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Background: Sickle cell disease (SCD) comprises a heterogeneous group of inherited hemolytic disorders that increases the risk of maternal and perinatal complications due to chronic systemic inflammatory response, endothelial damage and vaso-occlusion. The contribution of genotypes to the severity of outcomes during pregnancy is not completely established. Methods: A retrospective study of medical charts was performed to compare maternal and perinatal outcomes in Hb SS, Hb SC disease and sickle-beta thalassemia (Hb Sβ) pregnancies followed at a high-risk antenatal care unit over a 6-year period. A descriptive analysis of morphological findings was performed of the placenta when pathology reports were available. Results: Sixty-two SCD pregnant women [25 Hb SS (40 %), 29 Hb SC (47 %) and 8 Hb Sβ (13 %)] were included. Overall, SCD was associated with maternal complications (77 %), preterm birth (30 %), cesarean section (80 %) and a need of blood transfusion. In general there were no statistically significant differences between genotypes. The only significant difference was the hemoglobin level at first antenatal care visit which was lower for the homozygous genotype (7.7 g/dL) compared to Hb SC and Hb Sβ (9.7 g/dL and 8.4 g/dL, respectively; p-value = 0.01). Ten of 15 evaluated placentas showed abnormal morphological findings Conclusion: SCD, regardless of the underlying genotype, is associated with increased adverse maternal and perinatal outcomes and placental abnormalities associated with maternal vascular malperfusion.

Maternal immunization is a critical strategy to prevent both maternal and infant morbidity and mortality from several infectious diseases. When the first COVID-19 vaccines became available during the pandemic, there was mixed messaging and confusion amongst the broader public and among those associated with health care systems about the recommendations for COVID-19 vaccinations in pregnancy in many countries. A multi-country, mixed-methods study is being undertaken to describe how vaccine decision-making occurs amongst pregnant and postpartum women, with a focus on COVID-19 vaccines. The study is being conducted in Brazil, Ghana, Kenya, and Pakistan. In each country, participants are being recruited from either 2 or 3 maternity hospitals and/or clinics that represent a diverse population in terms of socio-economic and urban/rural status. Data collection includes cross-sectional surveys in pregnant women and semi-structured in-depth interviews with both pregnant and postpartum women. The instruments were designed to identify attitudinal, behavioral, and social correlates of vaccine uptake during and after pregnancy, including the decision-making process related to COVID-19 vaccines, and constructs such as risk perception, self-efficacy, vaccine intentions, and social norms. The aim is to recruit 400 participants for the survey and 50 for the interviews in each country. Qualitative data will be analyzed using a grounded theory approach. Quantitative data will be analyzed using descriptive statistics, latent variable analysis, and prediction modelling. Both the quantitative and qualitative data will be used to explore differences in attitudes and behaviors around maternal immunization across pregnancy trimesters and the postpartum period among and within countries. Each country has planned dissemination activities to share the study findings with relevant stakeholders in the communities from which the data is collected and to conduct country-specific secondary analyses.

Abstract Objective This study aims to create a new screening for preterm birth < 34 weeks after gestation with a cervical length (CL) ≤ 30 mm, based on clinical, demographic, and sonographic characteristics. Methods This is a post hoc analysis of a randomized clinical trial (RCT), which included pregnancies, in middle-gestation, screened with transvaginal ultrasound. After observing inclusion criteria, the patient was invited to compare pessary plus progesterone (PP) versus progesterone only (P) (1:1). The objective was to determine which variables were associated with severe preterm birth using logistic regression (LR). The area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were calculated for both groups after applying LR, with a false positive rate (FPR) set at 10%. Results The RCT included 936 patients, 475 in PP and 461 in P. The LR selected: ethnics white, absence of previous curettage, previous preterm birth, singleton gestation, precocious identification of short cervix, CL < 14.7 mm, CL in curve > 21.0 mm. The AUC (CI95%), sensitivity, specificity, PPV, and PNV, with 10% of FPR, were respectively 0.978 (0.961-0.995), 83.4%, 98.1%, 83.4% and 98.1% for PP < 34 weeks; and 0.765 (0.665-0.864), 38.7%, 92.1%, 26.1% and 95.4%, for P < 28 weeks. Conclusion Logistic regression can be effective to screen preterm birth < 34 weeks in patients in the PP Group and all pregnancies with CL ≤ 30 mm.

Maternal immunization is a critical strategy to prevent both maternal and infant morbidity and mortality from several infectious diseases. When the first COVID-19 vaccines became available during the pandemic, there was mixed messaging and confusion amongst the broader public and among those associated with health care systems about the recommendations for COVID-19 vaccinations in pregnancy in many countries. A multi-country, mixed-methods study is being undertaken to describe how vaccine decision-making occurs amongst pregnant and postpartum women, with a focus on COVID-19 vaccines. The study is being conducted in Brazil, Ghana, Kenya, and Pakistan. In each country, participants are being recruited from either 2 or 3 maternity hospitals and/or clinics that represent a diverse population in terms of socio-economic and urban/rural status. Data collection includes cross-sectional surveys in pregnant women and semi-structured in-depth interviews with both pregnant and postpartum women. The instruments were designed to identify attitudinal, behavioral, and social correlates of vaccine uptake during and after pregnancy, including the decision-making process related to COVID-19 vaccines, and constructs such as risk perception, self-efficacy, vaccine intentions, and social norms. The aim is to recruit 400 participants for the survey and 50 for the interviews in each country. Qualitative data will be analyzed using a grounded theory approach. Quantitative data will be analyzed using descriptive statistics, latent variable analysis, and prediction modelling. Both the quantitative and qualitative data will be used to explore differences in attitudes and behaviors around maternal immunization across pregnancy trimesters and the postpartum period among and within countries. Each country has planned dissemination activities to share the study findings with relevant stakeholders in the communities from which the data is collected and to conduct country-specific secondary analyses.

Abstract In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention – Vigilant Prenatal Care – Timely Delivery (Parturition) – Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

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

Abstract Background Globally, there are 42 million women and girls estimated to be forcibly displaced. Adolescent girls and young women in humanitarian settings have their sexual and reproductive health (SRH) neglected. This systematic review aimed to describe SRH obstacles that adolescent girls and young women (10–24 years old) face in humanitarian settings in line with the Sustainable Development Goals. Methods We conducted a mixed-methods systematic review in six databases, focusing on migrant women ages 10 – 24and their SRH outcomes. The mixed-methods appraisal tool was used to evaluate the quality of the studies. This review follows PRISMA and the Systematic Review Guidelines from the Centre for Reviews and Dissemination recommendations. Results Among the 1290 studies screened by abstracts, 32 met the eligibility criteria: 15 were qualitative, 10 were quantitative and seven were mixed-methods studies. Most studies were performed in the last four years, in African countries. They discussed the increased frequency of adolescent pregnancies (16–23%), lack of contraceptive use and access (8–32%), poor menstrual hygiene management (lack of water, shortage of menstrual hygiene supplies), ignorance and stigma about sexually transmitted infections and HIV, a higher number of child, early and forced marriage or partnership and sexual and gender-based violence, challenging to obtain SRH information/knowledge/access, and unmet SRH needs. Conclusion Migration is a current issue. Although there is a growing number of studies on adolescent girls and young women’s SRH in humanitarian settings, this population remains overlooked, and face several challenges in SRH. There is a need for targeting interventions on SRH.

Abstract Objective To compare cesarean section (CS) rates according to the Robson Ten Group Classification System (RTGCS) and its indications in pregnant women admitted for childbirth during the first wave of the coronavirus disease 2019 (COVID-19) pandemic with those of the previous year. Materials and Methods We conducted a cross-sectional study to compare women admitted for childbirth from April to October 2019 (before the pandemic) and from March to September 2020 (during the pandemic). The CSs and their indications were classified on admission according to the RTGCS, and we also collected data on the route of delivery (vaginal or CS). Both periods were compared using the Chi-squared (χ2) test or the Fisher exact test. Results In total, 2,493 women were included, 1,291 in the prepandemic and 1,202 in the pandemic period. There was a a significant increase in the CS rate (from 39.66% to 44.01%; p = 0.028), mostly due to maternal request (from 9.58% to 25.38%; p < 0.01). Overall, groups 5 and 2 contributed the most to the CS rates. The rates decreased among group 1 and increased among group 2 during the pandemic, with no changes in group 10. Conclusion There was an apparent change in the RTGSC comparing both periods, with a significant increase in CS rates, mainly by maternal request, most likely because of changes during the pandemic and uncertainties and fear concerning COVID-19.

Abstract The SARS-CoV-2 (COVID-19) pandemic impacted the health systems between and within countries, and in the course of the pandemic sexual and reproductive health services were the most disrupted. Findings from high-income settings have reported significant changes in preterm birth prevalence during the pandemic period. To understand the possible effects of the COVID-19 pandemic on preterm birth numbers at the Brazilian national level. We compare the number of preterm deliveries during the COVID-19 pandemic period (2020 and 2021) with previous years. We conducted a population-based cross-sectional study taking the period from January 2017 to December 2021 to account. We use individual-level live births data from the Brazilian Live Birth Information System (SINASC), and we estimate the odds ratio (OR) of preterm deliveries using propensity score weighting analysis in Brazil and its regions. During the study period (from 2017 to 2021), about 2.7 million live births were recorded per year, and the missing value for gestational age at delivery was less than 1.5%. The preterm birth prevalence slightly increased during the COVID-19 pandemic compared to the pre-pandemic period (11.32% in 2021 vs 11.09% in 2019, p-value

Abstract Objective To evaluate the impact of the race (Black versus non-Black) on maternal and perinatal outcomes of pregnant women with COVID-19 in Brazil. Methods This is a subanalysis of REBRACO, a Brazilian multicenter cohort study designed to evaluate the impact of COVID-19 on pregnant women. From February2020 until February 2021, 15 maternity hospitals in Brazil collected data on women with respiratory symptoms. We selected all women with a positive test for COVID-19; then, we divided them into two groups: Black and non-Black women. Finally, we compared, between groups, sociodemographic, maternal, and perinatal outcomes. We obtained the frequency of events in each group and compared them using X2 test; p-values < 0.05 were considered significant. We also estimated the odds ratio (OR) and confidence intervals (CI). Results 729 symptomatic women were included in the study; of those, 285 were positive for COVID-19, 120 (42.1%) were Black, and 165 (57.9%) were non-Black. Black women had worse education (p = 0.037). The timing of access to the health system was similar between both groups, with 26.3% being included with seven or more days of symptoms. Severe acute respiratory syndrome (OR 2.22 CI 1.17–4.21), intensive care unit admission (OR 2.00 CI 1.07–3.74), and desaturation at admission (OR 3.72 CI 1.41–9.84) were more likely to occur among Black women. Maternal death was higher among Black women (7.8% vs. 2.6%, p = 0.048). Perinatal outcomes were similar between both groups. Conclusion Brazilian Black women were more likely to die due to the consequences of COVID-19.

ABSTRACT Objective The objective was to compare the maternal and perinatal characteristics and outcomes between women with and without diabetes in a Brazilian cohort of women with preterm births. Methods This was an ancillary analysis of the Brazilian Multicenter Study on Preterm Birth, which included 4,150 preterm births. This analysis divided preterm births into two groups according to the presence of diabetes; pregestational and gestational diabetes were clustered in the same Diabetes Group. Differences between both groups were assessed using χ 2 or Student’s t tests. Results Preterm births of 133 and 4,017 women with and without diabetes, respectively, were included. The prevalence of diabetes was 3.2%. Pregnant women aged ≥35 years were more common in the Diabetes Group (31.6% versus 14.0% non-diabetic women, respectively). The rate of cesarean section among patients with diabetes was 68.2% versus 52.3% in non-diabetic cases), with a gestational age at birth between 34 and 36 weeks in 78.9% of the cases and 62.1% of the controls. Large-for-gestational-age babies were 7 times more common in the Diabetes Group. Conclusion Preterm birth among Brazilian women with diabetes was more than twice as prevalent; these women were older and had regular late preterm deliveries, usually by cesarean section. They also had a greater frequency of fetal morbidities, such as malformations and polyhydramnios, and a higher proportion of large-for-gestational-age and macrosomic neonates.

Abstract Background In 2019, WHO prioritized updating recommendations relating to three labour induction topics: labour induction at or beyond term, mechanical methods for labour induction, and outpatient labour induction. As part of this process, we aimed to review the evidence addressing factors beyond clinical effectiveness (values, human rights and sociocultural acceptability, health equity, and economic and feasibility considerations) to inform WHO Guideline Development Group decision-making using the WHO-INTEGRATE evidence-to-decision framework, and to reflect on how methods for identifying, synthesizing and integrating this evidence could be improved. Methods We adapted the framework to consider the key criteria and sub-criteria relevant to our intervention. We searched for qualitative and other evidence across a variety of sources and mapped the eligible evidence to country income setting and perspective. Eligibility assessment and quality appraisal of qualitative evidence syntheses was undertaken using a two-step process informed by the ENTREQ statement. We adopted an iterative approach to interpret the evidence and provided both summary and detailed findings to the decision-makers. We also undertook a review to reflect on opportunities to improve the process of applying the framework and identifying the evidence. Results Using the WHO-INTEGRATE framework allowed us to explore health rights and equity in a systematic and transparent way. We identified a lack of qualitative and other evidence from low- and middle-income settings and in populations that are most impacted by structural inequities or traditionally excluded from research. Our process review highlighted opportunities for future improvement, including adopting more systematic evidence mapping methods and working with social science researchers to strengthen theoretical understanding, methods and interpretation of the evidence. Conclusions Using the WHO-INTEGRATE evidence-to-decision framework to inform decision-making in a global guideline for induction of labour, we identified both challenges and opportunities relating to the lack of evidence in populations and settings of need and interest; the theoretical approach informing the development and application of WHO-INTEGRATE; and interpretation of the evidence. We hope these insights will be useful for primary researchers as well as the evidence synthesis and health decision-making communities, and ultimately contribute to a reduction in health inequities.

Abstract Objective To review literature and estimate the occurrence of preeclampsia and its complications in Brazil. Methods We performed an integrative review of the literature, and included observational studies published until August 2021 on the SciELO and PubMed databases that evaluated preeclampsia among pregnant women in Brazil. Other variables of interests were maternal death, neonatal death, hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and eclampsia. Three independent reviewers evaluated all retrieved studies and selected those that met inclusion criteria. A metanalysis of the prevalence of preeclampsia and eclampsia was also performed, to estimate a pooled frequency of those conditions among the studies included. Results We retrieved 304 studies after the initial search; of those, 10 were included in the final analysis, with a total of 52,986 women considered. The pooled prevalence of preeclampsia was of 6.7%, with a total of 2,988 cases reported. The frequency of eclampsia ranged from 1.7% to 6.2%, while the occurrence of HELLP syndrome was underreported. Prematurity associated to hypertensive disorders ranged from 0.5% to 1.72%. Conclusion The frequency of preeclampsia was similar to that reported in other international studies, and it is increasing in Brazil, probably due to the adoption of new diagnostic criteria. The development of a national surveillance network would be essential to understand the problem of hypertensive disorders of pregnancy in Brazil.

Abstract Sickle cell disease (SCD) is the most common monogenic disease worldwide, with a variable prevalence in each continent. A single nucleotide substitution leads to an amino-acid change in the β-globin chain, altering the normal structure of hemoglobin, which is then called hemoglobin S inherited in homozygosity (HbSS) or double heterozygosity (HbSC, HbSβ), and leads to chronic hemolysis, vaso-occlusion, inflammation, and endothelium activation. Pregnant women with SCD are at a higher risk of developing maternal and perinatal complications. We performed a narrative review of the literature considering SCD and pregnancy, the main clinical and obstetrical complications, the specific antenatal care, and the follow-up for maternal and fetal surveillance. Pregnant women with SCD are at a higher risk of developing clinical and obstetric complications such as pain episodes, pulmonary complications, infections, thromboembolic events, preeclampsia, and maternal death. Their newborns are also at an increased risk of developing neonatal complications: fetal growth restriction, preterm birth, stillbirth. Severe complications can occur in patients of any genotype. We concluded that SCD is a high-risk condition that increases maternal and perinatal morbidity and mortality. A multidisciplinary approach during pregnancy and the postpartum period is key to adequately diagnose and treat complications.

ABSTRACT OBJECTIVE To estimate the prevalence of unplanned pregnancy in eight public university hospitals, distributed in the five regions that make up Brazil. METHODS A secondary analysis of a national multicenter cross-sectional study, carried out in eight public university hospitals between June 1 and August 31, 2020, in Brazil. Convenience sample including women who gave birth within sixty consecutive days and met the following criteria: over 18 years old; gestational age over 36 weeks at delivery; with a single and live newborn, without malformations. RESULTS Sample composed of 1,120 postpartum women, of whom 756 (67.5%) declared that the pregnancy had not been planned. The median prevalence of unplanned pregnancy was 59.7%. The prevalence of unplanned pregnancy across hospitals differed significantly: Campinas (54.8%), Porto Alegre (58.2%), Florianópolis (59%), Teresina (61.2%), Brasília (64.3%), São Paulo (64.6%), Campo Grande (73.9%) and Manaus (95.3%) (p < 0.001). Factors significantly associated with unplanned pregnancy were maternal age, black color, lower family income, greater number of children, greater number of people living in household, and not having a partner. CONCLUSION In the studied sample, about two thirds of the pregnancies were declared as unplanned. The prevalence of unplanned pregnancies was related to social and demographic factors and varied significantly across the university hospitals evaluated.

Abstract Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04–3.04]), primary schooling or less (RR 2.16 [1.21–3.87]), being overweight (RR 4.34 [1.04–19.01]) or obese (RR 6.55 [1.57–27.37]), having public prenatal care (RR 2.16 [1.01–4.68]), planned pregnancies (RR 2.09 [1.15–3.78]), onset of infection in postpartum period (RR 6.00 [1.37–26.26]), chronic hypertension (RR 2.15 [1.37–4.10]), pre-existing diabetes (RR 3.20 [1.37–7.46]), asthma (RR 2.22 [1.14–4.34]), and anaemia (RR 3.15 [1.14–8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.

Abstract Objective To study maternal anxiety in pregnant women without comorbidities in the context of the COVID-19 outbreak in Brazil and to study maternal knowledge and concerns about the pandemic. Methods This is a secondary analysis from a national multicenter cross-sectional study performed in 10 cities, from June to August, 2020, in Brazil. Interviewed postpartum women, without medical or obstetrical comorbidities, were included in the present subanalysis. A structured questionnaire and the Beck Anxiety Inventory (BAI) were applied. Results Out of the 1,662 women, 763 (45.9%) met the criteria for the current analysis and 16.1% presented with moderate and 11.5% with severe maternal anxiety. Moderate or severe maternal anxiety was associated with high school education (odds ratio [OR]:1.58; 95% confidence interval [CI]:1.04–2.40). The protective factor was cohabiting with a partner (OR: 0.46; 95%CI: 0.29–0.73). There was a positive correlation between the total BAI score and receiving information about care in the pandemic (rpartial 0.15; p < 0.001); concern about vertical transmission of COVID-19 (rpartial 0.10; p = 0.01); receiving information about breastfeeding (rpartial 0.08; p = 0.03); concerns about prenatal care (rpartial 0.10; p = 0.01), and concerns about the baby contracting COVID-19 (rpartial 0.11; p = 0.004). The correlation was negative in the following aspects: self-confidence in protecting from COVID-19 (rpartial 0.08; p = 0.04), having learned (rpartial 0.09; p = 0.01) and self-confidence in breastfeeding (rpartial 0.22; p < 0.001) in the context of the pandemic. Conclusion The anxiety of pregnant women without medical or obstetrical comorbidities was associated to high school educational level and not living with a partner during the COVID-19 pandemic. Self-confidence in protecting against COVID-19 and knowledge about breastfeeding care during the pandemic reduced maternal anxiety.

Abstract Introduction Preeclampsia (PE) is a pregnancy complication associated with increased maternal and perinatal morbidity and mortality. The disease presents with recent onset hypertension (after 20 weeks of gestation) and proteinuria, and can progress to multiple organ dysfunction, with worse outcomes among early onset preeclampsia (EOP) cases (

Abstract Objective The coronavirus disease 2019 (COVID-19) is a pandemic viral disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of the disease among the obstetric population remains unclear, and the study of the placenta can provide valuable information. Adequate sampling of the placental tissue can help characterize the pathways of viral infections. Methods A protocol of placental sampling is proposed, aiming at guaranteeing representativity of the placenta and describing the adequate conservation of samples and their integrity for future analysis. The protocol is presented in its complete and simplified versions, allowing its implementation in different complexity settings. Results Sampling with the minimum possible interval from childbirth is the key for adequate sampling and storage. This protocol has already been implemented during the Zika virus outbreak. Conclusion A protocol for adequate sampling and storage of placental tissue is fundamental for adequate evaluation of viral infections on the placenta. During the COVID-19 pandemic, implementation of this protocol may help to elucidate critical aspects of the SARS-CoV-2 infection.

Abstract Objective The aim of the current review is to present a systematic evaluation of reported human placental findings in cases of zika virus (ZIKV) infection. Data sources We reviewed the EMBASE, PUBMED, and SCIELO databases until June 2019, without language restrictions. Selection of studies The search terms placenta AND zika virus were used. The inclusion criteria of the studies were studies that reported placental findings in humans. Experimental studies, reviews, notes or editorials were excluded. A total of 436 studies were retrieved; after duplicate exclusion, 243 articles had their titles screened, and 128 had their abstract read; of those, 32 were included in the final analysis (18 case reports, 10 case series, and 4 cohorts) Data collection We collected data concerning the author, year of publication, study design, number of participants, number of placental samples, onset of symptoms, perinatal outcomes, and main findings on histological analysis. Data synthesis The placental pathologic findings were described as mild and nonspecific, similar to those of other placental infections, including chronic placentitis, chronic villitis, increased Hofbauer cells, irregular fibrin deposits, increased mononuclear cells in the villus stroma, villous immaturity, edema, hypervascularization, stromal fibrosis, calcification, and focal necrosis of syncytiotrophoblasts. Conclusion Zika infection presents unspecific placental findings, similar to other infections in the toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes (TORCH)group. Characterizing and standardizing placental findings after zika virus infection is key to understanding the mechanisms of congenital diseases.

Abstract Background: Kidney transplantation is associated with fertility restoration in more than 50% of women with chronic kidney disease. Pregnancy after transplantation may affect women’s health and fetal development, with higher rates of abortion, fetal growth restriction, and neonatal deaths. Twin pregnancy is a condition of high-risk for adverse maternal and perinatal outcomes, and its occurrence in women with previous kidney transplantation is rare. Case: 32-year-old woman, recipient of living donor kidney transplantation, with a history of one pregnancy prior to transplantation, with current normal allograft function and no use of contraceptive method. At ten weeks of amenorrhea, ultrasound investigation showed a dichorionic diamniotic twin pregnancy. The following evaluation showed Chiari type II features in one fetus, and no detectable abnormality in the other one. There was appropriate blood pressure control with no need for an antihypertensive drug, and renal function remained normal without proteinuria. Calcium and a low dose of acetylsalicylic acid were used as preeclampsia prophylaxis. At 33 weeks of gestation, she presented premature rupture of membranes with spontaneous preterm labor. A cesarean section was performed due to the breech presentation of the first fetus. The patient persisted with normal graft function and without graft rejection during follow-up. Discussion and conclusion: Twin pregnancies after kidney transplantation are rare, and it is most frequently associated with preterm birth. We reported a successful twin pregnancy after kidney transplantation, with good perinatal and maternal outcomes, and without graft rejection or dysfunction.

Abstract Objective To assess maternal and perinatal outcomes of pregnancies in women with chronic hypertension (CH). Methods Retrospective cohort of women with CH followed at a referral center for a 5 year period (2012-2017). Data were obtained from medical charts review and described as means and frequencies, and a Poisson regression was performed to identify factors independently associated to the occurrence of superimposed preeclampsia (sPE). Results A total of 385 women were included in the present study; the majority were > than 30 years old, multiparous, mostly white and obese before pregnancy. One third had pre-eclampsia (PE) in a previous pregnancy and 17% of them had organ damage associated with hypertension, mainly kidney dysfunction. A total of 85% of the patients used aspirin and calcium carbonate for pre-eclampsia prophylaxis and our frequency of sPE was 40%, with an early onset (32.98 ± 6.14 weeks). Of those, 40% had severe features of PE, including 5 cases of HELLP syndrome; however, no cases of eclampsia or maternal death were reported. C-section incidence was high, gestational age at birth was 36 weeks, and nearly a third (115 cases) of newborns had complications at birth One third of the women remained using antihypertensive drugs after pregnancy. Conclusion Chronic hypertension is related with the high occurrence of PE, C-sections, prematurity and neonatal complications. Close surveillance and multidisciplinary care are important for early diagnosis of complications.

Objective To determine the accuracy of metabolomics in predicting hypertensive disorders in pregnancy.Design Systematic review of observational studies.Data sources and study eligibility criteria An electronic literature search was performed in June 2019 and February 2022. Two researchers independently selected studies published between 1998 and 2022 on metabolomic techniques applied to predict the condition; subsequently, they extracted data and performed quality assessment. Discrepancies were dealt with a third reviewer. The primary outcome was pre-eclampsia. Cohort or case–control studies were eligible when maternal samples were taken before diagnosis of the hypertensive disorder.Study appraisal and synthesis methods Data on study design, maternal characteristics, how hypertension was diagnosed, metabolomics details and metabolites, and accuracy were independently extracted by two authors.Results Among 4613 initially identified studies on metabolomics, 68 were read in full text and 32 articles were included. Studies were excluded due to duplicated data, study design or lack of identification of metabolites. Metabolomics was applied mainly in the second trimester; the most common technique was liquid-chromatography coupled to mass spectrometry. Among the 122 different metabolites found, there were 23 amino acids and 21 fatty acids. Most of the metabolites were involved with ammonia recycling; amino acid metabolism; arachidonic acid metabolism; lipid transport, metabolism and peroxidation; fatty acid metabolism; cell signalling; galactose metabolism; nucleotide sugars metabolism; lactose degradation; and glycerolipid metabolism. Only citrate was a common metabolite for prediction of early-onset and late-onset pre-eclampsia. Vitamin D was the only metabolite in common for pre-eclampsia and gestational hypertension prediction. Meta-analysis was not performed due to lack of appropriate standardised data.Conclusions and implications Metabolite signatures may contribute to further insights into the pathogenesis of pre-eclampsia and support screening tests. Nevertheless, it is mandatory to validate such methods in larger studies with a heterogeneous population to ascertain the potential for their use in clinical practice.PROSPERO registration number CRD42018097409.

Objective: To describe the sociodemographic characteristics, access to sexual and reproductive health (SRH) care, including contraceptives and to assess menstrual poverty of migrant Venezuelan adult women of childbearing age at the northwestern border between Venezuela and Brazil. Methods: Cross-sectional study coordinated by the Department of Obstetrics and Gynecology, University of Campinas, Campinas, SP, Brazil, conducted in Boa Vista, Roraima between January 18 and 24, 2021. We invited women aged 18 to 49 years to participate. A semi-structured self-response questionnaire was applied. The survey covered issues relating to SRH services, knowledge, access, and use of SRH services for women. We also applied a questionnaire regarding access to and quality of hygiene kits and toilets, and an open-ended question on “what does menstruation mean to you”? We excluded illiterate women and those with amenorrhea, those who had undergone hysterectomy or tubal ligation, and those with partners who had undergone vasectomy. Findings: The age (mean ± SD) of the 177 respondent women was 28 ± 6.8 years, 32.2% reported that they had more than three children, 38.4% referred at least one unplanned pregnancy, and 52.5% of the women indicated an intention to become pregnant in the near future. Furthermore, 40 (29.8%) women sought a healthcare service because they wanted a contraceptive method; among them, 16 did not receive the contraceptive that they chose, and 15 women wanted to use a contraceptive implant. Regarding menstrual poverty, 64 women stated that the menstrual hygiene products provided by humanitarian organizations were not enough for their needs, and 44 women claimed being unable to wash their hands anytime they wanted to. Conclusions: The vulnerabilities of this cohort of Venezuelan migrant women in Brazil who lived mainly out of the official shelters further increase when they struggle with no knowledge of how to access SRH services, lack of provision of LARC methods, risk of unplanned pregnancy, and inappropriate access to menstrual hygiene products and sanitary services. There are several challenges to be overcome to ensure SRH care for migrant women in Brazil.

Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.

Introduction The aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals.Methods and analysis A prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed.Ethics and dissemination Ethical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.

Abstract Objective To assess maternal and perinatal outcomes in pregnancies after kidney transplantation in a tertiary center in Brazil. Methods Retrospective cohort of pregnancies in women with kidney transplantation at the Universidade Estadual de Campinas, from January 1995 until December 2017. Medical charts were reviewed, andmaternal and perinatal outcomes were described as means and frequencies. Renal function and blood pressure were evaluated during pregnancy and postpartum. Results A total of 22 women had at least 1 pregnancy during the considered timeinterval, and 3 of them had > 1 pregnancy, totalizing 25 pregnancies. The mean age at transplantation was of 24.6 ± 4.2 years old, and the mean time interval until pregnancy was of 67.8 ± 46.3months. Themost frequent complication during pregnancywas hypertension, which affected 11 (64.7%)women. The gestational age at delivery was 34.7 ± 4weeks, and 47% of these pregnancies were preterm (< 37 weeks). A total of 88.2% of the women delivered by cesarean section. Renal function, measured by serum creatinine, remained stable during pregnancy, and the systolic blood pressure increased significantly, while the diastolic blood pressure did not differ during pregnancy. Conclusion Pregnancy after kidney transplantation is a rare event. Pre-eclampsia and prematurity were frequent complications, and cesarean section rates were very high. A specialized antenatal and postpartum care with a multiprofessional approach and continuous monitoring of graft function are essential for the early diagnosis of complications and improved outcomes.

Abstract Objective Several factors might affect the health and the quality of life of women who had a severe maternal morbidity (SMM) or a maternal near-miss (MNM) episode. The objective of the present study was to explore the perspectives of the professionals on the repercussions of SMM or of MNM after interviewing women who survived such episodes. Method Selected cases that captured the attention of professionals were reported. The professionals built individually 10 narratives, which were analyzed with the technique of content analysis. Results According to the perspectives of the professionals, women surviving a severe maternal condition and their families experienced clinical and psychosocial consequences. Some cases portrayed the intense psychological distress in mourning for the loss of the fetus or of their reproductive capacity and changes in family dynamics generating emotional overload, depression, and gender violence. Conclusion The analysis of narratives may offer an idea on the complexity of the perception of care by professionals and on the need for an interdisciplinary follow-up of women surviving an SMM or an MNM episode.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

IntroductionCOVID-19 pandemic posed major challenges in obstetric health care services. Preparedness, development, and implementation of new protocols were part of the needed response. This study aims to describe the strategies implemented and the perspectives of health managers on the challenges to face the pandemic in 16 different maternity hospitals that comprise a multicenter study in Brazil, called REBRACO (Brazilian network of COVID-19 during pregnancy).MethodsMixed-method study, with quantitative and qualitative approaches. Quantitative data on the infrastructure of the units, maternal and perinatal health indicators, modifications on staff and human resources, from January to July/2020. Also, information on total number of cases, and availability for COVID-19 testing. A qualitative study by purposeful and saturation sampling was undertaken with healthcare managers, to understand perspectives on local challenges in facing the pandemic.ResultsMost maternities early implemented their contingency plan. REBRACO centers reported 338 confirmed COVID-19 cases among pregnant and post-partum women up to July 2020. There were 29 maternal deaths and 15 (51.8%) attributed to COVID-19. All maternities performed relocation of beds designated to labor ward, most (75%) acquired mechanical ventilators, only the minority (25%) installed new negative air pressure rooms. Considering human resources, around 40% hired extra health professionals and increased weekly workload and the majority (68.7%) also suspended annual leaves. Only one center implemented universal screening for childbirth and 6 (37.5%) implemented COVID-19 testing for all suspected cases, while around 60% of the centers only tested moderate/severe cases with hospital admission. Qualitative results showed that main challenges experienced were related to the fear of the virus, concerns about reliability of evidence and lack of resources, with a clear need for mental health support among health professionals.ConclusionStudy findings suggest that maternities of the REBRACO initiative underwent major changes in facing the pandemic, with limitations on testing, difficulties in infrastructure and human resources. Leadership, continuous training, implementation of evidence-based protocols and collaborative initiatives are key to transpose the fear of the virus and ascertain adequate healthcare inside maternities, especially in low and middle-income settings. Policy makers need to address the specificities in considering reproductive health and childbirth during the COVID-19 pandemic and prioritize research and timely testing availability.

Introduction Hypertension is a very important cause of maternal morbidity and mortality worldwide, despite efforts on prevention. The lack of a tool to provide effective and early prediction of hypertension for a high-risk group may contribute to improving maternal and fetal outcomes. Metabolomics has figured out as a promised technology to contribute to the improvement of hypertension in pregnancy prediction.Methods and analysis Our primary outcome is hypertensive disorders of pregnancy. A detailed systematic literature search will be performed in electronic databases PubMed, EMBASE, Scopus, Web of Science, Latin America and Caribbean Health Sciences Literature, Scientific Electronic Library Online, Health Technology Assessment and Database of Abstracts of Reviews of Effects using controlled terms ‘pre-eclampsia’, ‘hypertensive disorders’, ‘metabolomics’ and ‘prediction’ (and their variations). Studies from the latest 20 years will be included, except case reports, reviews, cross-sectional studies, letter to editors, expert opinions, commentaries papers or non-human research. If possible, we will perform a meta-analysis. Two peer-reviewers will independently perform the search and in cases of discordance, a third reviewer will be consulted.Ethics and dissemination As a systematic review, ethics approval is not required. The results of this review will present the current use and performance of metabolomics for predicting gestational hypertension. Such data could potentially guide future studies and interventions to improve existing prediction models.PROSPERO registration number CRD42018097409.

Objectives To perform a multidimensional assessment of women who experienced severe maternal morbidity (SMM) and its short-term and medium-term impact on the lives and health of women and their children.Design A retrospective cohort study.Setting A tertiary maternity hospital from the southeast region of Brazil.Participants The exposed population was selected from intensive care unit admissions if presenting any diagnostic criteria for SMM. Controls were randomly selected among women without SMM admitted to the same maternity and same time of childbirth.Primary and secondary outcome variables Validated tools were applied, addressing post-traumatic stress disorder (PTSD) and quality of life (SF-36) by phone, and then general and reproductive health, functioning (WHO Disability Assessment Schedule), sexual function (Female Sexual Function Index (FSFI)), substance abuse (Alcohol, Smoking and Substance Involvement Screening Test 2.0) and growth/development (Denver Developmental Screening Test) of children born in the index pregnancy in a face-to-face interview.Results All instruments were applied to 638 women (315 had SMM; 323 were controls, with the assessment of 264 and 307 children, respectively). SF-36 score was significantly lower in the SMM group, while PTSD score was similar between groups. Women who had SMM became more frequently sterile, had more abnormal clinical conditions after the index pregnancy and a higher score for altered functioning, while proportions of FSFI score or any drug use were similar between groups. Furthermore, children from the SMM group were more likely to have weight (threefold) and height (1.5 fold) for age deficits and also impaired development (1.5-fold).Conclusion SMM impairs some aspects of the lives of women and their children. The focus should be directed towards monitoring these women and their children after birth, ensuring accessibility to health services and reducing short-term and medium-term repercussions on physical, reproductive and psychosocial health.

In 2015–2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by Aedes aegypti mosquitoes, however non-vector-dependent routes are also possible. Mechanisms of maternal-fetal transmission remain unknown, and the trans-placental route has been extensively studied in animal models and in human samples. The aim of this review was to summarize recent studies that helped to elucidate the mechanism of CZS in animal models and observational studies. There are still challenges in the diagnosis and prevention of CZS in humans, due to the large gap that remains in translating ZIKV research to clinical practice. Translational research linking governments, local health workers, scientists and industry is fundamental to improve care for mothers and children.

The detection of Zika virus (ZIKV) in immunoprivileged anatomical sites, potential sites for viral persistence, may guide the confirmation of undefined cases of ZIKV infection and also bring to light unknown pathways of viral transmission. Thus, this study aimed to characterize ZIKV infection in stratified, standardized placental samples in women with exanthematic febrile manifestations during pregnancy and compare findings to the standard investigation protocol of official health agencies. To this end, a case series of placental findings within a prospective cohort study was conducted over a period of 24 months. Serum/urine were obtained at the time of clinical case identification. Placental sampling was performed following standard investigation protocol (samples of 1.0 cm sent to a reference laboratory) and in a systematic way at various regions, such as chorionic plate, chorionic villi, basal plate, amniotic membrane, and umbilical cord, for subsequent ZIKV identification and quantification. Clinical information was obtained and histological preparation with hematoxylin–eosin staining for morphological evaluation was performed. This case series included 17 placentas systematically collected. Of these, 14 were positive by qRT-PCR for ZIKV, 5 in the umbilical cord, 7 in the amniotic membrane, 7 in the chorionic plate, 13 in the chorionic villi, and 7 in the basal plate, whereas none were reported by the reference laboratory. The most common morphological and anatomopathological findings were increased stromal cellularity, villitis, calcification, maternal vascular malperfusion, placental hypoplasia, and maternal–fetal hemorrhage (intervillous thrombi). Seven women presented positive testing for ZIKV in serological and/or molecular tests during gestation in urine. While viral quantification in urine ranged from 101 to 103 FFU eq/ml, that in different placental regions ranged from 103 to 108 FFU eq/g. Thus, ZIKV can infect different regions of the placenta and umbilical cord of pregnant women, showing that the systematic collection and adequate storage of the placenta is fundamental for the detection of ZIKV in this organ. The detection of ZIKV in the placenta after several months of initial symptoms suggests that this tissue may be a site for viral persistence during pregnancy.

Abstract Objective To review the existing recommendations on the prenatal care of women with systemic lupus erythematosus (SLE), based on currently available scientific evidence. Methods An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed), EMBASE and The Cochrane Library databases, using the medical subject headings (MeSH) terms “systemic lupus erythematosus” AND “high-risk pregnancy” OR “prenatal care.” Studies published in English between 2007 and 2017 were included; experimental studies and case reports were excluded. In cases of disagreement regarding the inclusion of studies, a third senior researcher was consulted. Forty titles were initially identified; four duplicates were excluded. After reading the abstracts, 7 were further excluded and 29 were selected for a full-text evaluation. Results Systemic lupus erythematosus flares, preeclampsia, gestation loss, preterm birth, fetal growth restriction and neonatal lupus syndromes (mainly congenital heartblock) were the major complications described. The multidisciplinary team should adopt a specific monitoring, with particular therapeutic protocols. There are safe and effective drug options that should be prescribed for a good control of SLE activity. Conclusion Pregnant women with SLE present an increased risk for maternal complications, pregnancy loss and other adverse outcomes. The disease activity may worsen and, thereby, increase the risk of other maternal-fetal complications. Thus, maintaining an adequate control of disease activity and treating flares quickly should be a central goal during prenatal care.

Abstract Objective To evaluate the use of tocolysis in cases of preterm birth due to spontaneous preterm labor in a Brazilian sample. Methods A sample of 1,491 women with preterm birth due to spontaneous preterm labor were assessed, considering treatment with tocolysis or expectant management, according to gestational age at birth (< 34 weeks and 34 to 36 þ 6 weeks) and drugs prescribed. The study took place in 20 Brazilian hospitals from April 2011 to July 2012. Bivariate analyses were conducted to evaluate associations with sociodemographic and obstetric characteristics and odds ratios with their respective 95% confidence intervals were estimated for maternal and neonatal outcomes. Results A total of 1,491 cases of preterm birth were considered. Tocolysis was performed in 342 cases (23%), 233 of which (68.1%) were delivered before 34 weeks. Within the expectant management group, 73% was late preterm and with more advanced labor at the time of admission. The most used drugs were calcium channel blockers (62.3%), followed by betamimetics (33%). Among the subjects in the tocolysis group, there were more neonatal and maternal complications (majority non-severe) and an occurrence of corticosteroid use that was 29 higher than in the expectant management group. Conclusion Tocolysis is favored in cases of earlier labor and also among thosewith less than 34 weeks of gestation, using preferably calcium channel blockers, with success in achieving increased corticosteroid use. Tocolysis, in general, was related to higher maternal and neonatal complication rates, which may be due to the baseline difference between cases at admission. However, these results should raise awareness to tocolysis use.

Abstract Objective The aim of this study is to evaluate the burden of indirect causes of maternal morbidity/mortality in Brazil. Methods Secondary analysis of a multicenter cross-sectional study conducted in 27 referral obstetric units within the Brazilian Network for Surveillance of Severe Maternal Morbidity. Results A total of 82,388 women were surveilled: 9,555 women with severe maternal morbidity were included, and 942 (9.9%) of them had indirect causes of morbidity/ mortality. There was an increased risk of higher severity among the indirect causes group, which presented 7.56 times increased risk of maternal death (prevalence ratio [PR]: 7.56; 95% confidence interval [95%CI]: 4.99-11.45). The main indirect causes of maternal death were H1N1 influenza, sepsis, cancer and cardiovascular disease. Non-public antenatal care (PR: 2.52; 95%CI: 1.70-3.74), diabetes (PR: 1.90; 95%CI: 1.24-2.90), neoplasia (PR: 1.98; 95%CI: 1.25-3.14), kidney diseases (PR: 1.99; 95%CI: 1.14-3.49), sickle cell anemia (PR: 2.50; 95%CI: 1.16-5.41) and drug addiction (PR: 1.98; 95%CI: 1.03-3.80) were independentlyassociatedwithworseresultsintheindirectcausesgroup.Someprocedures for the management of severity were more common for the indirect causes group. Conclusion Indirect causes were present in less than 10% of the overall cases, but they represented over 40% of maternal deaths in the current study. Indirect causes of maternal morbidity/mortality were also responsible for an increased risk of higher severity, and they were associated with worse maternal and perinatal outcomes. In middle-income countries there is a mix of indirect causes of maternal morbidity/ mortality that points to some advances in the scale of obstetric transition, but also reveals the fragility of health systems.

Abstract Introduction Preeclampsia, a multifactorial disease with pathophysiology not yet fully understood, is a major cause of maternal and perinatal morbidity and mortality, especially when preterm. The diagnosis is performed when there is an association between arterial hypertension and proteinuria or evidence of severity. There are unanswered questions in the literature considering the timing of delivery once preterm preeclampsia has been diagnosed, given the risk of developingmaternal complications versus the risk of adverse perinatal outcomes associated with prematurity. The objective of this systematic review is to determine the best timing of delivery for women diagnosed with preeclampsia before 37 weeks of gestation. Methods Systematic literature review, performed in the PubMed database, using the terms preeclampsia, parturition and timing of delivery to look for studies conducted between 2014 and 2017. Studies that compared the maternal and perinatal outcomes of women who underwent immediate delivery or delayed delivery, in the absence of evidence of severe preeclampsia, were selected. Results A total of 629 studies were initially retrieved. After reading the titles, 78 were selected, and their abstracts, evaluated; 16 were then evaluated in full and, in the end, 6 studies (2 randomized clinical trials and 4 observational studies) met the inclusion criteria. The results were presented according to gestational age range (< 34 weeks and between 34 and 37 weeks) and by maternal and perinatal outcomes, according to the timing of delivery, considering immediate delivery or expectant management. Before 34 weeks, thematernal outcomeswere similar, but the perinatal outcomes were significantly worse when immediate delivery occurred. Between 34 and 37 weeks, the progression to severe maternal disease was slightly higher among women undergoing expectant management, however, with better perinatal outcomes. Conclusions When there is no evidence of severe preeclampsia or impaired fetal wellbeing, especially before 34 weeks, the pregnancy should be carefully surveilled, and the delivery, postponed, aiming at improving the perinatal outcomes. Between 34 and 37 weeks, the decision on the timing of delivery should be shared with the pregnant woman and her family, after providing information regarding the risks of adverse outcomes associated with preeclampsia and prematurity.

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and “omics” sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent “boom” in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies.

A talassemia beta maior é uma doença hematológica hereditária rara em que deficiência na síntese de cadeias globínicas beta causa anemia grave. O tratamento consiste de transfusão sanguínea e quelação de ferro. Descrevemos dois casos de adolescentes com talassemia beta maior, com gestação não planejada e início tardio de pré-natal. Uma delas apresentou piora da anemia, necessidade transfusional aumentada, restrição de crescimento fetal e senescência placentária. A outra apresentava também hipotireoidismo e baixo peso materno, e foi internada por duas ocasiões durante a gestação, por choque hemorrágico do dengue e por infecção respiratória associada a vírus influenza H1N1. Uma delas apresentou restrição de crescimento fetal e teve parto vaginal no termo complicado com hipotonia uterina. Ambas necessitaram de transfusão sanguínea no pós-parto e optaram por medroxiprogesterona como método contraceptivo subsequentemente. Esse relato ressalta a importância de orientação contraceptiva para essas mulheres e o papel do cuidado pré-natal especializado em conjunto com hematologista.

PURPOSE: To describe maternal and neonatal outcomes in pregnant women undergoing hemodialysis in a referral center in Brazilian Southeast side. METHODS: Retrospective and descriptive study, with chart review of all pregnancies undergoing hemodialysis that were followed-up at an outpatient clinic of high- risk prenatal care in Southeast Brazil. RESULTS: Among the 16 women identified, 2 were excluded due to follow-up loss. In 14 women described, hypertension was the most frequent cause of chronic renal failure (half of cases). The majority (71.4%) had performed hemodialysis treatment for more than one year and all of them underwent 5 to 6 hemodialysis sessions per week. Eleven participants had chronic hypertension, 1 of which was also diabetic, and 6 of them were smokers. Regarding pregnancy complications, 1 of the hypertensive women developed malignant hypertension (with fetal growth restriction and preterm delivery at 29 weeks), 2 had acute pulmonary edema and 2 had abruption placenta. The mode of delivery was cesarean section in 9 women (64.3%). All neonates had Apgar score at five minutes above 7. CONCLUSIONS: To improve perinatal and maternal outcomes of women undergoing hemodialysis, it is important to ensure multidisciplinary approach in referral center, strict control of serum urea, hemoglobin and maternal blood pressure, as well as close monitoring of fetal well-being and maternal morbidities. Another important strategy is suitable guidance for contraception in these women.

During pregnancy, immune cells infiltrate the placenta at different stages of fetal development. NK cells and macrophages are the most predominant cell types. These immune cells play pleiotropic roles, as they control spiral artery remodeling to ensure appropriate blood supply and maintain long-term tolerance to a true allograft; yet, they must be able to mount appropriate immune defenses to pathogens that may threaten the fetus. Whether the same cell type accomplishes all these tasks or if there are dedicated subsets remains controversial. Here, we identify and characterize two distinct subsets of myeloid cells that differ in their pro-inflammatory/regulatory capacity. While one subset predominantly produces the immune-modulating cytokine IL-10, the second subset has superior capacity to secrete pro-inflammatory mediators, such as IL-1β and IL-6. The putative regulatory myeloid cells also express high levels of inhibitory receptors and their ligands, including programmed cell death 1 (PD1) ligands. Importantly, a large fraction of CD8 and CD4 cells in normal term human placenta are PD1 positive, suggesting that the PD1/PD1 ligands axis might be critical to maintain tolerance during pregnancy.

OBJECTIVE: To study the prevalence of potentially life-threatening maternal conditions and near miss in Brazil according to maternal age. METHODS: A secondary analysis of the 2006 Brazilian demographic health survey database using a validated questionnaire to evaluate maternal morbidity with a focus on age extremes. The study included 5,025 women with at least 1 live birth in the 5-year reference period preceding their interviews. Three age range periods were used: 15-19 years (younger age), 20-34 years (control), and 35-49 years (advanced maternal age). According to a pragmatic definition, any woman reporting eclampsia, hysterectomy, blood transfusion, or admission to the intensive care unit during her pregnancy/childbirth was considered a near-miss case. The associations between age and severe maternal morbidity were further assessed. RESULTS: For the 6,833 reported pregnancies, 73.7% of the women were 20-34 years old, 17.9% were of advanced maternal age, and only 8.4% were of younger age. More than 22% of the women had at least one of the complications appraised, and blood transfusion, which was more prevalent among the controls, was the only variable with a significant difference among the age groups. The overall rate of maternal near miss was 21.1 per 1000 live births. There was a trend of higher maternal near miss with increasing age. The only significant risk factor identified for maternal near miss was a lower literacy level among older women. CONCLUSIONS: There is a trend towards worse results with increasing age. The investigation of the determinants of maternal near miss at the community level using an innovative approach through a demographic health survey is an example suggested for under-resourced settings.

INTRODUCTION:Magnesium sulfate (MgSO4) is the drug of choice for the prevention and control of seizures in the management of severe preeclampsia/eclampsia. Several barriers have been identified in the use of MgSO4, especially in low and middle-income settings. OBJECTIVE:To describe the obstetrician's perception on possible reasons for underutilizing magnesium sulfate to treat preeclampsia/eclampsia. METHOD:A qualitative clinical study, based on phenomenological reference 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 a southeastern Brazilian city. RESULTS:Fear 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 adequate 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, ensuring safety of drug prescription and thus possibly reducing adverse outcomes related to PE.

Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations.To investigate the association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil.This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome.We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women.Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications.