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.

Mobil Monitoring Doppler Ultrasound (MoMDUS) study: protocol for a prospective, observational study investigating the use of artificial intelligence and low-cost Doppler ultrasound for the automated quantification of hypertension, pre-eclampsia and fetal growth restriction in rural Guatemala.

INTRODUCTION: Undetected high-risk conditions in pregnancy are a leading cause of perinatal mortality in low-income and middle-income countries. A key contributor to adverse perinatal outcomes in these settings is limited access to high-quality screening and timely referral to care. Recently, a low-cost one-dimensional Doppler ultrasound (1-D DUS) device was developed that front-line workers in rural Guatemala used to collect quality maternal and fetal data. Further, we demonstrated with retrospective preliminary data that 1-D DUS signal could be processed using artificial intelligence and deep-learning algorithms to accurately estimate fetal gestational age, intrauterine growth and maternal blood pressure. This protocol describes a prospective observational pregnancy cohort study designed to prospectively evaluate these preliminary findings. METHODS AND ANALYSIS: This is a prospective observational cohort study conducted in rural Guatemala. In this study, we will follow pregnant women (N =700) recruited prior to 18 6/7 weeks gestation until their delivery and early postpartum period. During pregnancy, trained nurses will collect data on prenatal risk factors and obstetrical care. Every 4 weeks, the research team will collect maternal weight, blood pressure and 1-D DUS recordings of fetal heart tones. Additionally, we will conduct three serial obstetric ultrasounds to evaluate for fetal growth restriction (FGR), and one postpartum visit to record maternal blood pressure and neonatal weight and length. We will compare the test characteristics (receiver operator curves) of 1-D DUS algorithms developed by deep-learning methods to two-dimensional fetal ultrasound survey and published clinical pre-eclampsia risk prediction algorithms for predicting FGR and pre-eclampsia, respectively. ETHICS AND DISSEMINATION: Results of this study will be disseminated at scientific conferences and through peer-reviewed articles. Deidentified data sets will be made available through public repositories. The study has been approved by the institutional ethics committees of Maya Health Alliance and Emory University.

Relationship between serum uric acid, nocturnal hypertension and risk for preeclampsia in high-risk pregnancies.

To analyze the possible association between serum uric acid (SUA) and nocturnal hypertension and to evaluate the ability of these variables (alone or in combination) to predict preeclampsia (PE) we conducted a historical cohort study in 532 high-risk pregnancies. Women were divided according to SUA values and nocturnal blood pressure (BP) into four groups: 1- normal SUA and nocturnal normotension; 2- high SUA and nocturnal normotension; 3- normal SUA and nocturnal hypertension and 4- high SUA and nocturnal hypertension. High SUA was defined by the top quartile values and nocturnal hypertension as BP ≥ 120/70 mmHg, using ambulatory blood pressure monitoring (ABPM), during nocturnal rest. Risks for PE were compared using logistic regression. SUA had a weak but significant correlation with daytime systolic ABPM (r = 0.11, p = 0.014), daytime diastolic ABPM (r = 0.13, p = 0.004), nighttime systolic ABPM (r = 0.16, p < 0.001) and nighttime diastolic ABPM (r = 0.18, p < 0.001). Also, all ABPM values were higher in women with high SUA. The absolute risk of PE increased through groups: 6.5%, 13.1%, 31.2%, and 47.9% for groups 1, 2, 3, and 4, respectively, p < 0.001. Compared with Group 1, Group 3 (OR 6.29 95%CI 3.41-11.60), but not Group 2 (OR 2.15 95%CI 0.88-5.24), had statistically significant higher risk for PE. Group 4 (women with both, high SUA and nocturnal hypertension) had the highest risk (OR 13.11 95%CI 6.69-25.70). Risks remained statistically significant after the adjustment for relevant variables. In conclusion, the combination of SUA > 4 mg/dL and nocturnal BP > 120/70 mmHg implies a very high risk to developed PE.

Can platelet activation markers predict preeclampsia and/or its severity?

OBJECTIVE: This study aimed to evaluate the value of platelet activation markers in predicting preeclampsia and its severity. Preeclampsia is a serious pregnancy complication that affects 3-5% of pregnancies and can lead to significant morbidity and mortality for both the mother and the fetus. METHODS: The study included 99 patients diagnosed with preeclampsia and 60 healthy pregnant women as a control group. Platelet activation markers such as mean platelet volume (MPV), platelet distribution width (PDW), platelet count, and plateletcrit were evaluated along with other clinical parameters. RESULTS: The results of the study showed that platelet activation markers, particularly PDW and MPV, are valuable in the diagnosis and follow-up of preeclampsia. However, they are not sufficient to predict the severity of the disease. CONCLUSION: The study suggests that platelet activation markers could aid in predicting, diagnosing, and managing preeclampsia. However, further research is needed to determine the role of these markers in predicting the severity of the disease. The findings of this study could contribute to the development of more effective strategies for the prevention and management of preeclampsia, which could ultimately improve maternal and fetal outcomes.

OBJETIVO: El estudio tuvo como objetivo determinar el valor de los marcadores de activación plaquetaria en la predicción de la preeclampsia y su gravedad. MÉTODO: Se incluyeron 99 pacientes diagnosticadas con preeclampsia, incluyendo 36 casos graves, y un grupo control de 60 mujeres embarazadas sanas. Se evaluaron diversas variables, como el volumen plaquetario medio, el recuento de plaquetas, el hematocrito plaquetario y la amplitud de distribución plaquetaria. RESULTADOS: Los resultados mostraron que el volumen plaquetario medio y la amplitud de distribución plaquetaria son parámetros valiosos en el diagnóstico y seguimiento de la preeclampsia, aunque no son suficientes para predecir su gravedad. El análisis estadístico reveló que la edad, el volumen plaquetario medio, la amplitud de distribución plaquetaria, la semana de gestación y los puntajes de Apgar al primer y quinto minuto fueron significativamente diferentes en el grupo de preeclampsia en comparación con el grupo control. CONCLUSIONES: En conclusión, estos resultados sugieren que los marcadores de activación plaquetaria pueden ser útiles para el diagnóstico y seguimiento de la preeclampsia, y que el volumen plaquetario medio y la amplitud de distribución plaquetaria, por ser parámetros económicos y accesibles, podrían ayudar a predecir, diagnosticar y manejar esta complicación durante el embarazo.

Potential urinary biomarkers in preeclampsia: a narrative review.

INTRODUCTION: Preeclampsia (PE) is a highly relevant pregnancy-related disorder. An early and accurate diagnosis is crucial to prevent major maternal and neonatal complications and mortality. Due to the association of kidney dysfunction with the pathophysiology of the disease, urine samples have the potential to provide biomarkers for PE prediction, being minimally invasive and easy to perform. Therefore, searching for novel biomarkers may improve outcomes. This narrative review aimed to summarize the scientific literature about the traditional and potential urinary biomarkers in PE and to investigate their applicability to screen and diagnose the disorder. METHODS: A non-systematic search was performed in PubMed/MEDLINE, Scopus, and SciELO databases. RESULTS: There is significant divergence in the literature regarding traditionally used serum markers creatinine, cystatin C, and albuminuria, accuracy in PE prediction. As for the potential renal biomarkers investigated, including vascular epithelial growth factor (VEGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase (sFlt-1), urinary levels of PlGF and sFtl-1/PlGF ratio in urine seem to be the most promising as screening tests. The assessment of the global load of misfolded proteins through urinary congophilia, podocyturia, and nephrinuria has also shown potential for screening and diagnosis. Studies regarding the use of proteomics and metabolomics have shown good accuracy, sensitivity, and specificity for predicting the development and severity of PE. CONCLUSION: However, there are still many divergences in the literature, which requires future and more conclusive research to confirm the predictive role of urinary biomarkers in pregnant women with PE.

Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Platelet indices and angiogenesis markers in hypertensive disorders of pregnancy.

INTRODUCTION: Activated platelets exert a key role in the pathogenesis of preeclampsia (PE). There is evidence of distinctive patterns of platelet indices in PE in comparison to healthy pregnancies, therefore these indices can be potential tools for PE detection, risk stratification, and management. Considering the vascular aspects of its pathophysiology, PE is characterized by the increased levels of soluble FMS-like tyrosine kinase-1 (sFlt-1) an antiangiogenic factor, and reduced placental growth factor (PlGF), a proangiogenic factor. This study aimed to assess the platelet indices in hypertensive disorders of pregnancy (HDP) and its correlation with angiogenesis-related biomarkers. METHODS: The groups for the study were: control (n = 114); gestational hypertension; (n = 112), and PE (n = 42). The platelet indices included were platelet counts (PLT-I and PLT-F), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR), and immature platelet fraction (IPF# and IPF%). Serum levels of sFlt-1 and PlGF were assessed. RESULTS: PLT-I, PLT-F, and PCT% were lower in PE, while MPV, PDW, P-LCR, IPF%, and IPF# were increased. The parameter MPV presented the best performance for the discrimination of PE. There was a moderate positive correlation between sFlt-1 levels and MPV, PDW, and P-LCR. CONCLUSION: Platelet indices can be potentially applied as additional tools for the diagnosis and management of HDP. Activated platelets may act as an extra source of sFlt-1 in PE.

Pre-eclampsia in low and middle-income settings: What are the barriers to improving perinatal outcomes and evidence-based recommendations?

OBJECTIVE: To discuss the points that still challenge low- and middle-income countries (LMICs) and strategies that have been studied to help them overcome these issues. METHODS: Narrative review addressing 20 years of articles concerning pre-eclampsia morbidity and mortality in LMICs. We summarized evidence-based strategies to overcome the challenges in order to reduce the pre-eclampsia impact on perinatal outcomes. RESULTS: Pre-eclampsia is the first or second leading cause in the ranking of avoidable causes of maternal death, and approximately 16% of all maternal deaths are attributable to eclampsia and pre-eclampsia. Considering the social and economic contexts, it represents a major public health concern, and prevention and early detection of pre-eclampsia seem to be a major challenge. Reducing maternal mortality related to hypertensive disturbances depends on public policies to manage these preventable conditions. Early and continuous recognition of signs of severity related to hypertensive disorders during pregnancy and childbirth, self-monitoring of symptoms and blood pressure, as well as preventive approaches such as aspirin and calcium, and magnesium sulfate, are lifesaving procedures that have not yet reached a universal scale. CONCLUSION: This review provides a vision of relevant points to support pregnant women in overcoming the constraints to healthcare access in LMICs, and strategies that can be applied in primary prenatal care units.

Cribado de preeclampsia / Screening for preeclampsia

INTRODUCCIÓN La preeclampsia es una de las principales causas de mortalidad y mor bilidad materna y neonatal. En España entre el 1 % - 2 % de los embarazos se ven afectados por la preeclampsia. Dados los elevados riesgos que conlleva esta enfermedad, la mejor estra tegia sería aquella que lograse identificar de forma temprana a las gestantes con un mayor riesgo de desarrollar preeclampsia. Los métodos actuales para la estimación del riesgo de desarrollar preeclampsia, que se basan principalmen te en la presencia en la historia clínica materna de determinados factores de riesgo, tienen una precisión limitada. Por eso, en la actualidad se está abogan do por la implantación de un cribado combinado de preeclampsia realizado al inicio de la gestación en el que, mediante algoritmos específicos, se ponderen distintos factores como son las características demográficas maternas, historia médica y obstétrica, marcadores biofísicos (tensión arterial media o índice de pulsatilidad de las arterias uterinas), así como marcadores bioquímicos (pro teína plasmática A asociada al embarazo o el factor de crecimiento placentario). La identificación precoz de embarazadas con mayor riesgo de desarrollar preeclampsia es importante porque éstas pueden beneficiarse de una mayor vigilancia y de recibir intervenciones a tiempo y porque permite iniciar trata mientos preventivos que reduzcan

INTRODUCTION Preeclampsia is one of the leading causes of maternal and neonatal mor bidity and mortality. In Spain, it occurs in 1 % to 2 % of pregnancies. Given the significant risks associated with this condition, the best strat egy involves identifying pregnant women at higher risk of developing preec lampsia at an early stage. The current methods for estimating the risk of de veloping preeclampsia, mainly based on risk factors in the maternal clinical history, are not very accurate. For this reason, efforts are currently focused on introducing a combined approach for preeclampsia screening in early preg nancy, using specific algorithms to weight various factors including maternal demographic characteristics and medical and obstetric history, as well as both biophysical (mean blood pressure and mean uterine artery pulsatility index) and biochemical (pregnancy-associated plasma protein A and placental growth factor) markers. Early identification of pregnant women at the highest risk of preeclamp sia is key because they are the ones who would most benefit from closer monitoring and timely interventions, and also it allows preventive measures to be taken to reduce the risk of developing preeclampsia in the first place. The current approach to preventin

[Inflammatory indexes and their association with the severity of preeclampsia]. / Índices inflamatorios y su asociación con la severidad de la preeclampsia.

Background: Recent studies have confirmed the relationship between some inflammatory indexes and preeclampsia (PE); however, they have not been analyzed in PE with and without severity criteria. Objective: To know the association between inflammatory indexes and the severity of PE. Material and methods: Analytical cross-sectional prolective study. Pregnant patients were included, divided into group 1 (PE without severity criteria); group 2 (PE with severity criteria); group 3 (normotensive pregnant women). Records were reviewed and inflammatory indexes [(neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], lymphocyte-monocyte ratio [LMR] and systemic immune index [SII]) were calculated. Results: 240 patients were analyzed, 80 per group; age 28 (IQR 27-29) years. A significant difference was observed between group 1, group 2 and group 3, NLR 3.29 (IQR 2.82-3.69), 3.59 (IQR 2.83-4.2) and 3.42 (IQR 3.17-3.92), respectively, p = 0.02; PLR 121.59 (IQR 103.78-132), 108.32 (IQR 92.96-127.43) 136 (IQR 115.18-157.56), respectively, p = 0.01; LMR and SII showed no difference between the groups. LMR made possible to distinguish PE with and without severity criteria, cut-off point of ≥ 3.20, sensitivity 56%, specificity 56%, AUC 0.56, p = 0.01, and cut-off point ≥ 3.24, sensitivity 58%, specificity 58%, AUC 0.57, p = 0.04, respectively; the LMR ≥ 3.24 was associated with PE without severity criteria (OR 2.02 [95%CI 1.08-3.80], p = 0.03). Conclusions: The MLR was the only inflammatory index analyzed that was associated with the presence of PE without severity data. No inflammatory index was associated with PE with severity data.

Introducción: estudios recientes han confirmado la relación que existe entre algunos índices inflamatorios y la preeclampsia (PE); sin embargo, no se han analizado en la PE con y sin criterios de severidad. Objetivo: conocer la asociación entre los índices inflamatorios y la severidad de la PE. Material y métodos: estudio transversal analítico prolectivo. Se incluyeron pacientes embarazadas, distribuidas en PE sin criterios de severidad (grupo 1), PE con criterios de severidad (grupo 2) y normotensión (grupo 3). Se revisaron expedientes y se calcularon los índices inflamatorios (índice neutrófilos linfocitos [INL], plaquetas linfocitos [IPL], linfocito monocito [ILM] e inmunosistémico [IIS]). Resultados: se analizaron 240 pacientes, 80 por grupo; edad de 28 años (RIC 27-29). Se observó diferencia significativa entre grupo 1, grupo 2 y grupo 3, INL 3.29 (RIC 2.82-3.69), 3.59 (RIC 2.83-4.2) y 3.42 (RIC 3.17-3.92), respectivamente, p = 0.02; IPL 121.59 (RIC 103.78-132), 108.32 (RIC 92.96-127.43) 136 (RIC 115.18-157.56), respectivamente, p = 0.01; ILM y ISS no mostraron diferencia entre los grupos. ILM permitió distinguir PE con y sin criterios de severidad, punto de corte ≥ 3.20, sensibilidad 56%, especificidad 56%, AUC 0.56, p = 0.01, y, punto de corte ≥ 3.24, sensibilidad 58%, especificidad 58%, AUC 0.57, p = 0.04, respectivamente; el ILM ≥ 3.24 se asoció con PE sin criterios de severidad (RM 2.02 [IC 95% 1.08-3.80], p = 0.03). Conclusiones: el ILM fue el único índice inflamatorio analizado que se asoció con la presencia de PE sin criterios de severidad. Ningún índice inflamatorio se asoció con la PE con datos de severidad.

Obesity Cut-Off Points Using Prepregnancy Body Mass Index according to Cardiometabolic Conditions in Pregnancy.

Aim: To suggest cut-off points for body mass index (BMI) using gestational hypertension, preeclampsia, and gestational diabetes mellitus (GDM) as cardiometabolic conditions in pregnancy. Methods: In this prospective study, singleton pregnant women from the fetal medicine service of the Brazilian Unified Health System were included. The pregnancy, perinatal, and newborn data were obtained from the clinical medical records. Maternal anthropometry included an assessment of weight and height and the prepregnancy BMI evaluation categorized according to the World Health Organization cut-off points. The area under the curve and confidence interval values from receiver operator curves were generated to identify the optimal cut-off points using prepregnancy BMI with better sensitivity and specificity. Results: Data on 218 pregnancies were analyzed, with 57.9% (n = 124) being classified as overweight/obese, 11% (n = 24) with GDM, 6.9% (n = 15) with preeclampsia, and 11.0% (n = 24) with gestational hypertension. The BMI cut-off points for predicting cardiometabolic conditions were 27.52 kg/m2 (S: 66.7%; E: 63.8%) for women with GDM; 27.40 kg/m2 (S: 73.3%; E: 62.4%; S: 79.2%; E: 64.9%; S: 70.3%; E: 66.3%) for women with preeclampsia, gestational hypertension, and gestational hypertension plus preeclampsia, respectively; and 27.96 kg/m2 (S: 69.6%; E: 65.6%) for women with preeclampsia plus GDM. Conclusion: The findings suggest that the optimal prepregnancy BMI cut-off point is around 27 kg/m2 for pregnant women with maternal cardiometabolic conditions.

The challenge of adequately reporting preeclampsia for epidemiological surveillance: An example from a referral center in a middle-income country.

Adequately reporting of preeclampsia is a challenge. The aim of this study was to compare the diagnosis of preeclampsia based on clinical and laboratory findings and ICD-10 codes (International Classification of Diseases) at admission and discharge in a referral center, over a one-year period. Among 2,839 women admitted for childbirth, 208 presented confirmed preeclampsia, based on chart audits. Among these, 77.4% at admission presented ICD-10 codes assigned as hypertension, and 47.1% at discharge. In 14.4% of confirmed preeclampsia, ICD-10 codes for hypertension were not used. Adequate reporting of preeclampsia is key for clinical surveillance, counselling and guiding public health interventions.

Increased adherence to ACOG diagnostic guidelines for HDP following a workshop in Bolivia, a LMIC.

OBJECTIVES: Hypertensive disorders of pregnancy (HDP) exert a heavy mortality burden in low- to middle-income countries (LMIC). ACOG revised HDP diagnostic guidelines to improve identifying pregnancies at greatest risk but whether they are used in LMIC is unknown. STUDY DESIGN: We held a workshop to review ACOG guidelines in La Paz, Bolivia (BO) and then reviewed prenatal, labor and delivery records for all HDP diagnoses and twice as many controls at its three largest delivery sites during the year before and the nine months after a workshop (n = 1376 cases, 2851 controls during the two periods). MAIN OUTCOME MEASURES: HDP diagnoses, maternal, and infant characteristics. RESULTS: Bolivian and ACOG criteria identified similar frequencies of gestational hypertension (GH) or eclampsia, but preeclampsia with severe features (sPE) was under- and preeclampsia without severe features (PE) over-reported during both periods. Increases occurred after the workshop in testing for proteinuria and the detection of abnormal laboratory values and severe hypertension in HDP women. Any adverse maternal outcome occurred more frequently after the workshop in women with BO PE or sPE diagnoses who met ACOG sPE criteria. CONCLUSIONS: Utilization of ACOG guidelines increased following the workshop and improved identification of PE or sPE pregnancies with adverse maternal outcomes. Continued use of a CLAP perinatal form recognizing HELLP as the only kind of sPE resulted in under-reporting of sPE. FUNDING: NIH TW010797, HD088590, HL138181.

Changes in the autonomic cardiorespiratory activity in parturient women with severe and moderate features of preeclampsia.

Background: Cardiorespiratory coupling (CRC) is a physiological phenomenon that reflects the mutual interaction between the cardiac and respiratory control systems. It is mainly associated with efferent vagal activity from the central autonomic network. Few studies have explored the autonomic changes of CRC in preeclampsia, a critical obstetric complication related to possible autonomic dysfunctions and inflammatory disturbances. This study examined the autonomic mechanisms of CRC in women with severe and moderate preeclampsia and healthy controls by applying nonlinear methods based on information theory, such as mutual information (MI) and Renyi's mutual information (RMI) and the linear and nonlinear analysis of the Pulse-Respiration Quotient (PRQ). Methods: We studied three groups of parturient women in the third trimester of pregnancy with a clinical diagnosis of preeclampsia without severe symptoms (P, 38.5 ± 1.4 weeks of pregnancy, n=19), preeclampsia with severe symptoms (SP, 37.5 ± 0.9 weeks of pregnancy, n=22), and normotensive control women (C, 39.1 ± 1.3 weeks of pregnancy, n=20). 10-minutes of abdominal electrocardiograms (ECG) and respiratory signals (RESP) were recorded in all the participants. Subsequently, we obtained the maternal beat-to-beat (RR) and breath-to-breath (BB) time series from ECG and RESP, respectively. The CRC between RR and BB was quantified by nonlinear methods based on information theory, such as MI and RMI, along with the analysis of the novel index of PRQ. Subsequently, we computed the mean PRQ (mPRQ) and the normalized permutation entropy (nPermEn_PRQ) from the PRQ time series generated from BB and RR. In addition, we examined the vagal activity in the three groups by the logarithm of the median of the distribution of the absolute values of successive RR differences (logRSA). Results: The MI and RMI values were significantly lower (p<0.05) in the preeclamptic groups compared to the control group. However, no significant differences were found between the preeclamptic groups. The logRSA and nPermEn_PRQ indices were significantly lower (p<0.05) in SP compared to C and P. Conclusion: Our data suggest that parturient women with severe and mild preeclampsia may manifest an altered cardiorespiratory coupling compared with normotensive control women. Disrupted CRC in severe preeclampsia could be associated with vagal withdrawal and less complex cardiorespiratory dynamics. The difference in vagal activity between the preeclamptic groups may suggest a further reduction in vagal activity associated with the severity of the disease.

Maternal Serum Activin A, Inhibin A and Follistatin-Related Proteins across Preeclampsia: Insights into Their Role in Pathogenesis and Prediction.

BACKGROUND: Within the endocrine-paracrine signalling network at the maternal-foetal interface, the activin-inhibin-follistatin system modulates extravillous trophoblast invasion, suggesting a potential role in preeclampsia pathogenesis. This study aimed to compile the evidence published in the last decade regarding the variation in maternal serum activins, inhibin- and follistatin-related proteins in preeclamptic pregnancies compared to healthy pregnancies, and to discuss their role in predicting and understanding the pathophysiology of preeclampsia. MATERIAL AND METHODS: A scoping review was conducted in MEDLINE, EMBASE and LILACS databases to identify studies published within the last ten years (2012-2022). RESULTS: Thirty studies were included. None of the studies addressed maternal serum changes of isoforms different from activin A, inhibin A, follistatin, and follistatin-like 3. Sixteen studies evaluated the potential of these isoforms in predicting preeclampsia through the area under the curve from a receiver operating characteristic curve. CONCLUSIONS: In preeclampsia, inhibin A is upregulated in all trimesters, whereas activin A increases exclusively in the late second and third trimesters. Serum follistatin levels are reduced in women with preeclampsia during the late second and third trimesters. However, changes in follistatin-like 3 remain inconclusive. Inhibin A and activin A can potentially serve as biomarkers of early-onset preeclampsia based on the outcomes of the receiver operating characteristic curve analysis. Further investigations are encouraged to explore the feasibility of quantifying maternal serum levels of activin A and inhibin A as a clinical tool in early preeclampsia prediction.

Cardiovascular diseases in women: a differentiated view and risk stratification.

Cardiovascular diseases are the main cause of mortality in men and women worldwide, surpassing mortality from all associated neoplasms. In women, its prevalence and mortality increase at menopause, but complications of reproductive age, such as preeclampsia and eclampsia, lead to increased cardiovascular risk throughout their lives. Coronary ischemic disease is is the leading cause of death in Brazil and worldwide, with atherosclerotic disease being the principal pathophysiological mechanism. However, in women, other mechanisms are associated with myocardial ischemia, such as microcirculation disease and/or vasospasm, due to the anatomical and hormonal characteristics of women in different stages of their lives. Knowledge of the most prevalent cardiovascular diseases in women, as well as the specific risk factors, the traditional ones with the greatest impact, and the under-recognized ones, is of fundamental importance in their risk stratification, diagnosis, and management, fundamentally aiming at reducing mortality.

The prevalence and perinatal repercussions of preeclampsia after the implementation of a prophylaxis protocol with aspirin.

OBJECTIVES: To evaluate the prevalence and perinatal repercussions of preeclampsia (PE) after the implementation of a prophylaxis protocol with aspirin in singleton pregnancy at Maternity School of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2015-2106). METHODOLOGY: PE prevalence according to gestational age (GA) and the prevalence ratio (PR) between PE and prematurity, small for gestational age (SGA), and fetal death were calculated in patients assisted during 2015 and 2016. RESULTS: PE occurred in 373(10.75%) of 3468 investigated cases, where PE < 37 weeks was of 2.79% and PE greater than 37 weeks was of 7.95%. A total of 413 (11.9%) prematurity cases, 320 SGA (9.22%), and 50 fetal deaths (1.44%) occurred. In the PE group, 97 premature newborns (PR 0.90) and 51 SGA (PR 1.16) were born, and two fetal deaths occurred (PR 7.46). Concerning PE < 37 weeks, 27 SGA cases (PR 1.42) and two fetal deaths (PR 2.62) were observed. Regarding PE greater than 37 weeks, 24 SGA (PR 1.09) were born, and no fetal deaths were observed. Our findings were compared to previously published results. CONCLUSIONS: PE was significantly associated with SGA newborns, especially premature PE. Prescribing aspirin for PE prophylaxis based only on clinical risk factors in a real-life scenario does not appear to be effective but resulted in a PE screening and prophylaxis protocol review and update at ME/UFRJ.

First-trimester plasma extracellular heat shock proteins levels and risk of preeclampsia.

Preeclampsia (PE) occurs annually in 8% of pregnancies. Patients without risk factors represent 10% of these. There are currently no first-trimester biochemical markers that accurately predict PE. An increase in serum 60- and 70-KDa extracellular heat shock proteins (eHsp) has been shown in patients who developed PE at 34 weeks. We sought to determine whether there is a relationship between first-trimester eHsp and the development of PE. This was a prospective cohort study performed at a third level hospital in Mexico City from 2019 to 2020. eHsp levels were measured during the first-trimester ultrasound in singleton pregnancies with no comorbidities. First-trimester eHsp levels and biochemical parameters of organ dysfunction were compared between patients who developed preeclampsia and those who did not. All statistical analyses and model of correlation (r) between eHsp and clinical parameter were performed using bootstrapping R-software. p-values <0.05 were considered significant. The final analysis included 41 patients. PE occurred in 11 cases. eHsp-60 and eHsp-70 were significantly higher at 12 weeks in patients who developed PE (p = 0.001), while eHsp-27 was significantly lower (p = 0.004). Significant differences in first-trimester eHsp concentration suggest that these are possible early biomarkers useful for the prediction of PE.