Maternal Th17 Profile after Zika Virus Infection Is Involved in Congenital Zika Syndrome Development in Children.

Brazil is one of the countries that experienced an epidemic of microcephaly and other congenital manifestations related to maternal Zika virus infection which can result in Congenital Zika Syndrome (CZS). Since the Zika virus can modulate the immune system, studying mothers' and children's immune profiles become essential to better understanding CZS development. Therefore, we investigated the lymphocyte population profile of children who developed CZS and their mothers' immune response in this study. The study groups were formed from the Plaque Reduction Neutralization Test (PRNT) (CZS+ group) result. To evaluate the lymphocyte population profile, we performed phenotyping of peripheral lymphocytes and quantification of serum cytokine levels. The immunophenotyping and cytokine profile was correlated between CSZ+ children and their mothers. Both groups exhibited increased interleukin-17 levels and a reduction in the subpopulation of CD4+ T lymphocytes. In contrast, the maternal group showed a reduction in the population of B lymphocytes. Thus, the development of CZS is related to the presence of an inflammatory immune profile in children and their mothers characterized by Th17 activation.

The perinatal epidemiology of child and adolescent marriage in Brazil, 2011-2018.

Brazil is one of the top contributors of girl child marriages in the world and one of the United Nations' members that committed to end child marriage by 2030 as part of the Sustainable Development Goals. Child marriage is an indicator of gender inequality associated with poor health outcomes. However, the perinatal epidemiology of minor mothers (<18 years) according to marital status has been insufficiently studied. We used 23,163,209 birth registrations (2011-2018) to describe the sociodemographic distribution of births to minor mothers. The association between adverse outcomes and marital status and maternal age was restricted to 7,953,739 births of mothers aged ≤15, 16-17, 18-19, 20-24 years. Multinomial logistic models were used for very (24-31 weeks) and moderately preterm birth (32-36 weeks), and severe (<3rd percentile) and moderately small-for-gestational age (SGA) (3rd to <10th percentile). Logistic models were used for binary outcomes. The proportion of births to minor mothers in the study period was 8.9%, composed of those of single (6.1%), common-law (2.4%) and married girls (0.4%). Births to minor mothers decreased over time (p-value <0.001), were more common in the North Region (13.2%) and among Indigenous (17.4%). Very and moderately preterm birth increased with decreasing age but within each age group, rates were highest among single, followed by common-law and lowest among married mothers. A similar pattern was observed for SGA, low Apgar and late prenatal care initiation. Repeat birth and low age-appropriate education were less common among married compared to single mothers in all age groups, except among ≤15-year-olds [Adjusted Odds Ratio (AOR): 2.56; 95% Confidence Interval (95%CI): 2.40, 2.74 and AOR: 1.30; 95%CI: 1.03, 1.64, respectively]. The association between perinatal indicators and marital status among adolescents is strongly modified by decreasing maternal age. Marital status is relevant for the understanding of early pregnancies.

Higher sugar intake is associated with periodontal disease in adolescents.

OBJECTIVES: Analyze the association between higher added sugar exposure and periodontal disease in adolescents (18-19 years old). MATERIALS AND METHODS: This was a cross-sectional study nested to RPS Cohorts Consortium, São Luís, Brazil (n = 2515). The exposure was percentage of daily calories from added sugar (≥ 10%), estimated from a quantitative food frequency. The outcome was periodontal disease estimated by the number of teeth affected by bleeding on probing, periodontal probing depth ≥ 4 mm, and clinical attachment level ≥ 4 mm at the same site. A theoretical model was depicted in a directed acyclic graph to identify the minimal sufficient adjustment set: household income, adolescent's educational level, sex, alcohol use, and smoking. Periodontal disease was categorized into < 2 teeth affected, 2 to 3 teeth affected, and ≥ 4 teeth affected to estimate prevalence ratios (PR) by multinomial logistic regression. To test for consistency, means ratio (MR) were estimated using zero-inflated Poisson. RESULTS: High sugar intake was associated with ≥ 4 teeth affected by periodontal disease (PR = 1.42; 95% confidence interval (CI) = 1.03-1.94; p = 0.030); consistency Poisson analysis reinforced these results (MR = 1.15; 95% CI = 1.03-1.29; p = 0.011). CONCLUSION: High level of added sugar intake was associated with greater extent of periodontal disease in adolescents. CLINICAL RELEVANCE: High sugar intake was associated with periodontal disease in adolescents, supporting the integrated hypothesis of dental caries and periodontal disease and giving impetus to future clinical investigation on the effect of restriction of added sugar consumption in periodontal parameters, which potentially may change traditional treatment protocols of periodontal disease.

Plaque Reduction Neutralization Test (PRNT) in the Congenital Zika Syndrome: Positivity and Associations with Laboratory, Clinical, and Imaging Characteristics.

The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 ± 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer ≥ 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic.

Author Correction: Changes in Infant and Neonatal Mortality and Associated Factors in Eight Cohorts from Three Brazilian Cities.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Changes in Infant and Neonatal Mortality and Associated Factors in Eight Cohorts from Three Brazilian Cities.

Stillbirth (SBR), perinatal (PMR), neonatal (NMR) and infant mortality rates (IMR) are declining in Brazil and the factors associated with these falls are still being investigated. The objective of the present study was to assess changes in SBR, PMR, NMR and IMR over time and to determine the factors associated with changes in NMR and IMR in eight Brazilian cohorts. All cohorts are population-based (Ribeirão Preto in 1978/79, 1994 and 2010; Pelotas in 1982, 1993 and 2004; and São Luís in 1997/98 and 2010). Were included data on 41440 children. All indicators were decreased, except in the city of Pelotas, from 1993 to 2004, and except SBR in São Luís. Sociodemographic variables seem to be able to explain reductions of NMR and IMR in Ribeirão Preto, from 1978/79 to 1994, and in São Luís. In Ribeirão Preto, from 1994 to 2010 declines in NMR and IMR seem to be explained by reductions in intrauterine growth restriction (IUGR). Newborn's gestational age had diminished in all cohorts, preventing even greater reductions of NMR and IMR. Improved sociodemographic variables and reduction of IUGR, seem to be able to explain part of the decrease observed. NMR and IMR could have been reduced even more, were it not for the worsening in gestational age distribution.

Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development.

Zika virus (ZIKV) has emerged as one of the most medically relevant viral infections of the past decades; the devastating effects of this virus over the developing brain are a major matter of concern during pregnancy. Although the connection with congenital malformations are well documented, the mechanisms by which ZIKV reach the central nervous system (CNS) and the causes of impaired cortical growth in affected fetuses need to be better addressed. We performed a non-invasive, metabolomics-based screening of saliva from infants with congenital Zika syndrome (CZS), born from mothers that were infected with ZIKV during pregnancy. We were able to identify three biomarkers that suggest that this population suffered from an important inflammatory process; with the detection of mediators associated with glial activation, we propose that microcephaly is a product of immune response to the virus, as well as excitotoxicity mechanisms, which remain ongoing even after birth.

Does height catch-up in schoolchildren have an effect on bone mass in adolescents? Analysis in a Brazilian birth cohort / Catch-up de estatura em escolares tem efeito sobre massa óssea em adolescentes? Análise em uma coorte brasileira de nascimento

Abstract Objective: To analyze the effect of height catch-up at school age on the bone mass of adolescents of a Brazilian birth cohort. Methods: A cohort study using data obtained from the three moments (birth, 7/9 years and 18/19 years of age) of the Cohorts-RPS study. Height catch-up was defined based on the difference between the schoolchild's z-score and birth z-score. The adolescents' bone mineral mass was analyzed using the z-score index for the lumbar spine measured by dual emission X-ray absorptiometry. A theoretical model was developed for the proposed analysis using directed acyclic graphs paired through the nearest-neighbor matching propensity score using the STATA software, version 14.0. The level of significance was set at 5%. Results: Of the 297 studied children, 24.5% achieved height catch-up. The bone mass below the expected for age was observed in 5.39% of the subjects. The mean lumbar spine z-score was −0.34 (±1.01). After the adjustment, no effect was observed between height catch-up at school age and bone mass in adolescents (Coeff = 0.598; 95% CI −0.117 to 1.313; p = 0.101). Conclusion: Even using the directed acyclic graphs and the causal inference method by adjusting the propensity score, the height catch-up did not seem to affect bone mass in adolescents, a result perhaps related to the sample size.

Resumo: Objetivo: Analisar o efeito do catch-up de estatura na idade escolar na massa óssea em adolescentes em uma coorte brasileira de nascimento. Métodos: Estudo de coorte, utilizando dados dos três momentos (nascimento, aos 7/9 anos e 18/19 anos) da pesquisa Coortes-RPS. Catch-up de estatura foi definida a partir da diferença entre o Z-score do escolar e Z-score do nascimento. Para a análise da massa óssea em adolescentes foi utilizado o índice Z-score da coluna lombar medido pela densitometria por dupla emissão de raio X. Para análise proposta, foi construído modelo teórico usando os gráficos acíclicos direcionados e pareado por escore de propensão do tipo vizinho mais próximo utilizando o software STATA versão 14.0. O nível de significância adotado foi de 5%. Resultados: Das 297 crianças, 24,58% realizaram o catch-up estatural. Massa óssea abaixo do esperado para a idade foi de 5,39%. O Z-score médio da coluna lombar foi −0,34 (± 1,01). Após ajuste, não foi observado efeito entre catch-up de estatura na idade escolar e massa óssea no adolescente (Coef = 0,598; IC 95% −0,117-1,313; p = 0,101). Conclusão: Mesmo com os gráficos acíclicos direcionados e o método de inferência causal por ajuste do escore de propensão, o catch-up de estatura parece não afetar a massa óssea em adolescentes, resultado talvez relacionado ao tamanho da amostra.

Does height catch-up in schoolchildren have an effect on bone mass in adolescents? Analysis in a Brazilian birth cohort.

OBJECTIVE: To analyze the effect of height catch-up at school age on the bone mass of adolescents of a Brazilian birth cohort. METHODS: A cohort study using data obtained from the three moments (birth, 7/9 years and 18/19 years of age) of the Cohorts-RPS study. Height catch-up was defined based on the difference between the schoolchild's z-score and birth z-score. The adolescents' bone mineral mass was analyzed using the z-score index for the lumbar spine measured by dual emission X-ray absorptiometry. A theoretical model was developed for the proposed analysis using directed acyclic graphs paired through the nearest-neighbor matching propensity score using the STATA software, version 14.0. The level of significance was set at 5%. RESULTS: Of the 297 studied children, 24.5% achieved height catch-up. The bone mass below the expected for age was observed in 5.39% of the subjects. The mean lumbar spine z-score was -0.34 (±1.01). After the adjustment, no effect was observed between height catch-up at school age and bone mass in adolescents (Coeff=0.598; 95% CI -0.117 to 1.313; p=0.101). CONCLUSION: Even using the directed acyclic graphs and the causal inference method by adjusting the propensity score, the height catch-up did not seem to affect bone mass in adolescents, a result perhaps related to the sample size.

Soft drink consumption and periodontal status in pregnant women.

BACKGROUND: Periodontal disease is associated with metabolic syndrome, and during pregnancy, it is linked to preeclampsia and preterm birth. We hypothesized that soft drink consumption, which has also been associated with metabolic disorders, may also be linked to periodontal disease. The purpose of this study was to evaluate the association between soft drink consumption and periodontal status in pregnancy. METHODS: This was a cross-sectional study nested in BRISA (Brazilian Ribeirão Preto and São Luís Birth Cohort Studies). Pregnant women (n = 1,185) completed a questionnaire and underwent periodontal examination from the 22nd to 25th week of pregnancy. The explanatory variable was the frequency of soft drink consumption (times per week). The outcome was periodontal status measured as the number of teeth with probing depth ≥4 mm with bleeding on probing (PD/BOP) or with clinical attachment level ≥4 mm (CAL). Means ratio (MR) was estimated using zero-inflated Poisson, adjusted for maternal age and income. RESULTS: The higher tertile of consumption of soft drinks during pregnancy was associated with PD/BOP (MR = 1.34; 95% confidence interval (CI): 1.03 to 1.75); while the highest tertile of diastolic blood pressure was also associated to CAL (MR = 1.21; 95% CI 1:07 to 1.35). CONCLUSION: High soft drink consumption was associated with the number of teeth with PD/BOP in pregnant women, suggesting that beverage consumption is a factor that contributes to the systemic inflammatory burden, which is common to periodontal disease, metabolic syndrome, and adverse pregnancy outcomes.

Prevalence and Risk Factors for Microcephaly at Birth in Brazil in 2010.

OBJECTIVES: To estimate the baseline prevalence and risk factors for microcephaly at birth before the Zika virus epidemic in 2 Brazilian cities. METHODS: We used population-based data from the Brazilian Ribeirão Preto (RP) and São Luís (SL) birth cohort studies of 2010 that included hospital deliveries by resident mothers. The final sample was 7376 live births in RP and 4220 in SL. Gestational age was based on the date of the mother's last normal menstrual period or obstetric ultrasonography, if available. Microcephaly at birth was classified according to the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century and the Brazilian Ministry of Health. Risk factors for microcephaly, proportionate and disproportionate microcephaly, and severe microcephaly were estimated in a hierarchized logistic regression model. RESULTS: According to the International Fetal and Newborn Growth Consortium for the 21st Century definition, the prevalence of microcephaly (>2 SDs below the mean for gestational age and sex) was higher in SL (3.5%) than in RP (2.5%). The prevalence of severe microcephaly (>3 SDs below the mean) was higher in SL (0.7%) than in RP (0.5%). Low maternal schooling, living in consensual union or without a companion, maternal smoking during pregnancy, primiparity, vaginal delivery, and intrauterine growth restriction were consistently associated with microcephaly. The number of cases of microcephaly is grossly underestimated, with an underreporting rate of ∼90%. CONCLUSIONS: The prevalence of severe microcephaly was much higher than expected in both cities. Our findings suggest that microcephaly was endemic in both municipalities before the circulation of the Zika virus.

Perinatal and early life factors associated with symptoms of depression in Brazilian children.

BACKGROUND: Few studies have been conducted on the association between perinatal and early life factors with childhood depression and results are conflicting. Our aim was to estimate the prevalence and perinatal and early life factors associated with symptoms of depression in children aged 7 to 11 years from two Brazilian birth cohorts. METHODS: The study was conducted on 1444 children whose data were collected at birth and at school age, in 1994 and 2004/2005 in Ribeirao Preto, where they were aged 10-11 years and in 1997/98 and 2005/06 in São Luís, where children were aged 7-9 years. Depressive symptoms were investigated with the Child Depression Inventory(CDI), categorized as yes (score ≥ 20) and no (score < 20). Adjusted and non-adjusted prevalence ratios (PR) were estimated by Poisson regression with robust estimation of the standard errors. RESULTS: The prevalence of depressive symptoms was 3.9% (95%CI = 2.5-5.4) in Ribeirão Preto and 13.7% (95%CI = 11.0-16.4) in São Luís. In the adjusted analysis, in Ribeirão Preto, low birth weight (PR = 3.98; 95%CI = 1.72-9.23), skilled and semi-skilled manual occupation (PR = 5.30; 95%CI = 1.14-24.76) and unskilled manual occupation and unemployment (PR = 6.65; 95%CI = 1.16-38.03) of the household head were risk factors for depressive symptoms. In São Luís, maternal schooling of 0-4 years (PR = 2.39; 95%CI = 1.31-4.34) and of 5 to 8 years (PR = 1.80; 95%CI = 1.08-3.01), and paternal age <20 years (PR = 1.92; 95%CI = 1.02-3.61), were independent risk factors for depressive symptoms. CONCLUSIONS: The prevalence of depressive symptoms was much higher in the less developed city, São Luís, than in the more developed city, Ribeirão Preto, and than those reported in several international studies. Low socioeconomic level was associated with depressive symptoms in both cohorts. Low paternal age was a risk factor for depressive symptoms in the less developed city, São Luís, whereas low birth weight was a risk factor for depressive symptoms in the more developed city, Ribeirão Preto.

Factors associated with height catch-up and catch-down growth among schoolchildren.

In developed countries, children with intrauterine growth restriction (IUGR) or born preterm (PT) tend to achieve catch-up growth. There is little information about height catch-up in developing countries and about height catch-down in both developed and developing countries. We studied the effect of IUGR and PT birth on height catch-up and catch-down growth of children from two cohorts of liveborn singletons. Data from 1,463 children was collected at birth and at school age in Ribeirão Preto (RP), a more developed city, and in São Luís (SL), a less developed city. A change in z-score between schoolchild height z-score and birth length z-score ≥ 0.67 was considered catch-up; a change in z-score ≤ -0.67 indicated catch-down growth. The explanatory variables were: appropriate weight for gestational age/PT birth in four categories: term children without IUGR (normal), IUGR only (term with IUGR), PT only (preterm without IUGR) and preterm with IUGR; infant's sex; maternal parity, age, schooling and marital status; occupation of family head; family income and neonatal ponderal index (PI). The risk ratio for catch-up and catch-down was estimated by multinomial logistic regression for each city. In RP, preterms without IUGR (RR = 4.13) and thin children (PI<10(th) percentile, RR = 14.39) had a higher risk of catch-down; catch-up was higher among terms with IUGR (RR = 5.53), preterms with IUGR (RR = 5.36) and children born to primiparous mothers (RR = 1.83). In SL, catch-down was higher among preterms without IUGR (RR = 5.19), girls (RR = 1.52) and children from low-income families (RR = 2.74); the lowest risk of catch-down (RR = 0.27) and the highest risk of catch-up (RR = 3.77) were observed among terms with IUGR. In both cities, terms with IUGR presented height catch-up growth whereas preterms with IUGR only had height catch-up growth in the more affluent setting. Preterms without IUGR presented height catch-down growth, suggesting that a better socioeconomic situation facilitates height catch-up and prevents height catch-down growth.

Prevalence of non-communicable diseases in Brazilian children: follow-up at school age of two Brazilian birth cohorts of the 1990's.

BACKGROUND: Few cohort studies have been conducted in low and middle-income countries to investigate non-communicable diseases among school-aged children. This article aims to describe the methodology of two birth cohorts, started in 1994 in Ribeirão Preto (RP), a more developed city, and in 1997/98 in São Luís (SL), a less developed town. METHODS: Prevalences of some non-communicable diseases during the first follow-up of these cohorts were estimated and compared. Data on singleton live births were obtained at birth (2858 in RP and 2443 in SL). The follow-up at school age was conducted in RP in 2004/05, when the children were 9-11 years old and in SL in 2005/06, when the children were 7-9 years old. Follow-up rates were 68.7% in RP (790 included) and 72.7% in SL (673 participants). The groups of low (<2500 g) and high (≥ 4250 g) birthweight were oversampled and estimates were corrected by weighting. RESULTS: In the more developed city there was a higher percentage of non-nutritive sucking habits (69.1% vs 47.9%), lifetime bottle use (89.6% vs 68.3%), higher prevalence of primary headache in the last 15 days (27.9% vs 13.0%), higher positive skin tests for allergens (44.3% vs 25.3%) and higher prevalence of overweight (18.2% vs 3.6%), obesity (9.5% vs 1.8%) and hypertension (10.9% vs 4.6%). In the less developed city there was a larger percentage of children with below average cognitive function (28.9% vs 12.2%), mental health problems (47.4% vs 38.4%), depression (21.6% vs 6.0%) and underweight (5.8% vs 3.6%). There was no difference in the prevalence of bruxism, recurrent abdominal pain, asthma and bronchial hyperresponsiveness between cities. CONCLUSIONS: Some non-communicable diseases were highly prevalent, especially in the more developed city. Some high rates suggest that the burden of non-communicable diseases will be high in the future, especially mental health problems.