Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress-related genes (FKBP5, NR3C1, OXTR) (n = 62) and diurnal cortisol (n = 29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (site 1: B = -22.33, p = .003; site 2: B = -15.60, p = .012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B = -2.17, p = .03) and higher evening salivary cortisol (B = 0.41, p = .03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B = -0.14, p-value ≤ .001). Our results are, to our knowledge, the first evidence that the methylation of the oxytocin receptor may contribute to the regulation of HPAA during infancy.

Insulin resistance phenotype is associated with vascular risk phenotype at the end of the second decade of life: a population-based study.

We hypothesize that early events of diabetes and cardiovascular disease continuums would be ongoing and associated in adolescents. We investigated the association between the Insulin Resistance Phenotype and the Vascular Risk Phenotype at the end of the second decade of life and indirect pathways from social vulnerability, alcohol consumption, and body fat mass. It is a population-based study in the RPS cohort of 18-19 years (n = 2,515), São Luís, Brazil. The theoretical model analyzed the association between Insulin Resistance Phenotype and Vascular Risk Phenotype by sex, using structural equation modeling (SEM). The Insulin Resistance Phenotype was a latent variable deduced from the correlations of Triglyceride to HDL ratio, Triglyceride Glycemic index, and VLDL; the Vascular Risk Phenotype was deduced from Systolic Blood Pressure, Diastolic Blood Pressure, and Pulse Wave Velocity. The Insulin Resistance Phenotype was directly associated with the Vascular Risk Phenotype in males (standardized coefficient SC = 0.183; p < 0.001) and females (SC = 0.152; p < 0.001). The Insulin Resistance Phenotype was an indirect pathway in the association of alcohol consumption and higher values of fat mass index with the Vascular Risk Phenotype. VLDL presented the highest factor loading, appearing as a marker of insulin resistance linked to cardiovascular risk in young people. Lower values of socioeconomic status, harmful use of alcohol, and high body fat values were also associated with higher values of the two phenotypes. The association of the Insulin Resistance Phenotype with the Vascular Risk Phenotype suggests common pathophysiological mechanisms present in early events in the continuums of diabetes and cardiovascular disease in adolescence.

Preterm birth and postpartum depression within 6 months after childbirth in a Brazilian cohort.

Preterm birth (PTB) and postpartum depression (PPD) are important public health issues, and although literature mainly supports the association between them, some reviews have highlighted methodological limitations in the studies in this field, restricting the interpretation of such finding. This study aimed at assessing the association between PTB and PPD, by comparing groups of preterm and full-term mothers in two Brazilian cities with contrasting sociodemographic indicators. This prospective convenience cohort study assessed 1421 women during pregnancy, at childbirth, and in the postpartum period. The Edinburgh Postnatal Depression Scale (EPDS) was administrated to assess PPD within 6 months after delivery and women were considered probably depressed if scores were EDPS ≥ 12. PTB was defined as the delivery before 37 completed weeks of pregnancy. A multivariate Poisson regression was used to estimate relative risk for PPD in mothers of preterm infants, and the final analysis models were adjusted for psychosocial variables, selected according to the directed acyclic graph (DAG) approach. Frequencies of PPD were not significantly different in mothers of preterm and full-term infants, in neither city. In the final adjusted model, PTB was not associated with PPD. The association between PTB and PPD was not confirmed in two large samples from two Brazilian cities with contrasting socioeconomic profile. However, maternal health during pregnancy plays an important role in predicting PPD. Prenatal care should promote maternal mental health as an effort towards decreasing unfavored outcomes for mothers, infants, and families.

Early fluid overload is associated with mortality and prolonged mechanical ventilation in extremely low birth weight infants.

Recent studies revealed that fluid overload is associated with higher mortality in critically ill children and adults. This study aimed to evaluate the association between fluid overload in the first 3 days of life and mortality in extremely low birth weight infants. This single-center retrospective cohort study included two hundred nineteen newborns with birth weight less than 1000 g who were admitted to the neonatal intensive care between January 2012 and December 2017. Overall mortality was 32.4%, the median gestational age was 27.3 (26.1-29.4) weeks, and birth weight was 770 (610-900) grams. In the group with severe fluid overload, we found a higher rate of deaths (72.2%); mean airway pressure was significantly higher and with longer invasive mechanical ventilation necessity.Conclusion: Early fluid overload in extremely low birth weight infants is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration in the first 7 days of life. What is Known: • Fluid overload is associated with a higher mortality rate and prolonged mechanical ventilation in children and adults. What is New: • Fluid overload in the first 72 h of life in an extremely premature infant is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration the first 7 days of life.

Cesarean Delivery and Hypertension in Early Adulthood.

The rate of cesarean delivery (CD) is high in many parts of the world. Birth via CD has been associated with adverse later health outcomes, such as obesity, asthma, and type 1 diabetes mellitus. Few studies have focused on hypertension. We investigated the associations of CD with hypertension, systolic blood pressure (BP), and diastolic BP and tested whether body mass index (BMI; weight (kg)/height (m)2) was a mediator of these associations in a birth cohort (n = 2,020) assembled in 1978-1979 and followed up in 2002-2004 in Ribeirão Preto, Brazil. The CD rate was 32.0%. Hypertension was present in 11.7% of persons born via CD and 7.7% of those born vaginally. Being born by CD increased the odds of hypertension by 51% (odds ratio = 1.51, 95% confidence interval (CI): 1.10, 2.07). After adjustment for confounders, this estimate changed little (odds ratio = 1.49, 95% CI: 1.07, 2.06). In a mediation analysis, odds ratios for the indirect and direct effects were 1.18 (95% CI: 1.11, 1.25) and 1.31 (95% CI: 0.97, 1.65), respectively. CD also had indirect effects on both systolic and diastolic BP via BMI. Our findings suggest that CD is associated with young-adult hypertension and that this association is at least partially mediated by BMI. This has implications for countries struggling with the burden of noncommunicable diseases and where CD rates are high.

The specific and combined role of domestic violence and mental health disorders during pregnancy on new-born health.

BACKGROUND: Addressing impaired foetal growth is recognized as a public health priority. Certain risk factors for this condition, such as poor nutritional status at birth, have been found to be highly correlated with poverty. However, the role of psychosocial factors, specifically the mother's mental health and exposure to violence during pregnancy, have yet to be further explored. Our objective was to determine if there is a measurable association between combined psychosocial factors, specifically domestic violence and mental disorders, and birth outcomes, specifically birth nutritional status and preterm delivery. METHODS: We followed 775 women from an underserved, urban area, beginning their 28th week of gestation. Diagnostic interviews were performed to determine if any of the mothers had any of the following disorders: mood disorder, anxiety, obsessive-compulsive disorder (OCD), substance dependence, psychotic disorder, or anti-social personality disorder. Physical, psychological, and sexual domestic violence were also assessed. RESULTS: Domestic violence and mental disorders were highly correlated in our sample. About 27.15% of the women in our study experienced domestic violence, and about 38.24% of them were diagnosed with mental disorders. The main association we found between combined psychosocial factors and neonate outcomes was between anxiety (IRR = 1.83; 95%CI = 1.06-3.17)/physical violence (IRR = 1.95; 95%CI = 1.11-3.42) and the rate of small-for-gestational age (SGA) in new-borns. More specifically, the combination of anxiety (beta = -0.48; 95%CI = -0.85/-0.10) and sexual violence (beta = -1.58; 95%CI = -2.61/-0.54) was also associated with birth length. Maternal risk behaviours such as smoking, drinking, inadequate prenatal care, and inadequate weight gain could not sufficiently explain these associations, suggesting that these psychosocial factors may be influencing underlying biological mechanisms. CONCLUSION: Domestic violence against women and mental disorders amongst pregnant women are extremely prevalent in under-resourced, urban areas and ultimately, have detrimental effects on birth outcomes. It is imperative that actions be taken to prevent violence and improve mental health during pregnancy.

Intergenerational consequences of violence: violence during pregnancy as a risk factor for infection in infancy.

Introduction: Psychosocial stress during pregnancy has long-lasting and important consequences in the following generations, as it can affect intrauterine development. The impact on the developing immune system is notoriously important due to the associated morbidity and mortality in the first years of life. Little attention has been given to the role of violence during pregnancy (VDP), especially its impact on infant infectious morbidity. Methods: We analyzed data from two Brazilian birth cohorts (n = 2,847) in two distinct cities (Ribeirão Preto and São Luís), collected during pregnancy and at the beginning of the second year of life. The association between VDP and infection in infancy was analyzed with structural equation modeling, using the WHO-VAW questionnaire as exposure and a latent variable for infection as the outcome. Results: VDP was reported by 2.48% (sexual), 11.56% (physical), and 45.90% (psychological) of the mothers. The models presented an adequate fit. In the city of São Luís, VDP was significantly associated with the latent construct for infection (standardized beta = 0.182; p = 0.022), while that was not the case for the Ribeirão Preto sample (standardized beta = 0.113; p = 0.113). Further analyses showed a gradient effect for the different dimensions of the exposure, from psychological to physical and sexual violence. Conclusion: Our results suggest an association of VDP with infant morbidity in a poorer socioeconomic setting, and highlight the importance of considering the different dimensions of intimate partner violence. These findings may have important implications for the comprehension of global health inequalities and of the effects of gender-based violence.

Causal Pathways Between the Acute Experience of Violence During Pregnancy and Fetal Intrauterine Growth Restriction: A Cohort Study.

Introduction: Violence during pregnancy (VDP) is a prevalent global issue with dire consequences for the mother and the developing fetus. These consequences include prematurity, low birthweight, and intrauterine growth restriction (IUGR), but its pathways remain elusive. This study investigated the causal pathways between VDP and IUGR using mediation analysis. Methods: A prospective population-based birth cohort was followed from the beginning of the third gestational trimester to the second year of life. IUGR was defined by the Kramer index, and information on VDP was collected using the WHO-Violence Against Women (WHO VAW) questionnaire. Cases were considered positive only when no other life episodes were reported. Ten different mediators were analyzed as possible pathways based on previous research. Path analysis was conducted to evaluate these relationships. Results: The path analysis model included 755 dyads and presented an adequate fit. Violence during pregnancy showed a direct effect (ß = -0.195, p = 0.041) and a total effect (ß = -0.276, p = 0.003) on IUGR. Violence was associated with gestational depression or anxiety, tobacco and alcohol consumption, changes in blood pressure, and the need for emergency care, but these did not constitute mediators of its effect on IUGR. The sum of the indirect effects, however, showed a significant association with IUGR (ß = -0.081, p = 0.011). Conclusion: The acute experience of violence during pregnancy was associated with IUGR, primarily via a direct pathway. An indirect effect was also present but not mediated through the variables analyzed in this study. The robust strength of these associations underscores the negative health consequences of violence against women for the succeeding generation.

Childbearing in adolescence: intergenerational dejà-vu? Evidence from a Brazilian birth cohort.

BACKGROUND: Pregnancy in adolescence tends to repeat over generations. This event has been little studied in middle and low-income societies undergoing a rapid epidemiological transition. To assess this association it is important to adjust for socioeconomic conditions at different points in lifetime. Therefore, the aim of this study is to analyze the independent effect of adolescent childbearing in a generation on its recurrence in the subsequent generation, after adjusting for socioeconomic status at different points in life. METHODS: The study was conducted on a prospective cohort of singleton liveborn females from the city of Ribeirão Preto, Brazil, evaluated in 1978/79, and their daughters assessed in 2002/04. A total of 1059 mother-daughter pairs were evaluated. The women who had their first childbirth before 20 years of age were considered to be adolescent mothers. The risk of childbearing in adolescence for the daughter was modeled as a function of the occurrence of teenage childbearing in her mother, after adjustment for socio-demographic variables in a Poisson regression model. RESULTS: The rate of childbearing during adolescence was 31.4% in 1978/79 and 17.1% in 2002/04. Among the daughters of the 1st generation adolescent mothers, this rate was 26.7%, as opposed to 12.7% among the daughters of non adolescent mothers. After adjustments the risk of adolescent childbearing for the 2nd generation was 35% higher for women whose mothers had been pregnant during adolescence - RR = 1.35 (95% CI 1.04-1.74). CONCLUSION: Adolescent childbearing in the 1st generation was a predictor of adolescent childbearing in the 2nd, regardless of socioeconomic factors determined at different points in lifetime.

Why are pediatricians uncomfortable with prescribing emergency contraception for adolescents?

OBJECTIVE: Emergency contraception (EC) is an effective and safe method for preventing unplanned pregnancy after unprotected sexual intercourse among adolescents but is infrequently prescribed by pediatricians. Because of the scarcity of data on the discomfort with EC prescription among physicians in Brazil, this study aimed to identify associated factors with discomfort with EC prescription among pediatricians in the state of Amazonas. METHODS: A web-based, cross-sectional study including sociodemographic data, knowledge, attitudes, and discomfort with EC prescription was used. Multivariate logistic regression and artificial intelligence methods such as decision tree and random forest analysis were used to identify factors associated with discomfort with EC prescriptions. RESULTS: Among 151 physicians who responded to the survey, 53.0% were uncomfortable with prescribing EC, whereas only 33.1% had already prescribed it. Inexperience was significantly associated with discomfort with EC prescription (odds ratio 4.47, 95% confidence interval 1.71-11.66). Previous EC prescription was protective against discomfort with EC prescription in the three models. CONCLUSIONS: EC is still infrequently prescribed by pediatricians because of inexperience and misconceptions. Training these professionals needs to be implemented as part of public health policies to reduce unplanned adolescent pregnancy.

Factor Analysis of the Brazilian Questionnaire on Adherence to Ketogenic Dietary Therapy: Keto-Check.

BACKGROUND: several strategies are used to assess adherence to ketogenic dietary therapies (KDTs), the most commonly used being ketonemia or ketonuria, despite their limitations. The purpose of this article is to carry out an exploratory and confirmatory factor analysis on the proposed Keto-check (adherence's KDT Brazilian questionnaire). METHODS: there was a methodological study of a quantitative nature, complementary to the analysis realized previously, with a complimentary sample. The factorial analysis was performed with Factor software for parallel exploratory analysis, replicability, and confirmatory factor analysis. Graphical representation was created according to the number of factors resulting from the analysis. RESULTS: 116 questionnaires were reached by complementary data collection (n = 69 actual data, complementing n = 47 previous data) through online forms. A polychoric correlation matrix suitability analysis resulted in a significant Bartlett statistic (p = 0.0001) and a Kaiser-Meyer-Olkin (KMO) test of 0.56. The parallel factorial analysis resulted in two factors, graphically represented as "efficacy" and "adherence". A confirmatory factor analysis, considered fair, indicated an RMSEA of 0.063, NNFI resulted in 0.872, CFI in 0.926, and GFI in 0.897. CONCLUSION: this study confirms the validity of Keto-check through a more detailed analysis. Adherence is the key to improving the effectiveness of KDTs; therefore, improving knowledge about it can lead to a better healthcare approach.

Prolactin does not seem to mediate the improvement on insulin resistance markers and blood glucose levels related to breastfeeding.

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Strategies to decrease this risk should be strongly encouraged. Lactation has been associated, for the mother, with reduction in future T2DM risk in several studies. The mechanisms behind this phenomenon, however, are poorly understood. The aims of this study were, first, to compare blood glucose levels and markers of insulin resistance (MIR) in early postpartum women with overweight/obesity according to their breastfeeding status and, second, to evaluate whether prolactin (PRL) levels could mediate improvements in these parameters. Methods: The prospective study followed 95 women older than 18 years from early pregnancy for up to 60 to 180 days postpartum. All participants had a BMI > 25 kg/m2 and a singleton pregnancy. At each visit, questionnaires and clinical and biochemical evaluations were performed. Participants were divided into two groups according to the breastfeeding status as "yes" for exclusive or predominant breastfeeding, and "no" for not breastfeeding. Results: Breastfeeding women (n = 44) had significantly higher PRL levels [47.8 (29.6-88.2) vs. 20.0 (12.0-33.8), p< 0.001]. They also had significantly lower fasting blood glucose levels [89.0 (8.0) vs. 93.9 (12.6) mg/dl, p = 0.04], triglycerides (TG) [92.2 (37.9) vs. 122.4 (64.4) mg/dl, p = 0.01], TG/HDL ratio [1.8 (0.8) vs. 2.4 (1.6) mg/dl, p = 0.02], TyG index [8.24 (0.4) vs. 8.52 (0.53), p = 0.005], fasting serum insulin [8.9 (6.3-11.6) vs. 11.4 (7.7-17.0), p = 0.048], and HOMA-IR [2.0 (1.3-2.7) vs. 2.6 (1.6-3.9), p = 0.025] in the postpartum period compared to the non-breastfeeding group. Groups were homogeneous in relation to prevalence of GDM, pre-gestational BMI, as well as daily caloric intake, physical activity, and weight loss at postpartum. Linear regression analysis with adjustments for confounders showed a statistically significant association of breastfeeding with fasting blood glucose [-6.37 (-10.91 to -1.83), p = 0.006], HOMA-IR [-0.27 (-0.51 to -0.04), p = 0.024], TyG index [-0.04 (-0.06 to -0.02), p = 0.001], and TG/HDL ratio [-0.25 (-0.48 to -0.01), p = 0.038]. Mediation analysis showed that PRL did not mediate these effects. Sensitivity analyses considering different cutoffs for PRL levels also did not show modification effect in the mediation analyses. Conclusion: Breastfeeding was associated with improvement in glucose metabolism and MIR 60 to 180 days after birth in overweight and obese women, even when adjusted for confounders. PRL levels were not found to mediate the association between breastfeeding and improvement in MIR.

[Cesarean section and association with intelligence quotient in adolescents: contribution from the RPS Cohort Consortium (Ribeirão Preto, Pelotas and São Luís), Brazil]. / Nascer de cesariana e associação com quociente de inteligência em adolescentes: contribuição do Consórcio de Coortes RPS (Ribeirão Preto, Pelotas e São Luís), Brasil.

This study aimed to evaluate the association between cesarean section and intelligence quotient (IQ) in adolescents from the Municipality of São Luís, Maranhão State, Brazil. This is a longitudinal study using data from the São Luís birth cohort, started in 1997. The approach occurred in the third phase of the cohort, in 2016, with adolescents aged 18 and 19 years. The exposure variable was mode of delivery and the outcome variable was IQ, measured by applying the third version of the Wechsler Adult Intelligence Scale (WAIS-III). In the data analysis, the average IQ was verified according to the covariates and multivariate linear regression was used. To control confounding factors, a theoretical model was elaborated using the directed acyclic graph. The confounding variables were socioeconomic variables at birth and perinatal variables. Their average IQ was 101.4. In the crude analysis, the IQ of adolescents born by cesarean section was 5.8 points higher than those born by vaginal delivery (95%CI: 3.8; 7.7, p ≤ 0.001), with statistical significance. In the multivariate analysis, the value decreased to 1.9 (95%CI: -0.5; 3.6, p = 0.141), without statistical significance. The result of the study showed that cesarean section is not associated with the IQ of adolescents in this sample and reflects that the differences can be explained by other factors, such as socioeconomic and perinatal aspects.

O objetivo do estudo foi avaliar a associação entre a cesariana e o quociente de inteligência (QI) em adolescentes do Município de São Luís, Maranhão, Brasil. Trata-se de um estudo longitudinal utilizando dados da coorte de nascimento em São Luís, iniciado no ano de 1997. A abordagem ocorreu na terceira fase da coorte, em 2016, com adolescente aos 18 e 19 anos de idade. A variável de exposição foi a via de nascimento e a variável de desfecho foi o QI, mensurada a partir da aplicação da terceira versão da Escala de Inteligência Wechsler para Adultos (WAIS-III). Na análise dos dados verificou-se a média do QI segundo as covariáveis e utilizou-se a regressão linear multivariada. Para controlar os fatores de confundimento foi elaborado um modelo teórico utilizando o gráfico acíclico dirigido. As variáveis confundidoras foram as socioeconômicas no momento do nascimento e as variáveis perinatais. A média do QI dos adolescentes foi 101,4. Na análise bruta, o QI dos adolescentes nascidos de cesariana foi 5,8 pontos maior em relação aos nascidos de parto vaginal (IC95%: 3,8; 7,7, p ≤ 0,001), com significância estatística. Na análise multivariada, o valor reduziu para 1,9 (IC95%: -0,5; 3,6, p = 0,141), sem significância estatística. O resultado do estudo mostrou que a cesariana não está associada ao QI dos adolescentes nessa amostra e reflete que as diferenças encontradas podem ser explicadas por outros fatores, como aspectos socioeconômicos e perinatais.

El objetivo del estudio fue evaluar la asociación entre la cesárea y el cociente de inteligencia (CI) en adolescentes del Municipio de São Luís, Maranhão, Brasil. Este es un estudio longitudinal que utiliza datos de la cohorte de nacimiento en São Luís, que comenzó en 1997. El abordaje ocurrió en la tercera fase de la cohorte, en 2016, con adolescente a los 18 y 19 años de edad. La variable de exposición fue la vía de nacimiento y la variable de resultado fue el CI, medido a partir de la aplicación de la tercera versión de la Escala de Inteligencia para Adultos (WAIS-III). En el análisis de datos se verificó el CI medio según las covariables y se utilizó la regresión lineal multivariada. Para controlar los factores de confusión se elaboró un modelo teórico utilizando el gráfico acíclico dirigido. Las variables de confusión fueron las socioeconómicas en el momento del nacimiento y las variables perinatales. El coeficiente intelectual promedio de los adolescentes fue de 101,4. En el análisis bruto, el CI de los adolescentes nacidos de cesárea fue 5,8 puntos mayor en relación a los nacidos de parto vaginal (IC95%: 3,8; 7,7, p ≤ 0,001), con significancia estadística. En el análisis multivariado, el valor se redujo a 1,9 (IC95%: -0,5; 3,6, p = 0,141), sin significación estadística. El resultado del estudio mostró que la cesárea no está asociada con el coeficiente intelectual de los adolescentes en esta muestra y refleja que las diferencias encontradas pueden explicarse por otros factores, como los aspectos socioeconómicos y perinatales.

Inattention symptoms in early pregnancy predict parenting skills and infant maltreatment during the first year of life.

OBJECTIVE: Maternal attention-deficit/hyperactivity disorder has not been investigated in relation to parenting skills in adolescent mothers. This study investigated whether maternal inattention and hyperactivity/impulsivity symptoms early in pregnancy predict poorer parenting skills and infant maltreatment during the first year of life in adolescent mothers living in adverse environmental conditions. METHODS: The participants in this study were 80 adolescent mothers aged 14-19 years and their babies who were taking part in a randomized controlled trial on the effects of a home-visiting program on infant development. Symptoms of maternal attention-deficit/hyperactivity disorder were assessed in the first trimester of pregnancy. Parenting skills (maternal competence, attachment to the baby, home environment) and child maltreatment were assessed when the infants were aged 6 and 12 months. Multilevel linear regression models were constructed to test the extent to which prenatal maternal inattention and hyperactivity/impulsivity symptoms predicted these parenting variables during the first year of the infant's life. RESULTS: Prenatal inattention symptoms significantly predicted lower maternal competence and attachment, a poorer home environment, and greater maltreatment during the first year of life. Hyperactivity did not significantly predict parenting skills or maltreatment. CONCLUSIONS: Our findings suggest that inattention symptoms may interfere with parenting abilities in adolescent mothers and should be considered in early intervention programs.

Obesity as a Thrombogenic and Cardiovascular Risk Factor in Children.

BACKGROUND/AIMS: Obesity leads to increased risk of thromboembolic events in adults, but few studies have addressed the relationship between obesity and thrombogenic risk during childhood. The aim of this study was to evaluate the prothrombotic state of obese children in comparison with healthy children. METHODS: Thrombin generation, fibrinogen, and D-dimer levels, along with metabolic parameters, were measured in 72 prepubertal children, of which 47 were obese and 25 eutrophic. RESULTS: A significant increase in thrombin generation, fibrinogen, and dyslipidemia was found among obese patients. CONCLUSION: A prothrombotic state develops in childhood obesity during the prepubertal phase.

The importance of viral load in the severity of acute bronchiolitis in hospitalized infants.

OBJECTIVE: The relationship between viral load and the clinical evolution of bronchiolitis is controversial. Therefore, we aimed to analyze viral loads in infants hospitalized for bronchiolitis. METHODS: We tested for the presence of human respiratory syncytial virus (HRSV) or human rhinovirus (HRV) using quantitative molecular tests of nasopharyngeal secretions and recorded severity outcomes. RESULTS: We included 70 infants [49 (70%) HRSV, 9 (13%) HRV and 12 (17%) HRSV+HRV]. There were no differences among the groups according to the outcomes analyzed individually. Clinical scores showed greater severity in the isolated HRSV infection group. A higher isolated HRSV viral load was associated with more prolonged ventilatory support, oxygen therapy, and hospitalization days, even after adjustment for the age and period of nasopharyngeal secretion collection. In the co-infection groups, there was a longer duration of oxygen therapy when the HRSV viral load was predominant. Isolated HRV infection and co-infection with a predominance of HRV were not associated with severity. CONCLUSION: Higher HRSV viral load in isolated infections and the predominance of HRSV in co-infections, independent of viral load, were associated with greater severity. These results contribute to the development of therapeutic and prophylactic approaches and a greater understanding of the pathophysiology of bronchiolitis.

Non-communicable diseases, sociodemographic vulnerability and the risk of mortality in hospitalised children and adolescents with COVID-19 in Brazil: a cross-sectional observational study.

OBJECTIVES: To analyse how previous comorbidities, ethnicity, regionality and socioeconomic development are associated with COVID-19 mortality in hospitalised children and adolescents. DESIGN: Cross-sectional observational study using publicly available data from the Brazilian Ministry of Health. SETTING: Nationwide. PARTICIPANTS: 5857 patients younger than 20 years old, all of them hospitalised with laboratory-confirmed COVID-19, from 1 January 2020 to 7 December 2020. MAIN OUTCOME MEASURE: We used multilevel mixed-effects generalised linear models to study in-hospital mortality, stratifying the analysis by age, region of the country, presence of non-communicable diseases, ethnicity and socioeconomic development. RESULTS: Individually, most of the included comorbidities were risk factors for mortality. Notably, asthma was a protective factor (OR 0.4, 95% CI 0.24 to 0.67). Having more than one comorbidity increased almost tenfold the odds of death (OR 9.67, 95% CI 6.89 to 13.57). Compared with white children, Indigenous, Pardo (mixed) and East Asian had significantly higher odds of mortality (OR 5.83, 95% CI 2.43 to 14.02; OR 1.93, 95% CI 1.48 to 2.51; OR 2.98, 95% CI 1.02 to 8.71, respectively). We also found a regional influence (higher mortality in the North-OR 3.4, 95% CI 2.48 to 4.65) and a socioeconomic association (lower mortality among children from more socioeconomically developed municipalities-OR 0.26, 95% CI 0.17 to 0.38) CONCLUSIONS: Besides the association with comorbidities, we found ethnic, regional and socioeconomic factors shaping the mortality of children hospitalised with COVID-19 in Brazil. Our findings identify risk groups among children that should be prioritised for public health measures, such as vaccination.

Medical students with performance difficulties need wide support: Initial results of an academic tutoring program.

BACKGROUND: Even students with previous academic success may face challenges that affect their academic performance. Many medical schools offer programs to students at the risk of academic failure, to ensure that they succeed in the course. OBJECTIVE AND METHODS: In this report we describe a pioneering academic tutoring program developed at a Brazilian medical school and discuss the initial results of the program based on the feedback from tutors and data regarding the progression of students in the medical course. RESULTS: In 2018, 33 students enrolled into the program. Students' performance difficulties were mainly associated with mental health problems and socioeconomic vulnerability. Of the 33 students, 27 (81.8%) were assisted by the Mental Health Support Service and 16 (48.5%) were assisted by the Social Assistance Service. In addition to the planning academic activity class load, tutors were able to assist students in solving socioeconomic issues, carrying out personal support interventions with the promotion of self-esteem, and presenting suggestions for behavioral changes in their routine. For most students (72%), the action plan proposed by the tutors was successful. Eight of the 14 (57%) students in the fourth year progressed to the final two years of in-hospital practical training (internship). CONCLUSIONS: The Academic Tutoring Program showed positive results for most of the students. Close monitoring and tutor intervention allowed students with poor academic performance to overcome the low performance cycle. These important tasks demand time and energy from tutors, and institutional recognition of these professionals is essential for the successful maintenance of the program.

Echocardiographic Follow-up of Perinatally HIV-infected Children and Adolescents: Results From a Single-center Retrospective Cohort Study in Brazil.

BACKGROUND: The effects of HIV and antiretroviral therapy on cardiovascular system of perinatally infected children throughout their development are not fully understood. OBJECTIVES: To determine the prevalence of cardiac abnormalities in a retrospective cohort of perinatally HIV-infected patients and to investigate associations between echocardiographic and clinical data during their follow-up. METHODS: Review of medical records and echocardiogram reports of 148 perinatally HIV-infected patients between January 1991 and December 2015. RESULTS: Four hundred and eighty echocardiograms were analyzed and 46 (31%) patients showed cardiac abnormalities, frequently subclinical and transient. Nadir CD4 count was higher in patients with consistently normal echocardiogram: 263 (4-1480) versus 202 (5-1746) cells/µL, P = 0.021. Right ventricular (RV) dilation was detected in 18.9%, left ventricular (LV) dilation in 21.6%, septal hypertrophy in 12.2%, LV posterior wall hypertrophy in 6%, LV systolic dysfunction in 8% and pulmonary hypertension in 8.7% of patients. Opportunistic infections were associated with RV dilation [odds ratio (OR = 4.34; 1.78-10.53; P < 0.01)], pulmonary hypertension (OR = 8.78; 2.80-27.51; P < 0.01) and LV systolic dysfunction (OR = 5.38; 1.55-18.71; P < 0.01). Longer duration of highly active antiretroviral therapy was associated with reduced risk of LV dilation (OR = 0.91; 0.85-0.97; P < 0.01) and systolic dysfunction (OR = 0.71; 0.59-0.85; P < 0.01). Protease inhibitors use was associated with reduced risk of RV dilation (OR = 0.54; 0.30-0.97; P < 0.05), LV dilation (OR = 0.35; 0.21-0.60; P < 0.01) and LV systolic dysfunction (OR = 0.07; 0.02-0.31; P < 0.01). Higher CD4 count was associated with lower risk of LV systolic dysfunction (OR = 0.82; 0.69-0.98; P < 0.05). CONCLUSIONS: Echocardiograms identified cardiac abnormalities among children with perinatally acquired HIV infection, and data suggest that immunologic status and therapeutic strategies throughout development can influence cardiac disease burden in this population.

Profile of health professionals who completed a master's, doctoral, or post-doctoral degree in one Brazilian pediatric program.

OBJECTIVE: This study aimed to determine the personal and professional characteristics, and the physical, psychiatric/psychological, and professional issues that exist among master's-, doctoral-, and post-doctoral-level health professionals. METHODS: A cross-sectional, online, self-reported survey of 452 postgraduates who completed master's, doctoral, or post-doctoral degrees in one graduate program in pediatrics in São Paulo, Brazil, was conducted. RESULTS: The response rate was 47% (211/453). The majority of participants were women (78%) and physicians (74%), and the median age was 47 years (28-71). Master's, doctoral, and post-doctoral degrees were reported by 73%, 53%, and 3%, respectively. High workload (>40 hours/week) occurred in 59%, and 45% earned ≥15 minimum wages/month. At least one participation in scientific meeting in the past year was reported by 91%, and 79% had published their research. Thirty-nine percent served as a member of a faculty of an institution of higher learning. The data were analyzed by two age groups: participants aged ≤48 years (group 1) and participants aged >48 years (group 2). The median rating of overall satisfaction with the profession in the past year [8 (0-10) vs. 9 (1-10), p=0.0113]; workload >40 hours/week (53% vs. 68%, p=0.034); and ≥15 minimum wages/month (37% vs. 56%, p=0.0083) were significantly lower in group 1. Further analysis by gender revealed that the median rating of overall satisfaction with the profession in the past year [8 (0-10) vs. 9 (3-10), p=0.0015], workload >40 hours/week (53% vs. 83%, p=0.0002), and ≥15 minimum wages/month (37% vs. 74%, p=0.0001) were significantly lower in women compared with men. The median rating of overall satisfaction with the mentorship supervision provided was significantly higher among the women 10 (5-10) vs. 10 (2-10), p=0.0324]. CONCLUSIONS: The majority of master's-, doctoral-, and post-doctoral-level health professionals were women and physicians, and had published their thesis. Younger postgraduates and women reported low salaries, less likelihood of working >40 hours/week, and less overall satisfaction with their profession. Further longitudinal and qualitative studies are warranted to assess career trajectories after graduation.