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.

Uterine vascular resistance and other maternal factors associated with the risk of developing hypertension during pregnancy

Gestational hypertension and pre-eclampsia are important causes of perinatal morbidity. The objective of the present study was to determine the increase in relative risk for developing hypertensive disorders of pregnancy based on the evaluation of pregnant women between 20 and 25 weeks of gestation, and to correlate the findings at this period with the outcome of pregnancy. We conducted a prospective cohort study, with a convenience sample of 1417 patients evaluated at this gestational age, of which 1306 were contacted at childbirth. We detected an increased relative risk of 2.69 (95%CI: 1.86 to 3.89) associated with pulsatility index of the uterine arteries, a 2.8 increase (95%CI: 1.58 to 5.03) in relative risk attributed to maternal age above 35 years, a 1.68 increase (95%CI: 1.17 to 2.40) attributed to parity greater than or equal to 3, and a 5.35 increase (95%CI: 4.18 to 6.85) attributed to chronic hypertension and obesity, with a progressive increase in relative risk according to the degree of overweight, i.e., grades 1, 2, 3, and morbid obesity (2.58, 3.06, 5.84, and 7.28, respectively).

Evaluation of angiogenic factors (PlGF and sFlt-1) in pre-eclampsia diagnosis / Avaliação dos fatores angiogênicos (PlGF e sFlt-1) no diagnóstico de pré-eclâmpsia

Abstract Objective: Recent observations support the hypothesis that an imbalance between angiogenic factors has a fundamental role in the pathogenesis of pre-eclampsia and is responsible for the clinical manifestations of the disease. The goal of the present study was to evaluate the sensitivity, specificity, and the best accuracy level of Soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in maternal serum and protein/creatinine ratio in urine sample to define the best cutoff point of these tests to discriminate between the patients with gestational hypertension and the patients with pre-eclampsia, to evaluate the possibility of using them as diagnostic methods. Methods: A prospective longitudinal study was performed, and blood samples were collected from 95 pregnant patients with hypertension to measure serum concentrations of biomarkers sFlt-1 and PlGF. Urine samples were collected for protein screening. Significance was set as p < 0.05. Results: The sFlt-1/PlGF ratio demonstrated a sensitivity of 57.5% and a specificity of 60% using 50.4 as a cutoff point. The test that showed the best accuracy in the diagnosis of pre-eclampsia was protein/creatinine ratio, with a sensitivity of 78.9% and a specificity of 70% using 0.4 as a cutoff point and showing an area under the receiver operating characteristic curve of 0.80 (p < 0.001). Conclusion: No studied laboratory test proved to be fairly accurate for the diagnosis of pre-eclampsia, except for the protein/creatinine ratio. The evidence is insufficient to recommend biomarkers sFlt-1 and PlGF to be used for the diagnosis of pre-eclampsia.

Resumo Objetivo: Pesquisas recentes sustentam a hipótese de que um desequilíbrio entre fatores angiogênicos desempenhe um papel fundamental na patogênese da pré-eclâmpsia e seja responsável pelas manifestações clínicas da doença. O objetivo do presente estudo foi avaliar a sensibilidade, a especificidade e o nível de melhor acurácia do Fator semelhante a tirosina quinase 1 (sFlt-1), Fator de crescimento placentário (PlGF), e relação sFlt-1/PlGF no soro materno e relação proteína/creatinina em amostra de urina e definir o melhor ponto de corte desses testes para distinguir pacientes com hipertensão gestacional daquelas com pré-eclâmpsia, a fim de avaliar a possibilidade de utilizá-los como métodos diagnósticos. Métodos: Foi realizado um estudo prospectivo longitudinal e foram coletadas amostras de sangue de 95 gestantes com hipertensão arterial para dosar as concentrações séricas dos biomarcadores sFlt-1 e PlGF. Amostras de urina foram coletadas para pesquisa de proteinúria. Foram consideradas significativas as diferenças com p < 0,05. Resultados: A relação sFlt-1/PlGF demonstrou sensibilidade de 57,5% e especificidade de 60% utilizando 50,4 como ponto de corte. O teste que apresentou a melhor acurácia no diagnóstico de pré-eclâmpsia foi a relação proteína/creatinina, com sensibilidade de 78,9% e especificidade de 70%, utilizando 0,4 como ponto de corte e demostrando uma área sob a curva receiver operating characteristic (ROC, na sigla em inglês) de 0,80 (p < 0,001). Conclusão: Nenhum método de rastreamento isolado se mostrou com boa acurácia para o diagnóstico de pré-eclâmpsia, exceto a relação proteína/creatinina. As evidências são insuficientes para recomendar os biomarcadores sFlt-1 e PlGF como diagnóstico de pré-eclâmpsia.

Pré-eclâmpsia/eclâmpsia / Pre-Eclampsia/Eclampsia

A pré-eclâmpsia é uma doença multifatorial e multissistêmica específica da gestação. É classicamente diagnosticada pela presença de hipertensão arterial associada à proteinúria em gestante previamente normotensa após a 20a semana de gestação. A pré-eclâmpsia também é considerada na ausência de proteinúria se houver lesão de órgão-alvo. A presente revisão tem uma abordagem geral focada em aspectos de interesse prático na assistência clínica e obstétrica dessas mulheres. Assim, explora a etiologia ainda desconhecida, aspectos atuais da fisiopatologia e do diagnóstico e diagnóstico diferencial de convulsões, a abordagem da predição da doença, seus resultados adversos e prevenção. A conduta baseia-se em princípios gerais, tratamento clínico não farmacológico e farmacológico de situações graves ou não graves, com ênfase na crise hipertensiva e eclâmpsia. O controle obstétrico se fundamenta na pré-eclâmpsia sem ou com sinais de deterioração clínica e/ou laboratorial, estratificação da idade gestacional abaixo de 24 semanas, entre 24 e menos de 34 semanas e 34 ou mais semanas de gestação e orientação na via de parto. Uma abordagem imediata do puerpério e repercussões na vida futura de gestantes que desenvolvem pré-eclâmpsia também foram apresentadas.(AU)

Pre-eclampsia is a multifactorial and multisystemic disease specific to gestation. It is classically diagnosed by the presence of hypertension associated with proteinuria manifested in a previously normotensive pregnant woman after the 20th week of gestation. Pre-eclampsia is also considered in the absence of proteinuria if there is target organ damage. The present review takes a general approach focused on aspects of practical interest in the clinical and obstetric care of these women. Thus, it explores the still unknown etiology, current aspects of pathophysiology and of the diagnosis, the approach to disease prediction, its adverse outcomes and prevention. Management is based on general principles, on nonpharmacological and on pharmacological clinical treatment of severe or nonsevere situations with emphasis on the hypertensive crisis and eclampsia. Obstetric management is based on preeclampsia without or with signs of clinical and/or laboratory deterioration, stratification of gestational age in < 24 weeks, between 24 and less than 34 weeks, and ≥ 34 weeks of gestation, and guidance on route of delivery. An immediate puerperium approach and repercussions in the future life of pregnant women who develop preeclampsia is also presented.(AU)

Estudio sobre la asociación de hipertrigliceridemia con los estados hipertensivos del embarazo / Study on the association of hypertriglyceridemia with hypertensive states of pregnancy

Resumen Antecedentes: La preeclampsia se presenta en el 8% de los embarazos y genera el 25% de las muertes perinatales. Aunque su etiología es multifactorial, algunas alteraciones metabólicas se asocian a la disfunción endotelial presente en la enfermedad, y su estudio podría identificar marcadores tempranos de daño. Objetivo: Determinar la relación existente entre concentración plasmática de triglicéridos en las pacientes embarazadas con enfermedad hipertensiva inducida por el embarazo. Método: Estudio prospectivo que incluyó 147 pacientes gestantes sanas y 120 mujeres con enfermedad hipertensiva inducida por el embarazo y se determinaron colesterol total, lipoproteínas de baja densidad (LDL), lipoproteínas de alta densidad (HDL), hemoglobina glucosilada (HbA1c), biometría hemática (BH), química sanguínea (QS), electrolitos séricos, nitritos séricos y pruebas de función hepática. Resultados: Se encontró una diferencia significativa en la concentración de triglicéridos entre las pacientes normotensas y con preeclampsia (261.22 ± 80.27 vs. 361.46 ± 135.17 mg/dl; p < 0.0008). Además, se observó una menor concentración sérica de nitritos en las pacientes con preeclampsia, que contribuye a explicar la vasoconstricción. Conclusiones: Se encontró una asociación entre la hipertrigliceridemia y la presencia de DM II con el desarrollo de la enfermedad hipertensiva inducida por el embarazo.

Abstract Background: Preeclampsia occurs in 8% of pregnancies and generates 25% of perinatal deaths. Although its etiology is multifactorial, some metabolic alterations are associated with the endothelial dysfunction present in the disease, and its study could identify early markers of damage. Objective: To determine the relationship between plasma concentration of triglycerides in pregnant patients with hypertensive disease induced by pregnancy. Methods: Prospective study that included 147 healthy pregnant women and 120 women with hypertensive disease induced by pregnancy. Total cholesterol, low-density lipoprotein, high-density lipoprotein, Hemoglobin A1c, triglycerides, BH, QS, serum electrolytes, serum nitrites and liver function tests were determined. Results: A significant difference was found in the concentration of triglycerides between normotensive and patients with preeclampsia (261.22 ± 80.27 vs. 361.46 ± 135.17 mg/dl, p < 0.0008). In addition, a lower serum concentration of nitrites was observed in patients with preeclampsia, which helps explain vasoconstriction. Conclusions: We found an association between hypertriglyceridemia and the presence of diabetes mellitus II with the development of hypertensive disease induced by pregnancy.

Vitamina D y riesgo de preeclampsia: revisión sistemática y metaanálisis / Vitamin D and risk of preeclampsia: A systematic review and meta-analysis

Resumen Introducción. Cada vez son más los hallazgos sobre la relación entre las concentraciones de vitamina D en el ser humano y diversas condiciones clínicas. Hay una gran cantidad de estudios que informan sobre dicha asociación, especialmente con complicaciones obstétricas, incluidas la preeclampsia y la diabetes mellitus de la gestación, entre otras, pero sus resultados todavía no son definitivos, por lo que se requieren estudios de intervención de calidad que confirmen la relación de la vitamina D con dichos resultados. Objetivo. Revisar la información plasmada en estudios en torno al papel de la vitamina D materna y el desarrollo de la preeclampsia. Materiales y métodos. La metodología usada siguió las recomendaciones de la guía Cochrane para la elaboración de revisiones sistemáticas y de la guía del grupo Meta-analysis of Observational Studies in Epidemiology (MOOSE) para los metaanálisis. La búsqueda incluyó estudios observacionales y ensayos clínicos controlados. Resultados. Los niveles bajos de vitamina D, medida con el examen de 25-hidroxivitamina D, son comunes en el embarazo. Los resultados de esta revisión sistemática y del metaanálisis sugieren una asociación inversa entre los niveles de vitamina D y el desarrollo de preeclampsia. Hubo heterogeneidad en los estudios en cuanto a su diseño, población y ubicación geográfica, así como a las definiciones de exposición y resultado. Los ensayos clínicos controlados aleatorizados se excluyeron del metaanálisis. Conclusión. Se encontró una asociación inversa que sugiere que, a mayores concentraciones de vitamina D, menor es la probabilidad de desarrollar preclampsia, a pesar de la heterogeneidad de la medida global en este tipo de análisis.

Abstract Introduction: Human vitamin D levels have been increasingly related to a wide range of clinical outcomes. There is a large amount of reports on its associations, especially with obstetric complications, including preeclampsia and gestational diabetes. These results are scarcely consistent and there is still a lack of quality intervention studies to confirm the role of vitamin D in those outcomes. Objective: To review the available scientific evidence on the role of maternal vitamin D in the development of preeclampsia. Materials and methods: The methodology used followed the recommendations of the Cochrane guide for the preparation of systematic reviews, and for metaanalysis, the Guide of the Metaanalysis of Observational Studies in Epidemiology group (MOOSE). The search included both observational studies and controlled clinical trials. Results: Low vitamin D levels, measured by the 25-hydroxyvitamin D test, are common in pregnancy. The results of this systematic review and metaanalysis suggest an inverse ratio between vitamin D levels and the development of preeclampsia. There was heterogeneity among the studies with regard to the design, population, geographic location, definitions of exposure, and the outcome. We excluded randomized controlled trials from this meta-analysis. Conclusion: The inverse association we found suggests that the higher the levels of vitamin D the lesser the probability of developing preeclampsia, in spite of the heterogeneity of the global measurement in this type of analysis.

Interleukin-6 contributes to myocardial damage in pregnant rats with reduced uterine perfusion pressure

Preeclampsia is one of the most frequent and difficult illnesses in pregnancy, which jeopardizes both mother and fetus. There are several diagnostic criteria for preeclampsia. However, the preeclampsia-associated myocardial damage has not been described. In this study, we employed reduced uterine perfusion pressure (RUPP) to generate a rat model of preeclampsia for the evaluation of myocardial damage in late-gestation rats. The expressions of cardiac injury markers were analyzed by immunohistochemistry and ELISA. The arterial pressure and myocardial tissue velocities were also measured. The role of interleukin (IL)-6 in RUPP-associated myocardial damage was further explored. The results showed that RUPP rats had significant myocardial damage, as demonstrated by the high expressions of myoglobin, creatine kinase isoenzyme, cardiac troponin I, and brain natriuretic peptide. In addition, RUPP increased the mean arterial pressure and the early transmitral flow velocity to mitral annulus early diastolic velocity ratio (E/Ea). Furthermore, IL-6 deteriorated these abnormalities, whereas inhibition of IL-6 significantly relieved them. In conclusion, our study demonstrated that RUPP rats displayed myocardial damage in an IL-6-dependent manner.

Inmunopatogenia de la enfermedad hipertensiva gravídica / Immune-Pathogenesis of Pregnant Hypertension

La enfermedad hipertensiva gravídica constituye una patología obstétrica relativamente frecuente. En los últimos años se ha avanzado en la comprensión de la patogenia de la enfermedad, al ser el sistema inmune uno de los actores de vital importancia en la aparición de este trastorno. Las células asesinas naturales de la decidua constituyen un componente fundamental en el remodelado vascular durante la formación de la placenta. Cuando existen alteraciones en esta población celular, se induce una isquemia placentaria que promueve la liberación de factores vasculares y mediadores de la inflamación que promueven el daño sistémico con aparición de los síntomas de la enfermedad(AU)

Pregnant hypertension is a frequent pregnancy disorder. Researchers has recentely advanced in understanding this disease pathogenesis. The immune system plays a key role in this disease onset. Decidual natural killer cells are fundamental component in vascular remodeling during placental development. When alterations occurs in this cell population, placental ischemia is induced promoting the release of vascular factors and inflammation mechanisms that cause these disease symptoms(AU)

Parálisis facial y preeclampsia / Facial paralysis and preeclampsia

La parálisis facial periférica es una afectación neurológica muy frecuente. En la mayor parte de los casos no se llega a establecer una etiología precisa, denominándolas idiopáticas o parálisis facial de Bell. La asociación de parálisis facial y embarazo es conocida. Es nuestro objetivo presentar a una paciente de 27 años de edad atendida en el Policlínico Universitario 26 de Julio, que tuvo esta afección asociada a su embarazo y a la preeclampsia grave(AU)

Peripheral facial paralysis is a very frequent neurological condition. In most cases, a precise etiology, called idiopathic or facial palsy of Bell, cannot be established. The association of facial palsy and pregnancy is known. It is our objective to present a 27-year-old female patient attending the University Polyclinic 26 de Julio, who had this condition associated with her pregnancy and severe preeclampsia(AU)

Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas / Fatores Maternos e Resultados Perinatais Adversos em Portadoras de Pré-eclâmpsia em Maceió, Alagoas

Abstract Background: Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. Objective: To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. Methods: Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. Results: We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. Conclusion: Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries.

Resumo Fundamento: A pré-eclâmpsia tem sido associada a vários fatores de risco e eventos. No entanto, esta doença é merecedora de mais investigações, tendo em vista a multiplicidade de fatores relacionados que acometem diferentes populações. Objetivo: Avaliar os fatores maternos e os resultados perinatais adversos em uma coorte de gestantes com pré-eclâmpsia da rede pública de saúde de Maceió. Métodos: Estudo de coorte prospectivo realizado em 2014 na rede pública de saúde do município com uma amostra de gestantes calculada com base na prevalência de pré-eclâmpsia de 17%, nível de confiança de 90%, poder de 80% e razão de 1:1. Foi aplicado um questionário para coleta de dados socioeconômicos, pessoais e antropométricos, e obtidas variáveis perinatais de prontuário e da declaração de nascido vivo. Análise realizada com regressão de Poisson e teste do qui-quadrado, considerando p < 0,05 como significativo. Resultados: Foram estudadas 90 gestantes com pré-eclâmpsia (GCP) e 90 gestantes sem pré-eclâmpsia (GSP). História prévia de pré-eclâmpsia (razão de prevalência [RP] = 1,57, intervalo de confiança de 95% [IC 95%] 1,47-1,67, p = 0,000) e cor da pele negra (RP = 1,15, IC 95% 1,00-1,33, p = 0,040) estiveram associadas à ocorrência de pré-eclâmpsia. Entre os recém-nascidos das GCP e GSP, 12,5% e 13,1%, respectivamente, eram pequenos para a idade gestacional (p = 0,907) e 25,0% e 23,2%, respectivamente, eram grandes para a idade gestacional (p = 0,994). Houve predomínio da via de parto cesariana. Conclusão: História pessoal de pré-eclâmpsia e cor da pele negra estiveram associadas à ocorrência de pré-eclâmpsia. Houve elevadas frequências de desvios de peso ao nascer e da via de parto cesariana.

Alterações hepáticas da gravidez / Liver disorders in pregnancy

A gestação é um período de significativas modificações no organismo materno, que objetivam promover a homeostase do binômio materno-fetal. Sob o ponto de vista hepático, demais das alterações conspícuas à gravidez, deve o obstetra detectar precocemente anomalias envolvendo o fígado, que complicam até 3% das gestações e são responsáveis por elevada mortalidade materna e perinatal. Por outro lado, certas doenças hepáticas têm sua história natural modificada quando ocorrem durante a gestação, demandando cuidados especiais de uma equipe multidisciplinar que envolva o obstetra e o hepatologista. Este artigo revisa as modificações fisiológicas do sistema hepático na gravidez, assim como suas alterações hepáticas mais prevalentes no Brasil. O objetivo é auxiliar e fornecer orientações ao obstetra e guiar o melhor cuidado das pacientes a fim de prevenir e reduzir as complicações hepáticas na gravidez.(AU)

Pregnancy is a period of significant changes in the mother's organism aimed at promoting the mother-fetus homeostasis. From the hepatic standpoint, the obstetrician should detect early the abnormalities attacking the liver, which complicates up to 3% of pregnancies and are responsible for high rates of maternal and perinatal mortality. On the other hand, some liver diseases have their natural evolution changed when they occur during the pregnancy, requiring special care of a multidisciplinary team involving obstetrician and hepatologist specialists. This study presents the physiological changes of the hepatic system during pregnancy, as well as the most prevalent pregnancy hepatic disorders occurring in Brazil. It aims to help the obstetrician and guide the best patient care to prevent and reduce hepatic complications in pregnancy.(AU)

Niveles de ácido úrico sérico y riesgo de desarrollar preeclampsia

Si bien se conoce que existe una asociación entre los niveles elevados de ácido úrico y la preeclampsia, el debate sobre su aplicación clínica aún está abierto. Nuestro objetivo fue estudiar la utilidad del dosaje periódico del ácido úrico sérico durante el embarazo para identificar gestantes con mayor riesgo de desarrollar preeclampsia. Realizamos un estudio retrospectivo en gestantes primíparas: 79 normotensas y 79 con preeclampsia atendidas en el Hospital Nacional Posadas durante el año 2010. Se analizaron los niveles séricos de ácido úrico, creatinina y urea, y los datos de proteinuria de las historias clínicas de las mujeres embarazadas. Los niveles de ácido úrico fueron similares en ambos grupos durante la primera mitad de la gestación. Sin embargo, a partir de la semana 20, el ácido úrico se incrementó 1.5 veces en gestantes preeclámpticas, sin cambios en la uremia y creatininemia, descartándose así el compromiso renal. Además, encontramos que niveles más altos de ácido úrico se correlacionaban con bajo peso del recién nacido. También vimos que las gestantes con antecedentes familiares de hipertensión eran más propensas a desarrollar esta condición. Por otro lado, no observamos una relación directa ni con el sexo fetal ni con el tiempo de aparición de los síntomas clínicos. Estos hallazgos sugieren que los cambios en las concentraciones de ácido úrico se deberían a alteraciones en los estadios iniciales de la preeclampsia. Por ello, la monitorización de los niveles del mismo durante el embarazo podría contribuir al abordaje precoz de este desorden gestacional.

It is well known that preeclampsia is associated to high uric acid levels, but the clinical assessment of this relationship is still under consideration. Our research was to evaluate if periodic doses of uric acid during pregnancy might help to identify a high risk group prior to the onset of preeclampsia. We conducted a retrospective investigation in 79 primary gestates with normal blood pressure and 79 women with preeclampsia who were assisted at Hospital Nacional Posadas during 2010. Serum uric acid levels, creatininemia, uremia, and proteinuria data from the clinical records of the pregnant women were considered. Uric acid levels were similar in both groups during the first half of gestation. However, as of the 20th week, uric acid increased 1.5-times in preeclamptic women with no changes in creatinine and urea, confirming that these patients had no renal complications. Furthermore, we noted that higher levels of uric acid correlated with low birth weight. We also observed that pregnant women with a family history of hypertension were more likely to develop this condition. Moreover, we did not find a direct relationship with the fetal sex or the appearance of clinical symptoms. The analytical evidence suggests that changes in uric acid concentrations may be due to metabolic alterations at the initial stages of preeclampsia. Therefore, we propose that monitoring levels of uric acid during pregnancy might contribute to the early control of this condition.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

Cirugía bariátrica y embarazo: revisión de la literatura / Bariatric surgery and pregnancy: literature review

La obesidad ha logrado proporciones epidémicas en la actualidad, tanto en Chile como en el mundo. Esta patología se asocia a diversas complicaciones maternas en todas las etapas del ciclo vital y durante el embarazo. El tratamiento médico no ha logrado controlar esta patología, por lo que a pesar de no ser la primera línea, la cirugía bariátrica ha ido en aumento durante los últimos años. Esta revisión de la literatura pretende mostrar los resultados actuales del tratamiento quirúrgico en la mujer antes y durante el embarazo, respecto a la fertilidad, diabetes gestacional, preeclampsia e hipertensión transitoria del embarazo. Además aborda los posibles efectos de esta cirugía en el feto en desarrollo, y su relación con el parto prematuro, macrosomía fetal, bajo peso al nacer y defectos del tubo neural; así como también se refiere a los resultados materno-fetales, principalmente en el ámbito de la nutrición. Finalmente nos permitimos plantear recomendaciones importantes en relación al rol de la anticoncepción, la nutrición y el lapso entre la cirugía y el embarazo, sugeridas de esta revisión.

Obesity has currently reached epidemic proportions, both in Chile and in the world. This condition is associated to a variety of maternal complications in all stages of the vital cycle and during pregnancy. Medical treatment has not proved successful thus resulting in an increase in bariatric surgery in recent years, even when it is not first line treatment. This literature review aims to report updated results of surgical treatment for obesity before and during pregnancy with respect to fertility, gestational diabetes, pre-eclampsia and pregnancy-induced hypertension. It also looks into the possible effects of surgery on fetal development, and its relation to premature delivery, fetal macrosomy, low birth weight and neural tube defects, as well as effects on maternal and fetal outcomes, mainly in nutrition. Lastly, we suggest some recommendations that arise from this review on the role of contraception, nutrition and time between surgery and pregnancy.

Pregnancy outcomes in pregnant women with abnormal glucose challenge test

Some studies have shown that pregnant women with abnormal glucose challenge test [GCT] and normal oral glucose challenge test [OGTT] have the chance of adverse pregnancy outcomes including macrosomia, pre-eclampsia and increase of cesarean section rate. This study was performed to determine the pregnancy outcomes in women with abnormal glucose challenge test. This case -control study was done on 60 pregnant women with abnormal GCT [more than 130 mg/dl] and normal OGTT and 67 pregnant women with normal GCT [less than 130 mg/dl] in Kermanshah, Iran during September 2010-March 2011. Delivery with Vacum, polyhydroamnus, pre-eclampsia pyelonephritis and low birth weight significantly was higher in cases than controls [P<0.05]. But there was a non significant difference in stillbirth, neonatal abnormality, neonatal respiratory distress and shoulder dystocia between case and control groups. Polyhydramnious, preeclampsia and pyelonephrities and low birth weight are more frequent in pregnant women with abnormal GCT and normal OGTT in compare to pregnant women with normal GCT

Evaluation of interleukin-10 [G-1082A] promoter polymorphism in preeclampsia

Preeclampsia is a pregnancy-specific syndrome that may be life-threatening, especially to the fetus. Several causes have been reported that may have a possible role in the development of the disorder. Interleukin-10 affect maternal intravascular inflammation, as well as endothelial dysfunction. The aim of this study was to investigate the association between IL-10 G-1082A polymorphism and pre-eclampsia. A total of eighty-eight pregnant women with preeclampsia and 100 women with normal pregnancy attending the Gynecological unit of Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the study. A standard amplification refractory mutation system [ARMS] PCR was carried out for genotyping IL-10 G-1082A promoter polymorphism in all the participants. Genotypic distribution of the control and patient groups were compared with values predicted by Hardy-Weinberg equilibrium using chi[2] test. Odd ratios [OR] and their respective 95% confidence intervals were used to measure the strength of association between IL-10 gene polymorphism and preeclampsia. The frequencies of IL-10 G-1082A genotypes, GG, GA and AA, were 17.8%, 41.09% and 41.09% in women with preeclampsia and 25%, 28% and 47% in the controls respectively. There was no significant difference in the distribution of genotypes and alleles of IL-10 G-1082A between the two groups [Test power=0.66]. The present study suggests that the IL-10 G-1082A gene promoter polymorphism is not a major genetic regulator in the etiology of preeclampsia

Revisão da leucina aminopeptidase no trabalho de parto pré-termo e na pré-eclampsia / Revision of the leucine aminopeptidase in preterm labor and in preeclampsia

Realizou-se um levantamento bibliográfico, com artigos de revisão, analisando e discutindo os trabalhos publicados sobre os efeitos da leucina aminopeptidase e aminopeptidase A no trabalho de parto pré-termo e na pré-eclampsia. A proposta deste trabalho sobre o tema é que grande parte das questões de saúde materna parece pueril, principalmente quanto ao atendimento voltado para os cuidados maternos, no qual, a cada 20minutos, morre uma mulher em decorrência de parto, no mundo todo. Por isso, tais doenças poderão receber mais atenção do que outras. Esse fato fez com que houvesse certa preocupação com o índice de natalidade e morbidade materna, bem como morbidade e mortalidade perinatal. Portanto, abordou-se sobre sua biologia geral, fisiologia de reprodução, síntese de evolução genética, habitação, alimentação, manejo, dor e eutanásia, técnicas de riscos desenvolvidos na experimentação animal, estudos de experimentos farmacológicos e toxicológicos observados dentro dos artigos de revisão. Embora tendências atuais preconizem a utilização de métodos alternativos (estudo in vitro), os modelos animais, como as ratas, apresentam como principal vantagem o fornecimento de informações sobre o organismo como um todo, fato que não é obtido com outros métodos, o que ainda possibilita o seu emprego em pesquisas científicas.

We have carried out a literature review, with review articles, analyzing and discussing the works that have already been published on the effects of leucine aminopeptidade and aminopeptidase A in pre-term labor and preeclampsia. The proposal of this work on the subject is that most of the issues of maternal health seems childish, especially for service oriented maternity care, where, every 20 minutes, a woman dies due to childbirth, worldwide. Therefore, such diseases may receive more attention than others. This led to worry about the birth rate and maternal morbidity and perinatal morbidity and mortality. Therefore, it was addressed their general biology, physiology of reproduction, synthesis of evolution, genetics, housing, feeding, pain and euthanasia techniques developed for animal experimentation risks, studies of pharmacological and toxicological experiments observed within the review articles. Although current trends have preconized the use of alternative methods (in vitro study), animal models, such as rats, have as main advantage the provision of information on the organism as a whole, a fact that is not achieved with other methods, which also allows its use in scientific research.

Enfermedad de membrana hialina en recién nacidos de pacientes preeclámpticas / Hyaline membrane disease in newborns of preclamptic patients

Comparar la incidencia de la enfermedad de membrana hialina del recién nacido de pacientes preeclámpticas con embarazadas normotensas sanas. Se realizó un estudio de cohortes en todas las pacientes con embarazos simples entre 24 y 36 más 5 semanas de gestación con fetos vivos en el período de enero de 1999 a septiembre de 2008. El diagnóstico de la enfermedad de membrana hialina se realizó por los criterios clínicos y radiológicos. Servicio de Ginecología y Obstetricia. Hospital Central “Dr. Urquinaona”. Maracaibo. Estado Zulia. El número de recién nacidos con diagnóstico de enfermedad de membrana hialina durante el período de estudio fue de 2 491 casos, representando un 7,73 por ciento de los recién nacidos vivos. Se encontraron 56 casos (11,24 por ciento) de la enfermedad de membrana hialina en los recién nacidos de los casos de pacientes preeclámpticas y 206 recién nacidos (10,33 por ciento) entre las pacientes controles (OR 1,098; IC 95 por ciento 0,803 - 1,502). Al seleccionar los recién nacidos con edad gestacional menor de 32 semanas, se encontró en las pacientes preeclámpticas un total de 92 recién nacidos de los cuales 28 de ellos (30,43 por ciento) desarrollaron enfermedad de membrana hialina, mientras que en el grupo de los controles se encontraron 261 recién nacidos de los cuales 70 (26,81 por ciento) desarrollaron la enfermedad (OR 1,194; IC 95 por ciento 0,708 - 2,012). No existe diferencia en la incidencia de la enfermedad de membrana hialina de recién nacido de pacientes preeclámpticas comparado con embarazadas normotensas

To compare the incidence of hyaline membrane disease in newborns of preeclamptic patients with normotensive pregnant patients. A cohort study was done with all patients with single pregnancies between 24 + 0 and 36 + 5 weeks of gestation with live fetuses in the period January 1999 to September 2008. Diagnosis of hyaline membrane disease was done over clinical criteria. Servicio de Ginecologia y Obstetricia. Hospital Central “Dr. Urquinaona”. Maracaibo. Estado Zulia. The number of newborn with diagnosis of hyaline membrane disease during the period was of 2 491 cases, representing 7.73 percent of all live newborns. There were 56 cases (11.45 percent) of hyaline membrane disease in newborn of cases and 206 newborns (10.33 percent) between control patients (OR 1.098; 95 percent IC 0.803 - 1.502). When newborn less than 32 weeks were selected, in preeclamptic patients, there were 92 newborns of whom 28 (30.43 percent) developed hyaline membrane disease, while in control group there were found 70 of 261 newborns who developed disease (OR 1.194; 95 percent IC 0.708 - 2.012). There is not difference in the incidence of hyaline membrane disease in newborn of preeclamptic patients compared with normotensive pregnant patients

Trombofilias: a prevenção direcionada a uma gravidez bem-sucedida / Thrombophilia: prevention targeted to a successful pregnancy

Vários efeitos adversos na gravidez, como pré-eclampsia, deslocamento de placenta, prematuridade e até mesmo perdas fetais recorrentes vêm sendo amplamente associados a estados trombofílicos. Uma vez que o número de trombofilias herdadas tem crescido rapidamente nos últimos anos com a identificação de vários fatores genéticos predispondo ao desenvolvimento de trombose venosa ou arterial, cada vez mais se torna de grande interesse a identificação de mulheres de risco, na tentativa de minimizar os problemas na gravidez e, principalmente, instituir regimes terapêuticos para a prevenção de perdas fetais. Esta revisão aborda os riscos associados à presença de alterações genéticas predispondo à trombose e a importância de um monitoramento adequado.

Many adverse effects during pregnancy, like preeclampsia, placental abruptions, prematurity and recurrent fetal loss have been widely associated with thrombophilic states. The number of inherited thrombophilias has grown rapidly in recent years with the identification of many predisponent genetic factors to the development of venous and/or arterial thrombosis. Therefore, the identification of women of risk becomes of great interest in the attempt to minimize the problems during pregnancy and mainly to institute therapeutical regimens for fetal loss prevention. This review approaches the risk associated to the presence of genetic alterations predisposing to thrombosis, and the importance of an adequate follow up.