Pregnancy-related Diseases Research Articles

Multicenter Cross-Sectional Study of Oral Health and Hygiene Practices Among Pregnant Women

Background: Hormonal, vascular, and behavioral changes during pregnancy can negatively impact a woman’s oral health, resulting in conditions such as gingivitis, dental sensitivity, and caries. Although oral health is critical during pregnancy, it remains frequently overlooked. In this study, the oral health status and hygiene practices of pregnant women attending two university hospitals in southern Italy were evaluated. Methods: A cross-sectional cohort study was conducted with 72 pregnant women. Data were collected through an anonymous questionnaire that evaluated oral hygiene habits, dental visits, and oral pathologies, followed by a clinical examination. The examination included the assessment of the Decayed, Missing, Filled Teeth (DMFT) index and the Oral Hygiene Index (OHI) scores. Results: Among the participants, 61% were in their 9th month of pregnancy. The mean DMFT score was 7.9, and the mean OHI score was 3.6. Only 19.4% of participants had visited a dentist in the past 6 months, while 97.2% reported brushing their teeth just once per day. Gingival bleeding was reported by 72.2% of the women, and 38.9% experienced dental sensitivity, with both conditions worsening during pregnancy. Conclusions: The need for greater oral hygiene education and regular dental care during pregnancy is highlighted in this study. Integrating oral health maintenance into prenatal care programs is essential for preventing pregnancy-related oral diseases and promoting maternal and fetal well-being.

Multidimensional Plasma Lipids Affect Preeclampsia/Eclampsia: A Mendelian Randomization Study.

Circulating lipids play a crucial role during pregnancy and may impact various pregnancy-related diseases. This study employed a two-sample Mendelian randomization (MR) framework to investigate the causal relationship between alterations in multidimensional plasma lipid levels and the risk of preeclampsia or eclampsia, offering deeper insight into this association. The inverse variance weighted (IVW) method was utilized as the main analysis. Summary statistics from plasma lipidomics of 7174 Finnish individuals and summary data on preeclampsia/eclampsia from the FinnGen consortium involving 219 817 European participants were employed. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. The study identified 17 lipid species from a total of 179 lipid species associated with susceptibility to preeclampsia/eclampsia. Notably, ten species, including six triacylglycerols (TAGs) (50:1, 48:1, 56:4, 49:2, 48:2, 54:3), a diacylglycerol (DAG) (16:1_18:1), and three sphingomyelins (SMs) (d36:1, d34:1, d38:1), were found to increase the risk of preeclampsia/eclampsia. Conversely, seven species, including five phosphatidylcholines (PCs) (16:1_20:4, O-18:1_20:4, 18:1_20:4, 16:0_20:4, 17:0_20:4) and two phosphatidylethanolamines (PEAs) (18:0_20:4, 16:0_20:4), all containing arachidonic acid (ARA) in the sn-2 position, were associated with a reduced risk of preeclampsia/eclampsia (all p < 0.05). The results of thestratified analysis were consistent with these findings. Furthermore, reverse MR analysis indicated that preeclampsia/eclampsia does not causally affect plasma levels of these lipids. Our findings established a causal relationship between specific plasma lipid species and modulation of preeclampsia/eclampsia risk, providing improved resolution for risk assessment and potential therapeutic targets in the disease.

Analysis of the evolution of placental oxidative stress research from a bibliometric perspective.

Research on placental oxidative stress is pivotal for comprehending pregnancy-related physiological changes and disease mechanisms. Despite recent advancements, a comprehensive review of current status, hotspots, and trends remains challenging. This bibliometric study systematically analyzes the evolution of placental oxidative stress research, offering a reference for future studies. To conduct a comprehensive bibliometric analysis of the literature on placental oxidative stress to identify research hotspots, trends, and key contributors, thereby providing guidance for future research. Relevant data were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, CiteSpace, and the bibliometrix package. An in-depth analysis of 4,796 publications was conducted, focusing on publication year, country/region, institution, author, journal, references, and keywords. Data collection concluded on 29 April 2024. A total of 4,796 papers were retrieved from 1,173 journals, authored by 18,835 researchers from 4,257 institutions across 103 countries/regions. From 1991 to 2023, annual publications on placental oxidative stress increased from 7 to 359. The United States (1,222 publications, 64,158 citations), the University of Cambridge (125 publications, 13,562 citations), and Graham J. Burton (73 publications, 11,182 citations) were the most productive country, institution, and author, respectively. The journal Placenta had the highest number of publications (329) and citations (17,152), followed by the International Journal of Molecular Sciences (122 publications). The most frequent keywords were "oxidative stress," "expression," "pregnancy," "preeclampsia," and "lipid peroxidation." Emerging high-frequency keywords included "gestational diabetes mellitus," "health," "autophagy," "pathophysiology," "infection," "preterm birth," "stem cell," and "inflammation." Over the past 3decades, research has concentrated on oxidative stress processes, antioxidant mechanisms, pregnancy-related diseases, and gene expression regulation. Current research frontiers involve exploring pathophysiology and mechanisms, assessing emerging risk factors and environmental impacts, advancing cell biology and stem cell research, and understanding the complex interactions of inflammation and immune regulation. These studies elucidate the mechanisms of placental oxidative stress, offering essential scientific evidence for future intervention strategies, therapeutic approaches, and public health policies.

Study of placenta histopathology in low birth weight deliveries: A prospective cross-sectional study at Nobel Medical College Teaching Hospital

Background: Placenta is the most important organ that represents the status of the mother and fetus. Its examination on gross and microscopy can reveal varied pregnancy-related diseases, decreasing future adverse pregnancy outcomes. This study aims to examine the placenta histopathologically among low birth weight pregnancies. Materials and methods: A prospective case-control study was conducted in the Department of Pathology over one year. The placenta of low birth weight (weight &lt; 2.5 kg) term pregnancies were histopathologically examined. The maternal demographics, co-morbidity, gravida, and hemoglobin levels were recorded. Descriptive statistics, and student t-test or Chi-square test were used for two-group analysis. Results: Thirty-two consecutive patients enrolled in each group. A significant proportion of the patients in the study group were anemic (9.2 vs. 11.5 gm/dl; p=0.03). Pregnancy-induced hypertension rate was significantly higher in the study group (31% vs. 9%; p = 0.042). Gross observations in low birth weight pregnancies were sub-chorionic fibrin deposition (75%), calcification (37%) and infarction (31%). On microscopy, chorionic vessel thrombosis was significantly higher in the study group (56% vs. 6%; p= 0.003). Furthermore, chorioamnionitis (34%) and placental floor infarction (12%) were also observed in a significantly higher number of placentas in the study group. Conclusions: Anemia and pregnancy-induced hypertension are important associated factors for low birth weight pregnancies. Pathological examinations reveal higher fibrin deposition, infarction, calcification, sub-chronic vessel thrombosis, and chorioamnionitis in low birth weight placenta.

The role of pyroptosis in the occurrence and development of pregnancy-related diseases.

Pyroptosis is a form of programmed cell death that is crucial in the development of various diseases, including autoimmune diseases, atherosclerotic diseases, cancer, and pregnancy complications. In recent years, it has gained significant attention in national and international research due to its association with inflammatory immune overactivation and its involvement in pregnancy complications such as miscarriage and preeclampsia (PE). The mechanisms discussed include the canonical pyroptosis pathway of gasdermin activation and pore formation (caspase-1-dependent pyroptosis) and the non-canonical pyroptosis pathway (cysteoaspartic enzymes other than caspase-1). These pathways work on various cellular and factorial levels to influence normal pregnancy. This review aims to summarize and analyze the pyroptosis pathways associated with abnormal pregnancies and pregnancy complications. The objective is to enhance pregnancy outcomes by identifying various targets to prevent the onset of pyroptosis.

Targeting Decidual CD16+ Immune Cells with Exosome-Based Glucocorticoid Nanoparticles for Miscarriage.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

IL-32 regulates trophoblast invasion through miR-205-NFκB-MMP2/9 axis contributing to the pregnancy-induced hypertension†.

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signaling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

Analysis of Differences in the Serum Levels of Various Vitamins During Pregnancy: Effects of Gestational Stage and Age

Background: Pregnant women exhibit an increased demand for nutrients, including vitamins, and a deficiency in vitamins can increase the risk of various pregnancy-related diseases. This study aims to evaluate the vitamin levels in women of different age groups and gestational stages in order to provide targeted dietary guidance and vitamin supplementation strategies. Methods: Pregnant women who registered and attended regular prenatal check-ups at Hangzhou Women’s Hospital from January to December 2021 were selected as study participants. Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to quantitatively determine the concentrations of vitamins A, D, E, K, B1, B2, B9 (folic acid), and B12 in the serum. Results: The serum vitamin A, B1, and B9 levels decreased with gestational age in the age-matched group, while the vitamin E level increased slightly (p &lt; 0.05). In the advanced-aged group, the levels of vitamins A, B1, B2, and B9 decreased with gestational age, but the levels of vitamins D3, E, K, and B12 slightly increased (p &lt; 0.05). In mid-pregnancy, age-matched women had slightly greater serum levels of vitamins E and K than did women in the advanced-aged group (Z = –2.67, p = 0.008; Z = –2.46, p = 0.014). In late pregnancy, significant differences existed in the serum levels of vitamins B2 and B12 between the two age groups (Z = –2.67, p = 0.008; Z = –2.50, p = 0.013). Conclusions: Vitamin levels varied by gestational stage and age during pregnancy, suggesting that vitamin supplementation should be individualized and stage-adjusted to improve maternal and child health.

O-094 Novel stem cell-based twin embryo model reveals inner cell mass division and enhanced endometrial adhesion in monochorionic twin development

Abstract Study question How do monochorionic twin embryos arise and develop during the pre- and peri-implantation stage? Summary answer Twinning involves inner cell mass division during blastocyst expansion and heightened endometrial adhesion, with twin blastoids showing greater implantation potential. What is known already The occurrence of monozygotic twins is between 0.4 and 0.5% of livebirths globally from natural conception, of which the majority are monochorionic. Monochorionic twins are associated with increased risk of complications and higher mortality rates during pregnancy due to twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence, developmental malformations and increased incidence of pregnancy-related diseases in the mother. The rarity of monochorionic twinning, combined with ethical constraints in human embryo research, renders the study of twinning practically infeasible, which presents in a significant knowledge gap regarding the origins and implications of early developmental monochorionic twin embryos development. Study design, size, duration In a stem cell-based model of the blastocyst-stage embryo (i.e., blastoid) conditions were identified that favor the generation of monochorionic twin blastoids. To obtain sufficient statistical power, screening experiments were performed using 3 culture wells per condition, each well containing at least 90 blastoids. Experiments were repeated 3 times and results were pooled. Blastoids were cultured for at least 3 days followed by 2 days on endometrium monolayers on-chip. Participants/materials, setting, methods Human naïve induced pluripotent stem cells and embryonic stem cells were used to form twin blastoids within custom microwell array platforms. Patient-derived endometrium epithelial cells were expanded as organoids and seeded as monolayers in microfluidic chips. Blastoids were infused into the chip, allowed to adhere for 2 days, followed by a controlled stepwise increase of flow rate after which the blastoid adhesion rate to the endometrium layer for both singleton and twin blastoids was quantified. Main results and the role of chance Twin blastoids contained a cystic GATA3+ single layered trophectoderm-like epithelium encasing two distinct inner cell masses (ICMs). Morphological and morphokinetic analyses revealed that twinning occurs during the blastocyst cavitation phase via division of the OCT4+ pluripotent cell mass. After three days of culture, twin blastoids measured 228±32 µm, which is in the upper range of the cyst diameter of a blastocyst. In addition, both sibling ICM-like clusters preserved similar epiblast and hypoblast cell proportions and were consistently positioned nearly 150° (146.6±26°) apart along the blastocoel lining (measured as 2D-projections and in 3D reconstructions), which suggests a minimal angular distance for establishing two separate condensed ICM clusters. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm-like region, indicative of implantation readiness. Under defined flow regimes, twin blastoids show increased adhesion capacity to endometrium monolayers compared to singleton blastoids (60% vs 38% at highest flow rate), suggestive of increased implantation potential possibly due to a larger adhesive surface area. Twin blastoids cultured on endometrium monolayers could develop into structures with two distinctive OCT4+ pluripotent cell clumps both delineated by SOX17+ hypoblast-like cells and as a whole encompassed by GATA3+ trophoblast-like cells, suggestive of post-implantation organization. Limitations, reasons for caution While twin blastoids adhered to the endometrium monolayer and maintained two separate OCT4 compartments after 48 hours in post-implantation culture, both singleton and twin blastoids did not establish organized 3D structures associated with later post-implantation development, including amniotic and yolk sac-like cavities. Wider implications of the findings Twin blastoids open new avenues for studying the various aspects of twinning, ranging from their formation processes to the effects of multiple ICMs on trophectoderm maturation and implantation potential. In the future, with more sophisticated endometrium platforms, this model may inform on how clinical complications arise in twin pregnancies. Trial registration number not applicable

Prevalence of hyperuricemia and associated factors among pregnant women in Vietnam: A cross-sectional study

PurposeHyperuricemia is a significant health concern worldwide. It is important to identify pregnant women who may be at risk to enhance pregnancy care. This study aims to investigate the prevalence of hyperuricemia and identify some factors associated with hyperuricemia among Vietnamese pregnant women. MethodsIn this cross-sectional study, 340 pregnant women were enrolled from May 2021 to December 2021. Demographic information, anthropometric data, and food frequency consumption (within 1 month before delivery) were collected from the participants. In addition, the biochemical indices of the participants were collected from medical records. Multivariate logistic regression was deployed to identify associated factors (p < 0.05). ResultsThe prevalence of hyperuricemia was estimated at 20.3 %. Factors associated with hyperuricemia risk among Vietnamese pregnant women include eating red meat (aOR: 2.3), eating animal organs (aOR: 2.5), not meeting vegetable recommendations (aOR: 6.7), hyper-total cholesterol (aOR: 2.4), disease during pregnancy (aOR: 3.5) and gestational weight gain below recommendations (aOR: 0.2). ConclusionsThe prevalence of hyperuricemia among pregnant women was relatively high at the National Hospital of Obstetrics and Gynecology, Hanoi, Vietnam. Consuming red meat and animal organs, not meeting vegetable recommendations, having high total cholesterol, and experiencing pregnancy-related diseases are the major factors associated with higher rates of hyperuricemia in this study.

CircPAPPA2 plays a role in preeclampsia pathogenesis via regulation of the miR-942/miR-5006-3p

CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia

BackgroundPreeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown.ResultsBy analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling.ConclusionsOur study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

Knowledge and Uptake of Community-Based Healthcare Financing in Management of Non-Communicable Diseases among Community Members in Anambra State, Nigeria

Background: Catastrophic health expenditure is one of the challenges people living with non-communicable disease face, especially in Nigeria. This has led to the emergence of community-based health insurance as a means to achieve universal health coverage and reduce out-of-pocket payments. However, lack of knowledge about the insurance scheme and how it helps to manage non-communicable diseases seems to affect utilization. Aim: The study assessed the knowledge and uptake of community based healthcare financing in the management of non-communicable diseases among community members in Anambra State. Materials and Methods: A descriptive cross-sectional survey design was adopted for the study, sample size was 444 and a multistage sampling technique was used. The instrument for data collection was a self structured questionnaire and data obtained were analyzed using Microsoft excel, descriptive statistics, inferential statistics for hypothesis testing and IBM statistical package for social Sciences (SPSS) version 29. Results: 64.1% had a good knowledge of community based healthcare financing; 51.4% managed their health condition through hospital visits under CBHI. There was a significant relationship between the level of education of respondents and their level of knowledge of community based health insurance (p-value 0.001 &lt; 0.05). Conclusion: Majority had a good knowledge; those suffering pregnancy related non-communicable diseases used the insurance more although half of the respondents still pay through their pocket. The following recommendations were made: increase access to community-based healthcare financing information, encourage those in the informal sector to enroll and plan benefit packages to have wide illness coverage.

Investigation of Adiponectin, Leptin and Ghrelin Levels and Evaluation of Metabolic Profiles in the Periparturient Period in Romanov Sheep

The periparturient period is very important especially in terms of pregnancy-related herd-based diseases. In this period, especially for early diagnosis of subclinical diseases, a metabolic profile test is used. In the periparturient period, important changes occur in adipose tissue. Blood samples were collected from 16 Romanov sheep in the periparturient in serum tubes on the 21st, 14th, 7th, and postpartum days, and 7th, 14th, and 21st days after delivery. Metabolic profile and Adiponectin, Leptin and Ghrelin parameters evaluated from the blood samples. In the periparturient period, ELISA analyzes of TNF-α were performed for inflammatory evaluation. As a result of the analyzes, Prenatal increase in NEFA concentrations, postpartum decrease in cholesterol concentrations, postpartum increase and decrease in AST concentrations, postpartum increase in GGT concentrations, prenatal and postnatal increases in total protein concentrations, postpartum increase in BUN and creatinine concentrations, postpartum decrease in magnesium concentrations, Prenatal increase in adiponectin concentrations and postpartum decrease, postpartum decrease in leptin concentrations and prenatal increase in ghrelin concentrations occurred. With the results obtained, it was concluded that the evaluation of metabolic profile and adipose tissue is important in the diagnosis of diseases in the periparturient period.

Enfermedades hepáticas relacionadas con el embarazo

Pregnancy-related liver diseases are an important cause of maternal and infant morbidity and mortality. The diagnosis should always be a diagnosis of exclusion (viral, autoimmune, or drug-related liver diseases or biliopancreatic diseases). Pregnancy-related liver diseases include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, preeclampsia, eclampsia, HELLP syndrome, and acute fatty liver of pregnancy.

The effect of histo-blood group ABO system transferase (BGAT) on pregnancy related outcomes：A Mendelian randomization study

Protein level of Histo-Blood Group ABO System Transferase (BGAT) has been reported to be associated with cardiometabolic diseases. But its effect on pregnancy related outcomes still remains unclear. Here we conducted a two-sample Mendelian randomization (MR) study to ascertain the putative causal roles of protein levels of BGAT in pregnancy related outcomes. Cis-acting protein quantitative trait loci (pQTLs) robustly associated with protein level of BGAT (P < 5 ×10−8) were used as instruments to proxy the BGAT protein level (N = 35,559, data from deCODE), with two additional pQTL datasets from Fenland (N = 10,708) and INTERVAL (N = 3301) used as validation exposures. Ten pregnancy related diseases and complications were selected as outcomes. We observed that a higher protein level of BGAT showed a putative causal effect on venous complications and haemorrhoids in pregnancy (VH) (odds ratio [OR]=1.19, 95% confidence interval [95% CI]=1.12–1.27, colocalization probability=91%), which was validated by using pQTLs from Fenland and INTERVAL. The Mendelian randomization results further showed effects of the BGAT protein on gestational hypertension (GH) (OR=0.97, 95% CI=0.96–0.99), despite little colocalization evidence to support it. Sensitivity analyses, including proteome-wide Mendelian randomization of the cis-acting BGAT pQTLs, showed little evidence of horizontal pleiotropy. Correctively, our study prioritised BGAT as a putative causal protein for venous complications and haemorrhoids in pregnancy. Future epidemiology and clinical studies are needed to investigate whether BGAT can be considered as a drug target to prevent adverse pregnancy outcomes.

Multilevel modeling of factors associated with eight or more antenatal care contacts in low and middle income countries: findings from national representative data

Background: Antenatal care (ANC) is the care provided by skilled health-care professionals to pregnant women in order to ensure the best health conditions for both mother and baby. Antenatal care provides a platform for important health-care functions including risk identification, prevention and management of pregnancy-related diseases. Inadequate ANC utilization is global problem especially for low and middle-income countries. The 2016 WHO ANC model with minimum of eight ANC visits was aimed to provide pregnant women with person specific care at every contact. However, there are limited studies that investigate the associated factors of inadequate ANC after the endorsement of the WHO 2016 guideline. Therefore, to enrich the evidence in the low and middle income countries (LMICs), this study aimed to determine the pooled prevalence and associated of eight or more ANC contacts during pregnancy. Methods: This study used data from 20LMICs that have a recent Demographic and Health Survey. About 43,720 women aged 15–49 years who had live births within the year prior to the surveys were included. To identify associated factors of 8 or more ANC contacts, we used multilevel binary logistic regression, and four models were constructed. The results have been presented as odds ratios with 95% confidence intervals, and P values&lt;0.05 were considered significant factors for ≥8 ANC contacts. Results: In LMICs, the pooled utilization of 8 or more ANC contact was 18.11% (95%CI: 12.64, 23.58) and it ranged from 0.27% in Rwanda to 76.62% in Jordan. In the final multilevel logistic regression model, women with higher education (AOR=3.83, 95% CI: 3.32, 4.41), husbands with higher education (AOR=1.98, 95% CI: 1.72, 2.28), women who have access to media (AOR=1.32, 95% CI: 1.19, 1.45), women with decision-making autonomy (AOR=1.52, 95% CI: 1.39, 1.66), women aged 35-49 years (AOR=1.70, 95% CI: 1.5, 1.91), women from communities with high media access (AOR=1.38, 95% CI: 1.23, 1.53), and husbands residing in communities with high literacy (AOR=1.76, 95% CI: 1.55, 1.98) were associated with higher odds of ≥8 ANC contacts. Conversely, women with a birth order of ≥6 (AOR=0.65, 95% CI: 0.56, 0.76), women who perceive distance to a health facility as a significant problem (AOR=0.90, 95% CI: 0.83, 0.96), those with unwanted pregnancies (AOR=0.85, 95% CI: 0.78, 0.93), delayed initiation of ANC (AOR=0.26, 95% CI: 0.23, 0.3), women from households with the richest wealth index (AOR=0.45, 95% CI: 0.40, 0.52), and rural residents (AOR=0.47, 95% CI: 0.43, 0.51) were associated with lower odds of ≥8 ANC contacts. Conclusion and recommendations: In compliance with the WHO guideline, the number of ANC contacts is low in LMICs. Individual-level, household-level, and community-level variables were associated with ≥8 ANC contacts. Therefore, implementation strategies should focus on the identified factors in order to achieve the newly WHO recommendation of ≥8ANC contacts.

Actively Targeted Nanomedicines: A New Perspective for the Treatment of Pregnancy-Related Diseases.

More than 20% of pregnant women experience serious complications during pregnancy, that gravely affect the safety of both the mother and the child. Due to the unique state of pregnancy, medication during pregnancy is subject to various restrictions. Nanotechnology is an emerging technology that has been the focus of extensive medical research, and great progress has recently been made in developing sensitive diagnostic modalities and efficient medical treatment. Accumulating evidence has shown that nanodrug delivery systems can significantly improve the targeting, reduce the toxicity and improve the bioavailability of drugs. Recently, some actively targeted nanomedicines have been explored in the treatment of pregnancy-related diseases. This article reviews common types of nanocarriers and active targeting ligands in common pregnancy-related diseases and complications such as preeclampsia, preterm birth, fetal growth restriction, and choriocarcinoma. Finally, the challenges and future prospects in the development of these nanomaterials are discussed, with the aim of providing guidance for future research directions.

Development and validation of nomograms to predict clinical outcomes of preeclampsia.

Preeclampsia (PE) is one of the most severe pregnancy-related diseases; however, there is still a lack of reliable biomarkers. In this study, we aimed to develop models for predicting early-onset PE, severe PE, and the gestation duration of patients with PE. Eligible patients with PE were enrolled and divided into a training (n = 253) and a validation (n = 108) cohort. Multivariate logistic and Cox models were used to identify factors associated with early-onset PE, severe PE, and the gestation duration of patients with PE. Based on significant factors, nomograms were developed and evaluated using the area under the curve (AUC) and a calibration curve. In the training cohort, multiple gravidity experience (p = 0.005), lower albumin (ALB; p < 0.001), and higher lactate dehydrogenase (LDH; p < 0.001) were significantly associated with early-onset PE. Abortion history (p = 0.017), prolonged thrombin time (TT; p < 0.001), and higher aspartate aminotransferase (p = 0.002) and LDH (p = 0.003) were significantly associated with severe PE. Abortion history (p < 0.001), gemellary pregnancy (p < 0.001), prolonged TT (p < 0.001), higher mean platelet volume (p = 0.014) and LDH (p < 0.001), and lower ALB (p < 0.001) were significantly associated with shorter gestation duration. Three nomograms were developed and validated to predict the probability of early-onset PE, severe PE, and delivery time for each patient with PE. The AUC showed good predictive performance, and the calibration curve and decision curve analysis demonstrated clinical practicability. Based on the clinical features and peripheral blood laboratory indicators, we identified significant factors and developed models to predict early-onset PE, severe PE, and the gestation duration of pregnant women with PE, which could help clinicians assess the clinical outcomes early and design appropriate strategies for patients.

Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies.

With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types. We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases. We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal-fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types. Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreover, most of the newly defined markers in one study were not observed in other studies. These discrepancies were confirmed by our analysis on trophoblast cell types, where hundreds of potential marker genes were identified in each study but with little overlap across studies. From 35461 and 23378 cells of high quality in the first trimester and term placentas, respectively, we obtained major placental cell types, including perivascular cells that previously had not been identified in the first trimester. Importantly, our meta-analysis provides marker genes for major placental cell types based on our extensive curation. This review and meta-analysis emphasizes the need for establishing a consensus for annotating placental cell types from scRNAseq data. The marker genes identified here can be deployed for defining human placental cell types, thereby facilitating and improving the reproducibility of trophoblast cell annotation.