Enhanced elimination of betamethasone in dichorionic twin pregnancies.

AIM: No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone pharmacokinetic parameters in singleton and dichorionic (DC) and monochorionic twin pregnancies in the third trimester of pregnancy. METHODS: Twenty-six pregnant women received 2 intramuscular doses of 6 mg of betamethasone sodium phosphate plus 6 mg betamethasone acetate due to preterm labour. Serial blood samples were collected for 24 hours after the first intramuscular dose of betamethasone esters. Betamethasone plasma concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry analytical method, and the pharmacokinetic parameters were obtained employing a noncompartmental model. Preliminary data on the betamethasone placental transfer are also presented. RESULTS: The geometric mean (95% confidence interval) of AUC0-∞ 645.1 (504.3-825.2) vs. 409.8 (311.2-539.6) ng.h/mL and CL/F 17.70 (13.84-22.65) vs. 27.87 (21.17-36.69) were significantly different, respectively, in singleton pregnancies when compared to DC twins. CONCLUSION: Data from this study suggest that the presence of 2 foetoplacental units may increase the betamethasone metabolism by hepatic CYP3A4 and/or placental 11ß-HSD2 enzymes. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether these betamethasone pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.

Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intra-uterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.

Postpartum depression screening by telephone: a good alternative for public health and research.

This study verified the reliability and validity of the Edinburg Postpartum Depression Scale (EPDS) administered by telephone interviews. In a cross-sectional study of a cohort from Brazil (BRISA), the EPDS was administered by telephone to 1,083 women within 12 months postpartum, and 257 (23.7 %) participants had an EPDS score ≥10. At 67 ± 48 days after their telephone interview, 199 (EPDS ≥10 = 96; EPDS <10 = 103) participants were interviewed face-to-face using the Structured Clinical Interview for DSM-IV (SCID) and completed the EPDS again by self-report. In 90 participants, the diagnosis of major depressive episode was confirmed by the SCID (EPDS ≥10 = 65; EPDS <10 = 25). The Cronbach's alpha coefficient was 0.861. The Spearman's correlation between the EPDS administered by telephone and the self-reported EPDS was 0.69 (p < 0.001). The receiver-operating characteristic (ROC) curve for the EPDS administered by telephone was 0.78 (95 % confidence interval (CI) = 0.72 to 0.84). Scores ≥10 showed a sensitivity of 72.2 %, a specificity of 71.6 %, and a positive predictive value of 67.7 %. The application of the EPDS by telephone is a suitable alternative for clinical practice and research and represents a method to optimize the diagnosis of postpartum depression.

Maternal blood pressure and heart rate response to pelvic floor muscle training during pregnancy.

OBJECTIVES: To assess whether maternal blood pressure (BP) and heart rate (HR) change significantly in response to pelvic floor muscle training during pregnancy. DESIGN: Longitudinal exploratory study with repeated measurements. SAMPLE: Twenty-seven nulliparous healthy women of mean age 23.3 years (range 18-36) and mean body mass index 23.4 (range 23.1-29.5). METHODS: Individual supervised pelvic floor muscle training from gestational week 20 till 36 with assessment of BP and HR at gestational weeks 20, 24, 28, 32 and 36. MAIN OUTCOME MEASURES: Systolic and diastolic BP was measured before and after each training session and HR was monitored during each session. RESULTS: Pelvic floor muscle training did not change BP. 77% (n = 21) of participants exceeded 70% of estimated maximum HR during at least one session. The time for exceeding 70% of estimated maximum HR was between 2.2 and 3.2 % of the total exercise session. Increases in BP and HR from gestational weeks 20 till 36 were within normal limits for pregnant women. CONCLUSIONS: Pelvic floor muscle training in nulliparous sedentary pregnant women does not increase BP. It significantly increases HR during the exercise sessions, but only for a limited period of time and with no negative long-term effect on BP or HR.

The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy.

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.

Assessment of female sexual function in pregnant women with gestational diabetes mellitus.

INTRODUCTION: Female sexual dysfunction is a frequent problem that may be caused by several factors, such as pregnancy and diabetes, and that can affect the woman's quality of life. AIM: The aim of this study was to assess the sexual function of pregnant women with gestational diabetes. METHODS: This is a cross-sectional clinical study involving 88 women, among which 33 were pregnant with gestational diabetes mellitus (GDM) and 55 were with low-risk pregnancy (LRP). MAIN OUTCOME MEASURES: Sexual function was assessed using the Female Sexual Function Index (FSFI), a self-applicable questionnaire validated in Portuguese. All the pregnant women answered the questionnaire between the 20th and 25th week of gestation. Data were submitted to descriptive analysis by using the SAS version 9.2 procedure PROC MEANS (SAS Institute Inc., Cary, NC, USA), whereas Student's t-test was applied by using the procedure PROC TTEST (SAS Institute Inc.) at a significance level of ≤5% for all analyses. RESULTS: The percentage of women presenting sexual dysfunction in each group was the following: 66.7% in Group GDM and 38.9% in the Group LRP, with significant difference between the groups (P = 0.03). However, no significant differences were found between the groups regarding sexual desire, excitement, lubrication, and pain. On the total score of FSFI, Group GDM had a score ≤26.55 (P = 0.03). CONCLUSION: Diabetic pregnant women were found to have a higher incidence of sexual dysfunction as their scores were lower for all FSFI domains compared with LRP females.

Prediction of Perinatal and Neurodevelopmental Outcomes in Newborns with a Birth Weight below the 3rd Percentile: Performance of Two International Curves - Prospective Cohort from a Brazilian City.

OBJECTIVES: To evaluate the performance of Intergrowth-21 st (INT) and Fetal Medicine Foundation (FMF) curves in predicting perinatal and neurodevelopmental outcomes in newborns weighing below the 3rd percentile. METHODS: Pregnant women with a single fetus aged less than 20 weeks from a general population in non-hospital health units were included. Their children were evaluated at birth and in the second or third years of life. Newborns (NB) had their weight percentiles calculated for both curves. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and area under the ROC curve (ROC-AUC) for perinatal outcomes and neurodevelopmental delay were calculated using birth weight < 3rd percentile as the cutoff. RESULTS: A total of 967 children were evaluated. Gestational age at birth was 39.3 (±3.6) weeks and birth weight was 3,215.0 (±588.0) g. INT and FMF classified 19 (2.4%) and 49 (5.7%) newborns below the 3rd percentile, respectively. The prevalence of preterm birth, tracheal intubation >24 hours in the first three months of life, 5th minute Apgar <7, admission to a neonatal care unit (NICU admission), cesarean section rate, and the neurodevelopmental delay was 9.3%, 3.3%, 1.3%, 5.9%, 38.9%, and 7.3% respectively. In general, the 3rd percentile of both curves showed low sensitivity and PPV and high specificity and NPV. The 3rd percentile of FMF showed superior sensitivity for preterm birth, NICU admission, and cesarean section rate. INT was more specific for all outcomes and presented a higher PPV for the neurodevelopmental delay. However, except for a slight difference in the prediction of preterm birth in favor of INT, the ROC curves showed no differences in the prediction of perinatal and neurodevelopmental outcomes. CONCLUSION: Birth weight below the 3rd percentile according to INT or FMF alone was insufficient for a good diagnostic performance of perinatal and neurodevelopmental outcomes. The analyzes performed could not show that one curve is better than the other in our population. INT may have an advantage in resource contingency scenarios as it discriminates fewer NB below the 3rd percentile without increasing adverse outcomes.

OBJETIVOS: Avaliar o desempenho das curvas de Intergrowth-21 st (INT) e Fetal Medicine Foundation (FMF) na predição de resultados perinatais e de neurodesenvolvimento de recém-nascidos com peso abaixo do percentil 3. MéTODOS: Foram incluídas gestantes de feto único com idade inferior a 20 semanas de uma população geral em unidades de saúde não hospitalares. Seus filhos foram avaliados ao nascimento e no segundo ou terceiro anos de vida. Os recém-nascidos tiveram seus percentis de peso calculados para ambas as curvas. Sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN) e área sob a curva ROC (ROC-AUC) foram calculados para desfechos perinatais e atraso de neurodesenvolvimento considerando o peso ao nascimento menor que o percentil 3 como ponto de corte. RESULTADOS: Um total de 967 crianças foram avaliadas ao nascimento e no segundo ou terceiro anos de vida. A idade gestacional ao nascer foi de 39,3 (±3,6) semanas e o peso ao nascimento foi de 3.215,0 (±588,0) g. INT e FMF classificaram 19 (2,4%) e 49 (5,7%) recém-nascidos abaixo do percentil 3, respectivamente. A prevalência de parto pré-termo, intubação traqueal > 24 horas nos primeiros três meses de vida, Apgar de 5° minuto < 7, internação em unidade de terapia intensiva neonatal (internação em UTIN), taxa de cesariana e atraso de neurodesenvolvimento foi 9,3%, 3,3%, 1,3%, 5,9%, 38,9% e 7,3% respectivamente. Em geral, o percentil 3 de ambas as curvas apresentou baixa sensibilidade e VPP e alta especificidade e VPN. O percentil 3 de FMF mostrou sensibilidade superior para parto prematuro, internação em UTIN e taxa de cesariana. INT foi mais específico para todos os desfechos e apresentou maior VPP para o atraso do neurodesenvolvimento. Entretanto, exceto por uma pequena diferença na predição de parto pré-termo em favor de INT, as curvas ROC não mostraram diferenças na predição de resultados perinatais e de desenvolvimento neurológico. CONCLUSãO: O peso ao nascer abaixo do percentil 3 segundo INT ou FMF isoladamente foi insuficiente para um bom desempenho diagnóstico de desfechos perinatais e de neurodesenvolvimento. As análises realizadas não puderam mostrar que uma curva é melhor que a outra em nossa população. INT pode ter vantagem em cenários de contingência de recursos, pois discrimina menos recém-nascidos abaixo do percentil 3 sem aumentar os desfechos adversos.

Maternal, obstetric, and fetal Doppler characteristics in a high-risk population: prediction of adverse perinatal outcomes and of cesarean section due to intrapartum fetal compromise.

Objective: To evaluate the capacity of fetal Doppler, maternal, and obstetric characteristics for the prediction of cesarean section due to intrapartum fetal compromise (IFC), a 5-min Apgar score < 7, and an adverse perinatal outcome (APO), in a high-risk population. Materials and Methods: This was a prospective cohort study involving 613 singleton pregnant women, admitted for labor induction or at the beginning of spontaneous labor, who underwent Doppler ultrasound within the last 72 h before delivery. The outcome measures were cesarean section due to IFC, a 5-min Apgar score < 7, and any APO. Results: We found that maternal characteristics were neither associated with nor predictors of an APO. Abnormal umbilical artery (UA) resistance index (RI) and the need for intrauterine resuscitation were found to be significant risk factors for cesarean section due to IFC (p = 0.03 and p < 0.0001, respectively). A UA RI > the 95th percentile and a cerebroplacental ratio (CPR) < 0.98 were also found to be predictors of cesarean section due to IFC. Gestational age and a UA RI > 0.84 were found to be predictors of a 5-min Apgar score < 7 for newborns at < 29 and ≥ 29 weeks, respectively. The UA RI and CPR presented moderate accuracy in predicting an APO, with areas under the ROC curve of 0.76 and 0.72, respectively. Conclusion: A high UA RI appears to be a significant predictor of an APO. The CPR seems to be predictive of cesarean section due to IFC and of an APO in late preterm and term newborns.

Objetivo: Avaliar a capacidade do Doppler fetal e características materno-obstétricas na predição de cesariana por comprometimento fetal intraparto (CFI), índice de Apgar de 5º min < 7 e desfecho perinatal adverso (DPA) em uma população de alto risco. Materiais e Métodos: Estudo de coorte prospectivo envolvendo 613 parturientes admitidas para indução ou em início de trabalho de parto espontâneo que realizaram ultrassonografia Doppler nas 72 horas anteriores ao parto. Os desfechos foram cesariana por CFI, índice de Apgar de 5º min < 7 e DPA. Resultados: As características maternas não foram associadas nem preditoras de DPA. Índice de resistência (IR) da artéria umbilical (AU) anormal (p = 0,03) e necessidade de medidas de ressuscitação intrauterina (p < 0,0001) permaneceram como fatores de risco significativos para cesariana por CFI. IR AU > 95º e razão cerebroplacentária (RCP) < 0,98 foram preditores de cesariana. Idade gestacional e IR AU > 0,84 foram os preditores de índice de Apgar de 5º min < 7 para recém-nascidos < 29 e ≥ 29 semanas, respectivamente. IR AU e RCP apresentaram acurácia moderada na predição de DPA (área sob a curva ROC de 0,76 e 0,72, respectivamente). Conclusão: IR UA mostrou-se preditor significativo de DPA. RCP revelou-se possível preditora de cesariana por CFI e DPA em recémnascidos prematuros tardios e a termo.

Sociodemographic and economic characteristics of families and health and education conditions of children in the BRISA cohort during the COVID-19 pandemic.

OBJECTIVE: To describe changes in sociodemographic, economic and variables related to the characterization of family, health and education during the COVID-19 pandemic in a birth cohort evaluated at 10-11 years of age. METHODS: Cross-sectional study involving 1,033 children from a cohort of children born in 2010/2011, in the city of Ribeirão Preto, SP, Brazil. Data were collected from July to October 2021 by telephone or video interview held with the person responsible for the child. The questionnaires discussed family organization, child behavior and health, school attendance, socioeconomic assessment and occurrence of COVID-19 during the period of social isolation due to the pandemic. Descriptive statistics were used to describe the data. The chi-square test was used to verify group differences by minimum wages (MW). RESULTS: Of the respondents, 47.6% reported worsening of their financial situation during the pandemic, which was more frequent in the group with a household income <3 MW compared to the group with >6 MW (59.1 vs. 15.7%; p<0.001). According to the respondents, 62% of the children exhibited behavioral changes during the period and anxiety was the most frequently reported condition. In addition, 61.4% of the children had learning difficulties and these problems were more prevalent among children from households with lower incomes compared to those with higher incomes (74.7 vs. 45.1%; p<0.001). CONCLUSION: The COVID-19 pandemic has changed different economic aspects of families, as well as educational, health and behavioral indicators of children. Lower-income families were the most affected both economically and in terms of other indicators.

Diagnosis and Management of Preeclampsia: Suggested Guidance on the Use of Biomarkers.

OBJECTIVE: It is a challenge to consider preeclampsia (PE) diagnosis and management in low and middle-income settings, where it represents a major public health concern. The placenta is the underlying cause of disease, and the plasma concentrations of proangiogenic and antiangiogenic factors released by the placenta can reflect the risks of disease progression. Antiangiogenic proteins, such as soluble fms-like tyrosine kinase 1 (sFlt-1), and proangiogenic, like placental growth factors (PlGF), are directly and inversely correlated with the disease onset, respectively. METHODS: Narrative review on the use of biomarkers (sFlt-1 to PlGF ratio) with a suggested guidance protocol. RESULTS: Key considerations on the use of biomarkers: the sFlt-1/PlGF ratio is mainly relevant to rule out PE between 20 and 36 6/7 weeks in cases of suspected PE; however, it should not replace the routine exams for the diagnosis of PE. The sFlt-1/PlGF ratio should not be performed after confirmed PE diagnosis (only in research settings). In women with suspected PE, sFlt-1/PlGF ratio < 38 can rule out the diagnosis of PE for 1 week (VPN = 99.3) and up to 4 weeks (VPN= 94.3); sFlt-1/PlGF ratio > 38 does not confirm the diagnosis of PE; however, it can assist clinical management. In cases of severe hypertension and/or symptoms (imminent eclampsia), hospitalization is imperative, regardless of the result of the sFlt-1/PlGF ratio. CONCLUSION: The use of biomarkers can help support clinical decisions on the management of suspected PE cases, especially to rule out PE diagnosis, thus avoiding unnecessary interventions, especially hospitalizations and elective prematurity.

OBJETIVO: É um desafio considerar o diagnóstico e o tratamento da pré-eclâmpsia (PE) em locais de baixa e média renda, onde a doença representa um grande problema de saúde pública. A placenta é a causa subjacente da doença, e as concentrações plasmáticas de fatores pró-angiogênicos e antiangiogênicos liberados pela placenta podem refletir os riscos de progressão da doença. Proteínas antiangiogênicas, como a tirosina quinase fms solúvel tipo 1 (sFlt-1), e pró-angiogênicas, como o fator de crescimento placentário (PlGF), estão direta e inversamente correlacionados com o início da doença, respectivamente. MéTODOS: Revisão narrativa sobre o uso de biomarcadores (razão sFlt-1/PlGF) com sugestão de protocolo de orientação para uso clínico. RESULTADOS: Principais considerações sobre o uso de biomarcadores: a razão sFlt-1/PlGF é principalmente relevante para descartar PE entre 20 e 36 6/7 semanas em casos de suspeita de PE; entretanto, não deve substituir os exames de rotina para o diagnóstico de PE. A relação sFlt-1/PlGF não deve ser realizada após a confirmação do diagnóstico de PE (apenas em ambientes de pesquisa). Em mulheres com suspeita de PE, a razão sFlt-1/PlGF < 38 pode descartar o diagnóstico de PE por 1 semana (VPN = 99,3) e até 4 semanas (VPN = 94,3); A relação sFlt-1/PlGF > 38 pode auxiliar no manejo clínico. Em casos de hipertensão grave e/ou sintomas (eclâmpsia iminente), a hospitalização é imprescindível, independentemente do resultado da relação sFlt-1/PlGF. CONCLUSãO: O uso de biomarcadores pode auxiliar na tomada de decisões clínicas no manejo de casos suspeitos de PE, principalmente para afastar o diagnóstico da doença, evitando intervenções desnecessárias, tais como internações e prematuridade iatrogênica.

Abuse, disrespect and mistreatment during childbirth care: contribution of the Ribeirão Preto cohorts, Brazil.

This study aimed to estimate the perception and frequency of abuse, disrespect and mistreatment (ADM) situations during childbirth care of 745 women from the Ribeirão Preto birt cohorts. Confidential questionnaires containing one question regarding perceived abuse during childbirth care and other questions addressing exposure to ADM situations were applied. The chi-squared test was used to compare the situations presented between women who did and did not report mistreatment using the Stata 14.0 software. Among the 745 women evaluated, 66.2% were exposed to some situation of ADM and 8.3% reported having perceived ADM. The most frequent situations were that the woman could not eat or drink (30.5%), the woman had her belly squeezed to help the child be born (27.5%), and the woman could not stay with a companion of her choice (25.5%). Women who reported to have suffered maltreatment more frequently responded positively to all situations of ADM when compared to the other participants, except for the following statements: "I was not allowed to eat or drink anything" (p = 0.975) and "I was forced to have a cesarean delivery against my will" (p = 0.073). Although most women of the Ribeirão Preto cohorts reported exposure to ADM situations during childbirth care, a minority perceived disrespect or mistreatment.

Factors associated with neonatal-near miss: birth cohorts in three Brazilian cities - Ribeirão Preto, Pelotas and São Luís, Brazil.

The aim of this study was to investigate the association of sociodemographic factors, lifestyle, maternal reproductive profile and prenatal and childbirth care with neonatal near miss (NNM) morbidity in four birth cohorts. This study involved four population-based birth cohorts: Ribeirão Preto (RP) and São Luís (SL) (2010), Pelotas 2004 (PEL04) and 2015 (PEL15). NNM was defined when one or more of the following conditions were present: birthweight <1,500 g, 5-minute Apgar score <7, gestational age <32 weeks, and report of congenital malformations. The covariates were obtained with questionnaires applied to the puerperal women. Some particularities between cohorts were identified. In the RP and SL cohorts, factors of the more distal levels (sociodemographic, lifestyle, and reproductive profile) were associated with NNM. On the other hand, proximal factors related to healthcare were more significant for the occurrence of NNM in PEL. Only the absence of prenatal care was associated with NNM in all cohorts: RP (OR=4.27, 95%CI 2.16-8.45), SL (OR=2.32, 95%CI 1.09-4.94), PEL04 (OR=4.79, 95%CI 1.59-14.46), and PEL15 (OR=5.10, 95%CI 2.60-9.97).

Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients.

PURPOSE: This study investigated the influence of gestational diabetes mellitus on the kinetic disposition and stereoselective metabolism of labetalol administered intravenously or orally. METHODS: Thirty hypertensive women during the last trimester of pregnancy were divided into four groups: non-diabetic and diabetic women treated with intravenous or oral labetalol. RESULTS: The pharmacokinetics of labetalol was not stereoselective in diabetic or non-diabetic pregnant women receiving the drug intravenously. However, oral administration of labetalol resulted in lower values of the area under the plasma concentration versus time curve (AUC) for the ß-blocker (RR) than for the other enantiomers in both diabetic and non-diabetic women. Gestational diabetes mellitus caused changes in the kinetic disposition of the labetalol stereoisomers when administered orally. The AUC values for the less potent adrenoceptor antagonist (SS) and for the α-blocking (SR) isomers were higher in diabetic than in non-diabetic pregnant women. CONCLUSIONS: The approximately 100% higher AUC values obtained for the (SR) isomer in diabetic pregnant women treated with oral labetalol may be of clinical relevance in terms of the α-blocking activity of this isomer.

Different profiles of circulating arginase 2 in subtypes of preeclampsia pregnant women.

BACKGROUND AND AIMS: Preeclampsia (PE) is a gestational hypertensive disease responsible for high maternal and fetal morbidity and mortality. The increase in blood pressure is associated with a decrease in the bioavailability of nitric oxide (NO). Arginase interferes with NO production consuming L-arginine, a substrate required by endothelial NO synthase to NO formation. No previous study has quantified the circulating levels of the two arginase isoforms (arginase 1 and arginase 2) in the plasma of pregnant women with PE. Therefore, our objective is to evaluate these plasma levels in healthy pregnant women and PE with or without severe features and who respond or not to antihypertensive therapy. METHODS: We compared 29 healthy pregnant women with 56 pregnant women with PE, who were also divided into with severe features (n = 24) or without severe features (n = 32) and into responsive (n = 29) or nonresponsive to antihypertensive therapy (n = 27). We quantified the plasmatic expression of arginase 1 and arginase 2 by ELISA kits. RESULTS: While similar levels of arginase 1 were found among groups, lower arginase 2 plasma levels were found in PE without severe features and responsive to antihypertensive drugs when compared to healthy pregnant women. There was no difference between arginase 2 levels in PE with severe features and nonresponsive group when compared to healthy pregnant women. CONCLUSION: This shows different circulation profiles of arginase 2 among groups, suggesting the existence of mechanisms of arginase 2 modulation in pregnant women with PE associated with the severity of the disease and responsiveness to antihypertensive treatment.

Pre-eclampsia: Universal Screening or Universal Prevention for Low and Middle-Income Settings?

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.

A Pré-eclâmpsia (PE) é uma doença grave que acomete ∼ 8% das gestações e representa importante causa de morbimortalidade, tanto materna quanto perinatal. O rastreamento da doença é motivo de estudos, porém a complexidade e as incertezas quanto a sua etiologia tornam esse objetivo bastante difícil. Além disso, os custos relacionados com o rastreamento, a heterogeneidade das populações mais afetadas e ainda a falta de métodos de prevenção de grande eficácia reduzem o potencial dos algoritmos de rastreamento. Assim, a Comissão Nacional Especializada sobre Hipertensão na Gravidez da Federação Brasileira das Associações de Ginecologia e Obstetrícia (CNE Hipertensão na Gravidez da FEBRASGO) considera que não há algoritmos de rastreamento que possam ser aplicados no país nesse momento e defende a utilização dos métodos de prevenção como ácido acetilsalicílico e cálcio de maneira ampla.

Prevalence of virological and serological markers of SARS-CoV-2 infection in the population of Ribeirão Preto, Southeast Brazil: an epidemiological survey.

INTRODUCTION: This epidemiological household survey aimed to estimate the prevalence of the current and past SARS-CoV-2 infections in Ribeirão Preto, a municipality of southeast Brazil. METHODS: The survey was conducted in two phases using a clustered sampling scheme. The first phase spanned May 1-3 and involved 709 participants. The second phase spanned June 11-14, 2020, and involved 646 participants. RESULTS: During the first phase, RT-PCR performed on nasopharyngeal swabs was positive at 0.14%. The serological tests were positive in 1.27% of the patients during the first phase and 2.79% during the second phase. People living in households with more than five members had a prevalence of 10.83% (95%CI: 1.58-74.27) higher than those living alone or with someone other. Considering the proportion of the positive serological test results with sex and age adjustments, approximately 2.37% (95%CI: 1.32-3.42) of the population had been cumulatively infected by mid-June 2020, which is equivalent to 16,670 people (95%CI: 9,267-24,074). Considering that 68 deaths from the disease in the residents of the city had been confirmed as at the date of the second phase of the survey, the infection fatality rate was estimated to be 0.41% (95%CI: 0.28-0.73). Our results suggest that approximately 88% of the cases of SARS-CoV-2 infection at the time of the survey were not reported to the local epidemiological surveillance service. CONCLUSIONS: The findings of this study provide in-depth knowledge of the COVID-19 pandemic in Brazil and are helpful for the preventive and decision-making policies of public managers.

Wernicke Encephalopathy as a Complication of Hyperemesis Gravidarum: Case Report.

Wernicke encephalopathy (WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism. We report a rare case of WE due to hyperemesis gravidarum in a 25-year-old pregnant patient at 13 weeks and 5 days of gestation. Initially, the disease manifested as weakness, mental confusion, anterograde amnesia, and visual and auditory hallucinations. The diagnosis was established after the detection of suggestive findings of WE in the thalamus by magnetic resonance imaging (MRI) and a rapid improvement in the patient's clinical status subsequent to treatment with thiamine. Hyperemesis is a rare cause of WE, which makes the reported case important in the literature and reinforces the need for attention in clinical practice to rare but important complications of this common condition (hyperemesis gravidarum).

A encefalopatia de Wernicke (EW) é uma condição neurológica aguda resultada da deficiência de vitamina B1, muito comum em etilistas crônicos. Relatamos um caso de EW secundário a um quadro de hiperêmese gravídica em uma gestante de 25 anos de idade e 13 semanas e 5 dias de idade gestacional. Inicialmente essa desordem se manifestou como fraqueza, confusão mental, amnésia anterógrada, e alucinações auditivas e visuais. O diagnóstico foi estabelecido depois da detecção de achados sugestivos de EW na ressonância nuclear magnética e da melhora do quadro clínico com reposição de tiamina. A hiperêmese gravídica não é uma causa comum de EW, o que faz com que o presente relato de caso tenha importância na literatura e reforça a necessidade de atenção na prática clínica para complicações raras mas importantes desse quadro tão comum (hiperêmese gravídica).

Inversion of traditional gender roles and intimate partner violence against pregnant women.

This study analyzed the association between the inversion of traditional gender roles and exclusive psychological and physical/sexual intimate partner violence, in a cross-sectional study of Brazilian pregnant women, identified through prenatal services in the municipalities of São Luís, Maranhão State (n = 992) and Ribeirão Preto, São Paulo State (n = 943). The pregnant women ranged from 12 to 45 years. Inversion of traditional gender roles was assessed by calculating differences in age, education and occupation between pregnant women and their co-residing intimate partners and identifying the largest contribution to family income. The conceptual model was tested with structural equation modeling and showed acceptable fit. The prevalence of any type of intimate partner violence was 29.8% in São Luís and 20.1% in Ribeirão Preto. In both municipalities, pregnant women were more likely to suffer exclusive psychological and physical/sexual violence when they had the highest income in the family (p < 0.005). In São Luís, physical/sexual violence was more common among women who were better educated than their partners (standardized coefficient, SC = -0.466; p = 0.007). In Ribeirão Preto, exclusive psychological violence was more frequent among women who had lower status occupations than their partners (SC = 0.236; p = 0.004). Inversion of traditional gender roles is associated with exclusive psychological and physical/sexual violence against pregnant women by their co-residing intimate partners. These findings suggest that women's empowerment at an individual level does not necessarily relieve them of intimate partner abuse in social contexts where traditional gender norms persist.

Stereoselective analysis of labetalol in human plasma by LC-MS/MS: application to pharmacokinetics.

Labetalol is clinically available as a mixture of two racemates (four stereoisomers). The stereoisomer (R,R) has as main activity the beta1-antagonism and the stereoisomer (S,R) is highly selective for the alpha1 adrenoceptor and is responsible for most of the alpha-blocker activity. In the present investigation, a method for the analysis of labetalol stereoisomers in human plasma was developed and applied to pharmacokinetic studies. Plasma samples (0.5 ml) were extracted with methyl tert-butyl ether at pH 9.5. The four labetalol stereoisomers were analyzed by LC-MS/MS on a Chirobiotic V column using a mobile phase consisting of methanol, acetic acid, and diethylamine, with a recovery of more than 90% for all four. The quantitation limit was 0.5 ng/ml and linearity was observed at 250 ng/ml plasma for each stereoisomer. Studies of precision and accuracy presented coefficients of variation and percentage inaccuracy of less than 15%, indicating that the method is precise and accurate. The method was applied to the study of the kinetic disposition of labetalol over a period of 12 h after oral administration of a single 100 mg dose to a hypertensive pregnant woman. The clinical study revealed stereoselectivity in the pharmacokinetics of labetalol, with a lower plasma proportion for the active stereoisomers (R,R)-labetalol and (S,R)-labetalol. The stereoselectivity observed after oral administration is due to the hepatic metabolism and the first pass effect, with an AUC(R,R)/AUC(S,S) ratio of 0.5.

Withdrawal of plasma estradiol is associated with increased anxiety reported by women in the first 12 hours after delivery.

The aim of this study was to verify if the fall of plasma concentrations of steroid hormones in the first 12 h postpartum would be associated with changes in the same period in the emotional state of healthy women. Subjective and hormonal data were collected from 14 women (28.5 ± 7.1 years old) at zero (only hormones), 1, 2, 6 and 12 h after delivery. Subjective measures were taken using the Visual Analogue Mood Scale (VAMS), which consists of four factors (anxiety, sedation, discomfort, and cognitive impairment). Cortisol was measured by radioimmunoassay and estradiol and progesterone by chemiluminescence immunoassay. Women reported a significant increase in anxiety (relative increase: 43.8%±77.6) and discomfort (125.9%±218.5) within the 12 h postpartum. There were also significant decreases in the plasma concentration of estradiol (relative decrease: 96.5%±3.1), progesterone (78.1%±8.7) and cortisol (71.7%±18.0). The relative decrease in estradiol concentrations was significantly correlated with the relative increase in anxiety. No significant associations between progesterone and cortisol concentrations and subjective measures were observed. Changes of estradiol but not of progesterone and cortisol concentrations were associated with changes in the reported emotional state of healthy women in the immediate postpartum period. The role of this association as a predictor of mood disorders in the postpartum period should be explored in further studies.