Hemorrhage as cause of obstetric complication in the Brazilian Network for Surveillance of Severe Maternal Morbidity

Orientadores: José Guilherme Cecatti, Maria Laura Costa do NascimentoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Objetivo: Avaliar a ocorrência de complicações graves e óbitos associadas a gravidez ectópica (GE) e a hemorragias ante e intraparto (HAI) e pós-parto (HPP) entre mulheres da Rede Brasileira de Vigilância de Morbidade Materna Grave. Métodos: Estudo de corte transversal multicêntrico realizado em 27 unidades de referência obstétrica no Brasil entre julho de 2009 e junho de 2010. Foi avaliada a ocorrência de condições potencialmente ameaçadoras da vida (CPAV), near miss materno (NMM) e mortes maternas (MM) associadas com GE, HAI e HPP em 9.555 mulheres identificadas como tendo alguma complicação obstétrica. Características sóciodemográficas e obstétricas e o uso de critérios de manejo nestas hemorragias graves também foram avaliados. Foram calculadas as razões de prevalência (RP) com seus respectivos intervalos de confiança de 95% ajustados para o efeito de cluster e análise de regressão logística múltipla para identificar os fatores associados de forma independente com a ocorrência de resultado materno grave (Severe Maternal Outcome - SMO=NMM+MM). Resultados: Das 9.555 mulheres com complicações obstétricas, 312 (3,3%) tiveram complicações por GE, sendo 286 (91,7%) CPAV, 25 (8,0%) NMM e 1 (0,3%) MM. HPP foi a causa principal entre 1192 mulheres (12,5%), sendo 981 CPAV, 181 NMM e 30 MM. HAI ocorreu em 8% (767) das mulheres que experimentam algum tipo de complicação obstétrica e foi responsável por 7,1% (613) dos casos de CPAV, 18,2 % (140) de NMM e 10% (14) das MM. Mulheres com GE complicada tiveram maior risco de transfusão sanguínea, laparotomia e menor risco de admissão em UTI e tempo prolongado de internação do que mulheres com outras complicações. Houve cuidado deficiente ou demoras no atendimento associado a casos de GE complicados. Os fatores associados ao melhor resultado foram uma cicatriz uterina prévia e ser não branca. Entre as mulheres que apresentaram HPP, a idade materna, idade gestacional precoce, cicatriz uterina anterior e cesariana prévia foram os principais fatores associados com maior risco de ocorrência de SMO. Essas mulheres também tiveram uma maior proporção de transfusão sanguínea e retorno para a sala operatória. Já para as que apresentaram HAI, a idade materna e cesariana anterior foram independentemente associadas a este maior risco. Conclusão: O aumento da morbidade materna devido a GE aumentou a conscientização sobre a doença e seu impacto sobre a vida reprodutiva feminina. A hemorragia pós-parto persiste como uma das principais complicações obstétricas e importante causa de morbidade e morte materna no Brasil. O conhecimento dos fatores associados a um maior risco de ocorrência de SMO pode ser útil para melhorar a qualidade da atenção obstétrica e dos resultados maternos. SMO devido a hemorragia ante e intraparto foi altamente prevalente entre as mulheres brasileiras. Alguns fatores de risco, em particular a idade materna e cesareana prévia, foram associados com a ocorrência desta complicação hemorrágica. Os serviços obstétricos devem desenvolver diretrizes e intervenções específicas para prevenir a morbidade materna grave para cada condição hemorrágica obstétrica específica identificadaAbstract: Objective: To evaluate the occurrence of severe obstetric complications associated with ectopic pregnancy (EP) and antepartum or intrapartum (AIH) and postpartum hemorrhage (PPH) among women in the Brazilian Network for the Surveillance of Severe Maternal Morbidity. Methods: A multicenter cross-sectional study conducted in 27 referral obstetric units in Brazil between July 2009 and June 2010. The occurrence of potentially life-threatening conditions (PLTC), maternal near miss (MNM) and maternal death (MD) associated with EP, AIH and HPP were evaluated among 9,555 women identified as having some obstetric complication. Socio demographic and obstetric characteristics and use of management criteria in these severe hemorrhages were also assessed. Prevalence ratios (PR) were calculated with their respective 95% confidence intervals adjusted for the cluster effect and multiple logistic regression analysis to identify factors independently associated with the occurrence of severe maternal outcome (SMO = MNM + MD) . Results: Among the 9,555 women with obstetric complications, 312 (3.3%) had complications due to EP, with 286 (91.7 %) PTLC, 25 (8.0%) MNM and 1 (0.3 %) MD. HPP was the leading cause in 1192 women (12.5 %), with 981 PTLC, 181 MNM and 30 MD. AIH occurred in 8% (767) of women experiencing any type of obstetric complication and accounted for 613 (7.1%) of the PTLC cases, 140 (18.2%) of MNM and 10% (14) of MD. Women with complicated PE had a higher risk of blood transfusion, laparotomy and lower risk of ICU admission and prolonged hospitalization than women with other complications. There was a substandard care or delays associated with cases of complicated EP. The factors associated with a better outcome were a previous uterine scar and to be non-white. Among women who had PPH, maternal age, early gestational age, previous uterine scar and previous cesarean delivery were the main factors associated with a risk of SMO. These women also had a higher proportion of blood transfusion and return to operating room. For those who had AIH, maternal age and previous cesarean section were independently associated with this increased risk. Conclusion: Increased maternal morbidity due to EP raised awareness about the condition and its impact on female reproductive life. Postpartum hemorrhage persists as one of the main obstetric complication and important cause of maternal morbidity and mortality in Brazil. The knowledge of factors associated with a severe maternal outcome (SMO=MNM+MD) could be useful for improving the quality of obstetric care and maternal outcomes. SMO due to antepartum and intrapartum hemorrhage was highly prevalent among Brazilian women. Some risk factors, maternal age and prior cesarean delivery in particular, were associated with the occurrence of this hemorrhagic complication. Care providers should develop specific guidelines and interventions to prevent severe maternal morbidity for each specific obstetric hemorrhagic condition identifiedDoutoradoSaúde Materna e PerinatalDoutor em Ciências da Saúd

Metabolomics applied to maternal and perinatal health : a review of new frontiers with a translation potential

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

Mean arterial blood pressure : potential predictive tool for preeclampsia in a cohort of healthy nulliparous pregnant women

Background: Prediction of preeclampsia is a challenge to overcome. The vast majority of prospective studies in large general obstetric populations have failed in the purpose of obtain a useful and effective model of prediction, sometimes based on complex tools unavaible in areas where the incidence of preeclampsia is the highest. The goal of this study was to assess mean arterial blood pressure (MAP) levels at 19–21, 27–29 and 37–39 weeks of gestation and performance of screening by MAP for the prediction of preeclampsia in a Brazilian cohort of healthy nulliparous pregnant women. Methods: This was a cohort approach to a secondary analysis of the Preterm SAMBA study. Mean arterial blood pressure was evaluated at three different time periods during pregnancy. Groups with early-onset preeclampsia, late-onset preeclampsia and normotension were compared. Increments in mean arterial blood pressure between 20 and 27 weeks and 20 and 37 weeks of gestation were also calculated for the three groups studied. The accuracy of mean arterial blood pressure in the prediction of preeclampsia was determined by ROC curves. Results: Of the 1373 participants enrolled, complete data were available for 1165. The incidence of preeclampsia was 7.5%. Women with early-onset preeclampsia had higher mean arterial blood pressure levels at 20 weeks of gestation, compared to the normotensive group. Women with late-onset preeclampsia had higher mean arterial blood pressure levels at 37 weeks of gestation, than the normotensive groups and higher increases in this marker between 20 and 37 weeks of gestation. Based on ROC curves, the predictive performance of mean arterial blood pressure was higher at 37 weeks of gestation, with an area under the curve of 0.771. Conclusion: As an isolated marker for the prediction of preeclampsia, the performance of mean arterial blood pressure was low in a healthy nulliparous pregnant women group. Considering that early-onset preeclampsia cases had higher mean arterial blood pressure levels at 20 weeks of gestation, future studies with larger cohorts that combine multiple markers are needed for the development of a preeclampsia prediction model

Identification of earlier predictors of pregnancy complications through wearable technologies in a Brazilian multicentre cohort : Maternal Actigraphy Exploratory Study I (MAES-I) study protocol

Introduction Non-invasive tools capable of identifying predictors of maternal complications would be a step forward for improving maternal and perinatal health. There is an association between modification in physical activity (PA) and sleep–wake patterns and the occurrence of inflammatory, metabolic, pathological conditions related to chronic diseases. The actigraphy device is validated to estimate PA and sleep–wake patterns among pregnant women. In order to extend the window of opportunity to prevent, diagnose and treat specific maternal conditions, would it be possible to use actigraphy data to identify risk factors for the development of adverse maternal outcomes during pregnancy? Methods and analysis A cohort will be held in five centres from the Brazilian Network for Studies on Reproductive and Perinatal Health. Maternal Actigraphy Exploratory Study I (MAES-I) will enrol 400 low-risk nulliparous women who will wear the actigraphy device on their wrists day and night (24 hours/day) uninterruptedly from 19 to 21 weeks until childbirth. Changes in PA and sleep–wake patterns will be analysed throughout pregnancy, considering ranges in gestational age in women with and without maternal complications such as pre-eclampsia, preterm birth (spontaneous or provider-initiated), gestational diabetes, maternal haemorrhage during pregnancy, in addition to perinatal outcomes. The plan is to design a predictive model using actigraphy data for screening pregnant women at risk of developing specific adverse maternal and perinatal outcomes

Incidence and risk factors for preeclampsia in a cohort of healthy nulliparous pregnant women : a nested case-control study

The objective of this study is to determine the incidence, socio-demographic and clinical risk factors for preeclampsia and associated maternal and perinatal adverse outcomes. This is a nested case-control derived from the multicentre cohort study Preterm SAMBA, in fve diferent centres in Brazil, with nulliparous healthy pregnant women. Clinical data were prospectively collected, and risk factors were assessed comparatively between PE cases and controls using risk ratio (RR) (95% CI) plus multivariate analysis. Complete data were available for 1,165 participants. The incidence of preeclampsia was 7.5%. Body mass index determined at the frst medical visit and diastolic blood pressure over 75mmHg at 20 weeks of gestation were independently associated with the occurrence of preeclampsia. Women with preeclampsia sustained a higher incidence of adverse maternal outcomes, including C-section (3.5 fold), preterm birth below 34 weeks of gestation (3.9 fold) and hospital stay longer than 5 days (5.8 fold) than controls. They also had worse perinatal outcomes, including lower birthweight (a mean 379g lower), small for gestational age babies (RR 2.45 [1.52–3.95]), 5-minute Apgar score less than 7 (RR 2.11 [1.03–4.29]), NICU admission (RR 3.34 [1.61–6.9]) and Neonatal Near Miss (3.65 [1.78–7.49]). Weight gain rate per week, obesity and diastolic blood pressure equal to or higher than 75mmHg at 20 weeks of gestation were shown to be associated with preeclampsia. Preeclampsia also led to a higher number of C-sections and prolonged hospital admission, in addition to worse neonatal outcomes

Clinical and epidemiological factors associated with spontaneous preterm birth : a multicentre cohort of low risk nulliparous women

The objective of this study was to determine incidence and risk factors associated with spontaneous preterm birth (sPTB). It was a prospective multicentre cohort study performed in fve Brazilian referral maternity hospitals and enrolling nulliparous women at 19–21 weeks. Comprehensive maternal data collected during three study visits were addressed as potentially associated factors for sPTB. Bivariate and multivariate analysis estimated risk ratios. The main outcomes measures were birth before 37 weeks due to spontaneous preterm labour or premature rupture of membranes (sPTB). The comparison group was comprised of women with term births (≥37weeks). Outcome data was available for 1,165 women, 6.7% of whom had sPTB, 16% had consumed alcohol and 5% had used other illicit drugs during the frst half of pregnancy. Current drinking at 19–21 weeks (RR 3.96 95% CI [1.04–15.05]) and a short cervix from 18–24 weeks (RR 4.52 95% CI [1.08–19.01]) correlated with sPTB on bivariate analysis. Increased incidence of sPTB occurred in underweight women gaining weight below quartile 1 (14.8%), obese women gaining weight above quartile 3 (14.3%), women with a short cervix (<25mm) at 18–24 weeks (31.2%) and those with a short cervix and vaginal bleeding in the frst half of pregnancy (40%). Cervical length (RRadj 4.52 95% CI [1.08–19.01]) was independently associated with sPTB. In conclusion, the incidence of sPTB increased in some maternal phenotypes, representing potential groups of interest, the focus of preventive strategies. Similarly, nulliparous women with a short cervix in the second trimester require further exploration

The food patterns of a multicenter cohort of Brazilian nulliparous pregnant women

Assessment of human nutrition is a complex process, in pregnant women identify dietary patterns through mean nutrient consumption can be an opportunity to better educate women on how to improve their overall health through better eating. This exploratory study aimed to identify a posteriori dietary patterns in a cohort of nulliparous pregnant women. The principal component analysis (PCA) technique was performed, with Varimax orthogonal rotation of data extracted from the 24-h dietary recall, applied at 20 weeks of gestation. We analysed 1.145 dietary recalls, identifying five main components that explained 81% of the dietary pattern of the sample. Dietary patterns found were: Obesogenic, represented by ultra-processed foods, processed foods, and food groups rich in carbohydrates, fats and sugars; Traditional, most influenced by natural, minimally processed foods, groups of animal proteins and beans; Intermediate was similar to the obesogenic, although there were lower loads; Vegetarian, which was the only good representation of fruits, vegetables and dairy products; and Protein, which best represented the groups of proteins (animal and vegetable). The obesogenic and intermediate patterns represented over 37% of the variation in food consumption highlighting the opportunity to improve maternal health especially for women at first mothering

Profile of calories and nutrients intake in a Brazilian multicenter study of nulliparous women

Objective: To assess the calorie intake and nutritional content of the maternal diet in regions with different culinary traditions and typical foods, and to understand the nutritional profile so as to provide information about the consumption of this population and promote maternal and perinatal health. Methods: From a cohort of 1145 pregnant women with diverse socio-backgrounds we analyzed the dietary characteristics profile according to three guidelines and compared the differences between regions of Brazil. Results: Women from the northeast had the lowest level of income, occupation, education, and age (P < 0.001). Intakes of unprocessed/minimally processed foods and processed foods were more prevalent in women from the northeast than in southern/southeastern women (P < 0.001). The consumption of dairy products and vegetables was less than the recommended intake, with lower intake in southern/southeastern women (P < 0.001). This study showed a lower consumption of dairy and vegetables, with a shortfall of vitamins K and D, iron, calcium, folate, magnesium, and chromium from natural and fortified foods. We observed a greater consumption of unprocessed or minimally processed food in women from the northeast of Brazil. Conclusion: Our findings indicate the importance of differentiating the source of calorie intake between regional nutritional guidance and the diversity of local cuisine

Proposal of MUAC as a fast tool to monitor pregnancy nutritional status : results from a cohort study in Brazil

Objective: In Brazil, although the assessment of maternal nutritional status is recommended using body mass index (BMI), this is only possible in settings adequately prepared. Midupper arm circumference (MUAC) is another biological variable identified as a tool for rapid assessment of nutritional status that is correlated with BMI. Therefore, we aim to surrogate BMI by MUAC cut-offs for rapid screening of maternal nutritional status starting at midpregnancy. Design: Analysis of the multicentre cohort study entitled ‘Preterm SAMBA’ using an approach of validation of diagnostic test. Setting: Outpatient prenatal care clinics from five tertiary maternity hospitals from three different Brazilian regions. Participants: 1165 pregnant women attending prenatal care services from 2015 to 2018 and with diverse ethnic characteristics who were enrolled at midpregnancy and followed in three visits at different gestational weeks. Primary and secondary outcome measures: Sensitivity, specificity, positive and negative predictive values, likelihood ratio and accuracy of MUAC being used instead of BMI for the assessment of nutritional status of women during pregnancy. Results: We found a strong correlation between MUAC and BMI, in the three set points analysed (r=0.872, 0.870 and 0.831, respectively). Based on BMI categories of nutritional status, we estimated the best MUAC cut-off points, finding measures according to each category: underweight 30.15 cm (19–21 weeks), >30.60 cm (27–29 weeks) and >30.25 cm (37–39 weeks) per gestational week. Therefore, we defined as adequate between 25.75–28.10 cm (19–21 weeks), 25.75–28.70 cm (27–29 weeks) and 25.75–29.45 cm (37–39 weeks) of MUAC. Conclusion: We conclude that MUAC can be useful as a surrogate for BMI as a faster screening of nutritional status in pregnant women

Head circumference as an epigenetic risk factor for maternal nutrition

Nutrition indicators for malnutrition can be screened by many signs such as stunting, underweight or obesity, muscle wasting, and low caloric and nutrients intake. Those deficiencies are also associated with low socioeconomic status. Anthropometry can assess nutritional status by maternal weight measurements during pregnancy. However, most studies have focused primarily on identifying changes in weight or Body Mass Index (BMI), and their effects on neonatal measures at present time. Whereas head circumference (HC) has been associated with nutrition in the past. When the mother was exposed to poor nutrition and unfavorable social conditions during fetal life, it was hypothesized that the intergenerational cycle was potentially mediated by epigenetic mechanisms. To investigate this theory, maternal head circumference (MHC) was associated with neonatal head circumference (NHC) in pregnant women without preexisting chronic conditions, differentiated by sociodemographic characteristics. A multiple linear regression model showed that each 1 cm-increase in MHC correlated with a 0.11 cm increase in NHC (β95% CI 0.07 to 0.15). Notwithstanding, associations between maternal and neonatal anthropometrics according to gestational age at birth have been extensively explained. Path analysis showed the influence of social status and the latent variable was socioeconomic status. A model of maternal height and head circumference was tested with effects on neonatal HC. The social variable lacked significance to predict neonatal HC in the total sample (p = 0.212) and in the South/Southeast (p = 0.095), in contrast to the Northeast (p = 0.047). This study highlights the potential intergenerational influence of maternal nutrition on HC, suggesting that maternal nutrition may be more relevant in families with major social vulnerability