Mental disorders in adults from Ribeirão Preto, Brazil: a cross-sectional analysis of two birth cohorts.

BACKGROUND: In Brazil, the prevalence of mental disorders is heterogeneous, with most studies conducted in large cities with high population density. This study aimed to assess the prevalence of mental disorders and psychiatric comorbidities among young adults (22-23 years old) and adults (37-38 years old) from Ribeirão Preto, a city located in the Northeast of the São Paulo state, with approximately 700,000 inhabitants, and to explore associations with sociodemographic variables, suicide risk, and health service usage. Second, we aimed to evaluate the performance of the Self-Report Questionnaire (SRQ-20) as a screening tool for mental disorders to be applied to the local population. METHODS: Participants from the 1978/1979 and 1994 Ribeirão Preto birth cohorts were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the SRQ-20 at mean ages of 22-23, and 37-38 years, respectively. RESULTS: Our sample comprised 1,769 individuals from the 1978/1979 cohort and 1,037 from the 1994 cohort. The prevalence of mental disorders ranged from 28.6% (1978/79) to 31% (1994), with frequent comorbid diagnoses (42.7% and 43.3%, respectively). Men and women had a similar prevalence of mental disorders in the younger cohort, while women had a higher prevalence in the older cohort. Low educational attainment was associated with higher rates of diagnosis. In both cohorts, alcohol and other psychoactive substance use was higher among those with a psychiatric diagnosis. Although those with a psychiatric diagnosis were less satisfied with their own health, only one-fifth had seen a mental health professional in the previous year. A psychiatric diagnosis increased the suicide risk by 5.6 to 9.1 times. Regarding the SRQ-20, the best cutoff points were 5/6 for men and 7/8 for women, with satisfactory performance. CONCLUSIONS: The prevalence and comorbidity of mental disorders were high in both cohorts and comparable to those in larger Brazilian cities. However, few individuals with a diagnosis had sought specialized care. These data suggest that the mental health gap is still significant in Brazil.

Circulating vascular endothelial growth factor receptor-3, a pro-lymphangiogenic and pro-angiogenic mediator, is decreased in pre-eclampsia.

OBJECTIVE: To compare circulating levels of vascular endothelial growth factor receptor 3 (VEGFR-3) in women with pregnancy-induced hypertension (PIH) and in non-pregnant (NP) and healthy pregnant (HP) women. METHODS: We conducted a case-control study including PIH (n = 135), HP (n = 68), and NP (n = 49) women from southeastern Brazil. PIH were diagnosed according to international guidelines, and defined as gestational hypertension (GH, n = 61) or pre-eclampsia (n = 74). VEGFR-3 was measured in plasma using ELISA. RESULTS: Plasma VEGFR-3 was increased in HP (1207 pg/mL) compared with NP (133 pg/mL) women; however, PIH (729 pg/mL) patients exhibited lower levels than HP women (both p < 0.05). In addition, plasma VEGFR-3 was decreased in pre-eclampsia compared with GH (537 versus 980 pg/mL; p < 0.05). When pre-eclampsia was classified according to different clinical presentations, plasma VEGFR-3 was further decreased in the cases identified as pre-eclampsia with severe features, preterm pre-eclampsia, and pre-eclampsia accompanied by small for gestational age (all p < 0.05). CONCLUSION: Our data indicate reduced circulating VEGFR-3 levels in patients with PIH, specifically in those diagnosed with pre-eclampsia. Moreover, decreased VEGFR-3 was associated with adverse clinical outcomes in pre-eclampsia. These findings expand previous evidence of reduced VEGFR-3 expression in pre-eclampsia. Future studies should investigate whether it can be used as a predictive biomarker and/or therapeutic target for pre-eclampsia.

In Vivo Activity of Intestinal P-Glycoprotein and Hepatic Organic Anion Transporters Polypeptide in Pregnancy and Postpartum.

This study investigates the influence of pregnancy on the in vivo activity of the intestinal P-glycoprotein (P-gp) and hepatic organic anion transporters polypeptide (OATP/BCRP) using, respectively, fexofenadine and rosuvastatin as probe drugs. Eleven healthy participants were investigated during the third trimester of pregnancy (Phase 1, 28 to 38 weeks of gestation) and in the postpartum period (Phase 2, 8 to 12 weeks postpartum). In both phases, after administration of a single oral dose of fexofenadine (60 mg) and rosuvastatin (5 mg), serial blood samples were collected for up to 24 h. Rosuvastatin and fexofenadine in plasma were analyzed by LC-MS/MS using previously validated methods. The pharmacokinetic parameters of fexofenadine and rosuvastatin (Phoenix WinNonLin software) with normal distribution (Shapiro-Wilk test) are presented as geometric mean and 90% confidence interval. Phases 1 and 2 were compared using the t test (P < .05). Fexofexadine AUC0-24 values do not differ (P-value: .0715) between Phase 1 (641.9 ng h/mL [500.6-823.1]) and Phase 2 (823.8 ng h/mL [641.5-1057.6]) showing that pregnancy (third trimester) does not alter intestinal P-gp activity. However, rosuvastatin AUC0-24 values are higher (P-value: .00005) in Phase 1 (18.7 ng h/mL [13.3-26.4]) when compared to Phase 2 (9.5 ng h/mL [6.7-13.4]), suggesting inhibition of OATP1B1/OATP1B3 transporters. In conclusion, pregnancy assessed during the third trimester does not alter the intestinal P-gp activity but reduces the activity of hepatic OATP1B1/OATP1B3 transporters. Therefore, adjustments in dosage regimens may be necessary for drugs with low therapeutic index, substrates of the OATP1B1/OATP1B3 transporters, administered during the third trimester of pregnancy.

Development of Automated Triggers in Ambulatory Settings in Brazil: Protocol for a Machine Learning-Based Design Thinking Study.

BACKGROUND: The use of technologies has had a significant impact on patient safety and the quality of care and has increased globally. In the literature, it has been reported that people die annually due to adverse events (AEs), and various methods exist for investigating and measuring AEs. However, some methods have a limited scope, data extraction, and the need for data standardization. In Brazil, there are few studies on the application of trigger tools, and this study is the first to create automated triggers in ambulatory care. OBJECTIVE: This study aims to develop a machine learning (ML)-based automated trigger for outpatient health care settings in Brazil. METHODS: A mixed methods research will be conducted within a design thinking framework and the principles will be applied in creating the automated triggers, following the stages of (1) empathize and define the problem, involving observations and inquiries to comprehend both the user and the challenge at hand; (2) ideation, where various solutions to the problem are generated; (3) prototyping, involving the construction of a minimal representation of the best solutions; (4) testing, where user feedback is obtained to refine the solution; and (5) implementation, where the refined solution is tested, changes are assessed, and scaling is considered. Furthermore, ML methods will be adopted to develop automated triggers, tailored to the local context in collaboration with an expert in the field. RESULTS: This protocol describes a research study in its preliminary stages, prior to any data gathering and analysis. The study was approved by the members of the organizations within the institution in January 2024 and by the ethics board of the University of São Paulo and the institution where the study will take place. in May 2024. As of June 2024, stage 1 commenced with data gathering for qualitative research. A separate paper focused on explaining the method of ML will be considered after the outcomes of stages 1 and 2 in this study. CONCLUSIONS: After the development of automated triggers in the outpatient setting, it will be possible to prevent and identify potential risks of AEs more promptly, providing valuable information. This technological innovation not only promotes advances in clinical practice but also contributes to the dissemination of techniques and knowledge related to patient safety. Additionally, health care professionals can adopt evidence-based preventive measures, reducing costs associated with AEs and hospital readmissions, enhancing productivity in outpatient care, and contributing to the safety, quality, and effectiveness of care provided. Additionally, in the future, if the outcome is successful, there is the potential to apply it in all units, as planned by the institutional organization. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55466.

Mid-pregnancy circulating cytokine levels, placental efficiency and their relationship with preterm birth.

Objective: To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD). Methods: Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20+0 to 25+6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve. Results: Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1ß, TNFß, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%. Conclusion: IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response.

Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

Assessment of obstetric history and cervical length as risk factors for preterm birth / Evaluación de la história obstétrica y la longitud cervical como factores de riesgo para el parto prematuro

Introduction: Preterm birth, before 37 weeks of gestation, is the main determinant of neonatal morbidity and mortality and is associated with serious consequences,including compromised quality of life for the affected individual and physical, psychological, and economic costs. Objective: To evaluate the correlation of obstetric history, cervicovaginal infections, and cervical length with preterm birth. A prospective, blind cohort study evaluated 1,370 pregnant women from Ribeirão Preto between 20 and 25 weeks of gestation. Materials and methods: The correlation between obstetric history, cervical length, and gestational age at birth was obtained by calculating the relative risk of the different variables. Results: The distribution of pregnant women according to cervical length (CL) showed a predominance of women with a cervix longer than 2.5 cm (n = 1,308, 95.8%), followed by women with a cervix between 2 and 2.49 cm (n = 42, 3.1%) and < 2 cm (n = 15, 1.1%). Among the 1,370 pregnant women evaluated, 133 had spontaneous preterm birth (< 259 days); 14 (10.5%) preterm births occurred in women under 19 years of age, 105 (79%) in women between 19 and 35 years, and 14 (10.5%) in women older than 35 years. Microbiological analysis showed the growth of Mycoplasma hominis, Ureaplasma urealyticum, and other bacteria in 8, 17, and 16 women with preterm birth, respectively. Among the 133 women with spontaneous preterm birth, CL was < 2.5 cm in 15 women, < 2 cm in 3, < 1.5 cm in 3, and < 1 cm in 2. Conclusion: The identification of pregnant women at high risk for preterm delivery can reduce the incidence of preterm birth. Although no gold standard test exists for the prediction of preterm birth, this study confirms that the measurement of CL is a good individual predictor.

Introducción: El nacimiento pretérmino, antes de las 37 semanas de gestación, es el principal determinante de la morbimortalidad neonatal y se asocia a graves consecuencias,incluyendo el compromiso de la calidad de vida del individuo afectado y costes físicos, psicológicos y económicos. Objetivo: Evaluar la correlación de los antecedentes obstétricos, infecciones cervicovaginales y longitud cervical con el parto prematuro. Estudio de cohorte prospectivo, ciego, evaluando 1.370 gestantes de Ribeirão Preto entre 20 y 25 semanas de gestación. Material y métodos: La correlación entre los antecedentes obstétricos, la longitud cervical y la edad gestacional al nacer se obtuvo calculando el riesgo relativo de las diferentes variables. Resultados: La distribución de las gestantes según la longitud cervical (LC) mostró un predominio de mujeres con cuello uterino mayor de 2,5 cm (n = 1,308, 95.8%), seguidas de mujeres con cuello uterino entre 2 y 2,49 cm (n = 42, 3.1%) y menor de 2 cm (n = 15, 1.1%). De las 1,370 embarazadas evaluadas, 133 tuvieron un parto prematuro espontáneo (< 259 días); 14 (10.5%) partos prematuros se produjeron en mujeres menores de 19 años, 105 (79%) en mujeres de entre 19 y 35 años, y 14 (10.5%) en mujeres mayores de 35 años. Los análisis microbiológicos mostraron la proliferación de Mycoplasma hominis, Ureaplasma urealyticum y otras bacterias en 8, 17 y 16 mujeres con parto prematuro, respectivamente. Entre las 133 mujeres con parto prematuro espontáneo, la CL fue < 2.5 cm en 15 mujeres, < 2 cm en 3, < 1.5 cm en 3 y < 1 cm en 2. Conclusión: La identificación de las gestantes con alto riesgo de parto prematuro puede reducir la incidencia de parto prematuro. Aunque no existe una prueba de referencia para la predicción del parto prematuro, este estudio confirma que la medición de la longitud cervical es una buena predicción individual.

The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy.

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.

Sociodemographic and reproductive risk factors associated with metabolic syndrome in a population of Brazilian women from the city of Ribeirão Preto: a cross-sectional study.

Objective: To identify sociodemographic and reproductive risk factors associated with MetS in women in their fourth decade of life. Methods: Cohort study conducted on women born from June 1978 to May 1979 in Ribeirão Preto, Brazil. Sociodemographic, clinical, and obstetric data were collected by interview and clinical evaluation. Univariable and multivariable binomial logistic regression models were constructed to identify the risk factors of metabolic syndrome and the adjusted relative risk (RR) was calculated. Results: The cohort included 916 women, and 286 (31.2%) of them have metabolic syndrome. MetS was associated with lack of paid work (RR 1.49; 95% CI 1.14-1.95), marital status of without a partner (RR 1.33; 95% CI 1.03-1.72), low educational level (less than 8 years of schooling [RR 1.72; 95% CI 1.23-2.41], 8 to 12 years of schooling [RR 1.37; 95% CI 1.06-1.76], when compared with more than 12 years of schooling), and teenage pregnancy (RR 2.00; 95% CI 1.45-2.77). There was no association between MetS, and the other covariates studied. Conclusion: Metabolic syndrome in a population of women in the fourth decade of life was associated with lack of employment, lack of a partner, low educational level, and teenage pregnancy.

Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy.

Impaired nitric oxide (NO) formation may be associated with endothelial dysfunction and increased cardiovascular disease risk in preeclampsia (PE). Functional single-nucleotide polymorphisms (SNPs) of nitric oxide synthase 3 (NOS3) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) (rs7692387) increase susceptibility to the adverse consequences due to inadequate generation of NO by the endothelium. However, no previous study has examined whether these SNPs affect NO formation in healthy pregnancy and in gestational hypertension (GH) and PE. Here, we compared the alleles and genotypes of NOS3 (rs3918226) and GUCY1A3 (rs7692387) SNPs in normotensive pregnant women (NP, n = 153), in GH (n = 96) and PE (n = 163), and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. We further examined whether the interaction among SNP genotypes is associated with GH and PE. Genotypes were determined using TaqMan allele discrimination assays, and plasma nitrite concentrations were determined by an ozone-based chemiluminescence assay. Multifactor dimensionality reduction was used to examine the interactions among SNP genotypes. Regarding NOS3 rs3918226, the CT genotype (p = 0.046) and T allele (p = 0.020) were more frequent in NP than in GH, and GH patients carrying the CT+TT genotypes showed lower nitrite concentrations than NP carrying the CT+TT genotypes (p < 0.05). Regarding GUCY1A3 rs7692387, the GA genotype (p = 0.013) and A allele (p = 0.016) were more frequent in PE than in NP, and NP women carrying the GG genotype showed higher nitrite concentrations than GH or PE patients carrying the GG genotype (p < 0.05). However, we found no significant interactions among genotypes for these functional SNPs to be associated with GH or PE. Our novel findings suggest that NOS3 rs3918226 and GUCY1A3 rs7692387 may affect NO formation and association with hypertensive disorders of pregnancy.

Mechanistic Framework to Predict Maternal-Placental-Fetal Pharmacokinetics of Nifedipine Employing Physiologically Based Pharmacokinetic Modeling Approach.

Nifedipine is used for treating mild to severe hypertension and preventing preterm labor in pregnant women. Nevertheless, concerns about nifedipine fetal exposure and safety are always raised. The aim of this study was to develop and validate a maternal-placental-fetal nifedipine physiologically based pharmacokinetic (PBPK) model and apply the model to predict maternal, placental, and fetal exposure to nifedipine at different pregnancy stages. A nifedipine PBPK model was verified with nonpregnant data and extended to the pregnant population after the inclusion of the fetoplacental multicompartment model that accounts for the placental tissue and different fetal organs within the Simcyp Simulator version 22. Model parametrization involved scaling nifedipine transplacental clearance based on Caco-2 permeability, and fetal hepatic clearance was obtained from in vitro to in vivo extrapolation encompassing cytochrome P450 3A7 and 3A4 activities. Predicted concentration profiles were compared with in vivo observations and the transplacental transfer results were evaluated using 2-fold criteria. The PBPK model predicted a mean cord-to-maternal plasma ratio of 0.98 (range, 0.86-1.06) at term, which agrees with experimental observations of 0.78 (range, 0.59-0.93). Predicted nifedipine exposure was 1.4-, 2.0-, and 3.0-fold lower at 15, 27, and 39 weeks of gestation when compared with nonpregnant exposure, respectively. This innovative PBPK model can be applied to support maternal and fetal safety assessment for nifedipine at various stages of pregnancy.

Risk factors associated with preterm birth: identification, prediction and evaluation in the BRISA cohort

Problem: Preterm birth is the leading cause of death and can result in significant long-term loss of physical and psychological capacity among survivors.Background: An estimated 15 million babies are born preterm every year. Prediction models based on machine learning methods have reported promising results.Aims: To identify risk factors associated with preterm birth and to develop and validate a prediction model for this outcome in a Brazilian birth cohort.Methods: Cross-sectional study of all births that occurred in Ribeirão Preto-SP and of one in three births that occurred in São Luís-MA, Brazil, in 2010. Questionnaires were applied to obtain pregnancy-related data. Multivariate adaptive regression splines were used to determine the independent variables. Preterm birth, defined as birth before 37 weeks gestational age, was the dependent variable. A random forest model was developed and its performance was evaluated by ROC analysis.Findings: The preterm birth rates were 12.7% (RP) and 14.1% (SL). The prediction and validation accuracies of the RF-based model were 91.3% and 85.5% respectively. The model can be applied starting in the third month of gestation and is more effective in identifying preterm infants with GA<31 weeks and 6 days (AUC=0.98).Discussion: It was possible to build a prediction model based on easily accessible low-cost data, without the need for complementary tests, providing results similar to those of other studies.Conclusions: Previous preterm birth and prenatal care were determinants. The use of an application for individualized patient monitoring an early stage can have positive effects on the quality of life of mother and child.

Mid-pregnancy circulating cytokine levels, placental efficiency and their relationship with preterm birth

Abstract Objective To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD). Methods Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20+0 to 25+6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve. Results Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1β, TNFβ, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%. Conclusion IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response.

How can we reduce maternal mortality due to preeclampsia? The 4P rule

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.

Sociodemographic and reproductive risk factors associated with metabolic syndrome in a population of Brazilian women from the city of Ribeirão Preto: a cross-sectional study

Abstract Objective: To identify sociodemographic and reproductive risk factors associated with MetS in women in their fourth decade of life. Methods: Cohort study conducted on women born from June 1978 to May 1979 in Ribeirão Preto, Brazil. Sociodemographic, clinical, and obstetric data were collected by interview and clinical evaluation. Univariable and multivariable binomial logistic regression models were constructed to identify the risk factors of metabolic syndrome and the adjusted relative risk (RR) was calculated. Results: The cohort included 916 women, and 286 (31.2%) of them have metabolic syndrome. MetS was associated with lack of paid work (RR 1.49; 95% CI 1.14-1.95), marital status of without a partner (RR 1.33; 95% CI 1.03-1.72), low educational level (less than 8 years of schooling [RR 1.72; 95% CI 1.23-2.41], 8 to 12 years of schooling [RR 1.37; 95% CI 1.06-1.76], when compared with more than 12 years of schooling), and teenage pregnancy (RR 2.00; 95% CI 1.45-2.77). There was no association between MetS, and the other covariates studied. Conclusion: Metabolic syndrome in a population of women in the fourth decade of life was associated with lack of employment, lack of a partner, low educational level, and teenage pregnancy.

Plasma eNOS Concentration in Healthy Pregnancy and in Hypertensive Disorders of Pregnancy: Evidence of Reduced Concentrations in Pre-Eclampsia from Two Independent Studies.

Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman's or Pearson's tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = -0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.

Maternal, obstetric, and fetal Doppler characteristics in a high-risk population: prediction of adverse perinatal outcomes and of cesarean section due to intrapartum fetal compromise.

Objective: To evaluate the capacity of fetal Doppler, maternal, and obstetric characteristics for the prediction of cesarean section due to intrapartum fetal compromise (IFC), a 5-min Apgar score < 7, and an adverse perinatal outcome (APO), in a high-risk population. Materials and Methods: This was a prospective cohort study involving 613 singleton pregnant women, admitted for labor induction or at the beginning of spontaneous labor, who underwent Doppler ultrasound within the last 72 h before delivery. The outcome measures were cesarean section due to IFC, a 5-min Apgar score < 7, and any APO. Results: We found that maternal characteristics were neither associated with nor predictors of an APO. Abnormal umbilical artery (UA) resistance index (RI) and the need for intrauterine resuscitation were found to be significant risk factors for cesarean section due to IFC (p = 0.03 and p < 0.0001, respectively). A UA RI > the 95th percentile and a cerebroplacental ratio (CPR) < 0.98 were also found to be predictors of cesarean section due to IFC. Gestational age and a UA RI > 0.84 were found to be predictors of a 5-min Apgar score < 7 for newborns at < 29 and ≥ 29 weeks, respectively. The UA RI and CPR presented moderate accuracy in predicting an APO, with areas under the ROC curve of 0.76 and 0.72, respectively. Conclusion: A high UA RI appears to be a significant predictor of an APO. The CPR seems to be predictive of cesarean section due to IFC and of an APO in late preterm and term newborns.

Objetivo: Avaliar a capacidade do Doppler fetal e características materno-obstétricas na predição de cesariana por comprometimento fetal intraparto (CFI), índice de Apgar de 5º min < 7 e desfecho perinatal adverso (DPA) em uma população de alto risco. Materiais e Métodos: Estudo de coorte prospectivo envolvendo 613 parturientes admitidas para indução ou em início de trabalho de parto espontâneo que realizaram ultrassonografia Doppler nas 72 horas anteriores ao parto. Os desfechos foram cesariana por CFI, índice de Apgar de 5º min < 7 e DPA. Resultados: As características maternas não foram associadas nem preditoras de DPA. Índice de resistência (IR) da artéria umbilical (AU) anormal (p = 0,03) e necessidade de medidas de ressuscitação intrauterina (p < 0,0001) permaneceram como fatores de risco significativos para cesariana por CFI. IR AU > 95º e razão cerebroplacentária (RCP) < 0,98 foram preditores de cesariana. Idade gestacional e IR AU > 0,84 foram os preditores de índice de Apgar de 5º min < 7 para recém-nascidos < 29 e ≥ 29 semanas, respectivamente. IR AU e RCP apresentaram acurácia moderada na predição de DPA (área sob a curva ROC de 0,76 e 0,72, respectivamente). Conclusão: IR UA mostrou-se preditor significativo de DPA. RCP revelou-se possível preditora de cesariana por CFI e DPA em recémnascidos prematuros tardios e a termo.

Sociodemographic and economic characteristics of families and health and education conditions of children in the BRISA cohort during the COVID-19 pandemic.

OBJECTIVE: To describe changes in sociodemographic, economic and variables related to the characterization of family, health and education during the COVID-19 pandemic in a birth cohort evaluated at 10-11 years of age. METHODS: Cross-sectional study involving 1,033 children from a cohort of children born in 2010/2011, in the city of Ribeirão Preto, SP, Brazil. Data were collected from July to October 2021 by telephone or video interview held with the person responsible for the child. The questionnaires discussed family organization, child behavior and health, school attendance, socioeconomic assessment and occurrence of COVID-19 during the period of social isolation due to the pandemic. Descriptive statistics were used to describe the data. The chi-square test was used to verify group differences by minimum wages (MW). RESULTS: Of the respondents, 47.6% reported worsening of their financial situation during the pandemic, which was more frequent in the group with a household income <3 MW compared to the group with >6 MW (59.1 vs. 15.7%; p<0.001). According to the respondents, 62% of the children exhibited behavioral changes during the period and anxiety was the most frequently reported condition. In addition, 61.4% of the children had learning difficulties and these problems were more prevalent among children from households with lower incomes compared to those with higher incomes (74.7 vs. 45.1%; p<0.001). CONCLUSION: The COVID-19 pandemic has changed different economic aspects of families, as well as educational, health and behavioral indicators of children. Lower-income families were the most affected both economically and in terms of other indicators.

RANTES and developmental defects of enamel in children: A Brazilian prenatal cohort (BRISA).

OBJECTIVE: Little is known about the effect of maternal immunological factors on the etiology of developmental defects of enamel (DDE). RANTES (Regulated on Activation Normal T Cell Expressed and Secreted) is a chemokine produced by fibroblasts, lymphoid and epithelial mucosa cells in response to various external stimuli. Despite its importance for embryogenesis, RANTES expression has been demonstrated in multiple diseases characterized by inflammation, tumor and immune response, and wound healing. We hypothesized that altered levels of RANTES during pregnancy are associated with the immune and inflammatory response in women, which could lead to the occurrence of DDE in utero (DDE-iu), directly or mediated by preterm birth. Therefore, this study aimed to evaluate the direct and indirect effects of serum levels of RANTES in pregnant women in the occurrence of DDE-iu in children. METHODS: This is a longitudinal case-control study. The mothers and their children (327) were evaluated in three moments: prenatal care, post childbirth, and when the child was between 12.3 and 36 months of age. The analysis was performed with structural equation modeling, estimating the standardized coefficient (SC), adopting α = 5%. RESULTS: There was a direct and negative effect of RANTES on the outcome (SC = -0.137; p = 0.022). This association was not mediated by preterm birth (SC = 0.007; P = 0.551). When considering the specific types of DDE-iu, RANTES had a direct effect on hypoplasia (SC = -0.190; p = 0.007), but not on opacity (SC = 0.343; p = 0.074). CONCLUSION: Lower serum levels of RANTES may contribute to a higher number of teeth with DDE-iu, specifically hypoplasia. However, more evidence supported by clinical, laboratory and epidemiological studies is still needed.