimental complications are collectively known as diabetic embryopathy or teratogenesis. The current study focuses to discover the therapeutic properties of the nigericin against the STZ-stimulated diabetic embryopathy via alleviation of maternal and embryonic oxidative stress. The male and female rats at a 1:1 ratio were permitted to mate overnight to establish the course of pregnancy. The pregnant rats were distributed into four groups control, diabetic pregnant (via administering 40mg/kg of STZ), and diabetic + 10 and 20mg/kg of nigericin-administered (via oral gavage from days 5 to 12) groups, respectively. The glucose level, urine output, diet intake, and body weight were determined carefully. The embryo and placenta weight and implantation rates were examined, and data were tabulated. The total protein and lipid profiles were assessed using respective kits. The oxidative stress markers and antioxidant enzymes were examined using respective assay kits. The 10 and 20mg/kg of nigericin treatment decreased the glucose level and urine output and improved the diet intake and body weight gain in diabetic pregnant rats. The nigericin also decreased the total protein, cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) and improved the high-density lipoprotein (HDL) in the serum of pregnant rats. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), and protein carbonyls were decreased by the nigericin in both liver and embryos of the pregnant rats. The levels of glutathione (GSH), total thiols, and activities of catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were improved by the nigericin in the diabetic pregnant rats. Altogether, these results provide evidence that nigericin treatment remarkably attenuates the diabetes-stimulated embryopathy in rats. The nigericin effectively decreased embryo lethality, reduced glucose and dyslipidemia, and relieves oxidative stress via upregulating the antioxidant enzyme activities. Hence, it can be a talented therapeutic agent to treat diabetic pregnancy-associated complications.

Evaluation of Lactate Dehydrogenase and Gamma Glutamyl Transferase Among Pregnant Women with Hypertensive Disorders and Their Association with Disease Severity in Jimma Medical Center, Ethiopia

Background & Objective: Pregnancy-induced hypertensive disorders (PIHD) are the main reasons for maternal and perinatal mortality, as they complicate 10% of pregnancies worldwide. Serum lactic acid dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) are possible markers reflecting the occurrence of pregnancy-associated complications like preeclampsia and eclampsia. There is a paucity of data with conflicting results showing serum LDH and GGT on PIHD in Ethiopia. This investigation aimed to assess the serum LDH and GGT levels in pregnant women with PIHD along with their correlation with the severity of the disease at Jimma Medical Center (JMC), Ethiopia.Materials & Methods: This hospital-based comparative cross-sectional study was undertaken from August 03 to September 27, 2020, in JMC. A total of 97 study participants were recruited. Serum GGT and LDH levels were determined using a fully automated Roche Cobas 6000 chemistry analyzer. The data were analyzed using SPSS 25.0. One-way ANOVA and independent samples t-test were employed to compare serum GGT and LDH levels with categories of PIHD.Results: The significantly highest mean serum levels of LDH (580.9±193.8 U/L) and GGT (86.1±29.2 U/L) were observed in eclamptic women compared to gestational hypertensive (276.7±60.7 and 38.3±16.9 U/L) and preeclamptic patients (353±132.8 and 48.8±29.9 U/L), respectively. Both serum GGT and LDH levels were found to correlate with the severity of preeclampsia, respectively significantly.Conclusion: Serum LDH and GGT were found to be at the highest levels in eclamptic than preeclamptic and gestational hypertensive women. Blood pressure, gestational age, and severity of hypertensive disorders of pregnancy were predictor variables associated with serum GGT and LDH.

P-576 Spontaneous pregnancy rates after the weight loss program in infertile PCOS women with obesity

Abstract Study question What is the spontaneous pregnancy rate in infertile polycystic ovary syndrome (PCOS) women with obesity after the weight loss program in womoen who achieve ≥ 5% BMI reduction? Summary answer Spontaneous pregnancy rate in infertile PCOS women is 29.4 % after the end of the weight loss program and reduction of BMI for ≥ 5%. What is known already PCOS affects 6 to 15% of reproductive age women and is the most common cause of anovulatory infertility. Twenty-five to 75 % of women with PCOS are overweight (BMI &amp;gt;25 kg/m2) or obese (BMI &amp;gt;30 kg/m2). Obesity aggravates symptoms of PCOS. Women with obesity and women with PCOS have lower spontaneous and IVF pregnancy rates. Pregnant women with PCOS and obesity have higher incidence of pregnancy-associated complications. Weight reduction of even 5% improves metabolic and hormonal profile as well as reproductive functions and weight reduction through lifestyle modification is the treatment of choice for overweight and obese women with PCOS. Study design, size, duration Twenty-seven infertile PCOS women with BMI &amp;gt;30 kg/m2 were prospectively included to the study. They attended a weight loss program prior to inclusion to IVF procedures. The program lasted for 8-12 consecutive weeks. Participants/materials, setting, methods Twenty-seven infertile women, aged less than 38 years, with PCOS and obesity were prospectively included to the weight loss program. The program consisted of lifestyle modifications (diet with daily caloric deficit) and physical exercise. Group trainings were held twice a week and were designed as circuit interval trainings. Individual aerobic activity (walking, brisk walking, cycling, walking up the hill) were also performed twice a week. Main results and the role of chance All women completed the prescribed weight loss program. Mean body weight before the program (106.43 kg ± 15.09 kg) was significantly (p &amp;lt; 0.001) higher than after the program (100.63 kg ± 14.67 kg). Mean BMI prior to the start was 37.65 ± 5.1 kg/m2 and after the end of the program 35.68 ± 4.9 kg/m2. The difference was statistically significant (p &amp;lt; 0.001). Of 27 included women, 17 (62.9 %) achieved the desirable BMI reduction of ≥ 5%. Of women who reduced their BMI by ≥ 5%, 5 (29.4 %) conceived spontaneously in three months after the end of the weight loss program. All other were included to IVF procedures. Besides weight loss, significantly more women reported on having healthier eating habits, started to exercise regularly, and improved their sleep after the end of the weight loss program. Limitations, reasons for caution The limitation of the present study is a relatively small sample size. Wider implications of the findings Weight loss represents an important approach towards treatment of obese infertile PCOS women prior to inclusion to IVF procedures. Almost 30 % of women who achieved the desirable BMI reduction conceived spontaneously. They were therefore spared of IVF procedures which has a beneficial health, psychological as well as financial impact. Trial registration number NCT04989244