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Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

To validate the use of fullPIERS to predict maternal and perinatal adverse outcomes in a referral center.Cross-sectional study including all pregnant women with preeclampsia (PE) at a referral center in southeast Brazil. The prevalence of PE and adverse outcomes were assessed. The fullPIERS score was tested on three composites of adverse outcomes: maternal adverse outcome; fetal adverse outcomes; and the combination of these two. Furthermore, the fullPIERS risk calculator, was considered to define the cutoff that better estimates adverse outcomes.2839 women were screened in a one year period, with 208 (7.3%) cases of PE; most were preterm (56.7%); with severe features (74.5%). HELLP syndrome (6.7%), eclampsia (3.8%) and placental abruption (2.4%) were the most frequent complications. FullPIERS assessement had a median of 1.2% (0.45 - 2.3%) and the score had an excelent performance to predict adverse maternal outcome (AUC = 0.845, confidence interval 0.776 - 0.914, p-value 0.01). For perinatal adverse outcomes (AUC = 0.699, confidence interval 0.581 - 0.816, p-value 0.01) and the composite of maternal and perinatal adverse outcome (AUC = 0.804, confidence interval 0.736 - 0.872, p-vale 0.01), fullPIERS score had a suboptimal performance. The cutoff value that best performed for the assessment of maternal adverse outcome was 2.15% (sensitivity of 75% and specificity of 83%).Preeclampsia was a significant complication during pregnancy. The fullPIERS model was an excellent tool to predict maternal adverse outcomes; with a cutoff value of 2.15% in the tested population.

Congenital infections are an important cause of morbidity and mortality worldwide, especially in low-income settings. This review discusses the main pathways of infections and associated adverse maternal and fetal outcomes, considering the TORCH pathogens, including Zika virus; the acronym stands for Toxoplasma gondii infection, other (Listeria monocytogenes, Treponema pallidum, and parvovirus B19, among others, including Zika virus), rubella virus, cytomegalovirus, and herpes simplex viruses type 1 and type 2.

Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other neonatal alterations. This review will discuss lessons learned from viral pathogenesis, epidemiology and clinical findings observed during the ZIKV outbreak occurred between 2014 and 2016 in Brazil.

BACKGROUND Increased incidence of cancer in women of childbearing age and improvements on treatment for preserving fertility have led to higher frequency of pregnancy during or after cancer treatment. OBJECTIVE This study aimed to describe maternal and perinatal outcomes associated with cancer and pregnancy and, as a secondary analysis, to compare outcomes of women with active disease and with remission before pregnancy. STUDY DESIGN We performed a retrospective study of women followed up at a referral center owing to a history of cancer or cancer diagnosed during pregnancy. Data on sociodemographic information, obstetrical history, types of neoplasia, treatments offered, antenatal follow-up, and maternal and perinatal outcomes were retrieved from medical chart review. A descriptive analysis was performed and a comparison among women with active and nonactive disease was performed using Student t-test and chi-square test. RESULTS A total of 66 women were included in a 5-year period. The most frequent types of cancer were breast (33%), hematologic (21%), brain (11%), cervical (9%), and ovarian (5%) cancers. There were 39 participants (59%) who had active disease and 26 who received oncological treatment during pregnancy, and 23 (34.8%) had a vaginal delivery. There were 4 women who needed intensive care unit admission postpartum. A total of 18 (29.5%) deliveries were at term, most newborns (59%) with adequate weight for gestational age and only 1 had Apgar score lower than 7 in the fifth minute of life. There was 1 stillbirth. The active invasive cancer during pregnancy group showed a higher rate of preterm birth and lower birthweight with significant statistical difference (P=.03 and P

Preeclampsia is one of the most challenging diseases of pregnancy, with unclear etiology, no specific marker for prediction, and no precise treatment besides delivery of the placenta. Many risk factors have been identified, and diagnostic and management tools have improved in recent years. However, this disease remains one of the leading causes of maternal morbidity and mortality worldwide, especially in under-resourced settings. A history of previous preeclampsia is a known risk factor for a new event in a future pregnancy, with recurrence rates varying from less than 10% to 65%, depending on the population or methodology considered. A recent review that performed an individual participant data meta-analysis on the recurrence of hypertensive disorders of pregnancy in over 99 000 women showed an overall recurrence rate of 20.7%; when specifically considering preeclampsia, it was 13.8%, with milder disease upon recurrence. Prevention of recurrent preeclampsia has been attempted by changes in lifestyle, dietary supplementation, antihypertensive drugs, antithrombotic agents, and others, with much uncertainty about benefit. It is always challenging to treat and counsel a woman with a previous history of preeclampsia; this review will be based on hypothetical clinical cases, using common scenarios in obstetrical practice to consider the available evidence on how to counsel each woman during pre-conception and prenatal consultations.La prééclampsie constitue l’une des complications de la grossesse les plus difficiles à prendre en charge, compte tenu de son étiologie floue, de l’absence de marqueur spécifique permettant d’en prédire la manifestation et de l’absence de traitement précis (outre la délivrance du placenta). De nombreux facteurs de risque ont été identifiés et les outils de diagnostic et de prise en charge ont connu une amélioration au cours des dernières années. Quoi qu’il en soit, cette complication demeure l’une des principales causes de morbidité et de mortalité maternelles à l’échelle mondiale, particulièrement au sein des milieux ne disposant que de faibles ressources. La présence d’antécédents de prééclampsie constitue un facteur de risque connu pour ce qui est de la survenue d’un nouvel événement dans le cadre d’une future grossesse, les taux de récurrence variant de moins de 10 % à 65 % (selon la population ou la méthodologie envisagée). Une récente méta-analyse de données individuelles portant sur la récurrence des troubles hypertensifs de la grossesse chez plus de 99 000 femmes a indiqué un taux global de récurrence de 20,7 %; lorsque l’on s’attardait plus particulièrement à la prééclampsie, ce taux passait à 13,8 %, une complication de moindre gravité étant constatée au moment de la récurrence. Des tentatives de prévenir la récurrence de la prééclampsie ont fait appel à des modifications du mode de vie, à une supplémentation alimentaire et à l’utilisation d’antihypertenseurs, d’antithrombotiques et d’autres agents, le tout étant marqué par une grande incertitude quant à l’efficacité de telles mesures. Il est toujours difficile de traiter et de conseiller une femme présentant des antécédents de prééclampsie; cette analyse se fonde sur des cas cliniques hypothétiques, en utilisant des scénarios courants de la pratique obstétricale pour soupeser les données disponibles quant à la façon de conseiller les patientes dans le cadre des consultations préconceptionnelles et prénatales.

Poor differentiation of trophoblasts is associated with placental dysfunction, predisposing women to multiple pregnancy disorders. Punicalagin, a prominent ellagitannin in pomegranate juice has been shown to exert anti-apoptosis and anti-oxidative effects in human trophoblasts. We hypothesized that punicalagin modulates trophoblast differentiation. We found that punicalagin-treated primary trophoblast showed reduced E-cadherin, higher Syncytin 1, more β-hCG, and increased GCM1, an upstream regulator of β-hCG. Punicalagin exposure of villous explants enhanced the number of cytotrophoblasts expressing the proliferation marker Ki67. We conclude that punicalagin enhances trophoblast differentiation and speculate that punicalagin might be used therapeutically in pregnancies at risk for placental dysfunction.

Background Eclampsia is the main cause of maternal death in Brazil. Magnesium sulfate is the drug of choice for seizure prevention and control in the management of severe preeclampsia and eclampsia. Despite scientific evidence demonstrating its effectiveness and safety, there have been delays in managing hypertensive syndrome, including timely access to magnesium sulfate. Objective To identify the potential causes of improper magnesium sulfate use. Method A situational analysis was conducted with a survey on information available at the official websites on the policy, regulation and availability of the medication, field analysis and interviews with local managers of public obstetric health services in Campinas, a city in the southeast of Brazil. We used the fishbone cause and effect diagram to organize study components. Interviews with managers were held during field observations. Results There was no access to magnesium sulfate in primary care facilities, urgent obstetric care was excluded from urgency care services and clinical protocols for professional guidance on the proper use of magnesium sulfate were lacking in the emergency mobile care service. Magnesium sulfate is currently only administered in referral maternity hospitals (Table). Conclusion The lack of processes that promote the integration between urgency/emergency care and specialized obstetric care favors the improper use of magnesium sulfate and contributes to the high maternal morbidity/mortality rates. Download : Download high-res image (873KB) Download : Download full-size image

Introduction Preeclampsia (PE) is one of the leading causes of maternal and neonatal morbidity and mortality worldwide. It is defined as new onset hypertension developing ⩾ 20 weeks and proteinuria or evidence of maternal organ dysfunction. The magnitude of proteinuria was a marker for severity and when higher than 2 g/24 h indicated aggressive treatment. This was recently revised and no longer defines severity, but there are still gaps in understanding how different levels of increased proteinuria impact on maternal and perinatal outcomes and its long term consequences. Objectives To review all cases of PE with proteinuria ⩾ 2 g/24 h followed at the State University of Campinas (UNICAMP) in a 5 year period, and compare maternal and perinatal outcomes according to the magnitude of proteinuria. Methods Retrospective cohort of all pregnant women with proteinuria ⩾ 2 g/24 h followed at UNICAMP from January 2009 to December 2013. Women with previous nephropathy, without diagnosis of PE or delivery elsewhere were excluded from the analysis. Data on demographic characteristics, onset of symptoms, laboratory findings, maternal and fetal/neonatal outcomes were recorded. Data were stored and analyzed using the Epi-Info 7; continuous variables were compared using ANOVA and categorical variables analyzed by x2 or Fisher exact tests. Results 269 women were screened for review, 19 were excluded for delivering elsewhere, 41 were excluded due to previous nephropathy, 8 due to absence of PE and 5 for post-partum PE (with normal proteinuria during gestation). The current analysis included 196 women. The median age was 28 ( ± 7.1), majority white (69%) and nearly half primigravidas. The average overall magnitude of proteinuria was 5.1 g/24 h ( ± 3.7). Cesarean delivery was the most frequent route of delivery (84%) and the mean gestational age at delivery 33 weeks ( ± 3.8). The majority of cases presented severe PE (80%). Less then half of the women attended postpartum care and among those, most remained with abnormal proteinuria in early (80%) and late (76%) puerperium (followed up to 3 months postpartum). We considered 3 groups of cases according to the magnitude of proteinuria: ⩾ 2 and ⩾ 5 and ⩾ 10 g/24 h (n = 18). A summarized comparison among these groups is in Table 1. Conclusions Quantification of proteinuria remains an important tool in the diagnosis of PE but its magnitude alone, should not guide management. Massive proteinuria presented significantly more in primigravida and proteinuria ⩾ 5 g/24 h presented decreased gestational age at resolution. Future studies must address systematic follow-up of these women during pregnancy, latency from diagnosis to resolution, and the women’s perspective upon diagnosis of massive proteinuria. A postpartum follow-up is critical, to assess long term consequences of massive proteinuria during pregnancy.

Introduction Magnesium sulfate is the drug of choice for the prevention and control of seizures in the management of severe preeclampsia/eclampsia. Despite its use in virtually 100% of eclampsia cases in Brazil, maternal mortality due to this disorder still remains elevated. It is assumed that there is a misuse of magnesium sulfate, leading to a delay in the management of severe cases of preeclampsia/eclampsia. Objective To describe the obstetrician’s perception on the major reasons for underutilizing magnesium sulfate in severe preeclampsia/eclampsia. Method A qualitative clinical study, based on phenomenological reference was carried out by semi-structured interviews and open-ended discussions with obstetricians of the public healthcare system in primary care units (PCU) and referral maternity hospitals (RMH), in Brazil. Results Fear instilled by awareness of the risk of drug toxicity was the major cause for not prescribing the medication in PCU. Fear was justified by insufficient technical, structural and organizational resources of healthcare facilities and by a shortage of physicians properly trained for correct drug use. Conclusion Fear of toxicity of magnesium sulfate was the main barrier towards timely and proper drug use. Periodic skill development and training of obstetricians, along with integration of the medical team in the work environment may contribute to decrease fear, broadening safety of drug prescription and thus reduce adverse outcomes related to PE and improving quality of maternal healthcare. Download : Download high-res image (576KB) Download : Download full-size image

Introduction Chronic hypertension (CH) and previous preeclampsia (PE) are considered risk factors for developing PE. Physical activity (PA) has been proposed as an important part of hypertension's treatment and has been studied as a possibility for the prevention of PE and its complications.PA is recommended during pregnancy because it may be beneficial to maternal health.Furthermore, it is considered a safe activity for the mother and fetus. Objectives The objective of this study was to assess the association between exercise in pregnant women with CH and/or previous PE and type of delivery, maternal and neonatal outcomes. Methods Randomized clinical trial performed between January, 2008 and November, 2011, at the Women's Hospital Dr.Jose Aristodemo Pinotti–CAISM/Unicamp, Brazil, enrolled 116 pregnant women presenting CH, previous PE or both factors associated.Women from 12 to 20 gestational weeks were selected from the prenatal outpatient clinic and randomly allocated to the study (SG) or non-interventional group (NIG). Women at the SG performed physical exercise using stationary bicycle (horizontal bench model) during 30min, once a week, under physical therapist supervision.The HR was maintained at 20% above resting heart rate and up to 140 beats per minute.The NIG followed regular prenatal routine.After birth the data related to type of delivery, maternal and neonatal outcomes were collected from medical records and analyzed comparing groups.The statistical analyzes was performed by Chi-square test and Fisher'sexact test.The program was SAS 9.1 version.Significance was assumed as p Results We had 6 drop-outs and 7 that did not deliver at our hospital and we could not retrieve the data.A total of 103 pregnant women were analyzed (53 in the SG and 50 in the NIG). The mean age was 31.4±5.9 and mean of Body Mass Index (BMI) was 34.9±7.9kg/m 2 .Considering the sociodemographic and clinical characteristics the SG and NIG were similar and homogeneous.The average exercise sessions conducted by the SG was 10.11 sessions.The cesarean rate was 69.9% in this study, and the most prevalent indication was cephalopelvic disproportion with 34.3%.However, no statistical differences was observed between groups on type of delivery ( p = 0.1901), indications for cesarean delivery and maternal outcomes, including maternal morbidity, rate of PE events and admission in the Intensive Unit Care (ICU). The neonatal outcomes were no significant differences:newborn weigh ( p =0.69), adequacy for gestational age ( p =0.40), gestational age by recent ultrasound ( p =0.20), Apgar 1 min scores ( p =0.12), Apgar 5 min score ( p =0.24), admission to the ICU ( p =0.95) and neonatal morbidity ( p =0.39). Conclusion Exercise using stationary bicycle in pregnant women of high risk for PE (CH and/or previous PE) performed once a week, under physical therapist supervision does not seem to interfere in the type of delivery or maternal and neonatal outcomes. This study suggests that exercise with controlled intensity is safe, with no additional harm towards newborn health and with possible benefits to women's future health.

Objectives Hypertensive disorders represent the major cause of maternal morbidity in middle income countries. Chronic hypertension occurs in up to 5% of pregnant women with special challenges to health care providers. Complications depend on the hypertension etiology, duration and severity. Chronic hypertension is a known risk factor for superimposed preeclampsia, with worse maternal-fetal outcomes. Objective: to describe maternal and perinatal outcomes of pregnancies complicated by chronic hypertension followed at the State University of Campina’s high risk outpatient clinic during an 18 months period. Methods Retrospective study with chart review of pregnancies complicated by chronic hypertension at the State University of Campinas (from January/2012 to June/2013). Results 113 women were considered, with mean age of 33 years, mostly white (56%), with partner (82%), multiparous (76%), education over elementary (62%). Mean duration of hypertension was 7 years and most women used anti-hypertensive drugs prior to pregnancy (65%) and were obese (53%). The majority used low dose aspirin and calcium during prenatal care (95%). Over 90% used anti-hypertensive drugs during pregnancy. Mean number of prenatal care visits was 9, with mean referral to high-risk clinic around 16 weeks. The majority of women were evaluated by a cardiologist (83%) with only 3.5% cardiac disease diagnosed. Superimposed preeclampsia occurred in 21% of all cases, with 13% of Intensive Care Unit admissions. Fetal assessment by Doppler velocimetry was systematically performed after 28 weeks of gestation, and only 9 pregnancies (8%) presented fetal distress. Mean gestational age at resolution was 37 weeks and mean fetal weight at birth 2960 g. C-section was performed in 68% of all cases and 58 women underwent postpartum tubal sterilization. Conclusions Pregnancies complicated by chronic hypertension should be referred to high-risk prenatal care assistance. There is increased risk of superimposed preeclampsia and clinical and fetal surveillance are essential to guarantee adequate outcomes. Disclosures M.T. Moreno: None. A.C. Cortez: None. F. Cavichiolli: None. M.A. Parpinelli: None. F.G. Surita: None. M. Costa: None.