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Placental Growth factor (PlGF) is one of the biomarkers useful for detecting pregnancy hypertension disorder, Pre‐eclampsia. Herein, we focus on developing a label‐free immunosensor using simple electrochemical methods to detect PlGF antigens for pre‐eclampsia diagnosis. The work includes the electrochemical deposition of Palladium nanoparticles (PdNPs) on the glassy carbon electrode (GCE) surface using amperometry followed by electropolymerization of diaminobenzoic acid (DABA) onto the PdNPs/GCE. Antibody (aPlGF) was covalently immobilized on the pDABA/PdNPs/GCE using EDC/NHS reaction. The interaction of the antibody with the antigen was measured using differential pulse voltammetric technique. The linear range obtained for the immunosensor is 1–25 ng mL−1 with a limit of detection of 53 pg mL−1. The stability and reproducibility of the sensor were obtained in the acceptable range. The developed sensor was used to detect PlGF antigen in artificial blood and urine samples by spike recovery analysis. [ABSTRACT FROM AUTHOR]

Background and objectives: Hypertensive disorders of pregnancy (HDPs) remain one of the leading causes of maternal mortality globally, especially in Low- and middle-income countries (LMICs). To reduce the burden of associated morbidity and mortality, standardized prompt recognition, evaluation, and treatment have been proposed. Health disparities, barriers to access to healthcare, and shortage of resources influence these conditions. We aimed to synthesize the literature evidence for the management of HDPs in LMICs. Methods: A scoping review was conducted in five databases (PubMed, Web of Science, Epistemonikos, Clinical Key and, Scielo) using MeSh terms, keywords, and Boolean connectors. We summarized the included studies according to the following categories: study design, objectives, settings, participant characteristics, eligibility criteria, interventions, assessed outcomes, and general findings. Results: Six hundred fifty-one articles were retrieved from the literature search in five databases. Following the selection process, 65 articles met the predefined eligibility criteria. After performing a full-text analysis, 27 articles were included. Three themes were identified from the articles reviewed: prevention of HDPs, management of HDPs (antihypertensive and non-hypertensive management) and pregnancy monitoring and follow-up. The topics were approached from the perspective of LMICs. Conclusions: LMICs face substantial limitations and obstacles in the comprehensive management of HDPs. While management recommendations in most LMICs align with international guidelines, several factors, including limited access to crucial medications, unavailability of diagnostic tests, deficiencies in high-quality healthcare infrastructure, restrictions on continuing professional development, a shortage of trained personnel, community perceptions of preeclampsia, and outdated local clinical practice guidelines, impede the comprehensive management of patients. The development and implementation of protocols, standardized guides and intervention packages are a priority. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first‐trimester screening for pre‐eclampsia in a large Asian population. Methods: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11–13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first‐trimester prediction of preterm pre‐eclampsia (<37 weeks), term pre‐eclampsia (≥37 weeks), and any pre‐eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. Results: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre‐eclampsia (0.82, 95% confidence interval [CI] 0.77–0.87 vs. 0.86, 95% CI 0.811–0.91, P = 0.019), term pre‐eclampsia (0.75, 95% CI 0.71–0.80 vs. 0.79, 95% CI 0.75–0.83, P = 0.006), and any pre‐eclampsia (0.78, 95% CI 0.74–0.81 vs. 0.82, 95% CI 0.79–0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre‐eclampsia, term pre‐eclampsia, and any pre‐eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80–0.89), 0.77 (95% CI 0.73–0.81), and 0.80 (95% CI 0.76–0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre‐eclampsia (P = 0.135) and term pre‐eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre‐eclampsia (P = 0.024). Conclusion: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre‐eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population. Synopsis: Machine learning model achieved comparable predictive performance to that of the FMF competing risk model in predicting preterm and term pre‐eclampsia in an Asian population. [ABSTRACT FROM AUTHOR]

Aberrant long non-coding RNA (lncRNA) expression has been shown to be involved in the pathological process of pre-eclampsia (PE), yet only a small portion of lncRNAs has been characterized concerning the function and molecular mechanisms involved in PE. This study aimed to investigate the regulatory mechanism of the lncRNA AC092100.1 (AC092100.1) in angiogenesis in PE. In our study, bioinformatics analysis was performed to screen for differentially expressed lncRNAs between normal subjects and PE patients. The levels of AC092100.1 in placental tissues of patients with or without PE were validated using qRT-PCR. The effect of AC092100.1 overexpression on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was investigated. The binding of AC092100.1 and YT521-B homology domain-containing 2 (YTHDC2) was predicted and verified. The effect of AC092100.1/YTHDC2 on the expression of vascular endothelial growth factor-A (VEGFA) in HUVECs was determined. Finally, a PE mice model was conducted. Fetal mouse growth, the abundance of mesenchymal morphology markers, including hypoxia-inducible factor 1-alpha (HIF-1α), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), Slug, and Vimentin, and endothelial markers, including placental growth factor (PLGF), CD31, and vascular endothelial (VE)-cadherin, in placental tissues were assessed. Here, we found that AC092100.1 was abnormally downregulated in placental tissues from PE patients. We established that AC092100.1 overexpression promoted HUVEC proliferation, migration, and tube formation in vitro. Mechanistically, AC092100.1 induced the accumulation of YTHDC2 and VEGFA through binding to YTHDC2 in HUVECs. Inhibition of YTHDC2 or VEGFA reversed AC092100.1-promoted tube formation. AC092100.1 overexpression contributed to alleviating fetal growth disorder, decreased levels of sEng, HIF-1α, sFlt-1, Slug, and Vimentin, and increased levels of VEGFA, PLGF, CD31, and VE-cadherin in PE mice. Our findings provided evidence supporting the role of the AC092100.1/YTHDC2/VEGFA axis in regulating angiogenesis, which demonstrated a therapeutic pathway for PE targeting angiogenesis. [ABSTRACT FROM AUTHOR]

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]

Hypertension has largely been viewed as a disorder of adulthood. Historically, blood pressure (BP) was not routinely measured in children because hypertension was considered uncommon in childhood. It was not until the 1970s that it was apparent that in childhood BP levels were normally lower compared with those in adults, were related to age and growth, and that abnormal BP in children needed different definitions. Based on the distribution of BP levels in available child cohorts, the 95th percentile of BP levels became the definition of hypertension in children and adolescents--an epidemiological definition. Subsequent clinical and epidemiological research identified associated risk factors in childhood that linked abnormal BP in youth with hypertension in adulthood. In the 1980s, the Barker hypothesis, based on observations that low birth weight could be linked to cardiovascular disease in adulthood, promoted further research spanning epidemiological, clinical, and basic science on the childhood origins of hypertension. This review focuses on recent findings from both longitudinal maternal-child cohorts and experimental models that examine both maternal and offspring conditions associated with risks of subsequent cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Pregnancy with raised renal parameters was considered high risk but the degree of this risk is unclear. Hence the present study was done to study the effect of raised renal parameters among women with preeclampsiaon adverse maternal and fetal outcomes. Methodology: A Case -Control study was conducted among 100 patients of Pre-eclampsia,50 patients of Preeclampsia with raised renal parameters were included in the study group as cases and 50 matched preeclamptic patients with normal renal parameters were chosen as controls for the study. Matching was done with respect to certain variables like age group, gestational age, gravida and associated co-morbid condition (Pre-Eclampsia) to avoid bias, for a period of one year to study the effect of altered renal function test sonmaterna land fetal outcome in preeclampsia. Results: Compared to women in the control group, women in the study group had 3.7 times increased odds of preterm delivery (OR, 3.7; 95% CI, 1.0-15.2) and 2.4 times increased odds of delivery via caesarean section (OR, 2.4; 95% CI, 1.09-5.4). Women in the study group was also associated with two-fold increased odds of low birth weight (OR, 2.1; 95% CI, 0.5-9.6). Raised renal parameters among pre-eclamptic women was not associated with increased risk of maternal death in the present study. Conclusion: Raised / abnormal renal parameters in pregnancy is independently associated with adverse maternal and fetal outcomes when other variables and a comorbid condition (Pre-eclampsia)was controlled by matching. [ABSTRACT FROM AUTHOR]

Pre-eclampsia, a hypertensive disorder occurring during pregnancy, poses significant risks to maternal and fetal health worldwide. Despite extensive research, the precise cause of pre-eclampsia remains unknown. Recent studies have indicated that trace elements, essential minerals crucial for various biological processes, might be significant factors in the development of pre-eclampsia. This study examines the intricate relationship between trace elements (magnesium, copper, zinc, calcium, phosphorus, and iron) and the severity of pre-eclampsia. The study involves a total of 150 participants, categorized into three distinct groups: 50 individuals with mild pre-eclampsia, 50 with severe pre-eclampsia, and 50 healthy pregnant controls. Specifically, out of the 100 pre-eclampsia cases, 5 were identified as early-onset and 95 as late-onset. Participants were recruited from a tertiary care hospital based on stringent inclusion and exclusion criteria. All the trace elements were quantitatively measured by direct colorimetric method using the Beckman Coulter AU480 analyzer system (Beckman Coulter, USA). Pre-eclampsia cases exhibited a significantly lowered level of magnesium (2.02 mg/dL), zinc (57.62 mg/dL), calcium (8.02 mg/dL), and phosphorus (3.93 mg/dL). These levels were approximately 14.4%, 20.2%, 21.1%, and 22.6% lower when compared to healthy pregnant women. Conversely, copper (151.67 mg/dL) and iron (53 μg/dL) levels were significantly elevated in pre-eclampsia cases. Age emerged as a significant risk factor, correlating with heightened pre-eclampsia susceptibility. Magnesium showed a protective effect, correlating negatively with age and positively with gestational age. The complex relationships between trace elements, age, and pre-eclampsia underline the need for personalized interventions, potentially including magnesium supplementation, in high-risk pregnancies. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms‐like tyrosine kinase‐1 (sFlt‐1)‐to‐placental growth factor (PlGF) ratio with that of a point‐of‐care test for glycosylated fibronectin (GlyFn) in women with suspected pre‐eclampsia (PE).This was a prospective, single‐center, double‐blinded, non‐interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt‐1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo‐Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt‐1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt‐1/PlGF ratio was classified as high or low using platform‐specific thresholds equivalent to a Roche sFlt‐1/PlGF ratio of 38, which were derived using Passing–Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 μg/mL and 510 μg/mL).Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty‐eight (37.3%) women had a sFlt‐1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt‐1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt‐1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 μg/mL and > 510 μg/mL, respectively. The negative predictive value (NPV) of the sFlt‐1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 μg/mL and > 510 μg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt‐1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 μg/mL and > 510 μg/mL.The predictive performance of different manufacturers' assays for the sFlt‐1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt‐1/PlGF ratio and GlyFn using a cut‐off of 263 μg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. Methods: We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. Results: The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89–1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60–1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41–1.48]). Conclusions: In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The aim of the present study was to evaluate the obstetric complications associated with isolated fetal congenital heart disease (CHD) by comparing pregnancies with and without this condition.In this retrospective matched comparative study at Siriraj Hospital, Thailand, we included 233 postnatally confirmed fetal CHD cases and 466 unaffected fetuses. Controls were selected at a 2:1 ratio, ensuring that they matched the cases in terms of maternal age, parity, and history of preterm deliveries.Fetal CHD was significantly associated with an increased risk of spontaneous preterm labor (30% vs 9.7%; adjusted odds ratio [aOR] 2.42; 95% confidence interval [CI]: 1.35–4.36; P = 0.003), delivery before 34 gestational weeks (11.6% vs 0.6%; aOR 12.33; 95% CI: 3.32–45.78; P < 0.001), and pre‐eclampsia (11.6% vs 2.8%; aOR 2.19; 95% CI: 1.01–4.76; P = 0.047). Newborns with CHD were significantly more likely to be small for gestational age (10.7% vs 5.2%; aOR 2.09; 95% CI: 1.11–3.94; P = 0.022). Intriguingly, a prenatal diagnosis of CHD was associated with a reduced risk of preterm delivery in affected pregnancies (P = 0.002).Pregnancies affected by isolated fetal CHD demonstrated a higher propensity for several adverse outcomes. These findings underscore the importance of prenatal CHD detection and tailored perinatal care to potentially improve both pregnancy outcomes and neonatal health. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The purpose of the present study was to assess the benefits of simulation for advancing knowledge and assisting healthcare staff in optimization of procedures when managing severe pre‐eclampsia/eclampsia (sPE/E).A randomized educational trial was conducted with two groups: Group I received theoretical training, while group II received the same training along with simulation scenarios based on the management of sPE/E. The study involved 199 healthcare providers, including physicians, midwives, skilled birth attendants, and nurses. The study analyzed the percentage of correct answers on both the multiple‐choice questions (MCQ) and the objective structured clinical examinations (OSCE) to evaluate theoretical knowledge and clinical skills objectively.Statistically significant differences were found immediately after training between groups I and II, whose mean percentages were 65.0% (±11.2) versus 71.0% (±9.8) (P < 0.001). A statistically significant reduction in the percentage of correct answers was found in both groups and demonstrated a discrepancy between immediate post‐training test and post‐training test at 3 months scores of 11.6% (±1.3) in group I versus 7.2% (±0.6) in group II. OSCE1 and OSCE2 scores were significantly higher in group II than in group I (P < 0.001).Simulation combined with theoretical training would appear to be an interesting method of training for advancing knowledge and improving skills of healthcare providers in their management of sPE/E. Our goal is for this method to be used to reduce real‐life maternal mortality in the South Kivu region of the Democratic Republic of Congo. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To assess variations in the presentation and clinical implications of pre‐eclampsia between Iranian and Afghan mothers at a maternity center in Tehran.We conducted a cross‐sectional study of Iranian and Afghan mothers diagnosed with pre‐eclampsia. Data were collected from March 2021 to February 2023 at a maternity center in Tehran, Iran. Demographic information, clinical characteristics, and laboratory findings were extracted from medical records. Statistical analyses were employed to compare differences between Iranian and Afghan mothers, including Mann–Whitney U, Pearson χ2 tests, and logistic regression models.We included 822 pregnant women with pre‐eclampsia, predominantly Iranian (75.5%) and Afghan (24.5%). Regarding the multivariate logistic regression model, Iranian mothers were older, with a higher proportion over 35 years. Although Afghan mothers showed higher gravidity counts and greater gestational ages at delivery, they had lower rates of hypothyroidism. Iranian women were more often categorized as obese than Afghan women, and the difference was statistically significant. Serum levels of alkaline phosphatase were significantly greater in Afghan women.Pre‐eclampsia poses significant maternal health risks, especially among Afghan refugees in Iran. Variances in age, gravidity, and hypothyroidism prevalence highlight the need for tailored healthcare strategies. Addressing cultural barriers and implementing targeted interventions can improve maternal and fetal outcomes in these populations. [ABSTRACT FROM AUTHOR]

The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development. [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: Placental dysfunction is one of the main causes of preeclampsia and hypertensive disorders of pregnancy. Material and methods: This is a prospective comparative study done on 30 pregnant women with pre-eclampsia and another 30 pregnant women as controls. In all these subjects the elasticity of the placenta was measured. Results: The results obtained showed that there was a significant difference in SWV values between the two groups (p value = 0.001). The mean SWV value of normal pregnant women was 0.99 m/ second as opposed to 1.99 m/second in pre-eclamptic pregnant women. Conclusion: Sonoelastography is a promising noninvasive tool in the detection of preeclampsia with high diagnostic accuracy. The SWV values measured at the central zones of the placenta with a cut-off value of 1.325 m/s identify the presence of pre-eclampsia with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve understanding of risk factors, diagnostic markers, and outcomes. Materials and Methods: This retrospective observational study involved 235 patients, 98 with pre-eclampsia and 137 without, monitored from 2015 to 2018 at the Obstetrics and Gynecology Department of the "Pius Brînzeu" Emergency County Clinical Hospital in Timișoara, Romania. Results: Women with pre-eclampsia were older, had higher BMIs, and more frequently had a family history of pre-eclampsia, hypertension, and diabetes. They also had lower educational and socioeconomic levels and fewer prenatal visits. Biochemical markers such as higher proteinuria, elevated sFlt-1, and lower PlGF were significant in diagnosing pre-eclampsia. Short-term maternal complications like eclampsia, HELLP syndrome, and acute kidney injury were more prevalent in the pre-eclampsia group. Neonatal outcomes included higher rates of preterm birth, low birth weight, and NICU admissions. Long-term mothers with a history of pre-eclampsia had higher incidences of chronic hypertension, cardiovascular disease, kidney problems, diabetes, and mental health disorders. Their children faced increased risks of neuropsychological delays, chronic respiratory issues, behavioral disorders, learning difficulties, and frequent infections. Conclusions: The study highlights the significant short- and long-term health impacts of pre-eclampsia on both mothers and their children. Early monitoring, intervention, and comprehensive management are crucial in mitigating these risks. These findings underscore the need for personalized care strategies to improve health outcomes for affected individuals. [ABSTRACT FROM AUTHOR]

Background: This study aims to examine risk of adverse pregnancy outcomes and mothers' characteristics in patients with chronic hypertension, gestational hypertension and preeclampsia. Methods: The study included all births born from women aged 15–45 years, in Lleida, Spain from 2012 to 2018. Pregnancy outcomes were retrieved by regional administrative databases. Logistic regression analysis was used to calculate adjusted odds ratios (OR) (OR 95% CI) for maternal characteristics or neonatal outcomes. Results: Among 17,177 pregnant women, different types of hypertension present varying risks for both the mother and fetus. There is an increased risk of cesarean section in patients with preeclampsia (OR 2.04, 95% CI: 1.43–2.88). For the newborn, a higher risk of preterm birth is associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91–4.83) and preeclampsia (OR 5.07, 95% CI: 3.28–7.65). Additionally, there is a higher risk of low birth weight in cases of maternal chronic hypertension (OR 3.2, 95% CI: 2.04–4.88), preeclampsia (OR 5.07, 95% CI: 3.34–7.52), and gestational hypertension (OR 2.72, 95% CI: 1.49–4.68). Furthermore, only newborns of patients with preeclampsia had a higher risk of an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45–5.38). Conclusions: In the study population adjusted for body weight, the different types of hypertension represent different risks in the mother and foetus. These complications were mostly associated with preeclampsia. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PE) is a severe pregnancy complication that is more common in patients with systemic lupus erythematosus (SLE). Although the exact causes of these conditions are not fully understood, the immune system plays a key role. To investigate the connection between SLE and PE, we analyzed genes associated with SLE that may contribute to the development of PE. We collected 9 microarray data sets from the NCBI GEO database and used Limma to identify the differentially expressed genes (DEGs). In addition, we employed weighted gene co-expression network analysis (WGCNA) to pinpoint the hub genes of SLE and examined immune infiltration using Cibersort. By constructing a protein-protein interaction (PPI) network and using CytoHubba, we identified the top 20 PE hub genes. Subsequently, we created a nomogram and conducted a receiver operating characteristic (ROC) analysis to predict the risk of PE. Our analysis, including gene set enrichment analysis (GSEA) and PE DEGs enrichment analysis, revealed significant involvement in placenta development and immune response. Two pivotal genes, BCL6 and MME, were identified, and their validity was confirmed using 5 data sets. The nomogram demonstrated good diagnostic performance (AUC: 0.82-0.96). Furthermore, we found elevated expression levels of both genes in SLE peripheral blood mononuclear cells (PBMCs) and PE placental specimens within the case group. Analysis of immune infiltration in the SLE data set showed a strong positive correlation between the expression of both genes and neutrophil infiltration. BCL6 and MME emerged as crucial genes in lupus-related pregnancies associated with the development of PE, for which we devised a nomogram. These findings provide potential candidate genes for further research in the diagnosis and understanding of the pathophysiology of PE. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PET) is a hypertensive disease that occurs during pregnancy or in the postpartum period. It complicates 2% to 8% of all pregnancies and is one of the causes of more than 50,000 maternal deaths and over 500,000 fetal deaths worldwide annually. Adverse birth outcomes due to pregnancy complications have been associated with three delays: delay in recognizing the complication, delay in reaching an appropriate facility, and delay in receiving adequate care when the facility is reached. Thus prevention, timely detection, and care of pregnancy complications can prevent maternal deaths and morbidity. The Internet of Things (IoT) and machine learning (ML) technologies have become the new revolution of research in the field of healthcare. These technologies can be utilized to interconnect various sensors, monitor the health status of a patient, and predict the occurrence of an ailment. This study has designed and prototyped a pre-eclampsia monitoring model based on IoT and machine learning for remotely monitoring the health status of an expectant woman and her unborn child, to enhance early diagnosis of pre-eclampsia and improve birth outcomes. The study involved researching the on most appropriate biosensors and then designing and prototyping the pre-eclampsia watch. To build the pre-eclampsia prediction model the best ML algorithm was empirically analysed. A Naïve Bayes pre-eclampsia prediction model was found to perform better in identifying pregnant women who are at risk of pre-eclampsia after evaluation of various pre-eclampsia models built using decision trees, Naïve Bayes, K Nearest Neighbor (KNN), logistic regression, support vector machines (SVM) and Artificial neural networks (ANN). Lastly, the predictive model was integrated with the pre-eclampsia model to assist in early diagnosis of pre-eclampsia. The prototype generates alerts when the expectant woman is at risk of Pre-eclampsia. The pre-eclampsia watch model can securely capture and transmit expectant women's vital to the cloud for processing and provide timely alerts when the woman is at risk. Further research on the performance and efficacy of the model in a real environment will be done by experimenting with it in a purposively selected sample. [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]

Objective Methods Results Conclusion To compare circulating levels of vascular endothelial growth factor receptor 3 (VEGFR‐3) in women with pregnancy‐induced hypertension (PIH) and in non‐pregnant (NP) and healthy pregnant (HP) women.We conducted a case–control study including PIH (n = 135), HP (n = 68), and NP (n = 49) women from southeastern Brazil. PIH were diagnosed according to international guidelines, and defined as gestational hypertension (GH, n = 61) or pre‐eclampsia (n = 74). VEGFR‐3 was measured in plasma using ELISA.Plasma VEGFR‐3 was increased in HP (1207 pg/mL) compared with NP (133 pg/mL) women; however, PIH (729 pg/mL) patients exhibited lower levels than HP women (both p < 0.05). In addition, plasma VEGFR‐3 was decreased in pre‐eclampsia compared with GH (537 versus 980 pg/mL; p < 0.05). When pre‐eclampsia was classified according to different clinical presentations, plasma VEGFR‐3 was further decreased in the cases identified as pre‐eclampsia with severe features, preterm pre‐eclampsia, and pre‐eclampsia accompanied by small for gestational age (all p < 0.05).Our data indicate reduced circulating VEGFR‐3 levels in patients with PIH, specifically in those diagnosed with pre‐eclampsia. Moreover, decreased VEGFR‐3 was associated with adverse clinical outcomes in pre‐eclampsia. These findings expand previous evidence of reduced VEGFR‐3 expression in pre‐eclampsia. Future studies should investigate whether it can be used as a predictive biomarker and/or therapeutic target for 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]

Prevention of pregnancy complications related to the "great obstetrical syndromes" (preeclampsia, fetal growth restriction, spontaneous preterm labor, and stillbirth) is a global research and clinical management priority. These syndromes share many common pathophysiological mechanisms that may contribute to altered placental development and function. The resulting adverse pregnancy outcomes are associated with increased maternal and perinatal morbidity and mortality and increased post-partum risk of cardiometabolic disease. Maternal nutritional and environmental factors are known to play a significant role in altering bidirectional communication between fetal-derived trophoblast cells and maternal decidual cells and contribute to abnormal placentation. As a result, lifestyle-based interventions have increasingly been recommended before, during, and after pregnancy, in order to reduce maternal and perinatal morbidity and mortality and decrease long-term risk. Antenatal screening strategies have been developed following extensive studies in diverse populations. Multivariate preeclampsia screening using a combination of maternal, biophysical, and serum biochemical markers is recommended at 11–14 weeks' gestation and can be performed at the same time as the first-trimester ultrasound and blood tests. Women identified as high-risk can be offered prophylactic low dose aspirin and monitored with angiogenic factor assessment from 22 weeks' gestation, in combination with clinical assessment, serum biochemistry, and ultrasound. Lifestyle factors can be reassessed during counseling related to antenatal screening interventions. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care that has the potential to significantly reduce pregnancy complications and associated later life cardiometabolic adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: The Doppler technique is a noninvasive method for evaluating the blood flow in the fetus and placenta. It is a potential screening tool for identifying pregnancies at higher risk of developing preeclampsia. This study aimed to identify any abnormalities in uterine artery Doppler among pregnant females between 19 and 26 weeks of gestation that may indicate potential complications like preeclampsia. Methods: The study was conducted at Zagazig University Hospital and El-Galaa Teaching Hospital, involving 150 pregnant women attending the antenatal care clinic. The participants had a gestational age between 19 and 26 weeks and were assessed and monitored using Doppler. Results: Out of the 150 pregnant patients enrolled in the study, 20 cases (13.3%) developed preeclampsia. Among these cases, 12 (8%) experienced perinatal complications, including Intrauterine fetal death (IUFD), intrauterine growth restriction (IUGR), antepartum hemorrhage, and postpartum hemorrhage. IUFD and IUGR were reported in 4 (2.7%) cases each, antepartum hemorrhage in 3 (2%) cases, and postpartum hemorrhage in 1 case (0.667%). We observed a significant increase in the mean uterine artery Resistance index (RI) and Pulsatility index (PI) in women who developed preeclampsia compared to those who did not (p<0.001). Conclusions: Uterine artery Doppler is an easy, fast, and non-invasive screening test that may add help in preeclampsia prediction. RI was a significant predictor for Uterine artery Doppler at a cutoff value of >0.58 with AUC 0.951 with 95% Sensitivity and 93.8% Specificity. PI was a significant predictor for Uterine artery Doppler at a cutoff value of >1.1 with AUC. [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]

Objective: To investigate whether angiogenic markers of placental function are associated with maternal cardiac function and hemodynamic responses at 19–23 weeks' gestation, controlling for maternal risk factors and pregnancy complications. Methods: This was a prospective study of women with singleton pregnancy attending King's College Hospital, London, UK, for a routine hospital visit at 19–23 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure (MAP), maternal heart rate, serum placental growth factor (PlGF) and soluble fms‐like tyrosine kinase‐1 (sFlt‐1). We also performed maternal echocardiography to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function. Results: Our cohort included 4006 women. Lower PlGF values were significantly associated with higher MAP (P < 0.0001), lower maternal heart rate (P < 0.0001), lower mitral valve s′ mean velocity (P = 0.027) and higher left atrial area (P = 0.022) after adjustment for maternal characteristics and pregnancy complications. sFlt‐1 was associated positively with relative wall thickness (P = 0.012), whereas sFlt‐1/PlGF ratio was associated negatively with mitral valve A (P = 0.006) and positively with left atrial area (P = 0.015) and MAP (P = 0.004). The magnitude of these associations was similar in the subgroup of women without any risk factors based on their obstetric and medical history. Conclusions: A continuous association of moderate strength between angiogenic factors and subclinical maternal cardiac function alterations is present in midgestation, independently of pre‐existing maternal risk factors and pregnancy complications. Impaired placental function appears to be related to mild systolic and diastolic dysfunction and cardiac remodeling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relative importance of ethnicity and socioeconomic deprivation in determining the likelihood and prevalence of placentally derived composite of adverse pregnancy outcomes (CAPO) and composite of severe adverse pregnancy outcomes (CAPO‐S). Methods: This was a single‐center retrospective cohort study of data obtained in a tertiary maternity unit. Data regarding ethnicity and socioeconomic deprivation (as measured with indices of multiple deprivation) were collected for 13 165 singleton pregnancies screened routinely in the first trimester for pre‐eclampsia using the Fetal Medicine Foundation combined risk‐assessment algorithm. CAPO was defined as the presence of one or more interrelated outcomes associated with placental dysfunction, namely, hypertensive disorders of pregnancy, preterm birth, birth weight ≤ 10th centile and stillbirth. CAPO‐S was defined as the presence of one or more of the following: hypertensive disorders of pregnancy at < 37 + 0 weeks, preterm birth at < 34 + 0 weeks, birth weight ≤ 5th centile and stillbirth at < 37 + 0 weeks. Results: The prevalence of CAPO was 16.3% in white women, 29.3% in black women and 29.3% in South Asian women. However, half (51.7%) of all CAPO cases occurred in white women. There was a strong interaction between ethnicity and socioeconomic deprivation, with a correlation coefficient of −0.223. Both ethnicity and socioeconomic deprivation influenced the prevalence of CAPO and CAPO‐S, with the contribution of ethnicity being the strongest. Conclusions: Black and Asian ethnicity, as well as socioeconomic deprivation, influence the prevalence of placenta‐mediated adverse pregnancy outcomes. Despite this, most adverse pregnancy outcomes occur in white women, who represent the majority of the population and are also affected by socioeconomic deprivation. For these reasons, inclusion of socioeconomic deprivation should be considered in early pregnancy risk assessment for placenta‐mediated CAPO. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. This article's abstract has been translated into Spanish and Chinese. Follow the links from the abstract to view the translations. [ABSTRACT FROM AUTHOR]

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-A165) 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-A165 (1 × 1010 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-A165 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-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 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. [ABSTRACT FROM AUTHOR]

Background: This systematic review explores the level of oxidative stress (OS) markers during pregnancy and their correlation with complications. Unlike previous studies, it refrains from directly investigating the role of OS but instead synthesises data on the levels of these markers and their implications for various pregnancy-related complications such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. Method: Study Design: Utilizing a systematic review approach, we conducted a comprehensive search across databases, including MEDLINE, CINAHL (EBSCOhost), ScienceDirect, Web of Science, and SCOPUS. Our search encompassed all publication years in English. Results: After evaluating 54,173 records, 45 studies with a low risk of bias were selected for inclusion. This systematic review has underscored the importance of these markers in both physiological and pathological pregnancy states such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. Conclusion: This systematic review provides valuable insights into the role of OS in pregnancy and their connection to complications. These selected studies delved deeply into OS markers during pregnancy and their implications for associated complications. The comprehensive findings highlighted the significance of OS markers in both normal and pathological pregnancy conditions, paving the way for further research in this field. [ABSTRACT FROM AUTHOR]

Aim: To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE). Methods: In in vitro experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the in vivo PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured. Results: The nanomedicine effectively reduced the expression of sFIt1 and had a strong ability to target placental tissues. It could significantly reduce the symptoms of pre-eclampsia and improve pregnancy outcomes in PE model rats. Conclusion: The constructed nanomedicine can improve pregnancy outcomes in a rat model of pre-eclampsia and provides a new strategy for the treatment of pre-eclampsia. Article highlights sFlt1 has been extensively studied and recognized as a key therapeutic target in pre-eclampsia. Treatment of pre-eclampsia using liposome-loaded siRNA-sFlt1 is a potential therapeutic approach that could complement existing treatment modalities. In this study, we evaluated the in-vivo and in-vitro efficacy of siRNA-sFlt1 nanoliposomes coupled with anti-EGFR antibodies for targeting the placenta in the treatment of pre-eclampsia. We used a Malvern particle sizer and TEM to determine that the size of the finished nanoliposomes was approximately 150 nm. After incubation with HTR-8/SVneo cells, the nanocarriers were assembled with fluorescently labeled siRNA-sFlt1, and a greater targeting efficiency of E-Lip-siRNA-sFlt1 was demonstrated by flow cytometry. Measurement of sFlt1 at the nucleic acid and protein levels was performed using qPCR and ELISA kits, respectively, and the results revealed a significant decrease in sFlt1 levels. Compared with the naked nucleic acid and nontargeted groups, the nanoliposome group encapsulating anti-EGFR antibodies showed more accumulation in the placenta. E-Lip-siRNA-sFlt1 improves pregnancy outcomes in a TNF-α-induced pre-eclampsia rat model. E-Lip-siRNA-sFlt1-treated rats in the pre-eclampsia model showed no signs of major organ damage. However, whether there are potential long-term effects on fetal rats that are delivered needs to be further studied. A rigorous evaluation is needed before conducting clinical studies. [ABSTRACT FROM AUTHOR]

The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. Pravastatin (PRA), a hydrophilic statin, has gained interest for the prevention and treatment of PE. The aim of the present study was to evaluate the ability of PRA to modulate factors involved in placentation, such as Epidermal Growth Factor-Like Domain 7 (EGFL7), in human chorionic villous culture from healthy controls and women with PE. A total of 18 women were enrolled: 10 controls and 8 cases. Chorionic villous explants were maintained in culture for 24 h with or without 10 μM Pravastatin, and the expression of EGFL7 and NOTCH1 pathway members was evaluated by qRT-PCR and Western blot analysis. The rationale of the present study was to establish an ex vivo model to identify potential different responses to PRA treatment of chorionic villous explants in order to clarify the molecular mechanism of PRA in the prevention and treatment of PE and to predict whether there are specific clinical conditions that modulate the response to the drug treatment. Within PE patients, two different groups were identified: the high responders, whose villous cultures exhibit significantly increased expressions of the EGFL7 and Notch pathways after PRA incubation; and the low responders, who are high-risk PE patients in which prophylaxis failed to prevent PE and PRA was not able to modulate EGFL7 expression. In conclusion, we identified EGFL7 as a new factor regulated by PRA, placing interest in early discrimination between low- and high- risk women, in which the well-known pharmacological prophylaxis seems to be ineffective, and to explore new potential prevention strategies. [ABSTRACT FROM AUTHOR]

Environmental changes can trigger endoplasmic reticulum (ER) stress and misfolded protein accumulation, potentially leading to pre-eclampsia (PE). Amyloid-β (Aβ) is a crucial misfolded protein that can overactivate autophagy. Our study assessed the expression of Aβ1−42 and autophagic activity in PE placental tissues and trophoblasts under ER stress. Placental tissues were surgically collected from normal pregnant women (NP) and pregnant women with late-onset PE (LOPE) delivering through cesarean section. The expression levels of Aβ1−42 were detected in both PE and NP placental tissues, as well as in tunicamycin (TM)-induced HTR-8/SVneo cells. Autophagy-related proteins, such as Beclin-1, the ratio of LC3-II to LC3-I, ATG5, and SQSTM1/p62 in the placental tissues and HTR-8/SVneo cells were measured by Western blot. The number and morphology of autophagosomes were observed using transmission electron microscopy (TEM). Potential targets associated with the unfolded protein response (UPR) in the placental tissues of NP and PE cases were screened using PCR Arrays. The misfolded protein was significantly upregulated in the PE group. In both PE placental tissues and TM-induced HTR-8/SVneo cells, not only was Aβ1−42 upregulated, but also Beclin-1, ATG5, and LC3BII/I were significantly increased, accompanied by an increase in autophagosome count, while SQSTM1/P62 was downregulated. A total of 17 differentially expressed genes (DEGs) associated with the UPR were identified, among which elevated calnexin (CANX) was validated in the placenta from both PE and TM-induced HTR-8/SVneo cells. Autophagy is significantly upregulated in PE cases due to ER stress-induced Aβ1−42 accumulation, likely mediated by autophagy-related proteins involved in the UPR. [ABSTRACT FROM AUTHOR]

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy–Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy–Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy–Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied. [ABSTRACT FROM AUTHOR]

Between September and November 2020, four pregnant women under 35 years of age were diagnosed with pneumonia and severe preeclampsia. The patients required admission to the intensive care unit (ICU), mechanical ventilation, and extracorporeal membrane oxygenation. Paraclinical tests showed increased C-reactive protein and lactate dehydrogenase, lymphopenia, and a reduced neutrophil/lymphocyte ratio. One newborn was positive for SARS-CoV-2. Three mothers and one newborn died. Preeclampsia has been associated with COVID-19 in pregnant women. The high mortality found and the vertical transmission in one case are noteworthy. In conclusion, the development of severe preeclampsia in all cases may have been an additional factor contributing to the fatal outcome in 3 of them. It is suggested that lymphopenia and the reduced neutrophil/lymphocyte ratio may be useful as prognostic factors. Future studies will help elucidate the consequences of COVID-19 in pregnancy.

Abstract Background and objectives Hypertensive disorders of pregnancy (HDPs) remain one of the leading causes of maternal mortality globally, especially in Low- and middle-income countries (LMICs). To reduce the burden of associated morbidity and mortality, standardized prompt recognition, evaluation, and treatment have been proposed. Health disparities, barriers to access to healthcare, and shortage of resources influence these conditions. We aimed to synthesize the literature evidence for the management of HDPs in LMICs. Methods A scoping review was conducted in five databases (PubMed, Web of Science, Epistemonikos, Clinical Key and, Scielo) using MeSh terms, keywords, and Boolean connectors. We summarized the included studies according to the following categories: study design, objectives, settings, participant characteristics, eligibility criteria, interventions, assessed outcomes, and general findings. Results Six hundred fifty-one articles were retrieved from the literature search in five databases. Following the selection process, 65 articles met the predefined eligibility criteria. After performing a full-text analysis, 27 articles were included. Three themes were identified from the articles reviewed: prevention of HDPs, management of HDPs (antihypertensive and non-hypertensive management) and pregnancy monitoring and follow-up. The topics were approached from the perspective of LMICs. Conclusions LMICs face substantial limitations and obstacles in the comprehensive management of HDPs. While management recommendations in most LMICs align with international guidelines, several factors, including limited access to crucial medications, unavailability of diagnostic tests, deficiencies in high-quality healthcare infrastructure, restrictions on continuing professional development, a shortage of trained personnel, community perceptions of preeclampsia, and outdated local clinical practice guidelines, impede the comprehensive management of patients. The development and implementation of protocols, standardized guides and intervention packages are a priority.

Abstract Background Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS). Results In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2′-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS. Conclusions This study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

Microalbuminuria is an initial indicator of kidney damage in diabetic nephropathy (DN), hypertensive nephropathy (HN), and pre-eclampsia (PE). This study aims to assess the diagnostic accuracy of urinary microalbumin to creatinine ratio (UM/CR) as an early diagnostic tool in patients with DN, HN, and PE.

Abstract Background Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. Methods We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. Results The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight

Background: According to a WHO report, the prevalence of anemia is the highest in children less than five years of age (40%) and pregnant women of the global population (37%). The prevalence of hypertensive disorders of pregnancy was 7.8% in India. 14% of maternal deaths are attributed to hypertensive disorders of pregnancy, according to a WHO report. Our study aimed to evaluate the variation of serum ferritin (SF) levels in four different groups: (1) normal pregnancy, (2) pregnancy with anemia, (3) pregnancy with hypertensive disorders, and (4) pregnancy with hypertensive disorders and anemia, to derive an association of SF in patients of anemia and hypertensive disorders of pregnancy. Methods: Thirty diagnosed cases of each predefined group of similar gestation were enrolled. A venous blood sample was collected from all subjects of all four groups for estimation of SF levels and hemoglobin levels. Results: SF level was found to be significantly around twofold higher in groups 3 and 4 with hypertensive disorders of pregnancy (60.6 ± 27.5 μg/dL and 54.4 ± 26 μg/dL, respectively) compared to normal pregnancy and pregnancy with anemia (31.3 ± 25 μg/dL and 23.3 ± 21.6 μg/dL, respectively). Hence, the Kruskal–Wallis test was conducted for four groups, and it was statistically significant. Conclusions: In our study, pregnant women with anemia had lower SF levels than normal pregnancy cases. However, in group 4 with hypertensive disorders of pregnancy with anemia SF levels were higher than group 2.

Abstract Background This study aims to examine risk of adverse pregnancy outcomes and mothers’ characteristics in patients with chronic hypertension, gestational hypertension and preeclampsia. Methods The study included all births born from women aged 15–45 years, in Lleida, Spain from 2012 to 2018. Pregnancy outcomes were retrieved by regional administrative databases. Logistic regression analysis was used to calculate adjusted odds ratios (OR) (OR 95% CI) for maternal characteristics or neonatal outcomes. Results Among 17,177 pregnant women, different types of hypertension present varying risks for both the mother and fetus. There is an increased risk of cesarean section in patients with preeclampsia (OR 2.04, 95% CI: 1.43–2.88). For the newborn, a higher risk of preterm birth is associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91–4.83) and preeclampsia (OR 5.07, 95% CI: 3.28–7.65). Additionally, there is a higher risk of low birth weight in cases of maternal chronic hypertension (OR 3.2, 95% CI: 2.04–4.88), preeclampsia (OR 5.07, 95% CI: 3.34–7.52), and gestational hypertension (OR 2.72, 95% CI: 1.49–4.68). Furthermore, only newborns of patients with preeclampsia had a higher risk of an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45–5.38). Conclusions In the study population adjusted for body weight, the different types of hypertension represent different risks in the mother and foetus. These complications were mostly associated with preeclampsia.

Abstract Pre-eclampsia (PET) is a hypertensive disease that occurs during pregnancy or in the postpartum period. It complicates 2% to 8% of all pregnancies and is one of the causes of more than 50,000 maternal deaths and over 500,000 fetal deaths worldwide annually. Adverse birth outcomes due to pregnancy complications have been associated with three delays: delay in recognizing the complication, delay in reaching an appropriate facility, and delay in receiving adequate care when the facility is reached. Thus prevention, timely detection, and care of pregnancy complications can prevent maternal deaths and morbidity. The Internet of Things (IoT) and machine learning (ML) technologies have become the new revolution of research in the field of healthcare. These technologies can be utilized to interconnect various sensors, monitor the health status of a patient, and predict the occurrence of an ailment. This study has designed and prototyped a pre-eclampsia monitoring model based on IoT and machine learning for remotely monitoring the health status of an expectant woman and her unborn child, to enhance early diagnosis of pre-eclampsia and improve birth outcomes. The study involved researching the on most appropriate biosensors and then designing and prototyping the pre-eclampsia watch. To build the pre-eclampsia prediction model the best ML algorithm was empirically analysed. A Naïve Bayes pre-eclampsia prediction model was found to perform better in identifying pregnant women who are at risk of pre-eclampsia after evaluation of various pre-eclampsia models built using decision trees, Naïve Bayes, K Nearest Neighbor (KNN), logistic regression, support vector machines (SVM) and Artificial neural networks (ANN). Lastly, the predictive model was integrated with the pre-eclampsia model to assist in early diagnosis of pre-eclampsia. The prototype generates alerts when the expectant woman is at risk of Pre-eclampsia. The pre-eclampsia watch model can securely capture and transmit expectant women's vital to the cloud for processing and provide timely alerts when the woman is at risk. Further research on the performance and efficacy of the model in a real environment will be done by experimenting with it in a purposively selected sample.

Abstract 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

Abstract Background This systematic review explores the level of oxidative stress (OS) markers during pregnancy and their correlation with complications. Unlike previous studies, it refrains from directly investigating the role of OS but instead synthesises data on the levels of these markers and their implications for various pregnancy-related complications such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. Method Study Design Utilizing a systematic review approach, we conducted a comprehensive search across databases, including MEDLINE, CINAHL (EBSCOhost), ScienceDirect, Web of Science, and SCOPUS. Our search encompassed all publication years in English. Results After evaluating 54,173 records, 45 studies with a low risk of bias were selected for inclusion. This systematic review has underscored the importance of these markers in both physiological and pathological pregnancy states such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. Conclusion This systematic review provides valuable insights into the role of OS in pregnancy and their connection to complications. These selected studies delved deeply into OS markers during pregnancy and their implications for associated complications. The comprehensive findings highlighted the significance of OS markers in both normal and pathological pregnancy conditions, paving the way for further research in this field.

Background: Stunting can be prevented by early detection when the mother is pregnant. Early detection can be carried out by looking for risk factors of stunting during pregnancy so that interventions can be early detected. This study aims to assess complications during pregnancy (disease and infection) and risk factors associated with stunting. Materials and Methods: The type of research was observational analytic with a case-control design on 450 mothers who were selected with simple random sampling (150 mothers who have stunting babies aged 0–2 months and 300 mothers who have not stunting babies aged 0–2 months in Malang Regency, Indonesia. This study used secondary data by looking at medical records, namely, laboratory examinations in the mother’s book and cohort records at the public health center. This study was conducted from December 2021 to August 2022. Bivariate analysis with Chi-square and multivariate logistic regression was carried out to determine the variables that most influenced the incidence of stunting. Results: The results of multivariate analysis with logistic regression of maternal complications during pregnancy, which are a risk as a factor causing stunting, are Sexually Transmitted Infections (STIs) (Odds Ratio [OR]: 6.36; 95% Confidence Interval [CI]: 2.97–13.62), coronavirus disease 2019 (COVID-19) accompanied by pneumonia (OR: 5.12; 95% CI: 1.87–14.052), human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (OR: 4.63; 95% CI: 1.10–19.59), hepatitis B (OR: 3.97; 95% CI: 1.253–12.565), pre-eclampsia (OR: 3.88; 95% CI: 1.81–8.30), and heart disease (OR: 3.373; 95% CI: 0.99–11.40). Conclusions: After recognizing the maternal factors that cause stunting, intervention should immediately be carried out on pregnant women with diseases (pre-eclampsia and heart disease) and infections (STI, COVID-19 + pneumonia, HIV/AIDS, and hepatitis B) to prevent stunting early.

Abstract Introduction Magnesium sulfate is the most utilized anticonvulsant for treating patients with eclampsia and pre-eclampsia. The purpose of this study is to determine whether the 12-h regimen of magnesium sulfate outweighs the 24-h regimen in both efficacy and safety in the management of patients with mild or severe pre-eclampsia and eclampsia. Methods We searched six electronic databases: PubMed, Scopus, Web of Science, Cochrane Library, Ovid, and Google Scholar. This search was conducted to yield any studies that were published until 15 January 2023. We did the statistical analysis plan by Review Manager Software version 5.4. Results We included 13 randomized control trials with 2813 patients in this systematic review. Our meta-analysis revealed that there were no statistically significant differences between the 12-h regimen of the magnesium sulfate group and the 24-h regimen of the magnesium sulfate group in our outcome of interest: occurrence of seizure (RD: -0.00, 95% CI [-0.01, 0.00], P = 0.56), diminished deep tendon reflexes (RD: -0.00, 95% CI [-0.01, 0.01], P = 0.80), respiratory depression (RD: -0.00, 95% CI [-0.02, 0.01], P = 0.57), and pulmonary edema (RD: -0.00, 95% CI [-0.01, 0.01], P = 0.85). Conclusion Our study showed no statistically significant difference in effectiveness and toxicity risk between the 12-h and 24-h regimens.

Background: Pre-eclampsia (PE) is a multi-system disorder that affects 3%–6% of human pregnancies and causes substantial maternal and foetal mortality and morbidity. Various studies have implicated testosterone as a causative factor in the pathogenesis of PE. The present study evaluated the association of serum testosterone levels with PE and maternal and foetal outcomes. Aim: The objectives of the study were to assess serum testosterone levels in PE compared to normotensive pregnant mothers, to look for its association with PE and to identify its utility as a biomarker for PE. Materials and Methods: A prospective cohort study was conducted in the 2nd trimester pregnant mothers (n = 110) attending the outpatient department at Vinayaka Mission’s Kirupananda Variyar Medical College Hospital, Salem. Serum testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP) and creatinine were evaluated and compared amongst the pre-eclamptic and normal pregnant women. Results: The mean serum testosterone level was higher in PE women (2.625 ± 1.40 ng/dL) when compared to normal pregnant women (1.217 ± 0.258 ng/dL) (P < 0.001). Serum testosterone was found to be positively correlated with uric acid (r = 0.517, P < 0.001), hsCRP (r = 0.307, P < 0.001), systolic blood pressure (BP) (r = 0.480, P < 0.000) and diastolic BP (r = 0.544 P < 0.001). Receiver operating characteristic curve analysis for serum testosterone levels was done (area under the curve = 0.815), with sensitivity and specificity of 78.18% and 78.18%, respectively. Conclusion: This study attempted to identify the association between serum testosterone levels, PE and pregnancy outcomes in a small South Indian population. Serum testosterone levels were found to be significantly elevated in pre-eclamptic women compared to normal pregnancies and could be used as a predictive biomarker. Serum uric acid and hsCRP also showed a significant positive association with PE.

Abstract Background Growth differentiation factor‐15 (GDF‐15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF‐15 and pre‐eclampsia (PE). Method The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF‐15 were measured by using enzyme‐linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF‐15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs). Results MOM of GDF‐15 in PE participants was higher compared with controls (1.588 vs. 1.000, p 1) had a 4.74‐fold (95% CI = 2.23–10.08, p

India is a vast and diverse country with a complex healthcare scheme that faces significant challenges in providing quality care to its population. Obstetric care is a complex area of healthcare. The history of clinical care pathways in obstetric care reflects a continued effort to improve the quality and safety of healthcare for mothers and infants. This comprehensive review provides an overview of clinical care pathways in obstetric care. It sheds light on the current evidence supporting the use of clinical care pathways for the management of anaemia during pregnancy, Gestational Diabetes Mellitus (GDM), pre-eclampsia, and Preterm Labour (PTL). The primary aim of this review is to recognise the accessibility and strength of evidence for the use of clinical care pathways in the management of common complications of pregnancy.