Pre-eclampsia in low and middle-income settings: What are the barriers to improving perinatal outcomes and evidence-based recommendations?

OBJECTIVE: To discuss the points that still challenge low- and middle-income countries (LMICs) and strategies that have been studied to help them overcome these issues. METHODS: Narrative review addressing 20 years of articles concerning pre-eclampsia morbidity and mortality in LMICs. We summarized evidence-based strategies to overcome the challenges in order to reduce the pre-eclampsia impact on perinatal outcomes. RESULTS: Pre-eclampsia is the first or second leading cause in the ranking of avoidable causes of maternal death, and approximately 16% of all maternal deaths are attributable to eclampsia and pre-eclampsia. Considering the social and economic contexts, it represents a major public health concern, and prevention and early detection of pre-eclampsia seem to be a major challenge. Reducing maternal mortality related to hypertensive disturbances depends on public policies to manage these preventable conditions. Early and continuous recognition of signs of severity related to hypertensive disorders during pregnancy and childbirth, self-monitoring of symptoms and blood pressure, as well as preventive approaches such as aspirin and calcium, and magnesium sulfate, are lifesaving procedures that have not yet reached a universal scale. CONCLUSION: This review provides a vision of relevant points to support pregnant women in overcoming the constraints to healthcare access in LMICs, and strategies that can be applied in primary prenatal care units.

Measuring resilience and stress during pregnancy and its relation to vulnerability and pregnancy outcomes in a nulliparous cohort study.

BACKGROUND: Resilience reflects coping with pregnancy-specific stress, including physiological adaptations of the maternal organism or factors arising from the socioeconomic context, such as low income, domestic violence, drug and alcohol use, lack of a support network and other vulnerability characteristics. Resilience is a dynamic characteristic that should be comparatively evaluated within a specific context; its association with perceived stress and social vulnerability during pregnancy is still not fully understood. This study aimed at exploring maternal resilience, perceived stress and social vulnerability during pregnancy and its associated factors and outcomes. METHODS: Prospective multicenter cohort study of nulliparous women in Brazil determining resilience (Resilience Scale; RS) and stress (Perceived Stress Scale; PSS) at 28 weeks of gestation (± 1 week). Resilience and stress scores were compared according to sociodemographic characteristics related to maternal/perinatal outcomes and social vulnerability, defined as having low level of education, being adolescent, without a partner or ethnicity other than white. RESULTS: We included 383 women who completed the RS and PSS instruments. Most women showed low resilience scores (median: 124.0; IQR 98-143). Women with a low resilience score (RS < 125) were more likely from the Northeast region, adolescents, other than whites, did not study or work, had a low level of education, low family income and received public antenatal care. Higher scores of perceived stress were shown in the Northeast, other than whites, at low levels of education, low annual family income and public antenatal care. Pregnant women with low resilience scores (n = 198) had higher perceived stress scores (median = 28) and at least one vulnerability criterion (n = 181; 91.4%). CONCLUSION: Our results reinforce the role of resilience in protecting women from vulnerability and perceived stress. It may prevent complications and build a positive experience during pregnancy.

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 (ß95% 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.

Performances of birthweight charts to predict adverse perinatal outcomes related to SGA in a cohort of nulliparas.

BACKGROUND: Small-for-gestational-age neonates (SGA) are at increased risk of neonatal morbidity. Nulliparity represents a risk factor for SGA; birthweight charts may perform differently for the detection of SGA among nulliparas. This study aimed at describing the prevalence of SGA in nulliparas according to different birthweight charts and evaluating the diagnostic performance of these charts to maternal and perinatal outcomes. METHODS: This is a secondary analysis of a Brazilian cohort of nulliparas named Preterm SAMBA study. Birthweight centiles were calculated using the Intergrowth-21st, WHO-Fetal Growth Charts, Birth in Brazil population chart and GROW-customised chart. The risks of outcomes among SGA neonates and their mothers in comparison to neonates with birthweights between the 40th-60th centiles were calculated, according to each chart. ROC curves were used to detect neonatal morbidity in neonates with birth weights below different cutoff centiles for each chart. RESULTS: A sample of 997 nulliparas was assessed. The rate of SGA infants varied between 7.0-11.6%. All charts showed a significantly lower risk of caesarean sections in women delivering SGA neonates compared to those delivering adequate-for-gestational-age neonates (OR 0.55-0.64, p < .05). The charts had poor performance (AUC 0.492 - 0.522) for the detection of neonatal morbidity related to SGA born at term. CONCLUSION: The populational and customised birthweight charts detected different prevalence of small-for-gestational-age neonates and showed similar and poor performance to identify related neonatal adverse outcomes in this population.

Preeclampsia among women with COVID-19 during pregnancy and its impact on maternal and perinatal outcomes: Results from a national multicenter study on COVID in Brazil, the REBRACO initiative.

OBJECTIVE: To evaluate the prevalence of preeclampsia among cases of COVID-19 infection during pregnancy and the association between both conditions, in a multicenter cohort of Brazilian women with respiratory symptoms. STUDY DESIGN: Ancillary analysis of the Brazilian Network of COVID-19 in Obstetrics (REBRACO) study. We performed a nested case-control analysis selecting all women with COVID-19 and compared outcomes between women with and without PE. MAIN OUTCOMES: Maternal, gestational, and clinical characteristics and perinatal outcomes. MEASURES: Prevalence ratio (PR) and its 95%CI for each of the predictors and outcomes. RESULTS: A total of 203 women were included: 21 (10.3%) in PE group and 182 (89.7%) in non-PE group. Preeclampsia was not different among women with and without COVID-19 (10.3% vs 13.1%, p-value = 0.41), neither complication such as eclampsia and HELLP syndrome. Chronic hypertension (33.4%) (p < 0.01) and obesity (60.0%) (p = 0.03) were the most frequent comorbidities in PE group, and they were significantly more frequent in this group. Women with PE had more cesarean section (RR 5.54 [1.33 - 23.14]) and their neonates were more frequently admitted to neonatal intensive care unit (PR 2.46[1.06 - 5.69]), most likely due to preterm-birth-related complications. CONCLUSION: The prevalence of PE among women with COVID-19 infection during pregnancy was around 10%; women with COVID-19 and a history of chronic hypertension or obesity are more likely to have preeclampsia. Cesarean section is increased among women with PE and COVID-19, with increased rates of neonatal admission to intensive care units, mostly due to prematurity.

Prediction of pregnancy-related hypertensive disorders using metabolomics: a systematic review.

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.

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.

Agreement between the short and long versions of the Resilience Scale: A validation among the obstetric population according to vulnerability status.

OBJECTIVE: To compare the 14-item Resilience Scale (RS-14) and the original 25-item scale (RS-25) in the obstetric population, including vulnerable and non-vulnerable women. METHODS: A Brazilian prospective cohort study was conducted of nulliparous singleton pregnant women from March 2018 to March 2020. Women who completed the RS-25 at 27-29 weeks of pregnancy were included in the analysis. RS-25 and RS-14 scores were converted to comparable scales of 0-100. Medians, standard deviations, and centiles between versions were compared for the general, vulnerable, and non-vulnerable populations. Correlation, concordance, and internal consistency and reliability analyses were performed. P < 0.05 was considered statistically significant. RESULTS: In total, 381 women who completed the RS-25 were included. Medians of RS-14 and RS-25 scores were significantly different (73.4 and 70.8, respectively; P < 0.001), regardless of the vulnerability status. The RS-14 showed a high correlation (Pearson´s correlation coefficient of -0.379 (P-value < 0.001)), but no agreement (Pitman's test of difference in variance: r = 0.422; P < 0.001) with the RS-25 version. RS-14 showed high internal consistency and reliability with only one component (Variance of 59.82%, Cronbach's Alpha 0.947). CONCLUSION: The RS-14 may overestimate the RS-25 score and different domains may not be assessed by the short version. The psychometric properties of the RS-14 and the clinical relevance of the variation between versions require further evaluation.

Dyspnea and COVID-19: A Review of Confounding Diagnoses during the Postpartum Period.

The puerperium is a complex period that begins with placental delivery and lasts for 6 weeks, during which readaptation of the female organism and redistribution of blood volume occur. This period is conducive to the occurrence of thromboembolic events. In the context of the SARS-CoV-2 pandemic, the virus responsible for COVID-19, the attention of the scientific community and health professionals has been focused on obtaining insights on different aspects of this disease, including etiology, transmission, diagnosis, and treatment. Regarding the pregnancy-postpartum cycle, it is opportune to review the clinical conditions that can occur during this period and to investigate dyspnea as a postpartum symptom in order to avoid its immediate association with COVID-19 without further investigation, which can lead to overlooking the diagnosis of other important and occasionally fatal conditions.

O puerpério é um período complexo que se inicia com a dequitação placentária e dura por 6 semanas, no qual a readaptação do organismo materno e a redistribuição do volume sanguíneo ocorrem, além de ser também um cenário propício para eventos pró-trombóticos. No contexto da pandemia de SARS-CoV-2, vírus responsável pela COVID-19, a atenção da comunidade científica e dos profissionais da saúde está voltada a elucidar os aspectos da doença, como a etiologia, a transmissão, o diagnóstico e o tratamento. Considerando o ciclo gravídico-puerperal, é oportuna a revisão de condições clínicas que ocorrem durante este período e que apresentam a dispneia como sintoma, a fim de evitar que ela seja automaticamente associada à COVID-19 sem investigações aprofundadas, o que pode levar à negligência do diagnóstico de outras condições importantes e que podem ser, por vezes, fatais.

Dyspnea and COVID-19: A Review of Confounding Diagnoses during the Postpartum Period / Dispneia e COVID-19: uma revisão de diagnósticos confundidores no período pós-parto

Abstract The puerperium is a complex period that begins with placental delivery and lasts for 6 weeks, during which readaptation of the female organism and redistribution of blood volume occur. This period is conducive to the occurrence of thromboembolic events. In the context of the SARS-CoV-2 pandemic, the virus responsible for COVID-19, the attention of the scientific community and health professionals has been focused on obtaining insights on different aspects of this disease, including etiology, transmission, diagnosis, and treatment. Regarding the pregnancy-postpartum cycle, it is opportune to review the clinical conditions that can occur during this period and to investigate dyspnea as a postpartum symptom in order to avoid its immediate association with COVID-19 without further investigation, which can lead to overlooking the diagnosis of other important and occasionally fatal conditions.

Resumo O puerpério é um período complexo que se inicia com a dequitação placentária e dura por 6 semanas, no qual a readaptação do organismo materno e a redistribuição do volume sanguíneo ocorrem, além de ser também um cenário propício para eventos pró-trombóticos. No contexto da pandemia de SARS-CoV-2, vírus responsável pela COVID-19, a atenção da comunidade científica e dos profissionais da saúde está voltada a elucidar os aspectos da doença, como a etiologia, a transmissão, o diagnóstico e o tratamento. Considerando o ciclo gravídico-puerperal, é oportuna a revisão de condições clínicas que ocorrem durante este período e que apresentam a dispneia como sintoma, a fimde evitar que ela seja automaticamente associada à COVID-19 sem investigações aprofundadas, o que pode levar à negligência do diagnóstico de outras condições importantes e que podem ser, por vezes, fatais.

Maternal Nutrition Status Associated with Pregnancy-Related Adverse Outcomes.

Although maternal nutrition has an impact on fetal development and gestational outcome, tracking maternal nutrition in outpatient practice is still complex and involves proper technical capacitation in this area. Nevertheless, the association between nutritional variables may broaden the ability to predict the occurrence of gestational disorders and prevention management. We aimed to identify factors that could indicate the probability of adverse outcomes in mid-pregnancy. From a cohort of 1165 nulliparous pregnant women without any previous disease, the nutritional status was assessed by body mass index (BMI) and mid-upper arm circumference (MUAC), associated with dietary patterns and sociodemographic characteristics. Two predictive models with nutritional status for screening the occurrence of adverse outcomes of preterm birth, gestational diabetes mellitus, small-for-gestational-age newborns and preeclampsia were developed. The odds of adverse outcomes were higher in non-white (p < 0.05) obese women and with high protein consumption. There was no significant difference between the models, with an overall accuracy of 63% for both models and a probability of success in predicting adverse outcomes (BMI = 61%, MUAC = 52%). This study of Brazilian pregnant nulliparous women offers two possible options for early tracking of adverse gestational outcomes that should be further externally validated.

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.

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 <25.75 cm (19-39 weeks); overweight 28.11-30.15 cm (19-21 weeks), 28.71-30.60 cm (27-29 weeks) and 29.46-30.25 cm (37-39 weeks); and obese >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.

Metabolomics for prediction of hypertension in pregnancy: a systematic review and meta-analysis protocol.

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.

Incidence and risk factors for hyperglycemia in pregnancy among nulliparous women: A Brazilian multicenter cohort study.

OBJECTIVE: To assess the incidence and risk factors for hyperglycemia in pregnancy in a cohort of Brazilian nulliparous pregnant women. MATERIALS AND METHODS: This is a secondary analysis of a multicenter cohort study that enrolled 1,008 nulliparous pregnant women at 19-21 weeks. Exclusion criteria included chronic exposure to corticosteroids and previous diabetes. Bivariate and multivariate analyses by Poisson regression were used to identify associated factors. RESULTS: The incidence of hyperglycemia in pregnancy was 14.9% (150/1,008), and 94.7% of these cases were gestational diabetes mellitus (142/150). Significant associated factors included a family history of diabetes mellitus, maternal overweight or obesity at enrollment, and previous maternal conditions (polycystic ovarian syndrome, thyroid dysfunctions and hypertensive disorders). A BMI ≥ 26.3Kg/m2 (RRadj 1.87 [1.66-2.10]) and a family history of diabetes mellitus (RRadj 1.71 [1.37-2.15]) at enrollment were independent risk factors for HIP. CONCLUSIONS: A family history of diabetes mellitus and overweight or obesity (until 19-21 weeks of gestation) may be used as selective markers for HIP in Brazilian nulliparous women. Given the scarcity of results in nulliparous women, our findings may contribute to determine the optimal diagnostic approach in populations of similar socioeconomic characteristics.

Perinatal outcomes from preterm and early term births in a multicenter cohort of low risk nulliparous women.

Preterm birth is the major contributor for neonatal and under-five years mortality rates and also accounts for a short- and long-term adverse consequences up to adulthood. Perinatal outcomes may vary according to lots of factors as preterm subtype, late prematurity, which account for the vast majority of cases, country and population characteristics. An under-recognition of the perinatal outcomes and its associated factors might have underpowered strategies to provide adequate care and prevent its occurrence. We aim to estimate the frequency of maternal and perinatal outcomes in women with different categories of preterm and term births, factors associated with poorer perinatal outcomes and related management interventions. A multicentre prospective cohort in five maternities in Brazil between 2015 and 2018. Nulliparous low-risk women with singletons were included. Comprehensive data were collected during three antenatal visits (at 19-21weeks, 27-29 weeks and 37-39 weeks). Maternal and perinatal outcomes were also collected according to maternal and neonatal medical records. Women who had spontaneous (sPTB) and provider-initiated (pi-PTB) preterm birth were compared to those who had term birth. Also, late preterm birth (after 34 weeks), and early term (37-38 weeks) were compared to full term birth (39-40 weeks). Bivariate analysis estimated risk ratios for maternal and adverse outcomes. Finally, a multivariate analysis was conducted to address factors independently associated with any adverse perinatal outcome (APO). In total, 1,165 women had outcome data available, from which 6.7% had sPTB, 4.0% had pi-PTB and 89.3% had a term birth. sPTB and pi-PTb were associated with poorer perinatal outcomes, as well as late sPTB, late pi-PTB and early term neonates. pi-PTB (RRadj 8.12, 95% CI [2.54-25.93], p-value 0.007), maternal weight gain between 20 and 27 weeks

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 five 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 first 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 (<25 mm) at 18-24 weeks (31.2%) and those with a short cervix and vaginal bleeding in the first 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.

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.

Metabolomics for predicting hyperglycemia in pregnancy: a protocol for a systematic review and potential meta-analysis.

BACKGROUND: Hyperglycemia in pregnancy (HIP) has been recently differentiated between diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM). The proposed protocol is relevant, and clinical concern is due to the higher risk of adverse pregnancy outcomes (APO) and long-term effects on both the mother and the fetus. Fasting plasma glucose level (FPG) and oral glucose tolerance test (OGTT) are current diagnostic tools. However, controversy persists concerning diagnostic criteria, cut-off points, and even selective or universal screening. The objective of this systematic review is to assess the performance of metabolomic markers in the prediction of HIP. METHODS: This is a protocol for a systematic review with potential meta-analysis. The primary outcome is GDM, defined as glucose intolerance identified in the second and third trimesters of pregnancy (any FPG ≥ 92 mg/dL and < 126 mg/dL OR when 75-g OGTT shows one altered value among these: FPG ≥ 92 mg/dL or 1-h post glucose load ≥ 180 mg/dL or 2-h post glucose load ≥ 153 mg/dL); the secondary outcome is HIP, defined as hyperglycemia detected in the first trimester of pregnancy (any FPG ≥ 126 mg/dL). A detailed systematic literature search will be carried out in electronic databases and conference abstracts, using the keywords "gestational diabetes mellitus," "metabolomics," "pregnancy," and "screening" (and their variations). We will include original peer-reviewed articles published from Jan 1, 1999, to Dec 31, 2018. Original studies including diabetes diagnosed before pregnancy (T2DM and T1DM), multiple pregnancies, and congenital malformations will be excluded. All results regarding samples, participant characteristics, metabolomic techniques, and diagnostic accuracy measures will be retrieved and analyzed. Since this is a systematic review, no ethical approval is necessary. DISCUSSION: This systematic review may have the potential to provide significant evidence-based findings on the prediction performance of metabolomics. There are short and long-term repercussions for the mother and the newborn. Therefore, both may benefit from an accurate prediction technique for HIP. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered in the PROSPERO platform under number CRD42018100175 .

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 five different 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 first medical visit and diastolic blood pressure over 75 mmHg 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 379 g 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 75 mmHg 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.