Synthesis of evidence for managing hypertensive disorders of pregnancy in low middle-income countries: a scoping review.

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on continuing professional development, a shortage of trained personnel, community perceptions of preeclampsia, and outdated local clinical practice guidelines, impede the comprehensive management of patients.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.

Calcium carbonate supplementation for the prevention of preeclampsia in high-risk pregnant women: a randomized clinical trial protocol.

BACKGROUND: Preeclampsia (PE) is a significant cause of maternal mortality worldwide, affecting 2% to 8% of pregnancies. The World Health Organization recommends the use of low-dose acetylsalicylic acid (100 mg of aspirin) and 1.5 to 2 g of calcium carbonate during pregnancy to prevent PE. However, robust evidence supporting the efficacy of calcium supplementation is still needed. This study aims to assess the efficacy of calcium carbonate in preventing preeclampsia in high-risk pregnant women. METHODS: A triple-blind, randomized clinical trial will be conducted at an outpatient clinic in Brazil between May 2024 and March 2026. Pregnant women at high risk of developing preeclampsia and with low dietary calcium intake will be randomly assigned to one of three groups: one group will receive calcium carbonate capsules (commercially available in Brazil) along with 100 mg of aspirin; the second group will receive calcium carbonate derived from Crassostrea sp. along with 100 mg of aspirin; and the control group will receive a placebo alongside 100 mg of aspirin. The primary outcome is the diagnosis of preeclampsia during pregnancy, while secondary outcomes evaluate maternal and fetal health indicators. DISCUSSION: This trial seeks to generate evidence on the efficacy of calcium carbonate in preeclampsia prevention, with a focus on comparing industrial calcium carbonate with calcium carbonate sourced from Crassostrea sp., a more sustainable alternative. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of the Federal University of Sergipe and registered in the Brazilian Registry of Clinical Trials (ReBEC), under the ID RBR-7hqhj3y. Registered on November 16, 2023.

Complete blood count as a biomarker for preeclampsia with severe features diagnosis: a machine learning approach.

OBJECTIVE: This study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models. METHODS: We used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model. RESULTS: Our boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490 / m m 3 yielded a sensitivity of 0.71 and specificity of 0.72. CONCLUSION: Our study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE. SIGNIFICANCE: Although preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE.

The optic nerve sheath in hypertensive disorders of pregnancy and perinatal outcomes: a cohort study.

BACKGROUND: Preeclampsia is implicated in 14% of maternal deaths worldwide, mostly due to complications such as intracranial hemorrhage and cerebral edema. Cerebral edema increases intracranial pressure, which can be predicted by ultrasonographic measurement of the optic nerve sheath diameter (ONSD). Greater diameters have been reported in women with preeclampsia and eclampsia; however, data are lacking on the possible association with maternal and neonatal adverse outcomes. This study aimed to determine whether there is an association between hypertensive disorders of pregnancy and the ONSD, and between this measurement and maternal and neonatal adverse outcomes. METHODS: This was a cohort study involving 183 women in the third trimester of pregnancy or within 24 h following childbirth, distributed as follows: control group (n = 30), gestational hypertension (n = 14), chronic hypertension (n = 12), preeclampsia without severe features (n = 12), preeclampsia with severe features (n = 62), superimposed preeclampsia (n = 23) and eclampsia (n = 30). The participants underwent ocular ultrasonography, and data on maternal and neonatal outcomes were collected from the medical records. To compare the groups, analysis of variance was used for the normally distributed numerical variables and the Kruskal-Wallis test was used for variables with non-normal distribution. Two-tailed p-values ≤ 0.05 were considered statistically significant. RESULTS: Overall comparison between the seven groups showed no statistically significant difference in the mean ONSD (p = 0.056). Nevertheless, diameters were significantly greater in the eclampsia group compared to the control group (p = 0.003). Greater diameters were associated with maternal admission to the intensive care unit (ICU) (p < 0.01) and maternal near miss (p = 0.01). There was no association between ONSD and admission to the neonatal ICU (p = 0.1), neonatal near miss (p = 0.34) or neonatal death (p = 0.26). CONCLUSIONS: No association was found between ONSD and the hypertensive disorders of pregnancy in the overall analysis; however, ONSD was greater in women with eclampsia compared to controls. Greater diameters were associated with maternal admission to the ICU and maternal near miss. These findings suggest a potential use for bedside ultrasound as an additional tool for stratifying risk in patients with hypertensive disorders of pregnancy.

How can we reduce maternal mortality due to preeclampsia? The 4P rule.

In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention - Vigilant Prenatal Care - Timely Delivery (Parturition) - Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

Preeclampsia and transport of ions and small molecules: A literature review.

Preeclampsia (PE) is a prevalent obstetric complication affecting approximately 3-5% of pregnancies worldwide and is a major cause of maternal and perinatal morbidity and mortality. Preeclampsia is considered a disease of the endothelial system that can progress to eclampsia, characterized by seizures. Early diagnosis and appropriate management are crucial to improving maternal and fetal outcomes, as preeclampsia can lead to severe complications such as placental abruption, fetal growth restriction, and stroke. The pathophysiology of PE is complex, involving a combination of genetic, acquired, and immunological factors. A central feature of the condition is inadequate placentation and impaired uteroplacental perfusion, leading to local hypoxia, endothelial dysfunction, vasoconstriction, and immunological dysregulation. Recent evidence suggests that dysregulation of ion transporters may play a significant role in the adaptation of uterine circulation during placentation. These transporters are essential for maintaining maternal-fetal homeostasis, influencing processes such as nutrient exchange, hormone synthesis, trophoblast cell migration, and the function of smooth muscle cells in blood vessels. In preeclampsia, adverse conditions like hypoxia and oxidative stress result in the downregulation of ion, solute, and water transporters, impairing their function. This review focuses on membrane transporters involved in PE, discussing functional alterations and their physiological implications. The goal of this investigation is to enhance understanding of how dysregulation of ion and small molecule transporters contributes to the development and progression of preeclampsia, underscoring the importance of exploring these signaling pathways for potential therapeutic interventions.

Rentabilidad de la ratio angiogénica en el seguimiento de gestantes de alto riesgo de preeclampsia precoz tratadas con ácido acetilsalicílico / Profitability of the angiogenic ratio in the follow-up of pregnant women at high risk of early preeclampsia treated with acetylsalicylic acid

Objetivo: Evaluar el valor predictivo negativo de la ratio antigénica y conocer su rentabilidad para descartar preeclampsia precoz en pacientes de alto riesgo de desarrollarla, con profilaxis de ácido acetilsalicílico. Métodos: Se realizó un estudio descriptivo transversal que recogió a las gestantes con cribado de preeclampsia precoz de alto riesgo (384 gestantes) en el Hospital Santa Lucía durante el año 2021, para lo que se usó test Elecsys® tabulado a un riesgo mayor a 1/150 en primer trimestre, y que tomaran ácido acetilsalicílico antes de la semana 16, quedando en 368 gestantes vistas en las semanas 20, 26, 31 y 36. Se realizó biometría, ratio angiogénica y doppler. Resultados: La incidencia de preeclampsia precoz en la población fue 4 casos (incidencia 1,08 %). Son significativos por su alto valor predictivo negativo del 100 % de preeclampsia precoz: la ratio angiogénica mayor a 38 en la semana 26 y el doppler de las uterinas en semana 20 y 26. Conclusión: En gestaciones con cribado de alto riesgo de preeclampsia que tomen ácido acetilsalicílico, una ratio angiogénica menor a 38 en la semana 26, además de un doppler uterino normal en semana 20 y 26 permite reducir el seguimiento gestacional(AU)

Objective: Our main objective was to evaluate the negative predictive value of the angiogenic ratio and to know its profitability to rule out early preeclampsia in patients at high risk of early preeclampsia with acetylsalicylic acid prophylaxis. Methods: A cross-sectional descriptive study was carried out that included pregnant women with high-risk early preeclampsia screening (384 pregnant women) at the Santa Lucía Hospital during the year 2021, for which the Elecsys® test tabulated at a risk >1/ was used. 150 in the first trimester, and who take acetylsalicylic acid before week 16, leaving 368 pregnant women seen in weeks 20, 26, 31 and 36, with biometry, angiogenic ratio and Doppler performed. Results: The incidence of early preeclampsia in the population was 4 cases (incidence 1.08%). They are significant due to their high negative predictive value of 100% of early preeclampsia: Angiogenic ratio > 38 in week 26, uterine Doppler in weeks 20 and 26. Conclusion: Pregnancies with high risk screening for preeclampsia who take acid acetylsalicylic acid, an angiogenic ratio < 38 at week 26 in addition to a normal uterine Doppler at weeks 20 and 26 allows for reduced gestational follow-up(AU)

Complicaciones maternas y perinatales en gestantes con lupus: Estudio de casos y controles / Maternal and Perinatal Complications in Pregnant Women with Lupus: Case control Study

Objetivo: Determinar la frecuencia de complicaciones materno-perinatales y factores clínicos asociados a estos resultados en estantes con lupus. Métodos: Se realizó un estudio de casos y controles a partir de historias clínicas de pacientes con diagnóstico Lupus Eritematoso Sistémico en embarazo, entre 2010-2022 en una institución de salud en Medellín-Colombia. Éstas se clasificaron como casos (pacientes con resultados adversos materno-perinatales) y controles (pacientes sin resultados adversos). Resultados: Se incluyó un total de 67 pacientes (35 casos y 32 controles). Las complicaciones maternas más frecuentes fueron los trastornos hipertensivos asociados al embarazo (71,4 %), incluyendo preeclampsia y una presentación importante de partos pretérmino (68,6 %). La nefritis lúpica previa y durante el embarazo, fue más frecuente en los casos que en los controles (31,4 % versus 9,4 %). Los compromisos cardiovasculares, de mucosas y musculo-esquelético, fueron más frecuentes durante el embarazo (31,4 %, 40 % y 34,3 %, respectivamente), coincidiendo con mayor actividad del lupus, principalmente durante el embarazo. El compromiso cardiovascular y de mucosas durante el embarazo, así como tener síndrome antifosfolípido se relacionaron con desenlace materno-perinatal adverso. Conclusión: Componentes clínicos propios de la enfermedad como la nefritis lúpica, el síndrome antifosfolípido, el compromiso cardiovascular, y de mucosas podrían predisponer a desenlaces maternos y/o perinatales adversos como trastornos hipertensivos asociados al embarazo, pretérmino, restricción de crecimiento fetal, entre otros(AU)

Objective: To determine the frequency of maternal-perinatal complications and the clinical factors associated with these outcomes in pregnant women with lupus. Methods: A case-control study was conducted using the medical records of patients diagnosed with pregnancy and lupus in a healthcare institution in Medellin, Colombia, between 2010 and 2022. The patients were classified as cases (patients with adverse maternal-perinatal outcomes) and controls (patients without adverse outcomes). Results: A total of 67 patients (35 cases and 32 controls) were included. The most frequent maternal complications were pregnancyassociated hypertensive disorders (71.4%), including preeclampsia and a significant presentation of preterm deliveries (68.6%). Lupus nephritis prior to and during pregnancy was more frequent in cases than in controls (31.4% versus 9.4%). Cardiovascular, mucosal and musculoskeletal compromises were more frequent during pregnancy (31.4%, 40% and 34.3%, respectively), coinciding with greater lupus activity, mainly during pregnancy. Cardiovascular and mucosal involvement during pregnancy, as well as having antiphospholipid syndrome, were related to adverse maternal-perinatal outcome. Conclusion: Clinical components of the disease such as lupus nephritis, antiphospholipid syndrome, cardiovascular and mucosal involvement, are factors that may predispose these patients to adverse maternal and/or perinatal outcomes, such as hypertensive disorders associated with pregnancy, low birth weight, preterm, fetal growth restriction, among others(AU)

Preeclampsia in the Context of COVID-19: Mechanisms, Pathophysiology, and Clinical Outcomes.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.

Time in therapeutic range and risk of preeclampsia in chronic hypertensive pregnant women.

Pregnancy Hypertensive Disorders (PHD), particularly Preeclampsia (PE), are significant contributors to maternal-fetal morbidity and mortality, with chronic arterial hypertension (CH) being a major risk factor. The prevalence of CH has risen alongside obesity and advanced maternal age. While antihypertensive treatment mitigates adverse pregnancy outcomes, the duration of effective blood pressure (BP) control, termed Time in Therapeutic Range (TTR), has not been extensively studied in pregnant women. TTR, reflecting the proportion of time BP remains within target ranges, predicts long-term cardiovascular and renal events in the general population but remains unexplored in pregnancy. This study investigates the association between TTR, assessed through office BP (OBP) and ambulatory BP monitoring (ABPM), and PE development in pregnant women with CH. In a retrospective longitudinal study, data from 166 pregnant women with HA referred to our hospital analyzed. BP was measured using OBP and ABPM from 10 weeks of gestation, with TTR calculated as the percentage of visits where BP remained within target ranges. The study defined four TTR control groups: 0%, 33%, 50-66%, and 100%. Results showed that 28% of the participants developed PE, with a higher incidence correlating with lower TTR in ABPM. TTR in ABPM was a significant predictor of PE risk, with the best-controlled group (100% TTR) demonstrating a 92% reduced risk compared to those with 0% TTR. The agreement between OBP and ABPM TTR was low, emphasizing the importance of ABPM for accurate BP monitoring in pregnancy. This study indicates that integrating ABPM for TTR assessment in high-risk pregnancies has the potential to reduce maternal and fetal complications.

Are vitamin D intake and serum levels in the mid-trimester of pregnancy associated with preeclampsia? Results from a Brazilian multicentre cohort.

OBJECTIVE: To explore the association between serum levels and food intake of Vitamin D (VD) among healthy women in mid-pregnancy and preeclampsia. STUDY DESIGN: In a Brazilian multicentre cohort of healthy nulliparous pregnant women from five maternity centres we developed a nested case-control analysis comparing cases with and without preeclampsia. Women were enrolled and followed during prenatal care, including only singleton pregnancies, without any fetal malformations or previous chronic maternal disease. We matched 87 cases of preeclampsia to eligible controls randomly selected in a 1:1 ratio, by age and region. MAIN OUTCOME MEASURES: Blood samples from these were collected, and a 24-hour recall of food intake was obtained in mid-pregnancy, between 19 and 21 weeks. VD serum levels (25-hydroxyvitamin D) were measured by liquid chromatography-tandem mass spectrometry and were categorized as deficient, insufficient, and sufficient. The dietary intake of VD was estimated with the 24-hour diet recall applied at the same time and from supplementation. Maternal characteristics and VD levels were compared between cases and controls with OR and respective 95 %CI. Multivariate analysis using the Path method was used to assess relationships among VD, PE, BMI, skin colour/ethnicity, and diet. RESULTS: The maternal characteristics of both groups were similar, except for the higher occurrence of obesity among women with preeclampsia (OR 3.47, 95 %CI 1.48-8.65). Dietary intake of VD was similar in both groups, and most of the women in both groups consumed insufficient VD (82.2 vs 79.3 % in the groups with and without PE). CONCLUSIONS: Levels and dietary intake of VD were not associated with PE in this Brazilian sample of healthy pregnant women; however, BMI and skin colour/ethnicity were associated with PE.

Placental growth factor mediates pathological uterine angiogenesis by activating the NFAT5-SGK1 signaling axis in the endometrium: implications for preeclampsia development.

After menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or preeclampsia (PE). Placental growth factor (PlGF) is a known contributing factor for pathological angiogenesis but the mechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine angiogenesis by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signaling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signaling. Taken together, perturbed PlGF-NFAT5-SGK1 signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs-endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.

Knowledge, Attitudes, and Perceptions of Maternity Care Providers on the Implementation of Calcium Supplementation during Pregnancy in Three Public Hospitals in Argentina: A Qualitative Study.

The aim of this study was to explore maternity care providers' knowledge, attitudes, and perceptions about the use of calcium supplements during pregnancy for the prevention of preeclampsia in three hospitals from Metropolitan Buenos Aires, Argentina. We conducted semi-structured interviews and followed a thematic analysis framework. Maternity care providers' knowledge, attitudes, and practices regarding calcium supplementation during pregnancy are linked to barriers to the potential implementation of calcium supplementation. Free provision of calcium supplements by the government, coupled with training that reinforces the scientific evidence supporting their use to prevent preeclampsia, along with documented recommendations from credible sources, would be crucial to ensure that health providers adopt the use of calcium supplements in antenatal care. Future studies should assess pregnant women and policymakers' perceptions about calcium supplementation during pregnancy, as well as local infrastructure to provide access to free-of-charge calcium supplements in antenatal care settings. Economic evaluation with local information could inform policymakers and advocate for the implementation of strategies to reduce preeclampsia.

Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

Maternal deaths caused by eclampsia in Brazil: a descriptive study from 2000 to 2021.

Objective: Eclampsia is a hypertensive disorder that occurs during pregnancy and can lead to death. The literature has gaps by not providing comprehensive data on the epidemiology of the disease, restricting analysis to limited temporal intervals and geographical locations. This study aims to characterize the epidemiological profile of women who died from eclampsia in Brazil from 2000 to 2021. Methods: The maternal mortality data were obtained from the Sistema de Informações sobre Mortalidade, with the following variables of interest selected: "Federative Unit," "Year," "Age Range," "Race/Color," and "Education Level." The collection of the number of live births for data normalization was conducted in the Sistema de Informações sobre Nascidos Vivos. Statistical analyses were performed using GraphPad Prism, calculating odds ratio for variables and fixing number of deaths per 100,000 live births for calculating maternal mortality ratio (MMR). Results: There was a downward trend in maternal mortality rate during the study period. Maranhão stood out as the federative unit with the highest MMR (17 deaths per 100.000 live births). Mothers aged between 40 and 49 years (OR = 3.55, CI: 3.11-4.05) presents higher MMR. Additionally, black women showed the highest MMR (OR = 4.67, CI: 4.18-5.22), as well as mothers with no educational background (OR = 5.83, CI: 4.82-7.06). Conclusion: The epidemiological profile studied is predominantly composed of mothers with little or no formal education, self-declared as Black, residing in needy states and with advanced aged. These data are useful for formulating public policies aimed at combating the issue.

Placental mitochondrial impairment and its association with maternal metabolic dysfunction.

The placenta plays an essential role in pregnancy, leading to proper fetal development and growth. As an organ with multiple physiological functions for both mother and fetus, it is a highly energetic and metabolically demanding tissue. Mitochondrial physiology plays a crucial role in the metabolism of this organ and thus any alteration leading to mitochondrial dysfunction has a severe outcome in the development of the fetus. Pregnancy-related pathological states with a mitochondrial dysfunction outcome include preeclampsia and gestational diabetes mellitus. In this review, we address the role of mitochondrial morphology, metabolism and physiology of the placenta during pregnancy, highlighting the roles of the cytotrophoblast and syncytiotrophoblast. We also describe the relationship between preeclampsia, gestational diabetes, gestational diabesity and pre-pregnancy maternal obesity with mitochondrial dysfunction.

A Narrative Review on the Pathophysiology of Preeclampsia.

Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Preeclampsia in pregnant women with COVID-19: a prospective cohort study from two tertiary hospitals in Southern Brazil.

Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia. Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed. Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant. Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.