Search

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

Neutrophil extracellular traps (NETs) and placental neutrophil reverse transmigration (r-TM) are implicated in the pathogenesis of pre-eclampsia (PE). However, the role of the comorbidity of PE and human immunodeficiency virus (HIV) infection in placental neutrophil r-TM and serum NETs remains unknown. Human placental tissue (n = 160) and serum (n = 80) samples were obtained post-ethical approval and divided by pregnancy type and HIV status and across the study population. Immunohistochemistry and morphometry were performed to localize and quantify junctional adhesion molecule-C (JAM-C) expression as an inverse marker of neutrophil r-TM within placental villi. An enzyme-linked immunosorbent assay (ELISA) was performed to quantify the concentration of citrullinated histone H3 (cit-H3) as a marker of NETs. GraphPad Prism (version 8.0.2) was used to compare the results, and a p value of p < 0.05 was considered statistically significant. The localization of JAM-C was observed on the syncytiotrophoblasts (STBs) and endothelial cells of placental villi. The immunoexpression of JAM-C was elevated in PE vs. normotensive (N) placentae. In the exchange villi, JAM-C immunoexpression was higher in the N+ve vs. N-ve group. However, in PE comorbid HIV infection, JAM-C expression was lower in the PE+ve vs. PE-ve group. Citrullinated histone-H3 concentration was lower in the N+ve vs. N-ve group but elevated in early-onset PE (EOPE)+ve vs. late-onset PE (LOPE)+ve group. These results indicate that PE and HIV-infected placentae individually express elevated JAM-C, manifesting in less neutrophil r-TM. However, in exchange villi of PE comorbid with HIV infection reduced JAM-C enhances neutrophil r-TM, thus supporting the synergistic effect of PE comorbid with HIV. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association of GDM and pre-eclampsia in women with obstetric cholestasis. Materials and methods: Pregnant women with > 28 weeks gestation attending ANC, OPD and labor room of J.N.M.C.H, AMU, Aligarh UP (India) from 2020 to 2022 were included in the study after taking informed consent and ethical approval from the Institute. Women were divided into 2 groups, i.e. group 1 having 200 women with IHCP and group 2 having 200 healthy pregnant women; both the groups were followed up for the development of GDM and pre-eclampsia. Results: A statistically significant association was observed between IHCP and development of GDM [26.5% and odds ratio (OR) 1.64] and pre-eclampsia (17% and OR: 1.95) (p < 0.05), an also GDM and pre-eclampsia were found to be significantly associated with the severity of cholestasis (p < 0.05). Thus, on calculating OR, we found higher odds of developing GDM and pre-eclampsia in IHCP group with raised serum bile acid levels, maximum at 60 μmol/L level as compared to 10–40 μmol/L (GDM: OR: 8.647 and pre-eclampsia: OR: 6.303). Induction and cesarean rates were significantly higher in IHCP group (p < 0.05). Conclusion: Our study concludes significant association of IHCP with GDM and pre-eclampsia as all three shares common pathogenetic pathways and greater risk of development at higher serum bile acid levels. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. Method: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. Results: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). Conclusion: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia. [ABSTRACT FROM AUTHOR]

In this prospective cohort study, the effectiveness of combining second trimester maternal serum β-HCG levels with Colour Doppler ultrasound measurements is assessed. The study aims to predict pre-eclampsia and intrauterine growth restriction (IUGR) in 88 primigravidae women. Significant associations were found between elevated β-HCG levels and abnormal Doppler indices, including increased Pulsatility Index (PI) and Resistance Index (RI), with the development of pre-eclampsia and IUGR. The combined utilisation of these biomarkers greatly enhanced the accuracy of predictions, resulting in a high level of sensitivity and specificity. This indicates their potential value in regular prenatal screening. This approach has the potential to facilitate earlier interventions, which could lead to a decrease in the negative outcomes linked to these conditions. [ABSTRACT FROM AUTHOR]

Leptin has important roles in numerous physiological functions, including those in the regulation of energy balance, and in immune and reproductive systems. However, in the recent years, evidence has implicated it in a number of obesity-related diseases, where its concentrations in serum are significantly elevated. Elevated serum leptin concentrations and increased placental leptin secretion have been reported in women with hypertensive disorders of pregnancy. Whether leptin is responsible for this disorder remains to be established. Leptin injections in healthy rats and mice during pregnancy result in endothelial activation, increased blood pressure and proteinuria. A potential role for leptin in the pathogenesis of pre-eclampsia is hypothesised, particularly in women who are overweight or obese where serum leptin concentrations are often elevated. This review summarises pertinent information in the literature on the role of leptin in puberty, pregnancy, and hypertensive disorders of pregnancy. In particular, the possible mechanism that may be involved in leptin-induced increase in blood pressure and proteinuria during pregnancy and the potential role of marinobufagenin in this disease entity. We hypothesise a significant role for oxidative stress in this, and propose a conceptual framework on the events that lead to endothelial activation, raised blood pressure and proteinuria following leptin administration. Leptin is necessary for normal pubertal development and pregnancy; however, raised concentrations of leptin may have serious adverse effects on pregnancy. This review summarises pertinent information in the literature on the role of leptin in puberty, pregnancy and, pregnancy hypertension. Evidence suggests a significant role for oxidative stress in this, and propose a conceptual framework on the possible events that lead to endothelial activation, raised blood pressure and proteinuria following leptin administration. Image by Harbindarjeet Singh and Fayez Almabhouh. [ABSTRACT FROM AUTHOR]