Hypertensive states of pregnancyEstados hipertensivos del embarazo / Estados hipertensivos del embarazo

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.(AU)

Los estados hipertensivos del embarazo (EHE) siguen siendo una de las principales causas de morbilidad y mortalidad materna y fetal relacionada con el embarazo en todo el mundo, incluyen la hipertensión crónica, la hipertensión gestacional y la preeclampsia. Las mujeres afectadas y los recién nacidos también tienen un mayor riesgo de sufrir enfermedades cardiovasculares en el futuro, independientemente de los riesgos tradicionales de la enfermedad cardiovascular. A pesar de estos riesgos, las recomendaciones para un diagnóstico y un tratamiento óptimo han cambiado poco en las últimas décadas, probablemente por el miedo a las repercusiones fetales de la disminución de la presión arterial y la posible toxicidad farmacológica. En ese documento revisamos los criterios diagnósticos y la clasificación de los EHE, así como aspectos importantes en cuanto a fisiopatología y la detección temprana que permita la identificación precoz de las mujeres en riesgo, con el objetivo de prevenir tanto las secuelas inmediatas como a largo plazo. También se revisa el tratamiento profiláctico con aspirina de forma precoz y se realiza una aproximación terapéutica que implica una estrecha vigilancia materna y fetal, y si es necesario, el uso de fármacos seguros en cada situación. Esta revisión pretende dar una visión actualizada para la prevención, diagnóstico y tratamiento de los EHE que sea de utilidad en nuestra práctica clínica habitual.(AU)

Value of Non-Coding RNA Expression in Biofluids to Identify Patients at Low Risk of Pathologies Associated with Pregnancy.

Pregnancy-related complications (PRC) impact maternal and fetal morbidity and mortality and place a huge burden on healthcare systems. Thus, effective diagnostic screening strategies are crucial. Currently, national and international guidelines define patients at low risk of PRC exclusively based on their history, thus excluding the possibility of identifying patients with de novo risk (patients without a history of disease), which represents most women. In this setting, previous studies have underlined the potential contribution of non-coding RNAs (ncRNAs) to detect patients at risk of PRC. However, placenta biopsies or cord blood samples are required, which are not simple procedures. Our review explores the potential of ncRNAs in biofluids (fluids that are excreted, secreted, or developed because of a physiological or pathological process) as biomarkers for identifying patients with low-risk pregnancies. Beyond the regulatory roles of ncRNAs in placental development and vascular remodeling, we investigated their specific expressions in biofluids to determine favorable pregnancy outcomes as well as the most frequent pathologies of pregnant women. We report distinct ncRNA panels associated with PRC based on omics technologies and subsequently define patients at low risk. We present a comprehensive analysis of ncRNA expression in biofluids, including those using next-generation sequencing, shedding light on their predictive value in clinical practice. In conclusion, this paper underscores the emerging significance of ncRNAs in biofluids as promising biomarkers for risk stratification in PRC. The investigation of ncRNA expression patterns and their potential clinical applications is of diagnostic, prognostic, and theragnostic value and paves the way for innovative approaches to improve prenatal care and maternal and fetal outcomes.

Clinical Analysis of Risk Factors and Perinatal Outcomes in Recurrent Pre-Eclampsia with Severe Features.

To analyze the differences in risk factors and pregnancy outcomes between recurrent and initial pre-eclampsia(PE) with severe features. Data from recurrent (n = 128) and initial (n = 904) PE with severe features who terminated their pregnancy or gave birth at 20 weeks of gestation or later at the tertiary teaching hospital (Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital) from January 2016 to December 2022 were collected. Risk factors for recurrent PE with severe features and differences in pregnancy outcomes between the two groups were assessed using the chi-square test, student t-test, or nonparametric test. Independent risk factors for recurrent PE with severe features were further analyzed by logistic regression. (1) Logistic regression analysis identified 3 independent risk factors for recurrent PE with severe features: history of cesarean section, rural residence and chronic hypertension. In addition, assisted reproductive technology (ART) is an independent risk factor for initial PE with severe features; (2) The incidence of oligohydramnios, chorioamnionitis, preterm birth, stillbirth, fetal growth restriction (FGR) and abnormal umbilical blood flow was higher in the recurrent PE with severe features group than in the initial PE with severe features group(P < 0.05). In contrast, the incidence of premature rupture of membrane (PROM) and postpartum hemorrhage (PPH) was higher in the group of initial PE with severe features(P < 0.05); (3) In the recurrent PE with severe features group, gestational age(GA) of birth and birth weight were lower than those in the initial PE with severe features group(P < 0.05). Also, the incidence of mild asphyxia, the rate of neonatal intensive care unit (NICU) hospitalization, length of stay in NICU, and the rate of abandoning treatment in the recurrent PE with severe features group were higher than those in the initial PE with severe features group(P < 0.05). 3 independent risk factors was identified for recurrent PE with severe features: history of cesarean section, rural residence and chronic hypertension. Women with recurrent PE with severe features are more likely to have adverse perinatal outcomes than those with initial PE with severe features.

Factors contributing to preterm birth in patients presenting at tertiary care hospitals in Punjab.

Objective: To determine the various causes and factors leading to preterm birth in women presenting at tertiary care hospitals. METHODS: The cross-sectional, prospective study was conducted from June 19, 2021, to January 19, 2022, at the Central Park Teaching Hospital, Lahore, Pakistan, in collaboration with other tertiary care teaching hospitals in Lahore, and comprised pregnant women aged 15-45 years with preterm birth. Demographic and obstetric data was collected. Depending on the factors contributing to preterm birth, the subjects were categorised as spontaneous labour group A, preterm prelabour rupture of membrane group B, and iatrogenic preterm birth group C. Data was analysed using SPSS 25. RESULTS: Of the 1,300 recorded births, 200(15.38%) were preterm. Group A had 86(43%) women with mean age 28.55±4.68 years, group B had 43(21,5%) women with mean age 27.14±3.25 years, and group C had 71(35.5%) women with mean age 28.28±3.74 years (p>0.05). There was significant difference among the groups with respect to body mass index (p=0.001) and parity (p=0.021). Vaginal and urinary tract infections were significantly higher in group A compared to the other groups (p<0.05). In group C, pre-eclampsia was the main reason for preterm birth 45(63.38%). Conclusion: Medically indicated preterm birth rate was found to be high, and pre-eclampsia was noted as the main cause in iatrogenic preterm birth.

Maternal and fetal outcomes in pregnancy complicated by pre-existing lupus nephritis: Insights from a developing country Pakistan.

BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. METHODS: A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth. RESULTS: The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months. CONCLUSION: The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.

Hypertensive disorders of pregnancy among women with cardiovascular disease in Norway: A historical cohort study.

INTRODUCTION: Women with cardiovascular disease may be at increased risk of hypertensive disorders of pregnancy (HDP). We aimed to: (1) Investigate the occurrence of HDP in a cohort of pregnant women with cardiovascular disease and compare it with the occurrence in the general population. (2) Assess the association between maternal cardiovascular risk and risk of HDP. MATERIAL AND METHODS: We reviewed clinical data on a cohort of 901 pregnancies among 708 women with cardiovascular disease who were followed at the National Unit for Pregnancy and Heart Disease and gave birth at Oslo University Hospital between 2003 and 2018. The exposure under study was maternal cardiovascular risk, classified as low, moderate, or high based on a modified classification by the World Health Organization. The main outcome of interest was HDP, which included pre-eclampsia and gestational hypertension. The proportion of HDP cases in the general population in the same period was extracted from the Medical Birth Registry of Norway. We used logistic regression to estimate crude and adjusted odds ratios (OR) of HDP, with associated 95% confidence intervals (CIs), for women with moderate- and high cardiovascular risk compared to women with low risk. RESULTS: The occurrence of HDP in the study cohort was 12.1% (95% CI: 10.0%-14.4%) and varied between 8.7% (95% CI: 6.5%-11.3%) in the low-risk group, 15.7% (95% CI: 11.1%-21.4%) in the moderate-risk group, and 22.2% (95% CI: 15.1%-30.8%) in the high-risk group. By contrast, the nationwide occurrence of HDP was 5.1% (95% CI: 5.1%-5.2%). In the study cohort, the proportions of pregnancies with gestational hypertension and pre-eclampsia were similar (6.3% and 5.8%, respectively). Compared to pregnancies with low cardiovascular risk, the adjusted OR of HDP was 2.04 (95% CI: 1.21-3.44) in the moderate-risk group and 2.99 (95% CI: 1.73-5.18) in the high-risk group. CONCLUSIONS: The occurrence of hypertensive disease of pregnancy in the study cohort was more than doubled compared to the general population in Norway. The risk of HDP increased with maternal cardiovascular risk group. We recommend taking into account maternal cardiovascular risk group when assessing risk and prophylaxis of HDP.

Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

A Rare Case of Postpartum Paraplegia: A Case Report.

In this case report, a 27-year-old woman who had pre-eclampsia in the past and had a cesarean section as a result of the condition presents with an uncommon and difficult form of postpartum paraplegia. She experienced bilateral lower limb paralysis and urine incontinence soon after the surgery, which quickly led to unconsciousness and required mechanical ventilator support and intensive care treatment. Comprehensive diagnostic testing, which included magnetic resonance imaging scans of the brain and spinal cord, identified signs typical of "Posterior Reversible Encephalopathy Syndrome (PRES)" and spinal cord infarction affecting segments C3 to D2. "Antiphospholipid Antibody Syndrome (APLA)" was identified by laboratory testing, highlighting the significance of taking a thorough approach to comprehending this uncommon clinical condition. Treatment included anticoagulant therapy, high-dose steroid therapy, and antihypertensive drugs, emphasizing the crucial importance of inter-disciplinary care in handling such complex situations. Even if the patient's symptoms have partially improved, their condition is still being closely monitored in the intensive care unit. In the context of postpartum neurological problems and the complex interplay between pre-eclampsia, spinal cord infarction, and related clinical symptoms, this case emphasizes the need for increased awareness and prompt management.

Magnesium sulfate and risk of hypoxic ischemic encephalopathy in a high-risk cohort.

BACKGROUND: Hypoxic ischemic encephalopathy contributes to morbidity and mortality among neonates ≥ 360 weeks' gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic ischemic encephalopathy and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with pre-eclampsia with severe features. OBJECTIVES: 1) Determine trends in incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate and hypoxic ischemic encephalopathy, 2) evaluate the association between hypertensive disorders of pregnancy and hypoxic ischemic encephalopathy and 3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We conducted an analysis of a prospective cohort of live births ≥360 weeks' gestation between 2012-2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization, and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic ischemic encephalopathy. RESULTS: Among 44,314 unique infants, the diagnosis of hypoxic ischemic encephalopathy, maternal hypertensive disorders of pregnancy and the use of magnesium sulfate increased over time. Compared to patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a higher risk population. They were more likely to be publicly insured, born 36-38 weeks' gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, preterm labor, fetal distress, and undergo operative delivery (all p-values <0.002). Hypertensive disorders of pregnancy were associated with hypoxic ischemic encephalopathy (aOR 1.26, 95% CI 1.13-1.40, p-value <.001) and specifically moderate/severe hypoxic ischemic encephalopathy (aOR 1.26, 95% CI 1.11-1.42, p-value <.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic ischemic encephalopathy (aOR 0.71, 95% CI 0.52-0.97, p-value= 0.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic ischemic encephalopathy (aOR 0.63, 95% CI 0.42-0.94, p-value=0.03). CONCLUSION: Hypertensive disorders of pregnancy are associated with hypoxic ischemic encephalopathy and specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with significant reduction in the odds of hypoxic ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to the NICU ≥360 weeks' gestation. The findings of this observational study cannot prove causality and are intended to be hypothesis generating for future clinical trials on MgSO4 in term infants.

Biomarker role of maternal soluble human leukocyte antigen G in pre-eclampsia: A meta-analysis.

INTRODUCTION: Human leukocyte antigen-G (HLA-G) is a non-classical class I HLA molecule shown to regulate the immunomodulation of maternal immune cells to prevent fetal tissue destruction. Low levels of freely circulating maternal soluble HLA-G (sHLA-G) have been observed in pre-eclampsia, however, no pooled evidence exists. This meta-analysis aimed to generate pooled findings on the association of sHLA-G levels with pre-eclampsia and is the first study to perform a trimester-wise comparison of the levels of sHLA-G in preeclamptic cases and normal pregnant controls. METHODS: The databases PubMed, Emba, Web of Science, and Google Scholar through May 31, 2023. Preeclamptic women were defined as cases and normal pregnancies as controls. Data on the level of sHLA-G in cases and controls was extracted and subjected to a meta-analysis using a random-effects model. The pooled effect was expressed in terms of standardized mean difference (SMD). Sensitivity analysis was performed to investigate the effect of the exclusion of each study on the pooled results. Publication bias was assessed statistically. RESULTS: Nine studies with altogether 567 PE cases and 1132 normal pregnancy controls were included in the meta-analysis. The first and third trimester levels of sHLA-G in PE cases were significantly lower than that of normal pregnant controls: (SMD: -0.84 [-1.29; -0.38]; p = .003; I2 = 54%) and (SMD: -0.39 [-0.71; -0.06]; p = .02; I2 = 79%) respectively. Sensitivity analysis revealed significant fluctuations in the pooled findings when few studies were excluded, raising questions on the consistency of results among studies. CONCLUSION: Although we found that first and third-trimester sHLA-G levels in pre-eclampsia are significantly lower, taking into consideration the inconsistent results from the sensitivity analysis, our findings advocate the demand for more studies with larger sample sizes to generate solid ground pooled evidence on the predictive role of sHLA-G in pre-eclampsia.

A meta-analysis on first-trimester blood count parameters-is the neutrophil-to-lymphocyte ratio a potentially novel method for first-trimester preeclampsia screening?

Objective: Meta-analysis focusing on the role of first-trimester neutrophil-to-lymphocyte ratio (NLR) in the prediction of preeclampsia. Data sources: PubMed, Scopus, Web of Science, Cochrane Library, and Embase databases were queried from inception up to December 31, 2022. Study eligibility criteria: The study included all types of original research that was conducted in humans and values of NLR were measured during the first trimester, among patients who later developed preeclampsia, compared to the values of control groups. Study appraisal and synthesis methods: Two reviewers independently performed data abstraction and quality appraisal, and disagreements were resolved by consensus and, if necessary, by the opinion of a third reviewer. During the analysis, PRISMA and MOOSE guidelines were followed. All statistical analyses were made with R. Results: For the research on the predictive role of NLR values in the first trimester for preeclampsia, a total of 6 studies were selected for analysis, covering 2,469 patients. The meta-analysis revealed a 95% confidence interval (CI) for the effect size of 0.641 to 1.523, with a prediction interval of 0.027 to 2.137. Conclusion: Based on the analysis, NLR is a promising biochemical marker for future pieces of research that try to find new screening methods for first-trimester preeclampsia. We encourage other researchers to examine NLR's predictive value combined with other markers in preeclampsia screening, this way being able to find new and affordable protocols for first-trimester preeclampsia screening. Systematic review registration: identifier CRD42023392663.

Ventricular Tachycardia in Patients With Pre-eclampsia: Prevalence, Predictors, and Associated In-Hospital Adverse Events.

Introduction Pre-eclampsia is a pregnancy-associated multisystem disorder; in rare cases, it can be complicated by arrhythmias such as ventricular tachycardia (VT). The purpose of this study was to determine the prevalence and predictors of VT among patients admitted with pre-eclampsia as well as to analyze the independent association of VT with in-hospital outcomes in this population. Methods Data were obtained from the National Inpatient Sample from January 2016 to December 2019. Patients with a primary diagnosis of pre-eclampsia were selected using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes. Subsequently, the study population was divided into patients who developed VT versus patients who did not develop this complication. We then assessed the predictors of VT in women with pre-eclampsia as well as the independent association of VT with outcomes taking into account confounders such as age, race, and comorbidities. Results Of 255,946 patients with pre-eclampsia, 92 developed VT (0.04%) during their hospital stay. Multivariate logistic regression showed that patients with VT were far more likely to develop cardiac arrest (adjusted odds ratio, or aOR: 92.582, 95% CI: 30.958-276.871, p=0.001), require permanent pacemaker implantation (aOR: 41.866, 95% CI: 14.800-118.432, p=0.001), develop postpartum hemorrhage (aOR: 2.932, 95% CI: 1.655-5.196, p=0.001), and require left heart catheterization (aOR: 19.508, 95% CI: 3.261-116.708, p=0.001). Predictors of VT included being African American (aOR: 1.939, 95% CI: 1.183-3.177, p=0.009), cerebrovascular disease (aOR: 23.109, 95% CI: 6.953-76.802, p=0.001), congestive heart failure (aOR: 50.340, 95% CI: 28.829-87.901, p=0.001), atrial fibrillation (aOR: 20.148, 95% CI: 6.179-65.690, p=0.001), and obstructive sleep apnea, or OSA (aOR: 3.951, 95% CI: 1.486-10.505, p=0.006). Patients in the VT cohort were found to have an increased length of hospital stay compared to the non-VT cohort (7.16 vs. 4.13 days, p=0.001). Conclusion In a large cohort of women admitted with pre-eclampsia, we found the prevalence of VT to be <1%. Predictors of VT included conditions such as atrial fibrillation, congestive heart failure, and OSA and being African American. VT was found to be independently associated with several adverse outcomes as well as an increased length of hospital stay.

Mendelian randomization supports genetic liability to hospitalization for COVID-19 as a risk factor of pre-eclampsia.

Background: Pre-eclampsia and eclampsia are among the major threats to pregnant women and fetuses, but they can be mitigated by prevention and early screening. Existing observational research presents conflicting evidence regarding the causal effects of coronavirus disease 2019 (COVID-19) on pre-eclampsia risk. Through Mendelian randomization (MR), this study aims to investigate the causal effect of three COVID-19 severity phenotypes on the risk of pre-eclampsia and eclampsia to provide more rigorous evidence. Methods: Two-sample MR was utilized to examine causal effects. Summary-level data from genome-wide association studies (GWAS) of individuals of European ancestry were acquired from the GWAS catalog and FinnGen databases. Single-nucleotide polymorphisms associated with COVID-19 traits at p < 5 × -8 were obtained and pruned for linkage disequilibrium to generate instrumental variables for COVID-19. Inverse variance weighted estimates were used as the primary MR results, with weighted median and MR-Egger as auxiliary analyses. The robustness of the MR findings was also evaluated through sensitivity analyses. Bonferroni correction was applied to primary results, with a p < 0.0083 considered significant evidence and a p within 0.083-0.05 considered suggestive evidence. Results: Critical ill COVID-19 [defined as hospitalization for COVID-19 with either a death outcome or respiratory support, OR (95% CI): 1.17 (1.03-1.33), p = 0.020] and hospitalized COVID-19 [defined as hospitalization for COVID-19, OR (95% CI): 1.10 (1.01-1.19), p = 0.026] demonstrated suggestive causal effects on pre-eclampsia, while general severe acute respiratory syndrome coronavirus 2 infection did not exhibit a significant causal effect on pre-eclampsia. None of the three COVID-19 severity phenotypes exhibited a significant causal effect on eclampsia. Conclusions: Our investigation demonstrates a suggestive causal effect of genetic susceptibility to critical ill COVID-19 and hospitalized COVID-19 on pre-eclampsia. The COVID-19 severity exhibited a suggestive positive dose-response relationship with the risk of pre-eclampsia. Augmented attention should be paid to pregnant women hospitalized for COVID-19, especially those needing respiratory support.

Prediction of preterm birth in women with fetal growth restriction - Is the weekly change in sFlt-1/PlGF ratio or PlGF levels useful?

INTRODUCTION: To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction. MATERIAL AND METHODS: A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth. RESULTS: The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell's C: 0.68). CONCLUSIONS: Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level.

An Unusual Case of Severe Pre-eclampsia and Pulmonary Edema Following Single Fetal Demise in an In Vitro Fertilization (IVF)-Conceived Twin Gestation: A Twisted Tale of Twins.

There has been a notable rise in instances of multiple-fetus pregnancies over the last decade, attributed to the widespread adoption of assisted reproductive technologies. Moreover, these pregnancies have been associated with the use of drugs to induce ovulation. While some cases involve the loss of one twin with minimal consequences for the surviving twin, the demise of a fetus after the first trimester, especially beyond three months into the pregnancy, can significantly impact the health of both the mother and the surviving fetus. Unfavorable outcomes linked to the loss of one twin after the first trimester include impaired physical growth of the surviving fetus, preterm delivery, neurological abnormalities, and, in certain instances, the death of the surviving twin. This report provides a detailed account of a specific case involving twin pregnancies where a single fetal death occurred at the 24th week of gestation, leading to severe pregnancy-induced hypertension and pulmonary edema. Upon reviewing peer-reviewed articles related to similar cases in online databases, no exact matches were identified for cases with a comparable presentation. The scarcity of literature on the development of pre-eclampsia following the death of a single fetus suggests a gap in obstetric research in this area. Consequently, the uniqueness of this case report arises from its distinctive circumstances and the limited existing literature on the subject within the obstetric community.

Early HbA1c Levels as a Predictor of Adverse Obstetric Outcomes: A Systematic Review and Meta-Analysis.

Background: The objective was to assess the association between early HbA1c levels and pregnancy complications and whether this relationship is affected when HbA1c thresholds are greater than or less than 39 mmol/mol (5.7%). Methods: Electronic searches of the MEDLINE and EMBASE databases up to October 2022 were conducted. We included retrospective and prospective observational studies. The inclusion criteria were as follows: HbA1c measurements taken at <20 weeks' gestation, singleton pregnancy, and no pre-existing diabetes mellitus. Results: We assessed the certainty of the evidence with the GRADE system. We determined the proportion of patients in each group who met the criteria for obstetrical outcomes and pooled data into two subgroups according to the HbA1c threshold: <39 mmol/mol or >39 mmol/mol (5.7%). Sixteen studies with a total of 43,627 women were included. An association between elevated early HbA1c levels and pre-eclampsia, large for gestational age (LGA), macrosomia, and preterm delivery (RR 2.02, 95% CI 1.53-2.66; RR 1.38, 95% CI 1.15-1.66; RR 1.40, 95% CI 1.07-1.83; and RR 1.67, 95% CI 1.39-2.0, respectively) was shown, with a moderate-high grade of certainty. According to the subgroup analysis of all studies, LGA, pre-eclampsia, and labour induction were associated with elevated HbA1c levels only in studies using an HbA1c threshold >39 mmol/mol (5.7%). The association between HbA1c levels and premature birth was statistically significant in studies using both higher and lower HbA1c thresholds. Conclusions: Women with high early HbA1c levels below the range of diabetes presented an increased risk of pregnancy complications such as macrosomia, LGA, and pre-eclampsia. An early HbA1c threshold of >39 mmol/mol (5.7%) showed the strongest association with pregnancy complications.

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labor, and pre-eclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This narrative synthesis summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidence-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early-pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Placental Dysfunction.

Background: This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting placental dysfunction and neonatal outcomes in twin pregnancies. Methods: Prospective study at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks' gestation. Results: Seventy patients were included, and 30% developed placental dysfunction. Differences were found in the mean sFlt-1/PlGF ratios at week 32 (13.6 vs. 31.8, p = 0.007). Optimal cutoffs at 12, 24, and 32 weeks to identify patients who develop placental dysfunction were 32.5, 8.5, and 30.5, respectively, with ORs of 4.25 (1.13-20.69 95% IC; p = 0.044), 13.5 (3.07-67.90 95% IC; p = 0.001), 14.29 (3.59-66.84 95% IC; p < 0.001). The sFlt-1/PlGF ratio at 32 weeks was associated with gestational age at birth. The sFlt-1/PlGF ratio in weeks 24 and 32 had a statistically significant negative correlation with the birth weight percentile in both twins. Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for placental dysfunction in twin pregnancies is underscored.

Pre-eclampsia: Re-visiting pathophysiology, role of immune cells, biomarker identification and recent advances in its management.

Pre-eclampsia (PE) is a hypertension condition that occurs exclusively during pregnancy and has the potential to impact nearly all organ systems. It is estimated to complicate approximately 2-8% of pregnancies worldwide. PE is a prominent medical disorder that poses a significant risk to pregnant mothers and their infants. This review commences by giving the most up-to- date concepts about the pathophysiology of PE. The condition involves atypical infiltration of trophoblast cells into the spiral arteries of the decidua and myometrium, resulting in an insufficient establishment of proper blood flow between the uterus and placenta. The aberrant activation of natural killer (NK) cells in both the peripheral blood and the decidua has been identified as one of the contributing factors to the development of PE. The strong evidence for the genetic etiology of PE is provided by the association between maternal killer cell immunoglobulin-like receptor (KIR) and Human Leukocyte Antigen (HLA-C) in trophoblast cells. Recent observations provide evidence that changes in the expression of anti-angiogenic factors in the placenta are the underlying cause of the clinical symptoms associated with the condition. This review also provides a comprehensive overview of the latest advancements in understanding the underlying causes of PE. It specifically highlights the emergence of new diagnostic biomarkers and their potential implications for therapeutic interventions in managing this medical condition.

The Strategy for Peptidomic LC-MS/MS Data Analysis: The Case of Urinary Peptidome Study.

The study of urinary peptidome is an important area of research, which concerns the characterization of endogenous peptides, as well as the identification of biomarkers for a wide range of socially significant diseases. First of all, this relates to renal and genitourinary pathologies and/or pathologies associated with proteinuria, such as kidney diseases, bladder, prostate and ovarian cancers, diabetic nephropathy, and pre-eclampsia. Unlike proteins, peptides do not require proteolytic hydrolysis, can be analyzed in their native form and can provide certain information about occurring (patho)physiological processes. Mass spectrometry (MS)-based approaches are the most unbiased and sensitive instruments with high multiplexing capacity and provided most of the current information about endogenous urine peptides. However, despite the large number of urine peptidomic studies, there are certain issues related to the insufficient comparability of their results due to the lack of consistent approaches to their interpretation. Also the development of a custom project-specific protein library for endogenous peptides search and identification is another important point that should be noted in the context of high-throughput peptidomic analysis. Here we propose the custom-specific urinary protein database and the grouping of endogenous urinary peptides with overlapping sequences as useful tools, which can facilitate the acquisition and analysis of LC-MS peptidomic data, as well as the comparison of results of different studies, which should facilitate their more efficient further application.