Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management.

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS). STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed. MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics and clinical outcomes. RESULTS: A total of 97 SARS-CoV-2 unvaccinated women with suspected infection were considered, 76 were COVID-19 positive cases and 21 COVID-19 negative. Among COVID-19 positive cases, 09 presented with SARS and 11 were diagnosed with PE, of which 6 had SARS-CoV-2 infection in first and second trimester (04 with sFlt-1/PlGF ≥ 38) and 05 with PE and COVID-19 diagnosed at the same time, during third trimester (03 with sFlt-1/PlGF ≥ 38). Five presented with PE with severe features. sFlt-1/PlGF ratio was significantly higher in the COVID-19 positive/PE positive group compared to COVID-19 positive/PE negative group (p-value = 0.005), with no increase in cases complicated by SARS. CONCLUSIONS: sFlt-1/PlGF ratio could be a useful tool for differential diagnosis and adequate counseling among cases of COVID-19 and PE, especially if severe disease. COVID-19 early in pregnancy could potentially be a risk factor for PE later during gestation.

The impact of maternal morbidity on cesarean section rates: exploring a Latin American network of sentinel facilities using the Robson's Ten Group Classification System

Background: Latin America has the highest Cesarean Section Rates (CSR) in the world. Robson's Ten Group Classification System (RTGCS) was developed to enable understanding the CSR in different groups of women, classified according to obstetric characteristics into one of ten groups. The size of each CS group may provide helpful data on quality of care in a determined region or setting. Data can potentially be used to compare the impact of conditions such as maternal morbidity on CSR. The objective of this study is to understand the impact of Severe Maternal Morbidity (SMM) on CSR in ten different groups of RTGCS. Methods: Secondary analysis of childbirth information from 2018 to 2021, including 8 health facilities from 5 Latin American and Caribbean countries (Bolivia, Guatemala, Honduras, Nicaragua, and the Dominican Republic), using a surveillance database (SIP-Perinatal Information System, in Spanish) implemented in different settings across Latin America. Women were classified into one of RTGCS. The frequency of each group and its respective CSR were described. Furthermore, the sample was divided into two groups, according to maternal outcomes: women without SMM and those who experienced SMM, considering Potentially Life-threatening Conditions, Maternal Near Miss and Maternal Death as the continuum of morbidity. Results: Available data were obtained from 92,688 deliveries using the Robson Classification. Overall CSR was around 38%. Group 5 was responsible for almost one-third of cesarean sections. SMM occurred in 6.7% of cases. Among these cases, the overall CSR was almost 70% in this group. Group 10 had a major role (preterm deliveries). Group 5 (previous Cesarean section) had a very high CSR within the group, regardless of the occurrence of maternal morbidity (over 80%). Conclusion: Cesarean section rate was higher in women experiencing SMM than in those without SMM in Latin America. SMM was associated with higher Cesarean section rates, especially in groups 1 and 3. Nevertheless, group 5 was the major contributor to the overall CSR. (AU)

Multidimensional assessment of women after severe maternal morbidity: the COMMAG cohort study.

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.

Risk stratification for small for gestational age for the Brazilian population: a secondary analysis of the Birth in Brazil study.

Risk-stratification screening for SGA has been proposed in high-income countries to prevent perinatal morbidity and mortality. There is paucity of data from middle-income settings. The aim of this study is to explore risk factors for SGA in Brazil and assess potential for risk stratification. This population-based study is a secondary analysis of Birth in Brazil study, conducted in 266 maternity units between 2011 and 2012. Univariate and multivariate logistic regressions were performed, and population attributable fraction estimated for early and all pregnancy factors. We calculated absolute risk, odds ratio, and population prevalence of single or combined factors stratified by parity. Factors associated with SGA were maternal lupus (ORadj 4.36, 95% CI [2.32-8.18]), hypertensive disorders in pregnancy (ORadj 2.72, 95% CI [2.28-3.24]), weight gain < 5 kg (ORadj 2.37, 95% CI [1.99-2.83]), smoking at late pregnancy (ORadj 2.04, 95% CI [1.60-2.59]), previous low birthweight (ORadj 2.22, 95% CI [1.79-2.75]), nulliparity (ORadj 1.81, 95% CI [1.60-2.05]), underweight (ORadj 1.61, 95% CI [1.36-1.92]) and socioeconomic status (SES) < 5th centile (ORadj 1.23, 95% CI [1.05-1.45]). Having two or more risk factors (prevalence of 4.4% and 8.0%) was associated with a 2 and fourfold increase in the risk for SGA in nulliparous and multiparous, respectively. Early and all pregnancy risk factors allow development of risk-stratification for SGA. Implementation of risk stratification coupled with specific strategies for reduction of risk and increased surveillance has the potential to contribute to the reduction of stillbirth in Brazil through increased detection of SGA, appropriate management and timely delivery.

The role of maternal infection in preterm birth: evidence from the Brazilian Multicentre Study on Preterm Birth (EMIP)

OBJECTIVES: Evidence suggests that infection or inflammation is a major contributor to early spontaneous preterm birth (sPTB). Therefore, this study aimed to investigate the development and causes of maternal infection associated with maternal and neonatal outcomes in women with sPTB. METHODS: This was a secondary analysis of a multicenter cross-sectional study with a nested case-control component, the Brazilian Multicentre Study on Preterm Birth (EMIP), conducted from April 2011 to July 2012 in 20 Brazilian referral obstetric hospitals. Women with preterm birth (PTB) and their neonates were enrolled. In this analysis, 2,682 women undergoing spontaneous preterm labor and premature pre-labor rupture of membranes were included. Two groups were identified based on self-reports or prenatal or hospital records: women with at least one infection factor and women without any maternal infection (vulvovaginitis, urinary tract infection, or dental infection). A bivariate analysis was performed to identify potential individual risk factors for PTB. The odds ratios (ORs) with their respective 95% confidence intervals were calculated. RESULTS: The majority of women with sPTB fulfilled at least one criterion for the identification of maternal infection (65.9%), and more than half reported having urinary tract infection during pregnancy. Approximately 9.6% of women with PTB and maternal infection were classified as having periodontal infection only. Apart from the presence of a partner, which was more common among women with infectious diseases (p=0.026; OR, 1.28 [1.03-1.59]), other variables did not show any significant difference between groups. CONCLUSION: Maternal infection was highly prevalent in all cases of sPTBs, although it was not clearly associated with the type of PTB, gestational age, or any adverse neonatal outcomes.

Trace biomarkers associated with spontaneous preterm birth from the maternal serum metabolome of asymptomatic nulliparous women - parallel case-control studies from the SCOPE cohort.

Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.

Postpartum psychoactive substance abuse after severe maternal morbidity.

OBJECTIVE: To evaluate drug use among mothers during the postpartum period after a severe pregnancy-related complication. METHODS: A retrospective cohort study of maternal morbidity including maternal near-miss and control groups conducted in a tertiary hospital in Campinas, Brazil, between July 2008 and June 2012. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to assess drug use during lifetime, pregnancy, and in the previous 3 months. RESULTS: Of 638 women evaluated, drug use was reported by 165 (25.8%). Alcohol was the most common substance used (n=133, 20.6%), followed by tobacco (n=85, 13.2%), and cocaine (n=15, 2.3%). The highest risk for postpartum drug use was among those using drugs during pregnancy. There were no differences between the morbidity and control groups, but there was a significant difference in the need for intervention to reduce alcohol consumption in the severe maternal morbidity group. Risk for substance abuse intervention increased three-fold in women with PTSD criteria, and all aspects of quality of life were worse among drug users. CONCLUSION: Drug use during pregnancy and maternal complications are linked to postpartum drug abuse. These women should be managed during pregnancy; postpartum follow-up requires updated guidance and must go beyond family planning.

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

OBJECTIVE: To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. METHODS: In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. RESULTS: There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. CONCLUSIONS: A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

Exploring the Concept of Degrees of Maternal Morbidity as a Tool for Surveillance of Maternal Health in Latin American and Caribbean Settings.

OBJECTIVES: To assess a birth registry to explore maternal mortality and morbidity and their association with other factors. STUDY DESIGN: Exploratory multicentre cross-sectional analysis with over 700 thousand childbirths from twelve Latin American and Caribbean countries between 2009 and 2012. The WHO criteria for maternal morbidity were employed to split women, following a gradient of severity of conditions, into (1) maternal death (MD); (2) maternal near miss (MNM); (3) potentially life-threatening conditions (PLTC); (4) less severe maternal morbidity (LSMM); (5) any maternal morbidity; and (6) women with no maternal morbidity. Their prevalence and estimated risks of adverse maternal outcomes were assessed. RESULTS: 712,081 childbirths had a prevalence of MD and MNM of 0.14% and 3.1%, respectively, while 38% of women had experienced morbidity. Previous maternal morbidity was associated with higher risk of adverse maternal outcomes and also the extremes of reproductive ages, nonwhite ethnicity, no stable partner, no prenatal care, smoking, drug and alcohol use, elective C-section, or induction of labour. Poorer perinatal outcomes were proportional to the severity of maternal outcomes. CONCLUSIONS: The findings corroborate WHO concept regarding continuum of maternal morbidity, reinforcing its importance in preventing adverse maternal outcomes and improving maternal healthcare in different settings.

Maternal near miss among women using the public health system in the Amazon and Northeast regions of Brazil / Morbilidad materna extremadamente grave entre las usuarias del sistema de salud pública en las regiones amazónica y noreste del Brasil

OBJECTIVE: To assess the prevalence of pregnancy complications identified as maternal near miss (MNM) and associated factors among women using the public health care system in the Amazon and Northeast regions of Brazil. METHODS: A secondary analysis of a population-based survey conducted in 2010 was performed focusing on women self-reporting maternal complications. The main outcome was MNM, pragmatically defined as intensive care unit admission, eclampsia, hysterectomy, or blood transfusion. In addition, the risk of MNM was estimated for certain sociodemographics and characteristics of care received. Poisson regression was performed, generating adjusted prevalence ratios (PRadj) with 95% confidence intervals (95%CI). RESULTS: A total of 13 044 women (77%) who had given birth during the prior year using the public health system were interviewed. At least one complication was reported by 37.5%, with hemorrhage (28.4%) and infection (8.3%) being the most frequent. The overall MNM ratio was 31.5 per 1 000 live births, higher for the Amazon region than for the Northeast. Factors with a higher risk for developing MNM were: indigenous ethnicity (PRadj 2.77; 95% CI: 1.50-5.14), more than one hour to reach the hospital (PRadj 1.55; 95%CI: 1.06-2.25), being refused by a full hospital and having to find another one (PRadj 1.49; 95%CI: 1.03-2.16), cesarean section (PRadj 2.56; 95%CI: 1.90-3.44), and public prenatal care (PRadj 1.95; 95%CI: 1.06-3.61). CONCLUSIONS: Users of public health system in the Amazon and Northeast regions of Brazil have high MNM rates. Some characteristics of the women and of the care they received represent inequalities associated with higher risk for MNM. Specific actions are required to improve maternal health programs in these expansive areas of the country.

OBJETIVO: Evaluar la prevalencia de las complicaciones del embarazo establecidas como morbilidad materna extremadamente grave (MMEG), y los factores asociados, entre las usuarias del sistema de atención de salud pública en las zonas amazónica y noreste del Brasil. MÉTODOS:Se realizó un análisis secundario de una encuesta poblacional llevada a cabo en el 2010 y centrado en las mujeres que autonotificaban complicaciones obstétricas. El principal resultado fue la MMEG, definida a efectos prácticos como ingreso en una unidad de cuidados intensivos, eclampsia, histerectomía o transfusión de sangre. Se calculó además el riesgo de MMEG para determinadas características sociodemográficas y de la atención recibida. Se llevó a cabo una regresión de Poisson y se generaron las razones de prevalencia ajustadas (RPa) con intervalos de confianza de 95% (IC 95%). RESULTADOS:Se entrevistó a un total de 13 044 mujeres (77%) que habían dado a luz durante el año previo en el sistema de salud pública. Un 37,5% notificó como mínimo una complicación; la hemorragia (28,4%) y la infección (8,3%) fueron las más frecuentes. El índice general de MMEG fue de 31,5 por 1 000 nacidos vivos, más elevado en la región amazónica que en la noreste. Los factores que comportaron un riesgo mayor de MMEG fueron la etnicidad autóctona (RPa 2,77; IC 95% = 1,50-5,14), precisar más de una hora para llegar al hospital (RPa 1,55; IC 95% = 1,06-2,25), no ser admitida en un hospital por estar completo y tener que encontrar otro (RPa 1,49; IC 95% = 1,03-2,16), la cesárea (RPa 2,56; IC 95% = 1,90-3,44), y la asistencia prenatal pública (RPa 1,95; IC 95% = 1,06-3,61). CONCLUSIONES: Las usuarias del sistema de salud pública en las regiones amazónica y noreste del Brasil muestran tasas elevadas de morbilidad materna extremadamente grave. Algunas características de las mujeres y de la atención recibida comportan desigualdades asociadas con un riesgo mayor de morbilidad materna extremadamente grave. Se requieren acciones específicas que mejoren los programas de salud materna en estas amplias zonas del país.

EXPERIENCE WITH THE BRAZILIAN NETWORK FOR STUDIES IN REPRODUCTIVE AND PERINATAL HEALTH: THE POWER OF COLLABORATION IN POSTGRADUATE PROGRAMS / EXPERIÊNCIA COM A REDE BRASILEIRA DE ESTUDOS EM SAÚDE REPRODUTIVA E PERINATAL: O PODER DA COLABORAÇÃO NA PÓS-GRADUAÇÃO

The scientific collaboration in networks may be developed among countries, academic institutions and among peer researchers. Once established, they contribute for knowledge dissemination and a strong structure for research in health. Several advantages are attributed to working in networks: the inclusion of a higher number of subjects in the studies; generation of stronger evidence with a higher representativeness of the population (secondary generalization and external validity); higher likelihood of articles derived from these studies to be accepted in high impact journals with a wide coverage; a higher likelihood of obtaining budgets for sponsorship; easier data collection on rare conditions; inclusions of subjects from different ethnic groups and cultures, among others. In Brazil, the Brazilian Network for Studies on Reproductive and Perinatal Health was created in 2008 with the initial purpose of developing a national network of scientific cooperation for the surveillance of severe maternal morbidity. Since the establishment of this Network, five studies were developed, some of them already finished and others almost being completed, and two new ones being implemented. Results of the activities in this Network have been very productive and with a positive impact on not only the Postgraduate Program of Obstetrics and Gynecology from the University of Campinas, its coordinating center, but also on other participating centers. A considerable number of scientific articles was published, master´s dissertations and PhD theses were presented, and post-doctorate programs were performed, including students from several areas of health, from distinct regions and from several institutions of the whole country. This represents a high social impact taking into account the relevance of the studied topics for the country.

As colaborações científicas em rede podem ocorrer entre países, instituições acadêmicas e entre pares de pesquisadores e, uma vez estabelecidas, contribuem para a disseminação do conhecimento e estruturação da pesquisa em saúde. Diversas vantagens são atribuídas ao trabalho em rede como: a inclusão de maior número de participantes nos estudos; gerar evidências mais fortes e com maior representatividade da população (generalização secundária e validade externa); maior facilidade das publicações oriundas dos estudos serem aceitas em periódicos de impacto e abrangência; maior probabilidade de obtenção de verbas para financiamento; maior facilidade na coleta de dados sobre condições raras; inclusão de participantes de diferentes grupos étnicos e culturas, entre outras. No Brasil a Rede Brasileira de Estudos em Saúde Reprodutiva e Perinatal foi criada em 2008 com o objetivo inicial de desenvolver rede nacional de cooperação científica para vigilância da morbidade materna grave. Desde sua formação, cinco estudos foram desenvolvidos, alguns já encerrados e outros em fase de finalização, com outros dois em fase final de implantação. Os resultados das atividades desta Rede têm sido bastante produtivos e impactaram positivamente não apenas no Programa de Pós-Graduação em Tocoginecologia da Universidade Estadual de Campinas, seu centro coordenador, mas também o de outros centros participantes, uma vez que expressivo número de artigos científicos foi publicado, mestrados e doutorados foram defendidos e pós-doutorados finalizados, de alunos de diversas áreas da saúde, de diferentes regiões e de várias instituições de todo o país, com alto impacto social dada a relevância dos temas estudados para o país.

Strategies in searching homogeneity in a faculty of a postgraduate program / Estratégias na busca da homogeneidade do corpo docente de um programa de pós-graduação

The professor plays a fundamental role in a graduate program, considering he/she is who plans and performs a great part of the tasks, and he/she is also responsible for spreading knowledge among students. The professor should use didactical resources for his/her continuous qualification, being responsible for situations favoring the development of students who should learn according to the best and easier way. The homogeneity in the postgraduate program consists of having subgroups of research corresponding to the Areas of Concentration, where each subgroup works with some distinct topics of research. It is desirable that the staff of postgraduate program has a significant and high quality scientific production, homogeneously distributed among them. The professors must systematically search for resources for research in agencies supporting research, not only for sponsoring the studies, but also for adding value to the researchers involved in the whole activities. The postgraduate programs need to support the professional qualification of their staff who should improve their knowledge on epidemiology for clinical studies, ethics in research and teaching skills. Two characteristics of the postgraduate system in Brazil are the nucleation and solidarity, based on the capacity and/or interest of those more structured programs to help those beginners, cooperating with their activities. The Capes (the national governmental agency responsible for coordinating and evaluating all postgraduate programs in Brazil) valorizes the social insertion in the context of postgraduate programs´ activities. It includes the recognition of activities with technological, cultural, educational and social impact as criteria for evaluation of the programs. Does exist an ideal model of postgraduate program? We think that there is no a mathematical formulae nor an ideal model for a postgraduate program. Each institution should make adaptations and search for improvements of their faculty and students´ teams.

O docente tem importância fundamental no programa de pós-graduação, pois é quem planeja e executa grande parte das tarefas, sendo também o responsável por difundir conhecimentos aos alunos. O professor deve utilizar recursos didáticos que o qualifiquem continuamente, criando condições favoráveis para que o aluno se desenvolva e aprenda da melhor maneira e com mais facilidade. A homogeneidade no grupo de pós-graduação consiste da presença de subgrupos de pesquisa correspondentes às Áreas de Concentração, onde cada subgrupo trabalhe com algumas linhas de pesquisas diversificadas. É desejável que o corpo docente tenha significativa produção científica, de qualidade e distribuída homogeneamente entre os docentes. Estes devem sistematicamente buscar recursos em agências de fomento para pesquisa, tanto para o custeio dos estudos, quanto para a valorização dos pesquisadores envolvidos em todas as atividades. Os programas de pós-graduação precisam investir na formação de seus docentes, os quais devem aprimorar seus conhecimentos em epidemiologia de estudos clínicos, ética em pesquisa e em didática. Duas das características do sistema de pós-graduação no Brasil são a nucleação e a solidariedade, embasadas na capacidade e/ou interesse dos mais estruturados se solidarizarem com os programas iniciantes, cooperando com as suas atividades. A Capes valoriza a inserção social no contexto das atividades dos programas de pós-graduação, prevendo nos critérios de avaliação o reconhecimento de atividades com impacto tecnológico, cultural, educacional e social. Existe um modelo ideal de pós-graduação? Partimos do pressuposto de que não há uma fórmula matemática ou modelo ideal de pós-graduação e sim que cada instituição deve se adequar e buscar aperfeiçoar seu corpo docente e discente.