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Histochemistry and Cell Biology Jun 2024Neutrophil extracellular traps (NETs) and placental neutrophil reverse transmigration (r-TM) are implicated in the pathogenesis of pre-eclampsia (PE). However, the role...
Placental neutrophil reverse trans-migration and maternal serum neutrophil extracellular trap expression in HIV infection co-morbid pre-eclampsia in women of African ancestry.
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.
PubMed: 38913117
DOI: 10.1007/s00418-024-02298-6 -
Indian Journal of Endocrinology and... 2024Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes before gestation....
INTRODUCTION
Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes before gestation. Unrecognized and untreated GDM confers significantly greater maternal and fetal risk, which is largely related to the degree of hyperglycemia. The specific risks of diabetes in pregnancy include but are not limited to, spontaneous abortion, pre-eclampsia, fetal anomalies, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, and respiratory distress syndrome. Additionally, GDM is also implicated in long-term metabolic derangements in the offspring in the form of obesity/overweight, hypertension, dysglycemia, insulin resistance, and dyslipidemias later in life. To determine the prevalence of anthropometric and metabolic derangements in children between 1 and 5 years of age, born to women with GDM.
METHODS
This hospital-based cross-sectional study was conducted between November 2019 and November 2021 at our Pediatric Endocrine Clinic. Women were diagnosed as having GDM based on the American Diabetes Association Criteria (2019). History regarding the treatment of the GDM (diet only/diet and medical treatment) and detailed physical examination, including anthropometry and blood pressure, were recorded. Blood samples were collected from children for the estimation of their metabolic profile.
RESULTS
Overweight, obesity, and severe obesity were present in 18 (11.3%), 2 (1.3%), and 2 (1.3%) children, respectively. Hypertension was found in 21 (19.4%) children. Elevated LDL, triglyceride, and total cholesterol were seen in 3 (1.9%), 84 (52.5%), and 1 (0.6%) children, respectively. Impaired fasting glucose (IFG) was found in 6 (3.8%) children, while 27 (16.9%) subjects were found to be having impaired glucose tolerance after OGTT. Insulin resistance was found in 30 (18.8%) children. GDM mothers with a higher BMI tended to have children with a higher BMI (correlation coefficient, r = .414, < .001). Higher serum triglyceride levels (r = -0.034, = 0.672) were recorded in children, irrespective of the BMI of their mothers. There was no significant correlation of maternal BMI with blood pressure (r = -0.134, = 0.091) or with HOMA-IR (r = 0.00, = 0.996) in children. However, mothers with a higher BMI had children with statistically higher fasting blood glucose (r = +0.339, = <0.001) as well as blood glucose 2 hours after OGTT (r = +0.297, = <0.001). This positive correlation of maternal BMI with the glucose metabolism of their offspring was observed for both male and female genders.
CONCLUSION
Children of women with GDM had a higher BMI, and the mode of treatment for GDM did not lead to differences in childhood BMI. The higher BMI of a GDM mother is associated with altered glucose metabolism in their offspring. Deranged levels of triglyceride across the gender were not found to be statistically significant. This has implications for future metabolic and cardiovascular risks in targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism as one potential strategy to prevent adverse metabolic health outcomes.
PubMed: 38911115
DOI: 10.4103/ijem.ijem_211_23 -
Reproductive Sciences (Thousand Oaks,... Jun 2024Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently...
Maternal Uterine Artery Adenoviral Vascular Endothelial Growth Factor (Ad.VEGF-A) Gene Therapy Normalises Fetal Brain Growth and Microglial Activation in Nutrient Restricted Pregnant Guinea Pigs.
Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A (1 × 10 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.
PubMed: 38907125
DOI: 10.1007/s43032-024-01604-w -
Journal of the American Academy of... Jun 2024
PubMed: 38906262
DOI: 10.1016/j.jaad.2024.05.087 -
Medicine Jun 2024Preeclampsia (PE) is a serious condition that threatens pregnancy with severe sequelae on both the mother and infant. Early detection of PE will lead to favorable... (Observational Study)
Observational Study
Preeclampsia (PE) is a serious condition that threatens pregnancy with severe sequelae on both the mother and infant. Early detection of PE will lead to favorable outcomes, and using readily available markers like hematological indices is an attractive choice. Examine the diagnostic utility of hematological indices in pregnant women to predict preeclampsia and its severity. In a retrospective case-control study that included 252 women, all had their complete blood picture evaluated during their first and third trimesters as part of their outpatient antenatal care during their pregnancy. They were also divided into 3 groups: healthy pregnant women (control), non-severe PE, and severe PE, each involving 84 women. The changes in platelet to lymphocyte ratio (PLR) between 1st and 3rd trimesters showed an excellent ability to differentiate between severe PE and control (area under the curve = 0.954, cutoff ≤ -5.45%) and a good ability to differentiate between severe PE and non-severe PE (area under the curve = 0.841, cutoff ≤ -7.89%). Neutrophil to lymphocyte ratio showed a good to excellent ability to differentiate between severe PE and non-severe PE compared to control in the first and third trimesters and the percentage change between them. Changes in neutrophil to lymphocyte ratio and PLR strongly predict preeclampsia and its severity since they offer more predictive values than measuring NLP and PLR at different stages of pregnancy individually.
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Retrospective Studies; Adult; Case-Control Studies; Severity of Illness Index; Lymphocyte Count; Platelet Count; Predictive Value of Tests; Biomarkers; Lymphocytes; Neutrophils
PubMed: 38905404
DOI: 10.1097/MD.0000000000038557 -
Journal of the American Heart... Jul 2024Gestational hypertension (GHTN) and preeclampsia are established risk indicators for chronic hypertension. While recurrence is associated with a greater risk, it is...
BACKGROUND
Gestational hypertension (GHTN) and preeclampsia are established risk indicators for chronic hypertension. While recurrence is associated with a greater risk, it is unclear whether there are differences in risk when these gestational complications occur for the first time in an earlier pregnancy versus first occurrence in a subsequent one. We hypothesized that the absence of recurrence reflects a transition toward a lower hypertension risk trajectory, whereas a new occurrence in a later pregnancy indicates a transition toward elevated risk.
METHODS AND RESULTS
We analyzed linked data in Quebec, Canada, from public health care insurance administrative databases and birth, stillbirth, and death registries. Our retrospective cohort study included mothers with 2 singleton deliveries between April 1990 and December 2012. The primary exposure was patterns of GHTN or preeclampsia across 2 pregnancies (GHTN/preeclampsia in neither, first only, second only, or both). The outcome was incident chronic hypertension. We performed an adjusted multivariable Cox regression analysis. Among 431 980 women with 2 singleton pregnancies, 27 755 developed hypertension during the follow-up period. Compared with those without GHTN/preeclampsia, those with GHTN/preeclampsia only in the first pregnancy had a 2.7-fold increase in hazards (95% CI, 2.6-2.8), those with GHTN/preeclampsia only in the second had a 4.9-fold increase (95% CI, 4.6-5.1), and those with GHTN/preeclampsia in both pregnancies experienced a 7.3-fold increase (95% CI, 6.9-7.6). Patterns and estimates were similar when we considered GHTN and preeclampsia separately.
CONCLUSIONS
The magnitude of hypertension risk is associated with the number and sequence of GHTN/preeclampsia-affected pregnancies. Considering both allows more personalized risk estimates.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Pre-Eclampsia; Adult; Hypertension, Pregnancy-Induced; Quebec; Risk Factors; Hypertension; Incidence; Young Adult; Risk Assessment; Chronic Disease; Recurrence; Blood Pressure; Time Factors; Registries
PubMed: 38904245
DOI: 10.1161/JAHA.124.034777 -
BMC Public Health Jun 2024Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the...
BACKGROUND
Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the regional influences to understand the geographical inequalities.
METHODS
Data from 180 respondents were prospectively collected from the Preeclampsia ward of Dhaka Medical College Hospital (DMCH), Bangladesh. Anaemia was defined as a blood haemoglobin level less than 11.0 g/dl. Preeclampsia was defined as systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) ≥ 90 mmHg with proteinuria. Factors associated with anaemia were explored using the chi-square test. Logistic regression (LR) was done to determine the level of association with the risk factors.
RESULTS
Among the participants, 28.9% were identified as having early onset and 71.1% reported late onset of PE. 38.9% of the subjects were non-anaemic, whereas mild, moderate, and severe anaemia was found among 38.3%, 17.8%, and 5% of patients respectively. The following factors were identified; including age range 25-34 (OR: 0.169, p < 0.05), a lower education level (OR: 3.106, p < 0.05), service-holder mothers (OR: 0.604, p < 0.05), pregnancy interval of less than 24 months (OR: 4.646, p < 0.05), and gestational diabetes mellitus (OR: 2.702, p < 0.05). Dhaka district (IR: 1.46), Narayanganj district (IR: 1.11), and Munshiganj district (IR: 0.96) had the highest incidence rates.
CONCLUSION
Determinants of anaemia must be considered with importance. In the future, periodic follow-ups of anaemia should be scheduled with a health care program and prevent maternal fatality and fetus morbidity in patients with PE.
Topics: Humans; Female; Bangladesh; Anemia; Pregnancy; Pre-Eclampsia; Adult; Cross-Sectional Studies; Risk Factors; Young Adult; Health Status Disparities; Socioeconomic Factors; Prospective Studies
PubMed: 38902634
DOI: 10.1186/s12889-024-18176-8 -
The British Journal of General Practice... Jun 2024Hypertensive disorders of pregnancy (HDP) affect approximately 10-15% of pregnancies and pre-eclampsia affects 3-5% of pregnancies. Women with previous pre-eclampsia or... (Review)
Review
What interventions are effective in reducing development of hypertension and other cardiovascular complications in women who have had hypertensive disorders of pregnancy? A systematic review.
BACKGROUND
Hypertensive disorders of pregnancy (HDP) affect approximately 10-15% of pregnancies and pre-eclampsia affects 3-5% of pregnancies. Women with previous pre-eclampsia or HDP are at increased risk of hypertension (2 to 5 times) and major cardiovascular disease (1.5 to 3 times). There is little guidance on how to reduce this risk.
AIM
To establish if there are interventions in women with previous HDP or pre-eclampsia that reduce the risk of developing adverse cardiovascular outcomes.
METHOD
A protocol was submitted to PROSPERO; inclusion and exclusion criteria were determined and a search strategy implemented. Primary outcomes were: development of hypertension or change in blood pressure and development of other cardiovascular complications. Records and full texts were screened independently by two reviewers. The Cochrane Risk of Bias tool was used for quality assessment.
RESULTS
3593 articles were screened. Nine articles were included. There were seven randomised-controlled trials and two quasi-experimental studies. One study trialled antihypertensive use, two studies looked at blood pressure monitoring and six studies focused on lifestyle interventions. Three trials reported significant reductions in diastolic blood pressure in the experimental group. No studies looked at the optimal time of intervention or the impact of interventions on the development of other long-term cardiovascular complications. Five studies reported participant feedback. The majority of studies were of low quality.
CONCLUSION
Further research needs to explore potential interventions and optimal timing of interventions to reduce cardiovascular risk. Women also need to be consulted about their preferences for discussions about cardiovascular risk and potential interventions.
Topics: Humans; Female; Pregnancy; Hypertension, Pregnancy-Induced; Antihypertensive Agents; Cardiovascular Diseases; Pre-Eclampsia; Hypertension; Blood Pressure
PubMed: 38902046
DOI: 10.3399/bjgp24X738069 -
Frontiers in Nephrology 2024Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), leads to significant kidney inflammation and damage and drastically increases... (Review)
Review
Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), leads to significant kidney inflammation and damage and drastically increases mortality risk. Predominantly impacting women in their reproductive years, LN poses specific risks during pregnancy, including pre-eclampsia, growth restrictions, stillbirth, and preterm delivery, exacerbated by lupus activity, specific antibodies, and pre-existing conditions like hypertension. Effective management of LN during pregnancy is crucial and involves carefully balancing disease control with the safety of the fetus. This includes pre-conception counseling and a multidisciplinary approach among specialists to navigate the complexities LN patients face during pregnancy, such as distinguishing LN flare-ups from pregnancy-induced conditions. This review focuses on exploring the complex dynamics between pregnancy and LN, emphasizing the management difficulties and the heightened risks pregnant women with LN encounter.
PubMed: 38895665
DOI: 10.3389/fneph.2024.1390783 -
Frontiers in Endocrinology 2024The prevalence of obesity among women of reproductive age is increasing worldwide, with implications for serious pregnancy complications. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of obesity among women of reproductive age is increasing worldwide, with implications for serious pregnancy complications.
METHODS
Following PRISMA guidelines, a systematic search was conducted in both Chinese and English databases up to December 30, 2020. Pregnancy complications and outcomes including gestational diabetes mellitus (GDM), gestational hypertension (GHTN), pre-eclampsia, cesarean section (CS), induction of labor (IOL), and postpartum hemorrhage (PPH) were analyzed. Random-effects or fixed-effects models were utilized to calculate the odds ratio (OR) with 95% confidence intervals (CIs).
RESULTS
Women with overweight and obesity issues exhibited significantly higher risks of GDM (OR, 2.92, 95%CI, 2.18-2.40 and 3.46, 95%CI, 3.05-3.94, respectively) and GHTN (OR, 2.08, 95%CI, 1.72-2.53 and 3.36, 95%CI, 2.81-4.00, respectively) compared to women of normal weight. Pre-eclampsia was also significantly higher in women with overweight or obesity, with ORs of 1.70 (95%CI, 1.44-2.01) and 2.82 (95%CI, 2.66-3.00), respectively. Additionally, mothers with overweight or obesity issues had significantly higher risks of CS (OR, 1.44, 95%CI, 1.41-1.47, and 2.23, 95%CI, 2.08-2.40), IOL (OR, 1.33, 95%CI, 1.30-1.35 and 1.96, 95%CI, 1.85-2.07), and PPH (OR, 1.67, 95%CI, 1.42-1.96 and 1.88, 95%CI, 1.55-2.29).
CONCLUSION
Women with overweight or obesity issues face increased risks of pregnancy complications and adverse outcomes, indicating dose-dependent effects.
Topics: Humans; Pregnancy; Female; Pregnancy Complications; Pregnancy Outcome; Body Mass Index; Obesity; Diabetes, Gestational; Pre-Eclampsia; Cesarean Section; Overweight; Postpartum Hemorrhage
PubMed: 38894748
DOI: 10.3389/fendo.2024.1280692