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.

Prediction of pre-eclampsia in diabetic pregnant women

Background & objectives: Gestational or preexisting diabetes is one of the risk factors of pre-eclampsia. Both are responsible for higher maternal and fetal complications. The objective was to study clinical risk factors of pre-eclampsia and biochemical markers in early pregnancy of women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) for the development of pre-eclampsia. Methods: The study group comprised pregnant women diagnosed with GDM before the 20 wk of gestation and DM before pregnancy and the control group had age-, parity- and period of gestation-matched healthy women. Sex hormone-binding globulin (SHBG), insulin-like growth factor-I (IGF-I) and 25-hydroxy vitamin D [25(OH)D] levels and the polymorphism of these genes was evaluated at recruitment. Results: Out of 2050 pregnant women, 316 (15.41%) women (296 had GDM and 20 DM before pregnancy) were included in the study group. Of these, 96 women (30.38%) in the study group and 44 (13.92%) controls developed pre-eclampsia. Multivariate logistic regression analysis indicated those who belonged to the upper middle and upper class of socio-economic status (SES) were likely to be at 4.50 and 6.10 times higher risk of developing pre-eclampsia. The risk of getting pre-eclampsia among those who had DM before pregnancy and pre-eclampsia in their previous pregnancy was about 2.34 and 4.56 times higher compared to those who had no such events, respectively. The serum biomarkers [SHBG, IGF-I and 25(OH)D] were not found to be useful in predicting pre-eclampsia in women with GDM. To predict risk of development of pre-eclampsia, the fitted risk model by backward elimination procedure was used to calculate a risk score for each patient. Receiver operating characteristic (ROC) curve for pre-eclampsia showed that area under the curve was 0.68 (95% confidence interval: 0.63-0.73); P<0.001. Interpretation & conclusions: The findings of this study suggested that pregnant women with diabetes were at a higher risk for pre-eclampsia. SES, history of pre-eclampsia in previous pregnancy and pre-GDM were found to be the risk factors.

Evaluation of first- and third-trimester afamin levels in preeclampsia

SUMMARY OBJECTIVE: The aim of this study was to investigate serum afamin levels in the first and third trimesters in preeclampsia. METHODS: Serum samples from 118 patients in the first and third trimesters were analyzed. Serum samples were collected from pregnant women who had enrolled in the first trimester. Blood was then collected from pregnant women who had developed preeclampsia and from healthy controls in the third trimester. The collected blood samples were resolved for analysis, and serum afamin concentrations were measured in the first and third trimesters. Preeclampsia and healthy controls were compared. RESULTS: There was no significant difference between the control and preeclampsia groups in terms of age, body mass index, and smoking. Afamin levels in the first and third trimesters were higher in the preeclampsia group than in the control group (p<0.05). In the subgroup analysis of the preeclampsia group, afamin levels were higher in the early-onset preeclampsia group than in the late-onset preeclampsia group in the first and third trimesters (p<0.05). In the receiver operating characteristic analysis afamin levels were 96.23 ng/mL in the first trimester and 123.57 ng/mL in the third trimester as cut-off values for preeclampsia. CONCLUSION: Serum afamin levels are useful for predicting preeclampsia in the first trimester in pregnant women and can be used in clinical practice as a supportive biomarker for the diagnosis of preeclampsia in the third trimester. Meta-analyzes are needed to investigate the effect of afamin levels in the prediction and diagnosis of preeclampsia and to determine the cut-off value.

Exposição ao cádmio e Síndromes Hipertensivas da Gestação: uma revisão sistemática / Cadmium exposure and Hypertensive Disorders of Pregnancy: a systematic review

RESUMO As Síndromes Hipertensivas da Gestação (SHG) são uma das principais causas de morbimortalidade materna. Evidências crescentes indicam a associação entre a exposição ao cádmio e a hipertensão arterial na população em geral, mas não as SHG. Afim de investigar esse tema, realizou-se uma revisão sistemática seguindo as diretrizes PRISMA, nas bases de dados BVS/Lilacs, PubMed/Medline e SciELO e no repositório da Universidade de São Paulo (USP) até agosto de 2021. A qualidade metodológica foi avaliada pelo checklist Downs and Black. Selecionaram-se dezenove artigos, sendo treze caso-controle, quatro coortes e dois seccionais. No total, 11.451 participantes foram avaliadas, sendo 1.445 (12,6%) com SHG e, destas, 1.071 (74,1%) com pré-eclâmpsia. Observou-se o ajuste inadequado para confundimento em onze estudos. Dos sete estudos considerados de boa qualidade metodológica, quatro relataram associação positiva e três não a observaram, enquanto somente um estudo observou diferença de média, que foi maior nas gestantes com SHG. Atribuiu-se a divergência dos resultados às diferenças metodológicas e ao ajuste inadequado para os fatores de confusão. Como o cádmio é um metal tóxico que pode levar ao aumento do estresse oxidativo, que desempenha papel importante na fisiopatologia das SHG, estudos adicionais são necessários para elucidar esta associação.

ABSTRACT Hypertensive Disorders of Pregnancy (HDP) are one of the main causes of maternal morbimortality. Strong evidence point to an association between cadmium and hypertension in the general population, but not HDP. A systematic review was carried out to investigate this potential relationship, following PRISMA guidelines, in the BVS/LILACS, PubMed/MEDLINE, and SciELO databases and a repository (University of São Paulo - USP) until August 2021. The methodological quality was assessed using the Downs and Black checklist. Nineteen articles were selected, thirteen of which were case-control, four were cohorts, and two were cross-sectional. A total of 11.451 participants were evaluated, 1.445 (12.6%) with HDP, and of these 1.071 (74.1%) with preeclampsia. The inadequate adjustment for confounding was observed in eleven studies. Out of the seven studies considered good methodological quality, four reported a positive association, and three did not observe it. In contrast, only one observed a mean difference, which was higher in HDP. The inconsistency of the results was attributed to the methodological differences and inadequate adjustment for confounding. As cadmium is a toxic metal that can induce an increase in oxidative stress, which plays an essential role in the pathophysiology of HDP, additional studies are needed to elucidate this association.

Definición de la presión arterial normal a las 11-14 semanas de gestación según riesgo / Definition of normal blood pressure at 11 to 14 weeks' gestation according to risk

Resumen Objetivo: Definir la presión arterial normal en el primer trimestre de la gestación según el desempeño para predecir preeclampsia. Método: Estudio de cohorte en embarazos de feto único, según el modelo de riesgos en competencia para preeclampsia. La presión arterial se midió de manera estandarizada entre las 11 y 14 semanas de gestación. Resultados: En 797 embarazos incluidos hubo 40 (5.0%, intervalo de confianza del 95% [IC 95%]: 3.6-6.4) partos con preeclampsia. Las presiones arteriales sistólica, diastólica y media fueron respectivamente de 101 (9), 68 (8) y 79 (8) mmHg en las embarazadas que no desarrollaron preeclampsia, frente a 109 (10), 75 (8) y 86 (8) mmHg en las que sí (p < 0.001, prueba t de Student). Las áreas bajo la curva fueron 0.707 (0.637-0.777), 0.728 (0.661-0.795) y 0.738 (0.673-0.803). A 3% de falsos positivos, los puntos de corte fueron 119, 83 y 94 mmHg con valores predictivos negativos del 95.6%. Conclusiones: Es factible definir normalidad para la presión arterial en el embarazo con base bioestadística y clínica.

Abstract Objective: To define normal blood pressure at first trimester of pregnancy by performance for pre-eclampsia prediction. Method: A cohort study in singleton pregnancies, according to the competing risks model for pre-eclampsia. Blood pressure was measured according to a standardized method at 11 to 14 weeks' gestation. Results: Among 797 pregnancies included, there were 40 (5.0%, IC95 3.6; 6.4) deliveries with pre-eclampsia. The systolic, diastolic, and mean arterial blood pressures were respectively of 101(9), 68(8) and 79(8) mmHg in pregnant women who did not develop pre-eclampsia, against 109(10), 75(8) and 86(8) in those who did (p < 0.001, t-test). The areas under the curves were 0.707 (0.637; 0.777), 0.728 (0.661; 0.795), and 0.738 (0.673; 0.803). At a 3% of false positive rate, the cut-off points were 119, 83 and 94 mmHg with predictive values of negative of 95.6%. Conclusions: It is feasible to define the normal values for blood pressure in pregnancy on biostatistic and clinical basis.

Ultrassonografia morfológica de primeiro trimestre: importante ferramenta para rastreio de aneuploidias e pré-eclâmpsia / First-trimester morphological ultrasound: important tool for aneuploidy and pre-eclampsia screening

No início do século 20, as altas taxas de mortalidade materna e infantil estimularam o desenvolvimento de um modelo de atendimento pré-natal que mantivesse características parecidas até os dias atuais. Nesse modelo, haveria maior concentração de visitas durante o final do terceiro trimestre de gestação, devido às maiores taxas de complicações nas fases finais da gestação e à dificuldade de prever a ocorrência de resultados adversos durante o primeiro trimestre. Atualmente, a avaliação clínica durante o primeiro trimestre, com auxílio da ultrassonografia e marcadores bioquímicos, pode prever uma série de complicações que acometem a gestação, incluindo cromossomopatias, pré-eclâmpsia, restrição de crescimento fetal, anomalias fetais e trabalho de parto pré-termo.

At the beginning of the 20th century, the high rates of maternal and infant mortality stimulated the development of a model of prenatal care that maintained similar characteristics until the present day. In this model, there would be a greater concentration of visits during the end of the third trimester of pregnancy, due to the higher rates of complications in the final stages of pregnancy and the difficulty in predicting the occurrence of adverse outcomes during the first trimester. Currently, clinical evaluation during the first trimester, with the aid of ultrasound and biochemical markers, can predict a series of complications that affect pregnancy, including chromosomal disorders, preeclampsia, fetal growth restriction, fetal anomalies and preterm labor.

MATERNAL NEAR MISS: AN INDIAN TERTIARY CARE CENTRE AUDIT

BACKGROUND: Despite advances in medical sciences and increased awareness of measures for safe child birth, unacceptably high maternal morbidity and mortality continues in developing countries like India. Ours being a tertiary care centre, draws a lot number of high risk pregnancies and referrals. By auditing the near miss cases2 i.e., a critically ill pregnant or recently delivered woman who was on the verge of death but survived a problem during pregnancy, childbirth, or within 42 days of the pregnancy's termination, we aim to identify the causes, factors leading to near miss2 and the management given to near miss2 and maternal deaths. The AIMS AND OBJECTIVES: present study aims to determine the magnitude, as well as to identify the pattern of Maternal Near Miss2 (MNM), at Siddhartha Medical College, Vijayawada, during the study period of two years. To anal OBJECTIVES: yse 1)Adverse events leading to a maternal near-miss2, 2) Disorders underlying these cases, 3)Sociodemographic factors and 4)Contributing factors A hospital based retros METHODOLOGY: pective observational study to assess the frequency and nature of maternal near miss2 events among the obstetric cases managed at Siddhartha Medical College, Vijayawada over a period of two years. The followi RESULTS: ng are the major causes identified leading to maternal near miss2 during our study Severe Eclampsia 17%, Post-partum Haemorrhage 17%, Pulmonary Edema due to severe pre eclampsia3 9%, Antepartum Eclampsia 9%, HELLP 9%, Ruptured ectopic pregnancy 7%, Cardiac failure 7%, Postpartum Eclampsia 7%, Imminent Eclampsia 4%, Abruption 4%, Rupture uterus 2%. In our study Maternal near miss2 ratio incidence: 0.0254, Severe maternal outcomes ratio : 3, Maternal near miss2 to mortality ratio: 0.433 CONCLUSION: We observed in majority of the cases level 1 and level 2 delays in reporting to our institution

Importancia de la prevención y detección oportuna de la preeclampsia/eclampsia / Importance of prevention and timely detection of preeclampsia/eclampsia

La preeclampsia/eclampsia constituyen una manifestación de la enfermedad hipertensiva que se puede presentar después de la semana 20 del embarazo. Esta tiene la capacidad de generar múltiples complicaciones en la gestante y el feto. Su diagnóstico oportuno y la toma de medidas preventivas ante sus factores de riesgo tienen la potencialidad para reducir la morbimortalidad por esta causa.

Preeclampsia/eclampsia is a manifestation of a hypertensive disease that can occur after the 20th week of pregnancy by generating multiple complications in the pregnant woman and the fetus. Its timely diagnosis and the taking of preventive measures against its risk factors can reduce morbidity and mortality.

Pregnancy-Induced Hypertension - Ayurvedic Understanding

Pregnancy-induced hypertensive disorders are included among the most common medical complications of pregnancy with an incidence of 5–10%. Hypertension that develops as a direct result of gravid state is referred to as ‘pregnancy-induced hypertension’. The timely management of pregnancy complicated with hypertensive disorders is significant, otherwise it can lead to adverse fetal, neonatal and maternal outcomes. The basic pathology in pre-eclampsia, one of the types of hypertensive disorders is endothelial dysfunction and intense vasospasm due to abnormal placentation compromising blood flow to the foetoplacental unit. There is no direct reference of pregnancy-induced hypertension in Ayurveda classics, but the manifested symptoms can be explained within the purview of Ayurveda. Abnormality in placentation can be considered as impairment in the normal functioning of Vata dosha and when the pathology progresses further; Kapha, Pitta also play their own roles. In a woman with or without a previous history of pre-eclampsia, intervention should begin from pre-conceptional period. Planned pregnancy after pre-conceptional care followed by Garbhini paricharya along with the use of Garbhasthapaka dravya, Rasayana dravya, Masanumasika Garbhasravahara dravya can play significant roles in the prevention as well as management of pregnancy-induced hypertension thus improving the maternal and foetal outcomes.

Aspects cliniques et évolutifs de la pré-éclampsie sévère traitée à la maternité Befelatanana, Madagascar / Clinical aspects and outcome of severe pre-eclampsia treated at the Befelatanana maternity hospital, Madagascar

Pre-eclampsia is a major public health problem and is one of the main causes of maternal-fetal morbidity. The main objective of this study is to describe the clinical and evolutionary aspects of severe pre-eclampsia. Methods: This was a retrospective, monocentric, descriptive, observational and cross-sectional study of 6 months, from January 01, 2019 to June 30, 2019, conducted at the level of the resuscitation service of the university hospital of gynecology obstetrics Befelatanana (CHU GOB). Results: Three hundred and fourteen (5.10%) cases out of 6153 admissions of severe pre-eclampsia were collected in the study; the average age was 27.29 ±7.47 years. Eclampsia (30.25%, n= 95), retroplacental hematoma (13.38%, n= 42) and acute renal failure (7.96%, n= 25) were the most frequent maternal complications. Maternal prognosis was favorable in 92.36% of cases (n= 290). Maternal death represented 3.18% (n= 10). Prematurity (44.82%, n= 95), fetal hypotrophy (37.26%, n= 79) and fetal asphyxia (14.15%, n= 30) were the most common fetal complications. Fetal death was 26.47% (n= 81). Conclusion: It is necessary to reinforce the information and education of parturients on the first signs for an early detection, diagnosis and management

Indicación profiláctica de aspirina para prevención de preeclampsia y sus complicaciones en embarazos de alto y moderado riesgo / Prophylactic use of aspirin for the prevention of preeclampsia and its complications in high and moderate risk pregnancies

Resumen OBJETIVO: Sintetizar la evidencia disponible de los últimos 10 años respecto de la indicación de la aspirina para prevenir la preeclampsia y sus complicaciones en embarazos de alto y moderado riesgo. METODOLOGÍA: Revisión de cinco bases de datos [Pubmed/Medline, ProQuest, Lilacs, HINARI y Cochrane Central Register of Controlled Trials (CENTRAL)]. Se incluyeron ensayos clínicos aleatorizados, controlados, escritos en español o inglés publicados entre enero de 2010 y enero de 2020. Se emplearon los términos de vocabulario controlado DeCS y MeSH en las distintas interfases. En el caso de ProQuest se introdujeron, además, términos de vocabulario libre. Los detalles de la estrategia de búsqueda se visualizan en anexos. RESULTADOS: Se identificaron 410 estudios, de los que se seleccionaron 8 que reunieron los criterios de elegibilidad. En dos estudios se encontró un efecto reductor de la aspirina en la incidencia de preeclampsia en comparación con placebo; otros dos estudios encontraron el mismo efecto en la incidencia de preeclampsia con parto pretérmino. No se encontraron estudios con bajo riesgo de sesgo que hubieran reportado un efecto significativo de la aspirina en las complicaciones de preeclampsia, ni en preeclampsia con y sin criterios de severidad. CONCLUSIONES: La evidencia señala que la aspirina en bajas dosis, indicada antes de las 16 semanas de embarazo, reduce la incidencia de preeclampsia debido a su efecto reductor en el parto pretérmino. A pesar de lo encontrado, la información sigue siendo limitada; de ahí la necesidad de contar con una mayor cantidad de estudios con bajo riesgo de sesgo.

Abstract OBJECTIVE: To synthesize the available evidence of the last 10 years regarding the use of aspirin for the prevention of preeclampsia and its complications in high and moderate risk pregnancies. Methodology: Five electronic databases [Pubmed/Medline, ProQuest, Lilacs, HINARI, and Cochrane Central Register of Controlled Trials (CENTRAL)] were reviewed. Randomized controlled clinical trials in Spanish and English published between 01/01/2010 and 01/01/2020 were considered. The DeCS and MeSH controlled vocabulary terms were used in the different interfaces. In the case of ProQuest, free vocabulary terms were also introduced. The details of the search strategy are displayed in annexes. RESULTS: 410 studies were identified, of which 8 studies that met the eligibility criteria were selected. 2 studies found a reducing effect of aspirin on the incidence of preeclampsia compared to placebo and another 2 studies found the same effect on the incidence of preeclampsia with preterm delivery. No studies with low risk of bias were found that have reported a significant effect of aspirin on the complications of preeclampsia, nor on preeclampsia with and without criteria of severity. CONCLUSIONS: there is evidence indicating that low-dose aspirin before 16 weeks of gestation reduces the incidence of preeclampsia, this is due to the reducing impact it has on the incidence of preeclampsia with preterm delivery. Despite the results found, the information is still limited, and it is necessary to have a greater number of studies with low risk of bias.

Trombosis de seno venoso en paciente en puerperio mediato. Reporte de caso / Venous sinus thrombosis in a patient during the immediate puerperium. Case report

Resumen ANTECEDENTES: La trombosis del seno venoso representa el 1% de los eventos vasculares cerebrales; su incidencia es de 5 casos por cada millón de habitantes y su mortalidad es del 10%. Los senos sagital superior y venoso transversal son los más afectados. El embarazo es un factor de riesgo especial pues la trombosis se registra en el 0.01% de las gestaciones. CASO CLÍNICO: Paciente de 40 años, primigesta, con embarazo gemelar bicorial biamniótico de 33.6 semanas. Se ingresó al servicio de Urgencias debido al diagnóstico de preeclampsia con criterios de severidad, con presión arterial de 160-100 mmHg y transaminasemia. Se le indicó tratamiento antihipertensivo y sulfato de magnesio intravenoso. Se decidió la finalización del embarazo por cesárea. Al cuarto día poscesárea tuvo disminución de la fuerza en ambos brazos, pérdida del tono muscular en los miembros pélvicos, cefalea holocraneana y alteración del estado de alerta (Glasgow de 14). Mediante resonancia magnética se evidenció la oclusión del seno longitudinal superior e isquemia en la región parieto occipital izquierda. Se le administraron anticoagulantes y analgésicos con los que evolucionó adecuadamente; se dio de alta sin complicaciones. CONCLUSIONES: La trombosis del seno venoso implica un reto cuando no se tiene una alta sospecha diagnóstica en pacientes con signos y síntomas neurológicos y, más aún, cuando se agregan factores de riesgo protrombóticos, como el embarazo y el puerperio. El diagnóstico oportuno brinda la oportunidad de iniciar el tratamiento adecuado y disminuir los síntomas y comorbilidades.

Abstract BACKGROUND: Venous sinus thrombosis accounts for 1% of cerebral vascular events; its incidence is 5 cases per million population and its mortality is 10%. The superior sagittal and transverse venous sinuses are the most affected. Pregnancy is a special risk factor since thrombosis is registered in 0.01% of pregnancies. CLINICAL CASE: A 40-year-old primigravida patient with a 33.6 week biamniotic twin pregnancy. She was admitted to the Emergency Department due to the diagnosis of preeclampsia with severity criteria, with blood pressure of 160-100 mmHg and transaminasemia. She was prescribed antihypertensive treatment and intravenous magnesium sulfate. It was decided to terminate the pregnancy by cesarean section. On the fourth post-cesarean day she had decreased strength in both arms, loss of muscle tone in the pelvic limbs, holocranial headache and altered alertness (Glasgow of 14). Magnetic resonance imaging showed occlusion of the superior longitudinal sinus and ischemia in the left parietooccipital region. He was administered anticoagulants and analgesics with which he evolved adequately; he was discharged without complications. CONCLUSIONS: Venous sinus thrombosis implies a challenge when there is no high diagnostic suspicion in patients with neurological signs and symptoms and, even more so, when prothrombotic risk factors are added, such as pregnancy and puerperium. Timely diagnosis provides the opportunity to initiate appropriate treatment and reduce symptoms and comorbidities.

Simultaneous rupture of the patellar and contralateral quadriceps tendons in a nephropathy patient / Ruptura simultânea de tendão patelar e quadricipital contralateral em paciente nefropata

ABSTRACT Simultaneous rupture of the patellar and contralateral quadriceps tendons in patients with chronic renal failure is an extremely rare condition, with few cases described in the medical literature. Several systemic pathological conditions that lead to a decline in kidney function can predispose individuals to spontaneous tendon rupture, such as rheumatological and endocrine diseases, and even gestational conditions, such as eclampsia. Objective: In this case report, we describe the case of a 39-year-old woman with chronic renal failure on dialysis due to a previous history of eclampsia that caused the simultaneous rupture of the patellar and contralateral quadriceps tendons. Methods: Data were collected by interviews, direct observation, and medical examinations, and include information about the case history, the patient's characteristics, the former interventions, and the results obtained. Results: The surgery to repair the patellar and contralateral quadriceps tendons was performed by transosseous tunnels and the Krackow technique with nonabsorbable sutures was used. The semitendinosus tendon was removed and used as reinforcement. Conclusion: Patient under follow-up with good functional results in both knees. Level of Evidence V, Expert Opinion.

RESUMO A ruptura simultânea de tendão patelar e tendão quadricipital contralateral em paciente com insuficiência renal crônica é uma condição extremamente rara, havendo poucos casos descritos na literatura médica. Diversas condições patológicas sistêmicas que levam ao declínio das funções renais podem predispor à ruptura tendinosa espontânea, como doenças reumatológicas e endócrinas, até mesmo condições gestacionais, como a eclâmpsia. Objetivo: Neste relato de caso, descrevemos o caso de uma mulher de 39 anos com insuficiência renal crônica dialítica decorrente de quadro pregresso de eclâmpsia que culminou na ruptura simultânea de tendão patelar e tendão quadricipital contralateral. Métodos: Estudo realizado com dados coletados por meio de entrevista, observação direta e exames médicos. Os dados incluem informações sobre o histórico do caso, as características do paciente, as intervenções realizadas e os resultados obtidos. Resultados: A cirurgia para reparo da lesão de tendão patelar contralateral e tendão quadricipital foi realizada por túneis transosseos e a rafia foi feita com pontos Krakow utilizando fios não absorvíveis. Além disso, o tendão semitendinoso foi retirado e usado como reforço. Conclusão: A paciente apresentou bons resultados funcionais em ambos os joelhos operados. Nível de Evidência V, Opinião do Especialista.

The ophthalmic artery resistive index as a predictor of choriocapillaris ischemia in multivariate logistic models / Índice de resistência da artéria oftálmica como preditor de isquemias focais da coriocapilar em modelos logísticos multivariados

ABSTRACT Objective Vascular findings in preeclampsia are usually attributed to increased vascular tone. Recently, however, important studies have improved the understanding of the main pathophysiological events in this condition, especially vascular brain remodeling, impaired autoregulation, and damage of the blood-brain barrier, which are well recognized features of cerebral overperfusion. Methods In this study, the association between choriocapillaris ischemia with ophthalmic artery blood flow parameters on orbital Doppler ultrasound is reported for the first time using multivariate logistic models. Multivariate logistic models with ophthalmic artery blood flow parameters, as well as major clinical and laboratory predictive variables were established for choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment. Results In a series of 165 patients, 46 (28%) presented choriocapillaris ischemia; among them, 20 (12%) presented associated retinal detachment. The ophthalmic artery resistive index was the main predictor for choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment in multivariate logistic models. Ophthalmic artery resistance lower than 0.56 was associated with a significantly high incidence of both outcomes. Conclusion This study supports that the branching pattern of choroidal arterioles and the lobular organization of choriocapillaris are the major morphological aspects underlying endothelial damage and lobular ischemia in the context of choroidal overperfusion. Overperfused lobules bordering areas of choriocapillaris ischemia produce a perfusion pressure gradient, with lobular reperfusion, leakage from reperfused choriocapillaris, and retinal detachment. Ophthalmic artery-resistive index lower than 0.56 is proposed as a major predictor of the overperfusion-related choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment in preeclampsia.

RESUMO Objetivo Os achados vasculares na pré-eclâmpsia são usualmente atribuídos ao aumento do tônus vascular. Recentemente, no entanto, importantes estudos têm melhorado a compreensão dos principais eventos fisiopatológicos nessa condição, especialmente o remodelamento vascular cerebral, a perda de autorregulação e a ruptura da barreira hematoencefálica, características bem reconhecidas de hiperperfusão cerebral. Métodos Neste estudo, a associação entre a isquemia da coriocapilar e parâmetros de fluxo sanguíneo da artéria oftálmica no Doppler orbitário é relatada pela primeira vez por meio de modelos logísticos multivariados. Modelos logísticos multivariados com parâmetros de fluxo sanguíneo de artéria oftálmica, assim como os principais preditores clínicos e laboratoriais, foram estabelecidos para isquemia da coriocapilar e coriocapilar associada a descolamento de retina. Resultados Em uma série de 165 pacientes, 46 (28%) apresentaram isquemia da coriocapilar; dentre eles, 20 (12%) apresentaram descolamento de retina associado. O índice de resistência da artéria oftálmica foi o principal preditor para isquemia da coriocapilar e isquemia da coriocapilar associada a descolamento de retina em modelos logísticos multivariados, e índice de resistência da artéria oftálmica menor que 0,56 foi associado a uma incidência significativamente elevada de ambos os desfechos. Conclusão Este estudo sustenta que o padrão de ramificação das arteríolas coroidianas e a organização lobular da coriocapilar são os principais aspectos morfológicos subjacentes ao dano endotelial e à isquemia lobular no contexto do hiperfluxo coroidiano. O hiperfluxo de lóbulos adjacentes às áreas de isquemia da coriocapilar estabelece um gradiente de pressão de perfusão, o que produz reperfusão lobular, extravasamento a partir de coriocapilares reperfundidos e descolamento da retina. O índice de resistência da artéria oftálmica inferior a 0,56 é proposto como um importante preditor de isquemia da coriocapilar e isquemia da coriocapilar associada a descolamento de retina relacionados ao hiperfluxo na pré-eclâmpsia.

Impact of early-onset preeclampsia on feeding tolerance and growth of very low birth weight infants during hospitalization / Efeito da pré-eclâmpsia precoce na tolerância alimentar e no crescimento de recém-nascidos de muito baixo peso durante a hospitalização

ABSTRACT Objective: The provision of adequate enteral nutrition to preterm infants is a great challenge, and preeclampsia (PE) may have a detrimental effect on the safety of nutrition supply. This study aims to investigate the influence of early-onset PE on preterm infants' enteral feeding tolerance and growth during hospitalization. Methods: This is a prospective study with 55 preterm infants <34 weeks born to PE mothers matched by gestational age with 55 preterm infants born to normotensive mothers from 2013 to 2016. We evaluated maternal, gestational, and neonatal clinical data. The outcomes were feeding intolerance and growth during hospitalization. Comparison between groups was performed by Student's t-test or Mann-Whitney U test, chi-square test, or Fisher's exact test. Multiple logistic regression was used to investigate whether PE was an independent risk factor for feeding intolerance. Results: The mean gestational age was 30 weeks. Preterm infants of mothers with PE had lower birth weight and were smaller at discharge. Feeding intolerance was frequent, but necrotizing enterocolitis was rare in this sample (PE=4% vs. control=2%) with no difference between groups. Preterm infants of mothers with PE had worse growth outcomes; however, PE was not an independent risk factor for feeding intolerance. The increase in gestational age was a protective factor, and being born small for gestational age (SGA) increased the risk of feeding intolerance by six times. Conclusions: Preterm infants of mothers with early-onset PE were more likely to be born SGA and had a worse growth trajectory during hospitalization. In adjusted analyses, however, low gestational age and SGA were independent predictors of feeding intolerance.

RESUMO Objetivo: A nutrição enteral adequada para recém-nascidos prematuros é um grande desafio, e a pré-eclâmpsia (PE) pode comprometer a segurança da oferta alimentar. O objetivo deste estudo é investigar a influência da PE de início precoce na tolerância alimentar e no crescimento de prematuros durante a hospitalização. Métodos: Estudo prospectivo, com 55 prematuros <34 semanas de mães com PE pareados por idade gestacional e com 55 prematuros de mães normotensas, de 2013 a 2016. Foram avaliados dados clínicos maternos, gestacionais e neonatais. Os desfechos foram intolerância alimentar e crescimento durante a hospitalização. Na comparação entre grupos, utilizaram-se teste t de Student ou de Mann-Whitney e teste qui-quadrado ou exato de Fisher. Regressão logística múltipla foi usada para investigar se a PE é fator de risco para intolerância alimentar. Resultados: A idade gestacional média foi de 30 semanas. Prematuros de mães com PE tiveram menor peso ao nascer e eram menores na alta. A intolerância alimentar foi frequente, mas a enterocolite necrosante foi rara nesta amostra (PE=4% vs. controle=2%), sem diferença entre grupos. Prematuros de mães com PE tiveram pior crescimento, mas a PE não foi fator independente de risco para intolerância alimentar. O aumento da idade gestacional foi fator de proteção, e nascer pequeno para a idade gestacional (PIG) aumentou em seis vezes o risco de intolerância alimentar. Conclusões: Prematuros de mães com PE de início precoce tiveram maior probabilidade de nascer PIG e pior trajetória de crescimento na hospitalização. Em análises ajustadas, baixa idade gestacional e PIG foram preditores independentes de intolerância alimentar.

Histopathological, ultrastructural, and immunohistochemical examination of changes in the placenta as a result of severe preeclampsia

Purpose: To investigate the role of hypoxia-inducible transcription factor-1 alpha (HIF-1α) and angiogenetic factor endothelin-1 (ET-1) expression in regulating hypoxia and placental development by routine histopathological methods. Methods: Twenty preeclamptic and normal placentas were used. Placenta tissue pieces were examined histopathologically after routine paraffin follow-ups. HIF-1α and ET-1 proteins were examined immunohistochemically, and placental tissues were examined ultrastructurally. Results: Increase in syncytial proliferation, endothelial damage in vessels, and increase in collagen were observed in preeclamptic placentas. As a result of preeclampsia, an increase was observed in HIF-1α and ET-1 protein levels in the placenta. Dilatation of endoplasmic reticulum and loss of cristae in mitochondria were observed in trophoblast cells in preeclamptic placental sections. Conclusion: High regulation of oxygen resulting from preeclampsia has been shown to be a critical determinant of placentagenesis and plays an important role in placental differentiation, changes in maternal and fetal blood circulation, trophoblastic invasion, and syncytial node increase. It has been thought that preeclampsia affects secretion by disrupting the endoplasmic reticulum structure and induces mitochondrial damage, and that ET-1 may potentially help in the induction of stress pathways as a result of hypoxia in preeclampsia.

Current status and prospect of pravastatin in pregnancy / 中华围产医学杂志

Cholesterol-lowing statins such as pravastatin have been contraindicated in pregnant women for a long time, but recent clinical evidence has demonstrated its safety. Studies have found that pravastatin can correct the imbalance in angiogenesis, reduce vascular inflammation and improve the conditions in patients with placental and maternal vascular dysfunction-related diseases, such as preeclampsia, fetal growth restriction and antiphospholipid syndrome. However, universal administration of pravastatin in pregnancy still requires more evidence on its safety from human clinical trials with larger sample sizes. This article reviews the current situation and prospect of pravastatin in pregnancy.

Mechanism for regulation of trophoblast invasion through piR-3127964 via PIWIL-3/sialophorin pathway / 中华围产医学杂志

Objective:To investigate the molecular mechanism for regulation of trophoblast invasion by piR-3127964, which is differentially expressed in placental tissues of preeclamptic and healthy pregnant women.Methods:Placenta samples of healthy (control group, n=12) and preeclamptic pregnant (PE group, n=10) women who delivered by caesarean section and chorionic villi specimens of patients undergoing artificial abortion were collected in the Department of Obstetrics of the First Affiliated Hospital of Chongqing Medical University during November 2020 to August 2021. Total RNA was extracted from placenta samples and sequenced and the expression of piR-3127964 in different tissues was determined by real-time quantitative-polymerase chain reaction (qRT-PCR). The expressions of PIWI proteins including PIWIL-1, PIWIL-2 and PIWIL-3 in different tissues were detected by Western blot. The expressions of two candidate targets, guanine nucleotide-binding protein-like 3-like (GNL3L) mRNA and sialophorin (SPN) mRNA were evaluated by qRT-PCR after exogenous treating HTR-8/SVneo cells with mimics, inhibitor or negative control of piR-3127964, respectively. qRT-PCR was also used to detect the relative expression of GNL3L and SPN at mRNA level in placentas of all women. The interactions between GNL3L/SPN and piR-3127964 were analyzed by double luciferase reporter gene detection. The localization of piR-3127964 and SPN in chorionic villi was detected by fluorescence in situ hybridization and immunofluorescence. Transwell assay was performed to analyze the influence of piR-3127964 on the invasion of HTR-8/SVneo cells and the possible mechanism. Independent sample t-test, analysis of variance, and LSD post test were used for analysis Results:(1) Enrichment pathways of candidate targets predicted by differentially expressed piR-3127964 were associated with cell motility. There were statistically significant differences in piR-3127964 expression in villi, healthy and preeclamptic placentas (2.950±0.853 vs 1.036±0.303 vs 0.254±0.155, F=27.35, P<0.05), and piR-3127964 was predominantly expressed in extravillous cytotrophoblasts (EVTs). (2) The expression of PIWIL-3 protein in placentas of preeclamptic patients was significantly lower than that in healthy placentas and villi (0.810±0.400 vs 3.175±0.429 and 6.843±1.379, F=49.36, P<0.05). (3) Compared with the control group, exogenous piR-3127964 mimics (piR-mimics) and inhibitors (piR-inhibitor) significantly affected the expression of SPN mRNA (0.971±0.045 vs 0.732±0.010, F=6.50; 1.076±0.073 vs 1.293±0.092, F=7.58; both P<0.05), while the expression of GNL3L mRNA had no significant correlation with piR-3127964 level. (4) The luciferase activity of wild-type SPN (SPN-WT) plasmids was significantly affected by piR-mimics (1.010±0.049 vs 0.645±0.047, t=9.34, P<0.05) and piR-inhibitor (1.035±0.058 vs 1.397±0.015, t=－10.60, P<0.05). (5) SPN mRNA was significantly upregulated in placentas of preeclamptic patients than in healthy placentas (2.097±0.239 vs 1.305±0.290, t=－4.22, P<0.05), but no significant difference in the expression of GNL3L mRNA was observed. Immunofluorescence experiment showed that SPN was expressed in EVTs. (6) The invasive potential of HTR8/SVneo cells treated with piR-inhibitor was significantly inhibited, but this effect could be reversed by SPN knockdown (160.714±53.860 vs 371.667±103.061 and 344.333±120.267, F=9.76, both P<0.05). Conclusions:piR-3127964 expression is abnormally downregulated in placentas of preeclamptic patients, resulting in inhibition of trophoblasts invasion through upregulation of SPN expression, which may be related to the pathogenesis of preeclampsia.

Endoplasmic reticulum aminopeptidase 1 and genetic susceptibility to pre-eclampsia / 中华围产医学杂志

Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.