Complicaciones maternas y embarazo adolescente en América Latina: Revisión sistemática y metaanálisis / Maternal complications and adolescent pregnancy in Latin America: A systematic review and meta-analysis

RESUMEN Objetivo: Evaluar el riesgo de complicaciones maternas en el embarazo adolescente en Latinoamérica y El Caribe durante el periodo 2012 al 2021. Métodos: Se realizó una búsqueda sistemática en 6 bases de datos: PubMed, SCOPUS, Web Of Science, EMBase, LILACS y Scielo. Los artículos incluidos fueron procedentes de paises de Latinoamérica y contaron con cualquiera de las siguientes variables: preeclampsia, eclampsia, hemorragia puerperal y sepsis puerperal publicados desde el 2012 al 2021 y que compararan adolescentes y adultas embarazadas. Se excluyeron artículos que no presentaron hallazgos separados de Latinoamérica y/o El Caribe, que no se encontraban disponibles la versión completa y que estaban enfocados en pacientes con alguna enfermedad en específico. Para el riesgo de sesgo se empleó la Escala de Newcasttle-Ottawa para estudios de casos y controles. La medida de resumen empleada fue el Odds Ratio con un intervalo de confianza al 95% para cada estudio. Resultados: Se incluyeron 4 estudios. No se evidenció el riesgo de preeclampsia en adolescentes embarazadas (OR = 0.93, IC 95% 0.69 - 1.25) ni hemorragia puerperal (OR = 0.86, IC 95% 0.74 - 0.99). Por otro lado, se mostró el riesgo de eclampsia (OR = 2.43, IC 95% 1.29 - 4.58) en adolescentes embarazadas, pero con alta heterogeneidad entre los estudios (I2 = 76%). Conclusiones: Se evidenció un riesgo de eclampsia en adolescentes embarazadas, pero no en preeclampsia ni hemorragia puerperal; sin embargo, estos resultados deben de tomarse con cautela. Registro de protocolo: CRD42021286725 (PROSPERO)

ABSTRACT Objective: To assess whether maternal complications are a risk in adolescent pregnancy in Latin America and the Caribbean during the period 2012 to 2021. Methods: A systematic search was carried out in 6 databases: PubMed, SCOPUS, Web of Science, EMBase, LILACS and Scielo. The articles included were from Latin American countries and had any of the following variables: preeclampsia, eclampsia, puerperal hemorrhage and puerperal sepsis published from 2012 to 2021 and comparing pregnant adolescents and adults. Articles that did not present separate findings from Latin America and/or the Caribbean, that the full version was not available, and that were focused on patients with a specific disease were excluded. For risk of bias, the Newcastle-Ottawa Scale Case-Control Studies was used. The summary measure used was the Odds Ratio with a 95% confidence interval for each study. Results: 4 studies were included. The risk of preeclampsia in pregnant adolescents and postpartum hemorrhage (OR = 0.86, 95% CI 0.74 - 0.99) were not evidenced (OR = 0.93, 95% CI 0.69 - 1.25). On the other hand, the risk of eclampsia (OR = 2.43, 95% CI 1.29 - 4.58) in pregnant adolescents was shown, but with high heterogeneity between studies (I2 = 76%). Conclusions: A risk of eclampsia was evidenced in pregnant adolescents, but not in preeclampsia nor postpartum hemorrhage. However, these results should be taken with caution. Protocol record: CRD42021286725 (PROSPERO)

Prevención de la preeclampsia y su relevancia en el contexto latinoamericano: una revisión narrativa / Prevention of preeclampsia and its relevance in the Latin American context: a narrative review

La preeclampsia es un trastorno hipertensivo de la gestación que se evidencia durante las últimas semanas de esta. Globalmente, la preeclampsia es la segunda causa de mortalidad materna. Se estima que su incidencia es de aproximadamente un 16% en los países en vías de desarrollo, y llega a superar el 25% en algunos países de Latinoamérica. Se describirán las principales estrategias de prevención de la preeclampsia y su relevancia en el contexto latinoamericano. La búsqueda de información tuvo lugar en PubMed y BVS para las publicaciones realizadas sobre prevención de la preeclampsia, utilizando la expresión de búsqueda (“Disease Prevention” OR “Primary Prevention”) AND (Pre-eclampsia OR Preeclampsia OR “Pre eclampsia”) AND (“Latin America” OR “Central America” OR “South America” OR Caribbean). En PubMed se encontraron 60 y en BVS 42 resultados que responden a la expresión de búsqueda, y fueron seleccionados 18 artículos que discuten estrategias de prevención de la preeclampsia en Latinoamérica. Con estos resultados, se pueden afirmar que, describir las mejores estrategias de prevención de la preeclampsia en Latinoamérica es una tarea pendiente, pues existe una relativa carencia de publicaciones. En consecuencia, se espera que esta revisión motive futuras investigaciones y sea un recurso útil en la actualización médica.

Preeclampsia is a hypertensive disorder of pregnancy that is evident during the last weeks of it. Globally, preeclampsia is the second leading cause of maternal mortality. It is estimated that the incidence is approximately 16% in developing countries, and reaches over 25% in some Latin American countries. The main strategies for the prevention of preeclampsia and their relevance in the Latin American context will be described. The search for information took place in PubMed and BVS for publications on preeclampsia prevention, using the search expression (“Disease Prevention” OR “Primary Prevention”) AND (Pre-eclampsia OR Pre-eclampsia OR “Pre eclampsia”) AND (“Latin America” OR “Central America” OR “South America” OR Caribbean). In PubMed we found 60 and in VHL 42 results that respond to the search expression, and 18 articles were selected that discuss prevention strategies for preeclampsia in Latin America. With these results, it is possible to afirm that describing the best strategies for the prevention of preeclampsia in Latin America is a pending task, since there is a relative lack of publications. Consequently, it is hoped that this review will motivate future research and be a useful resource in medical updating.

Prevención de la preeclampsia: desde la dieta hasta la aspirina: revisión de la literatura / Prevention of preeclampsia: from diet to aspirin: review of the literature

Introducción y objetivo: Explorar las estrategias de prevención de la preeclampsia que se han propuesto a lo largo de la historia. Método: Revisión narrativa de la literatura sobre la evidencia científica histórica disponible entre 2016 y 2023 acerca de la aspirina y otras estrategias de prevención de la preeclampsia, en bases de datos bibliográficas computarizadas de estudios publicados en revistas indexadas. Resultados: Varios estudios confirman la efectividad de la aspirina para prevenir la preeclampsia en población de alto riesgo, siendo un medicamento con bajo riesgo de complicaciones, con mayor evidencia de efectividad si se inicia antes de las 16 semanas de gestación y con un aparente efecto dependiente de la dosis. Intervenciones como la disminución del consumo de sal, el reposo en cama, la suplementación con ácidos grasos, antioxidantes, L-arginina, zinc o magnesio, y el uso de diuréticos o de inhibidores de la bomba de protones, no han mostrado su utilidad en la prevención de la preeclampsia. Conclusiones: La aspirina a dosis baja es un medicamento seguro en el embarazo y efectivo para prevenir la preeclampsia en población de alto riesgo. Es la estrategia de prevención más ampliamente estudiada a lo largo de la historia para la disfunción endotelial durante la gestación.

Introduction and objective: To explore the different prevention strategies for preeclampsia that have been proposed throughout the history. Method: A narrative review of the historical, scientific evidence available between 2016 and 2021 on aspirin and other preeclampsia prevention strategies in computerized bibliographic databases of studies published in indexed journals. Results: Several studies confirm the effectiveness of aspirin to prevent preterm preeclampsia in high-risk populations, considering this as a safe drug with low risk of complications, with greater evidence of effectiveness when started before 16 weeks of gestation and apparently with a dose-dependent effect. Interventions such as reducing salt intake, bed rest, supplementation with fatty acids, antioxidants, L-arginine, zinc, magnesium, the use of diuretics or proton pump inhibitors have not shown its usefulness in the prevention of high risk preeclampsia patients. Conclusions: Low-dose aspirin is a safe drug in pregnancy and is effective to prevent preeclampsia in high-risk populations. Is the most widely studied throughout history prevention strategy for endothelial dysfunction during pregnancy.

Expression levels of methylated SIM2,GNA12 and CTGF in pregnant women with preeclampsia and its predictive value for disease / 国际检验医学杂志

Objective To investigate the plasma levels of methylated DNA in the pregnant women with preeclampsia and its predictive value for the occurrence of preeclampsia.Methods A total of 82 pregnant women with preeclampsia admitted to the hospital from January to December 2022 were included as the obser-vation group,and another 82 healthy pregnant women were included as the control group.Total DNA was ex-tracted,and the relative expression levels of methylated single-intention homolog 2(SIM2),guanine nucleo-tide-binding protein(GNA12),and connective tissue growth factor(CTGF)genes in plasma were detected by real-time fluorescence quantitative PCR(qRT-PCR)after DNA bisulfite modification.The value of methyla-ted DNA in predicting preeclampsia was evaluated by correlation analysis and receiver operating characteristic(ROC)curve.Results The relative expression levels of methylated SIM2,GNA12 and CTGF in plasma in the observation group were significantly higher than those in the control group(P＜0.05),and the relative expres-sion levels of methylated SIM2,GNA12 and CTGF in severe preeclampsia group was higher(P＜0.05).Corre-lation analysis showed that the relative expression levels of methylated SIM2,GNA12 and CTGF in plasma were significantly positively correlated with the occurrence of preeclampsia in pregnant women(P＜0.05).ROC curve analysis results showed that the relative expression levels of plasma methylation SIM2,GNA12,and CTGF,both individually and in combination,had good predictive efficacy in predicting preeclampsia in pregnant women,and the combined detection of the three had the highest predictive efficacy(area under the curve was 0.888,95％CI:0.827-0.949).Conclusion Compared with healthy pregnant women,the relative expression levels of methylated SIM2,GNA12 and CTGF in plasma are higher in pregnant women with pre-eclampsia,which are positively correlated with the occurrence of preeclampsia and the severity of the disease.The relative expression levels of methylated SIM2,GNA12 and CTGF are expected to be important predicting indicators for preeclampsia.

The Association between Ophthalmic Artery Doppler Variables and the Severi-ty of Pre-eclampsia:a Meta-analysis / 实用妇产科杂志

Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95％confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95％CI-0.92～-0.20,P=0.000),higher EDV levels(SMD 0.47,95％CI 0.12～0.83,P=0.028)and higher PR levels(SMD0.96,95％CI 0.13～1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.

Efficacy analysis of a preeclampsia risk prediction model based on exosomal multiple miRNA expression levels / 天津医药

Objective To investigate the feasibility of constructing a preeclampsia(PE)risk model based on multiple exosomal micrornas(miRNA)expression levels and to verify its efficacy in predicting PE.Methods A total of 1037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects.The expression of exosomal miRNA(including miR-155-5p,miR-215-5p,miR-203a-3p,miR-199a-5p and miR-125a-3p)in all samples was detected by qRT-PCR.Then,all patients were followed up to the end of pregnancy.The occurrence of PE during the follow-up period was counted,and all samples were divided into the PE group and the control group according to results.Cox regression was used to analyze the influencing factors of PE.The multi-miRNA risk model was constructed with ggrisk package,and the predictive effect of the model on PE was evaluated by receiver operating characteristic(ROC)curve.Results By the end of follow-up on October 31,2022,974 cases were finally followed up,and the follow-up completion rate was 93.92%.Among all the 974 patients who completed the follow-up,65 patients developed PE,so they were finally divided into the PE group,and 909 cases were used as the control group.The age,pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group(P＜0.05).The proportions of smoking history and drinking history were higher in the PE group than those of the control group(P＜0.05).The contents of triglyceride(TG),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),alanyl aminotransferase(ALT),aspartate aminotransferase(AST),platelet distribution width(PDW),mean platelet volume(MPV),miR-155-5p,miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group,while contents of thyroid stimulating hormone(TSH),miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group(P＜0.05).The expression levels of miR-125a-3p,miR-155-5p,miR-199a-5p and miR-215-5p were independent predictors of PE(P＜0.05).The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE(AUC=0.998),with a sensitivity of 98.46%(63/65)and a specificity of 93.94%(854/909).Conclusion miR-125a-3p,miR-155-5p,miR-199a-5p,miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE,and the PE prediction model constructed with the above five miRNAs has better effect.

The predictive value of MP hypertension monitoring system combined with PLGF and PI for preeclampsia / 天津医药

Objective To establish a clinical prediction model for preeclampsia by monitoring risk rating of MP gestation and levels of placental growth factor(PLGF)combined with uterine artery pulsatility index(PI)measured during examination of fetal nuchal translucency(NT).Methods Twenty-four patients with preeclampsia who met the inclusion criteria were selected as the case group,and 95 healthy pregnant women during the same period were randomly selected as the control group.Serum concentrations of PLGF,uterine artery PI values measured by quantitative immunofluorescence assay at 11-14 weeks of gestation,risk ratings for MP hypertension monitoring at 11-20 weeks of gestation,and other relevant data,BMI,age,gestation,mode of delivery,neonatal birth weight and Apgar score were collected in the two groups.Results Results of univariate regression analysis showed that BMI,age,high risk of PI,MP and PLGF<12 were influencing factors for adverse outcomes.Results of multivariate regression analysis showed that high PI,medium high risk in MP and PLGF<12 were independent risk factors for adverse outcomes.The prediction model of PE established was logit(P)=-15.767 + 0.020×PI + 0.072×MP risk(medium-high risk = 1,low risk = 0)+ 0.181×PLGF classification(＜12 = 1,≥12 = 0),with an AUC area of 0.883,specificity of 0.816 and sensitivity of 0.846.Conclusion The combination of PI,MP risk and PLGF to establish a clinical predictive model for preeclampsia has certain value,and its combined predictive value is higher than that of single application.

Screening of characteristic genes in early-onset pre-eclampsia and analysis of their association with immune cell infiltration based on bioinformatics analysis and machine-learning algorithms / 中华围产医学杂志

Objective:To screen the characteristic genes of early-onset pre-eclampsia (EOSP) and to analyze their association with immune cell infiltration based on bioinformatics analysis and machine learning methods.Methods:In the Gene Expression Omnibus (GEO) database, the mRNA sequences of placental tissues from women with EOSP and normal pregnancy were retrieved using the term "early-onset pre-eclampsia". The R language was used for background correction, standardization, summarization, and probe quality control. Annotation packages were downloaded for ID conversion and the expression matrices were extracted. The differentially expressed genes (DEGs) between the EOSP and the normal pregnancy in the metadata were analyzed after correcting for batch effects using the limma package. Characteristic genes were identified through the support vector machine (SVM) -recursive feature elimination (RFE) method and the LASSO regression model. The area under the curve (AUC) was calculated to judge the diagnostic efficiency of the characteristic genes. Placental tissues were retrospectively collected for verification from 15 patients with EOSP and 15 with normal pregnancy who were delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 1, 2022, to February 28, 2023. The expression of characteristic genes was verified using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, which were further validated in the validation dataset. Finally, the CIBERSORT algorithm was used to analyze the relative proportion of infiltrating immune cell in EOSP. A t-test was used for differential analysis. Results:Three gene datasets were downloaded, including GSE44711 (eight cases each for EOSP and normal pregnancy), GSE74341 (seven cases for EOSP and five cases for normal pregnancy), and GSE190639 (13 cases each for EOSP and normal pregnancy). A total of 29 DEGs were screened after combining the GSE44711 and GSE74341 datasets, including 27 upregulated and two downregulated genes. Gene ontology enrichment analysis showed that these genes are mainly involved in the secretion of gonadotropins, female pregnancy, regulation of endocrine processes, secretion of endocrine hormones, and negative regulation of hormone secretion. Eight characteristic genes ( EBI3, HTRA4, TREML2, TREM1, NTRK2, ANKRD37, CST6, and ARMS2) were screened using the LASSO regression algorithm combined with SVM-RFE algorithm and the expression differences of these characteristic genes were verified as statistically significant by qRT-PCR and Western blot (all P<0.05, except for CST6). Logistic regression algorithm showed that the AUC (95% CI) of TREML2, ANKRD37, NTRK2, TREM1, HTRA4, EBI3, and ARMS2 were 0.979 (0.918-1.000), 0.969 (0.897-1.000), 0.969 (0.892-1.000), 0.979 (0.918-1.000), 0.990 (0.954-1.000), 0.990 (0.954-1.000), and 0.903 (0.764-1.000). Immune cell infiltration analysis indicated that the infiltration ratio of M2 macrophages in the placental tissue from EOSP was significantly lower than that in the normal pregnancy (0.167±0.074 vs. 0.462±0.091, P=0.002), but the infiltration ratios of monocytes and eosinophils were significantly higher (0.201±0.004 vs. 0.085±0.006; 0.031±0.001 vs. 0.001±0.000, both P<0.05). The correlation analysis between characteristic genes and infiltrating immune cells found that the seven characteristic genes were closely related to the immune cells (all P<0.05). Conclusion:Seven characteristic genes that are critical for the prediction and early diagnosis of EOSP are screened using bioinformatics analysis and machine-learning algorithms in this study, which provides new research targets and a basis for the prevention and treatment of preeclampsia in the future.

Expression of TFDP2 in placentas of women with preeclampsia and its effect on apoptosis of trophoblast cells / 中华围产医学杂志

Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.

Evaluation of left ventricular function in patients with pregnancy-induced hypertension using echocardiography / 中国基层医药

Objective:To investigate the clinical value of tissue Doppler echocardiography in the evaluation of left ventricular function in patients with pregnancy-induced hypertension.Methods:This is a case-control study, including 100 patients with pregnancy-induced hypertension who received treatment at the Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2019 to May 2022, and an additional 100 healthy pregnant women who underwent physical examination during the same period. All participants underwent two-dimensional echocardiography, pulsed Doppler echocardiography, and tissue Doppler echocardiography. Ultrasound parameters related to left ventricular morphology and function were collected from all participants. The ultrasound parameters related to left ventricular morphology and function between patients with different types of pregnancy-induced hypertension and healthy controls were compared. The correlation between left ventricular function ultrasound parameters and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels was investigated.Results:Patients with pregnancy-induced hypertension, patients with mild preeclampsia, patients with severe preeclampsia, and healthy controls demonstrated differences in interventricular septum thickness during diastole [(10.24 ± 1.18) mm, (11.39 ± 1.24) mm, (11.57 ± 1.29) mm, (8.81 ± 0.95) mm], left ventricular end-diastolic diameter [(47.31 ± 2.81) mm, (49.82 ± 2.89) mm, (52.03 ± 2.94) mm, (46.82 ± 2.76) mm], left ventricular posterior wall thickness [(9.73 ± 1.06) mm, (10.62 ± 1.13) mm, (11.75 ± 1.21) mm, (8.96 ± 0.97) mm], left ventricular inner diameter [(32.82 ± 2.34) mm, (35.48 ± 2.39) mm, (36.04 ± 2.45) mm, (30.41 ± 2.27) mm], and left ventricular mass index [(98.41 ± 7.83) g/m 2, (105.73 ± 8.26) g/m 2, (108.63 ± 8.57) g/m 2, (96.59 ± 7.69) g/m 2]. All of these parameters showed significant differences between patients with different types of pregnancy-induced hypertension and healthy controls ( F = 13.47, 12.61, 16.59, 13.26, 19.73, all P < 0.001). Significant differences were also observed in echocardiographic indices of left ventricular function such as peak velocity ratio of E and A waves, systolic motor amplitude, early peak diastolic velocity to late peak diastolic velocity, and Tei index between patients with different types of pregnancy-induced hypertension and healthy controls ( F = 12.84, 11.27, 14.64, 21.43, all P < 0.001). In patients with pregnancy-induced hypertension, peak velocity ratio of E and A waves, systolic motor amplitude, and early peak diastolic velocity to late peak diastolic velocity were moderately negatively correlated with serum NT-proBNP level ( r = -0.56, -0.43, -0.54, P = 0.029, 0.042, 0.031), while Tei index showed a positive correlation with serum NT-proBNP level ( r = 0.77; P = 0.003). Conclusion:Two-dimensional echocardiography, pulsed Doppler echocardiography combined with tissue Doppler echocardiography can be used to effectively evaluate the changes in left ventricular structure and function in patients with different types of pregnancy-induced hypertension. Monitoring the Tei index using tissue Doppler echocardiography can accurately reflect myocardial injury and functional changes, which has a great clinical application value.

Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes

Abstract Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups. Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102). Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE. Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE.

Eucommia granules activate Wnt/ß-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats

Purpose: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. Methods: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/ß-catenin pathway-related protein expression was detected using Western blot. Results: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/ß-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. Conclusions: EG may activate the Wnt/ß-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/ß-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Hypertensive disorders during pregnancy as a major cause of preterm birth and adverse perinatal outcomes: findings from a Brazilian National Survey

ABSTRACT Objective This study aimed to evaluate the prevalence of hypertensive disorders during pregnancy among Brazilian women with preterm births and to compare the epidemiological characteristics and perinatal outcomes among preterm births of women with and without hypertension. Methods This was a secondary cross-sectional analysis of the Brazilian Multicenter Study on Preterm Birth. During the study period, all women with preterm births were included and further split into two groups according to the occurrence of any hypertensive disorder during pregnancy. Prevalence ratios were calculated for each variable. Maternal characteristics, prenatal care, and gestational and perinatal outcomes were compared between the two groups using χ2 and t-tests. Results A total of 4,150 women with preterm births were included, and 1,169 (28.2%) were identified as having hypertensive disorders. Advanced maternal age (prevalence ratio (PR) 2.49) and obesity (PR= 2.64) were more common in the hypertensive group. The gestational outcomes were worse in women with hypertension. Early preterm births were also more frequent in women with hypertension. Conclusion Hypertensive disorders of pregnancy were frequent among women with preterm births, and provider-initiated preterm births were the leading causes of premature births in this group. The factors significantly associated with hypertensive disorders among women with preterm births were obesity, excessive weight gain, and higher maternal age.

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

Abstract 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.

Impactos da covid-19 sobre a gestaçãono desenvolvimento da pré-eclâmpsia: revisão integrativa / Impacts of COVID-19 during pregnancy on the development of pre-eclampsia: an integrative review

Objetivo: Identificar as evidências cientificas acerca da associação da covid-19 e o desenvolvimento de pré-eclâmpsia. Método: Trata-se de uma revisão integrativa, realizada em abril de 2022, mediante acesso às bases de dados: Medical Literature Analysis and Retrieval System Online (MEDLINE) e Portal Regional da Biblioteca Virtual em Saúde (BVS). A partir da utilização dos descritores em saúde: Gestantes, Pré-eclâmpsia e COVID-19. Resultados: Foram incluídos 15 estudos na síntese avaliativa, onde 13 foram provenientes da PubMed (86,6%) e 02 da BVS (13,3%). Quanto ao desenho, seis (40%) estudos foram do tipo relato ou estudo de caso, cinco (33,3%) do tipo revisão sistemática, com destaque para três revisões com meta-análise, dois (13,3%) se tratou estudos observacionais, um (6,6%) estudo descritivo e um (6,6%) estudo de coorte. Conclusão: Foram identificados estudos que associaram o desenvolvimento da pré-eclâmpsia à infecção causada pelo Covid-19, no entanto, outros estudos destacam a detecção de uma síndrome semelhante a pré-eclâmpsia, destacando a necessidade da realização de um diagnóstico diferencial.(AU)

Objective: To identify the scientific evidence on the association between covid-19 and the development of pre-eclampsia. Method: This is an integrative review, carried out in April 2022, through access to the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) and Regional Portal of the Virtual Health Library (VHL). Using the health descriptors: Pregnant women, Pre-eclampsia and COVID-19. Results: 15 studies were included in the evaluation synthesis, of which 13 came from PubMed (86.6%) and 02 from the VHL (13.3%). In terms of design, six (40%) studies were of the case report or study type, five (33.3%) were of the systematic review type, with emphasis on three reviews with meta-analysis, two (13.3%) were observational studies, one (6.6%) was a descriptive study and one (6.6%) was a cohort study. Conclusion: Studies were identified that associated the development of pre-eclampsia with infection caused by Covid-19, however, other studies highlight the detection of a syndrome similar to pre-eclampsia, highlighting the need for a differential diagnosis.(AU)

Objetivo: Identificar las evidencias científicas sobre la asociación entre el covid-19 y el desarrollo de preeclampsia. Método: Se trata de una revisión integradora, realizada en abril de 2022, a través del acceso a las bases de datos: Medical Literature Analysis and Retrieval System Online (MEDLINE) y Portal Regional de la Biblioteca Virtual en Salud (BVS). Utilizando los descriptores de salud: Embarazadas, Preeclampsia y COVID-19. Resultados: 15 estudios fueron incluidos en la síntesis de evaluación, de los cuales 13 procedían de PubMed (86,6%) y 2 de la BVS (13,3%). En cuanto al diseño, seis (40%) estudios fueron del tipo informe o estudio de caso, cinco (33,3%) fueron revisiones sistemáticas, especialmente tres revisiones con meta-análisis, dos (13,3%) fueron estudios observacionales, uno (6,6%) fue un estudio descriptivo y uno (6,6%) fue un estudio de cohortes. Conclusión: Fueron identificados estudios que asocian el desarrollo de preeclampsia con infección causada por Covid-19, sin embargo, otros estudios destacan la detección de un síndrome semejante a la preeclampsia, enfatizando la necesidad de realizar un diagnóstico diferencial.(AU)

Gestational hypertension as a factor associated with chronic kidney disease: the importance of obstetric history of women undergoing hemodialysis / Hipertensão gestacional como fator associado à doença renal crônica: a importância do histórico obstétrico de mulheres submetidas à hemodiálise

ABSTRACT Introduction: Pregnancy-related complications may impact women's reproductive cycle and health through their lives. The objective of this study was to evaluate the sociodemographic, clinical, and obstetric history of women undergoing hemodialysis. Methods: We performed a cross-sectional study in a specialized health facility with four hemodialysis units. Sociodemographic characteristics, clinical and personal history, obstetric and perinatal results of women with pregnancies before hemodialysis were evaluated. Prevalence, bivariate, and logistic regression analyses were performed. Results: We included 208 (87.76%) women. Hypertension was the main cause of chronic kidney disease (CKD) (128 women). Rates of adverse perinatal outcomes, including prematurity, low birth weight, miscarriage, fetal death, and neonatal death, were 19.3%, 14.5%, 25.5%, 12.1%, and 5.3%, respectively. Hypertensive syndromes during pregnancy occurred in 37.0% of women, with 12.5% reporting preeclampsia and 1.4% reporting eclampsia. Up to 1 year after birth, 45.2% of women reported hypertension. Hemodialysis due to hypertension was associated with a history of hypertension during pregnancy (OR 2.33, CI 1.27 - 4.24), gestational hypertension (2.41, CI 3.30 - 4.45), and hypertension up to one year after birth (OR 1.98, CI 1.11 - 3.51). Logistic regression showed that gestational hypertension was independently associated with CKD due to hypertension (aOR 2.76, CI 1.45 - 5.24). Conclusion: Women undergoing hemodialysis due to hypertension were more likely to have gestational hypertension or hypertension up to one year after birth. To delay end-stage renal disease, it is necessary to identify women at risk of kidney failure according to their reproductive history.

RESUMO Introdução: Complicações relacionadas à gestação podem afetar o ciclo reprodutivo e a saúde das mulheres ao longo de suas vidas. Este estudo visou avaliar histórico sociodemográfico, clínico e obstétrico de mulheres em hemodiálise. Métodos: Realizamos estudo transversal em unidade de saúde especializada com quatro unidades de hemodiálise. Avaliou-se características sociodemográficas, histórico clínico e pessoal, resultados obstétricos e perinatais de mulheres com gestações anteriores à hemodiálise. Foram realizadas análises de prevalência, bivariadas e regressão logística. Resultados: Incluímos 208 (87,76%) mulheres. Hipertensão foi a principal causa de doença renal crônica (DRC) (128 mulheres). Taxas de desfechos perinatais adversos, incluindo prematuridade, baixo peso ao nascer, aborto espontâneo, óbito fetal e neonatal, foram de 19,3%, 14,5%, 25,5%, 12,1% e 5,3%, respectivamente. Síndromes hipertensivas durante a gestação ocorreram em 37,0% das mulheres, com 12,5% relatando pré-eclâmpsia e 1,4% relatando eclampsia. Até 1 ano após o parto, 45,2% das mulheres relataram hipertensão. Hemodiálise devido à hipertensão foi associada ao histórico de hipertensão na gestação (OR 2,33; IC 1,27 - 4,24), hipertensão gestacional (2,41; IC 3,30 - 4,45), e hipertensão até um ano após o parto (OR 1,98; IC 1,11 - 3,51). A regressão logística mostrou que hipertensão gestacional foi independentemente associada à DRC devido à hipertensão (ORa 2,76; IC 1,45 - 5,24). Conclusão: Mulheres submetidas à hemodiálise por hipertensão foram mais propensas a apresentar hipertensão gestacional ou hipertensão até um ano após o parto. Para retardar a doença renal em estágio terminal, deve-se identificar mulheres em risco de insuficiência renal de acordo com sua história reprodutiva.

COVID-19 and Preeclampsia: A Systematic Review of Pathophysiological Interactions / COVID-19 e pré-eclâmpsia: uma revisão sistemática de interações fisiopatológicas

Abstract Objective: To review the literature and synthesize evidence on pathophysiological interactions attributed to the simultaneous occurrence of COVID-19 and preeclampsia. Methods: A systematic review was conducted from November (2021) to January (2022) to retrieve observational studies published on the PubMed, LILACS, SciELO Brazil and Google Scholar databases. The search was based on the descriptors [(eclampsia OR preeclampsia) AND (COVID-19)]. Quantitative studies that pointed to pathophysiological interactions were included. Literature reviews, studies with HIV participants, or with clinical approach only were excluded. The selection of studies was standardized and the evaluation was performed by pairs of researchers. Results: In this review, 155 publications were retrieved; 16 met the inclusion criteria. In summary, the physiological expression of angiotensin-converting enzyme-2 (ACE-2) receptors is physiologically increased in pregnant women, especially at the placental site. Studies suggest that the coronavirus binds to ACE-2 to enter the human cell, causing deregulation of the renin-angiotensin-aldosterone system and in the ratio between angiotensin-II and angiotensin-1-7, inducing manifestations suggestive of preeclampsia. Furthermore, the cytokine storm leads to endothelial dysfunction, vasculopathy and thrombus formation, also present in preeclampsia. Conclusion: The studies retrieved in this review suggest that there is a possible overlap of pathophysiological interactions between COVID-19 and preeclampsia, which mainly involve ACE-2 and endothelial dysfunction. Given that preeclampsia courses with progressive clinical and laboratory alterations, a highly quality prenatal care may be able to detect specific clinical and laboratory parameters to differentiate a true preeclampsia superimposed by covid-19, as well as cases with hypertensive manifestations resulting from viral infection.

Resumo Objetivo: Revisar a literatura e sintetizar evidências sobre interações fisiopatológicas atribuídas à ocorrência simultânea de COVID-19 e pré-eclâmpsia. Métodos: Uma revisão sistemática foi conduzida entre novembro (2021) a janeiro (2022) para recuperar estudos observacionais publicados no PubMed, LILACS, SciELO Brasil e Google scholar. A busca foi baseada nos descritores [(eclâmpsia OR pré-eclâmpsia) AND (COVID-19)]. Estudos quantitativos que apontaram interações fisiopatológicas foram incluídos. Estudos de revisão, com participante HIV e apenas com enfoque clínico foram excluídos. A seleção dos estudos foi padronizada com avaliação por duplas de pesquisadores. Resultados: Nesta revisão, 155 publicações foram recuperadas; 16 preencheram os critérios de inclusão. Em síntese, a expressão fisiológica de receptores da enzima conversora da angiotensina-2 (ECA-2) é fisiologicamente potencializada em gestantes, especialmente no sítio placentário. Os estudos sugerem que o coronavírus se liga à ECA-2 para entrar na célula humana, ocasionando desregulação do sistema renina-angiotensina-aldosterona e da razão entre angiotensina-II e angiotensina-1-7, induzindo manifestações sugestivas de pré-eclâmpsia. Ademais, a tempestade de citocinas conduz à disfunção endotelial, vasculopatia e formação de trombos, também presentes na pré-eclâmpsia. Conclusão: Os estudos recuperados nesta revisão sugerem que a superposição de alterações fisiopatológicas entre a COVID-19 e a pré-eclâmpsia envolve, principalmente, a ECA-2 e disfunção endotelial. Tendo em vista que a pré-eclâmpsia cursa com alterações clínicas e laboratoriais progressivas, a atenção pré-natal de qualidade pode ser capaz de detectar parâmetros clínicos e laboratoriais importantes para diferenciar a pré-eclâmpsia verdadeira sobreposta por COVID-19, bem como os casos que mimetizam a doença hipertensiva consequente à infecção viral.

Placental expression of striatin & endothelial nitric oxide synthase in women with & without pre-eclampsia

Background & objectives: Striatin is a multi-domain scaffolding protein essential for activating endothelial nitric oxide synthase (eNOS). However, its role in pre-eclampsia remains use explored. Hence, this study aimed to investigate the association between striatin and eNOS in regulating nitric oxide (NO) production in the placenta of women with and without pre-eclampsia. Methods: Forty pregnant women each without (controls) and with pre-eclampsia (cases) were enrolled in the study. Blood striatin and NO concentrations were detected by the ELISA. Protein expression of striatin, phosphorylated eNOS (peNOS), inducible NOS (iNOS) and phosphorylated NF-?B were measured in the placental tissues by Western blot. Twenty four hour urinary protein and serum urea, uric acid and creatinine were analyzed as an autoanalyzer. Placental histology was analyzed by haematoxylin and eosin staining. Results: Compared to normotensive pregnant women, the levels of serum NO and striatin were decreased in pre-eclamptic women. The protein expression of striatin and peNOS was significantly reduced (P<0.05) while p65NF-?B and iNOS were upregulated considerably (P<0.05) in the placenta of cases compared to controls. Interpretation & conclusions: Our results show for the first time that decreased striatin expression was associated with decreased peNOS protein expression in the placental tissue of pre-eclamptic women. Interestingly, no significant difference was found in blood striatin or NO levels between controls and cases. Thus, therapies that improve placental striatin expression are attractive possibilities, both for prevention as well as treatment of endothelial dysfunction in pre-eclampsia.