Symptoms for early diagnosis of chronic kidney disease in children - a machine learning-based score.

The objective of this study was to reveal the signs and symptoms for the classification of pediatric patients at risk of CKD using decision trees and extreme gradient boost models for predicting outcomes. A case-control study was carried out involving children with 376 chronic kidney disease (cases) and a control group of healthy children (n = 376). A family member responsible for the children answered a questionnaire with variables potentially associated with the disease. Decision tree and extreme gradient boost models were developed to test signs and symptoms for the classification of children. As a result, the decision tree model revealed 6 variables associated with CKD, whereas twelve variables that distinguish CKD from healthy children were found in the "XGBoost". The accuracy of the "XGBoost" model (ROC AUC = 0.939, 95%CI: 0.911 to 0.977) was the highest, while the decision tree model was a little lower (ROC AUC = 0.896, 95%CI: 0.850 to 0.942). The cross-validation of results showed that the accuracy of the evaluation database model was like that of the training. CONCLUSION: In conclusion, a dozen symptoms that are easy to be clinically verified emerged as risk indicators for chronic kidney disease. This information can contribute to increasing awareness of the diagnosis, mainly in primary care settings. Therefore, healthcare professionals can select patients for more detailed investigation, which will reduce the chance of wasting time and improve early disease detection. WHAT IS KNOWN: • Late diagnosis of chronic kidney disease in children is common, increasing morbidity. • Mass screening of the whole population is not cost-effective. WHAT IS NEW: • With two machine-learning methods, this study revealed 12 symptoms to aid early CKD diagnosis. • These symptoms are easily obtainable and can be useful mainly in primary care settings.

Clusters of preterm live births and respiratory distress syndrome-associated neonatal deaths: spatial distribution and cooccurrence patterns.

BACKGROUND: Prematurity and respiratory distress syndrome (RDS) are strongly associated. RDS continues to be an important contributor to neonatal mortality in low- and middle-income countries. This study aimed to identify clusters of preterm live births and RDS-associated neonatal deaths, and their cooccurrence pattern in São Paulo State, Brazil, between 2004 and 2015.  METHODS: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥ 400 g, without congenital anomalies from mothers living in São Paulo State, Brazil, during 2004-2015. RDS-associated neonatal mortality was defined as deaths < 28 days with ICD-10 codes P22.0 or P28.0. RDS-associated neonatal mortality and preterm live births rates per municipality were submitted to first- and second-order spatial analysis before and after smoothing using local Bayes estimates. Spearman test was applied to identify the correlation pattern between both rates. RESULTS: Six hundred forty-five thousand two hundred seventy-six preterm live births and 11,078 RDS-associated neonatal deaths in São Paulo State, Brazil, during the study period were analyzed. After smoothing, a non-random spatial distribution of preterm live births rate (I = 0.78; p = 0.001) and RDS-associated neonatal mortality rate (I = 0.73; p = 0.001) was identified. LISA maps confirmed clusters for both, with a negative correlation (r = -0.24; p = 0.0000). Clusters of high RDS-associated neonatal mortality rates overlapping with clusters of low preterm live births rates were detected. CONCLUSIONS: Asymmetric cluster distribution of preterm live births and RDS-associated neonatal deaths may be helpful to indicate areas for perinatal healthcare improvement.

Temporal Trend and Risk Factors for Respiratory Distress Syndrome-Associated Neonatal Mortality in Preterm Infants: A Population-Based Study in a Middle-Income Country.

OBJECTIVE: This article aimed to report a temporal series of respiratory distress syndrome (RDS)-associated neonatal mortality rates in preterm live births in São Paulo state, Brazil, and to identify social, maternal, and neonatal characteristics associated with these deaths. STUDY DESIGN: This is a population-based study of all live births with gestational age (GA) between 22 and 36 weeks, birth weight ≥400 g, without congenital anomalies from mothers living in São Paulo state during 2004 to 2015. RDS-associated neonatal mortality was defined as death up to 27 days after birth with ICD-10 codes P22.0 or P28.0. RDS-associated neonatal mortality rate (annual percent change [APC] with 95% confidence intervals [95% CIs]) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that the RDS-associated neonatal death occurred. Poisson's regression model compared social maternal and neonatal characteristics between preterm live births that survived the neonatal period and those with RDS-associated neonatal deaths, with results expressed in incidence rate ratio and 95% CI. RESULTS: A total of 645,276 preterm live births were included in the study, of which 612,110 survived and 11,078 had RDS-associated neonatal deaths. RDS-associated neonatal mortality rate was 17.17 per thousand preterm live births, with a decreasing annual trend (APC: -6.50%; 95% CI: -9.11 to -3.82%). The median time of these deaths was 48 hours after birth. The following risk factors for RDS-associated neonatal death were identified: maternal schooling ≤7 years (1.18; 1.09-1.29), zero to three prenatal care visits (1.25; 1.18-1.32), multiple pregnancy (1.24; 1.16-1.33), vaginal delivery (1.29; 1.22-1.36), GA 22 to 27 weeks (106.35; 98.36-114.98), GA 28 to 31 weeks (20.12; 18.62-21.73), male sex (1.16; 1.10-1.22), and 5-minute Apgar scores of 0 to 3 (6.74; 6.08-7.47) and 4 to 6 (3.97; 3.72-4.23). CONCLUSION: During the study period, RDS-associated neonatal mortality rates showed significant reduction. The relationship between RDS-associated neonatal deaths and social, maternal, and neonatal factors suggests the need for perinatal strategies to reduce prematurity and to improve the initial management of preterm infants. KEY POINTS: · RDS is associated with preterm live births.. · Impact of RDS-associated neonatal mortality in middle-income countries is scarce.. · Qualified perinatal care can reduce RDS-associated neonatal mortality..

Spiritual Well-Being and Its Association with Coronary Artery Disease.

Cardiovascular diseases are the main cause of mortality in the world, generating important socioeconomic and cultural impacts. Spirituality has been associated with the main risk factors for acute myocardial infarction, influencing lifestyle, and drug treatment compliance. Estimate the level of spiritual well-being and its association with coronary artery disease. We conducted a case-control study with 88 adults (42 cases and 46 controls) individually interviewed. Using a spiritual well-being scale and collecting socioeconomic and demographic information. We compared groups by Chi-square and Mann-Whitney tests. Friedman's analysis of variance was used to evaluate the differences between the values assigned to the scale items in each group. Statistically, there was no significant difference between categories and levels of spiritual well-being in any of the groups. Both had high rates, driven by the high level of religious well-being. There was no difference between the rates attributed to the items on the subscale of religious well-being, in the case or control groups (p = 0.959 and p = 0.817). However, the existential well-being subscale revealed variability between the scores attributed to each item in both groups (p < 0.001). The results revealed a high level of spiritual well-being in the analyzed sample. There was no correlation between the levels of spiritual, religious, and existential well-being with coronary artery disease, possibly due to the reduced ability of the religious well-being subscale to discriminate between groups.

Access to treatment for chronic kidney disease by children and adolescents in Brazil.

BACKGROUND: This study aimed to identify main factors associated with child and adolescent access to chronic kidney disease (CKD) treatment in Brazil. METHODS: Multi-center cross-sectional study conducted in eight pediatric nephrology centers across all Brazilian geographic regions. Information was collected on characteristics associated with referral and treatment of patients with CKD. The following outcomes were analyzed as follows: (1) age at first consultation, and (2) time elapsed between referral and treatment at the specialized service. RESULTS: Three hundred thirty-five children were assessed. Variables associated with age at first consultation were as follows: CAKUT (HR=1.7; 95%CI 1.3-2.2, p<0.01); private health plan (HR=1.54; 95%CI 1.06-2.23, p=0.02); modified Medical Outcomes Study Social Support Survey mMOS-SS score (HR=1.02; 95%CI 1.00-1.03, p=0.024); maternal age (HR=0.96; 95%CI 0.95-0.97, p<0.01); and number of siblings in the household (HR=0.86; 95%CI 0.79-0.83, p<0.01). Significant variables associated with time elapsed between referral and treatment at the specialized service were as follows: each additional occupant sharing the household (HR=0.94; 95%CI:0.89-0.99, p=0.02), residing in the Northeast (HR=0.81; 95%CI:0.67-0.98, p=0.03) and having someone to take them to the physician (HR=1.36; 95%CI 1.07-1.74, p=0.01). The median time interval between patient referral and treatment by the service was 11 days (IQR 10-31). CONCLUSION: There are potentially modifiable factors hampering access of children with CKD to specialized treatment. The importance of the role of social support for the two outcomes should serve as an alert for health managers and professionals to consider this aspect throughout all steps of the care process of children with CKD.

Annual trend of neonatal mortality and its underlying causes: population-based study - São Paulo State, Brazil, 2004-2013.

BACKGROUND: Population-based studies analyzing neonatal deaths in middle-income countries may contribute to design interventions to achieve the Sustainable Development Goals, established by United Nations. This study goal is to analyze the annual trend of neonatal mortality in São Paulo State, Brazil, over a 10-year period and its underlying causes and to identify maternal and neonatal characteristics at birth associated with neonatal mortality. METHOD: A population-based study of births and deaths from 0 to 27 days between 2004 and 2013 in São Paulo State, Brazil, was performed. The annual trend of neonatal mortality rate according to gestational age was analyzed by Poisson or by Negative Binomial Regression models. Basic causes of neonatal death were classified according to ICD-10. Association of maternal demographic variables (block 1), prenatal and delivery care variables (block 2), and neonatal characteristics at birth (block 3) with neonatal mortality was evaluated by Poisson regression analysis adjusted by year of birth. RESULTS: Among 6,056,883 live births in São Paulo State during the study period, 48,309 died from 0 to 27 days (neonatal mortality rate: 8.0/1,000 live births). For the whole group and for infants with gestational age 22-27, 28-31, 32-36, 37-41 and ≥ 42 weeks, reduction of neonatal mortality rate was, respectively, 18 %, 15 %, 38 %, 53 %, 31 %, and 58 %. Median time until 50 % of deaths occurred was 3 days. Main basic causes of death were respiratory disorders (25 %), malformations (20 %), infections (17 %), and perinatal asphyxia (7 %). Variables independently associated with neonatal deaths were maternal schooling, prenatal care, parity, newborn sex, 1st minute Apgar, and malformations. Cesarean delivery, compared to vaginal, was protective against neonatal mortality for infants at 22-31 weeks, but it was a risk factor for those with 32-41 weeks. CONCLUSIONS: Despite the significant decrease in neonatal mortality rate over the 10-year period in São Paulo State, improved access to qualified health care is needed in order to avoid preventable neonatal deaths and increase survival of infants that need more complex levels of assistance.

Effects of probiotics in the treatment of food hypersensitivity in children: a systematic review.

INTRODUCTION: Food allergy is considered a public health problem for children. The modulation of the intestinal microbiota seems a promising strategy for the control of allergic reactions. OBJECTIVE: To describe the effects of different forms of probiotics in pediatric food hypersensitivity treatment. DATA SOURCE: We conducted a systematic review based on clinical trials published in the PubMed and Web of Science databases. The searches were carried out using the MeSH terms "Food Hypersensitivity," "Probiotics," "Lactobacillus," and "Bifidobacterium". DATA SYNTHESIS: The final selection resulted in 18 clinical trials, which were predominantly samples of infants and pre-school children. The most-often used strain, either alone or in combination, was Lactobacillus rhamnosus GG; a placebo was mainly used in the control group. As for the vehicle, the most common forms were capsules and infant formulas, and the period of intervention ranged from four weeks to 24 months, with weekly or monthly visits to measure the outcomes. In these 18 trials, 46 analyses were performed with 27 different types of outcomes to evaluate the effects of probiotics (12 laboratory and 15 clinical). Twenty-seven of these analyses demonstrated the benefits of using these microorganisms. The SCORAD (atopic dermatitis index) and IgE levels and cytokines were the outcomes mostly evaluated. CONCLUSION: The use of probiotics is beneficial in promoting immunomodulation and reducing clinical symptoms. However, more methodologically based research is needed to clarify the effect from each type, dose, and time of using them for the establishment of definitive care protocols.

Inequality in pediatric kidney transplantation in Brazil.

BACKGROUND: The aim of this study was to describe the access and factors associated with kidney transplantation for children in different regions of Brazil. METHODS: We analyzed a cohort of 1211 children enrolled on the transplant list from January 2011 to December of 2013. We fitted regression models to investigate factors associated with: (a) undergoing kidney transplantation from a deceased donor, and (b) being removed from the waiting list. RESULTS: The incidence of transplantation was uneven across regions, with the lowest rate at 0.4 per million age-related population (pmarp) in the Midwest and the highest incidence rate of 8.3 cases pmarp in the South. Children from the North and the Midwest regions had a 3-4 times lower probability of undergoing a deceased donor transplant (p < 0.05). Apart from the geographic region, age of recipients and GDP influenced the outcome. The likelihood of undergoing transplantation was very low in the youngest children in the North and Midwest. The number of transplant centers was not associated with either outcome. CONCLUSIONS: Factors of inequality in transplantation in Brazil are of macroeconomic origin, but there is room to reduce inequalities. Training existing transplant center professionals in the care of children could diminish the discrepancies.

Factors associated with avoidable hospitalisation of children younger than 2 years old: the 2006 Brazilian National Demographic Health Survey.

INTRODUCTION: Ambulatory Care Sensitive Conditions (ACSC) are conditions for which hospitalisation is thought to be avoidable with the use of effective preventive care and early disease management. The objective of this study was to estimate the rate of avoidable hospitalisations in children younger than 24 months of age participating in a Brazilian national representative survey and to identify the risk factors for such hospitalisations. METHODS: We analysed data from a cross-sectional study of 1901 children from the 2006 Brazilian National Demographic Health Survey of Women and Children (NDHS). The children's socioeconomic, biological and maternal characteristics, nutritional status, and access to healthcare were tested; variables with p < 0.20 were selected to fit a Poisson regression. RESULTS: The prevalence of avoidable hospitalisation was 11.8% (95% Confidence Interval [CI], 9.0, 15.2); the prevalence was higher in the Southeast (40.1%) and Northwest (21.7%) macro-regions. The multivariate model identified five risk factors for avoidable hospitalisation: male gender (Prevalence Ratio [PR] = 1.48, p = 0.004), low socioeconomic level (PR = 1.51, p = 0.005), children from mothers younger than 20 years of age (PR = 1.41, p = 0.031), not breastfed within the first hour of life (PR = 1.29, p = 0.034), and neonatal hospitalisation (PR = 1.66, p = 0.043). CONCLUSIONS: To decrease the costs associated with avoidable hospitalisations, health managers and professionals should focus their efforts on providing effective primary healthcare to families of low socioeconomic levels, particularly prenatal and paediatric care, as well as encouraging breastfeeding and supporting young mothers. Strategies to improve children's health by controlling such hospitalisations in Brazil should consider all residence areas and geopolitical macro-regions.

Prevalence and determinants of vitamin A deficiency among Brazilian children under 2 years of age from the 2006 National Demographic Health Survey.

BACKGROUND: Vitamin A deficiency is prevalent among infants, primarily in undeveloped communities, compromising immune system competence and raising morbidity and mortality rates. Understanding the risk factors associated with vitamin A deficiency is essential to create informed health policies. OBJECTIVE: To identify and quantify risk factors for vitamin A deficiency in a probabilistic sample of children under 2 years of age participating in a national survey in Brazil and to provide a comprehensive risk factor model to inform health strategies and policies. METHODS: We analyzed data from a cross-sectional study of 1,436 children from the 2006 Brazilian National Survey on Demography and the Health of Women and Children. Vitamin A deficiency was defined as retinol levels below 0.70 µg/dL. RESULTS: The prevalence of vitamin A deficiency was estimated at 16.1% (95% CI, 12.7 to 20.2). The Poisson regression model identified three risk factors for vitamin A deficiency: urban residence (prevalence ratio [PR] = 1.47, p = .023), no consumption of animal meat within the past week (PR = 1.41, p = .031), and a mother older than 25 years (PR = 1.31, p = .048). CONCLUSIONS: Strategies to control infant vitamin A deficiency should include health promotion and nutrition education for families from all socioeconomic levels. Improvements in lifestyle quality, based on adequate food consumption by all infants, must be achieved by communities, especially in urban areas and for older mothers.

Mortality trends and sociodemographic factors associated with early death in sickle cell disease patients in the state of São Paulo.

OBJECTIVE: To estimate trends in mortality rate and average age of death, and identify sociodemographic factors associated with early death in patients with sickle cell disease (SCD). METHODS: An ecological and cross-sectional study was conducted using data from the Mortality Information System. All deaths of patients residing in the state of São Paulo from 1996 to 2015 with at least one International Disease Code for SCD in any field of the death certificate were included. Simple linear regression was used to estimate trends. The Log-rank test and multiple Cox regression were used to identify factors associated with early death. RESULTS: The age-standardized mortality rate per million inhabitants increased by 0.080 per year (R2=0.761; p<0.001). When the events were stratified by age at death, the increase was 0.108 per year for those occurring at age 20 years or older, (R2=0.789; p<0.001) and 0.023 per year for those occurring before age 20 years old (R2=0.188; p=0.056). The average age at death increased by 0.617 years (7.4 months) per year (R2=0.835; p<0.001). Sociodemographic factors associated with early death identified were male gender (hazard ratio - HR=1.30), white race (HR=1.16), death occurring in the hospital (HR=1.29), and living in the Greater São Paulo (HR=1.13). CONCLUSIONS: The mortality rate and the average age of death in patients with SCD have increased over the last two decades. Sociodemographic factors such as gender, race, place of occurrence, and residence were found to be associated with early death.

Troponin I as an Independent Biomarker of Outcome in Children with Systemic Inflammatory Response.

Cardiac troponin-I (cTnI) is a biomarker of myocardial injury with implications for clinical outcomes. May other contributing factors that could affect outcomes have not been uniformly considered in pediatric studies. We hypothesized that there is an association between admission serum cTnI and outcomes in critically ill children taking into account the magnitude of the acute systemic inflammatory response syndrome (SIRS), serum lactate concentrations, and nutritional status. Second, we tested for potential factors associated with elevated serum cTnI. This was a prospective cohort study in 104 children (median age: 21.3 months) consecutively admitted to a pediatric intensive care unit (PICU) of a teaching hospital with SIRS and without previous chronic diseases. Primary outcome variables were PICU-free days, ventilator-free days, and 30-day mortality. Exposure variables were serum cTnI concentration on admission, revised pediatric index of mortality (PIM2), pediatric logistic organ dysfunction (PELOD-2), hypotensive shock, C-reactive protein, procalcitonin, and serum lactate on admission, and malnutrition. Elevated cTnI (>0.01 µg/L) was observed in 24% of patients, which was associated with the reduction of ventilator-free days (ß coefficient = - 4.97; 95% confidence interval [CI]: -8.03; -1.91) and PICU-free days (ß coefficient = - 5.76; 95% CI: -8.97; -2.55). All patients who died had elevated serum cTnI. The increase of 0.1 µg/L in cTnI concentration resulted in an elevation of 2 points in the oxygenation index (ß coefficient = 2.0; 95% CI: 1.22; 2.78, p < 0.001). The PIM2 score, hypotensive shock in the first 24 hours, and serum lactate were independently associated with elevated cTnI on admission. We conclude that elevated serum cTnI on admission is independently associated with adverse outcomes in children with SIRS and without associated chronic diseases.

Assessment of trace elements in critically ill patients with systemic inflammatory response syndrome: A systematic review.

BACKGROUND: Zinc (Zn), copper (Cu), and selenium (Se) are involved in immune and antioxidant defense. Their role in systemic inflammatory response syndrome (SIRS) treatment and outcomes remains unclear. This systematic review aimed to describe trace element concentrations in different types of biological samples and their relationship with morbidity and mortality in patients with SIRS. METHODS: Literature was systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The search results were screened and evaluated for eligibility, and data were extracted and summarized in tables and figures. RESULTS: Most of the 38 included studies evaluated Se (75%), followed by Zn (42%) and Cu (22%). Plasma was the main biological sample evaluated (58%). Thirteen studies found lower plasma/serum concentrations of Zn, Se, and Cu in SIRS patients than in controls upon admission, 11 studies on adults (intensive care unit-ICU) and two in pediatric ICU (PICU). Three ICU studies found no difference in erythrocyte trace element concentrations in patients with SIRS. In all studies, the two main outcomes investigated were organ failure and mortality. In seven ICU studies, patients with lower plasma or serum Zn/Se levels had higher mortality rates. A study conducted in the PICU reported an association between increased Se variation and lower 28-day mortality. In an ICU study, lower erythrocyte selenium levels were associated with higher ICU/hospital mortality, after adjustment. Five ICU studies associated lower plasma/serum Zn/Se levels with higher organ failure scores and one PICU study showed an association between higher erythrocyte Se levels and lower organ dysfunction scores. CONCLUSION: There was no difference in erythrocyte Se levels in patients with SIRS. Serum/Plasma Zn and serum/plasma/erythrocyte Se are associated with organ dysfunction, mortality, and inflammation. Trace element deficiencies should be diagnosed by erythrocyte, or complementary measurements in the presence of inflammation.

Clinical and laboratory differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2.

OBJECTIVE: The aim of this study was to identify clinical and complete blood count differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2 and compare the complete blood count of patients with sickle cell disease infected by SARS-CoV-2 before hospitalization and on admission. METHODS: This study was a single-center prospective cohort. Data were collected from medical records of pediatric inpatients with sickle cell disease under 18 years old infected or not with SARS-CoV-2 from the first visit to the hospital until discharge and from the last medical appointment. All patients were tested for SARS-CoV-2 by the real-time reverse transcription polymerase chain reaction. RESULTS: Among 57 pediatric patients with sickle cell disease hospitalized from March to November 2020 in a Brazilian academic hospital, 11 (19.3%) had a positive result for SARS-CoV-2. Patients infected by SARS-CoV-2 had a higher prevalence of comorbidities than the ones who were not infected (63.6 vs. 30.4%; p=0.046). During hospital stay, no clinical or complete blood count differences between groups were found. There was a decrease in eosinophil count on hospital admission in patients with sickle cell disease infected by SARS-CoV-2 (p=0.008). CONCLUSIONS: Pediatric hospitalized patients with sickle cell disease infected by SARS-CoV-2 had more comorbidities and had a decrease in eosinophil count between hospital admission and the last medical appointment.

Prevalence of psychoactive substance use by adolescents in public schools in a municipality in the São Paulo Metropolitan Area, Brazil.

This study aimed to estimate the prevalence of psychoactive substance use by adolescents from public schools. This is a cross-sectional study that used a random sample of adolescents from five public schools located in a municipality in the central-west region of the São Paulo Metropolitan Area, Brazil. Information on demographic, socioeconomic, and drug use was collected using self-report questionnaires. The sample consisted of 1,460 students, 716 (49%) males, aged 10-19 years (13.19±2.04 years). The prevalence of psychoactive substance use in the last month was 51% for analgesics; 48.8% for alcohol; 37.3% for tobacco; 30.8% for tranquilizers; 23.1% for marijuana; 22.6% for anabolic steroids; 21.6% for ecstasy; 15.3% for amphetamines/stimulants; 13.4% for phencyclidine; 12.9% for cocaine/crack; 12.6% for inhalants/solvents; 11.5% for opiates; 11.4% for hallucinogens; and 16.2% for other unclassified drugs. Elementary and middle school students were more likely to consume tobacco (OR = 2.306; 95%CI: 1.733-3.068; p < 0.001), and male students were more likely to consume any type of substance. We identified a high use of psychoactive substances among this study participants, with a higher prevalence among male students.

Congenital diaphragmatic hernia in a middle-income country: Persistent high lethality during a 12-year period.

BACKGROUND: In high- and middle-income countries, mortality associated to congenital diaphragmatic hernia (CDH) is high and variable. In Brazil, data is scarce regarding the prevalence, mortality, and lethality of CDH. This study aimed to analyze, in São Paulo state of Brazil, the temporal trends of prevalence, neonatal mortality and lethality of CDH and identify the time to CDH-associated neonatal death. METHODS: Population-based study of all live births with gestational age ≥ 22 weeks, birthweight ≥400g, from mothers residing in São Paulo State, Brazil, during 2004-2015. CDH definition and its subgroups classification were based on ICD-10 codes reported in the death and/or live birth certificates. CDH-associated neonatal death was defined as death up to 27 days after birth of infants with CDH. CDH prevalence, neonatal mortality and lethality were calculated and their annual percent change (APC) with 95% confidence intervals (95%CI) was analyzed by Prais-Winsten. Kaplan-Meier estimator identified the time after birth that CDH-associated neonatal death occurred. RESULTS: CDH prevalence was 1.67 per 10,000 live births, with a significant increase throughout the period (APC 2.55; 95%CI 1.30 to 3.83). CDH neonatal mortality also increased over the time (APC 2.09; 95%CI 0.27 to 3.94), while the lethality was 78.78% and remained stationary. For isolated CDH, CDH associated to non-chromosomal anomalies and CDH associated to chromosomal anomalies the lethality was, respectively, 72.25%, 91.06% and 97.96%, during the study period. For CDH as a whole and for all subgroups, 50% of deaths occurred within the first day after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, CDH prevalence and neonatal mortality showed a significant increase, while lethality remained stable, yet very high, compared to rates reported in high income countries.

Temporal Trend, Causes, and Timing of Neonatal Mortality of Moderate and Late Preterm Infants in São Paulo State, Brazil: A Population-Based Study.

Moderate and late preterm newborns comprise around 85% of live births < 37 weeks gestation. Data on their neonatal mortality in middle-income countries is limited. This study aims to analyze the temporal trend, causes and timing of neonatal mortality of infants with 320/7-366/7 weeks gestation without congenital anomalies from 2004-2015 in the population of São Paulo State, Brazil. A database was built by deterministic linkage of birth and death certificates. Causes of death were classified by ICD-10 codes. Among 7,317,611 live births in the period, there were 545,606 infants with 320/7-366/7 weeks gestation without congenital anomalies, and 5782 of them died between 0 and 27 days. The neonatal mortality rate decreased from 16.4 in 2004 to 7.6 per thousand live births in 2015 (7.47% annual decrease by Prais-Winsten model). Perinatal asphyxia, respiratory disorders and infections were responsible, respectively, for 14%, 27% and 44% of the 5782 deaths. Median time to death was 24, 53 and 168 h, respectively, for perinatal asphyxia, respiratory disorders, and infections. Bottlenecks in perinatal health care are probably associated with the results that indicate the need for policies to reduce preventable neonatal deaths of moderate and late preterm infants in the most developed state of Brazil.

Epidemiological trends of isolated and non-isolated central nervous system congenital malformations in live births in a middle-income setting.

OBJECTIVES: This study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015. METHODS: Population-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004-2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00-Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00-Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained. RESULTS: 7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC -1.66; 95%CI -3.09 to -0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth. CONCLUSIONS: During a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth.

The burden of inappropriate birth weight on neonatal survival in term newborns: a population-based study in a middle-income setting.

Introduction: Premature birth, perinatal asphyxia, and infections are the main causes of neonatal death. Growth deviations at birth also affect neonatal survival according to week of gestation at birth, particularly in developing countries. The purpose of this study was to verify the association between inappropriate birth weight and neonatal death in term live births. Methods: This is an observational follow-up study with all term live births from 2004 to 2013 in Sao Paulo State, Brazil. Data were retrieved with the deterministic linkage of death and birth certificates. The definition of very small for gestational age (VSGA) and very large for gestational age (VLGA) used the 10th percentile of 37 weeks and the 90th percentile of 41 weeks + 6 days, respectively, based on the Intergrowth-21st. We measured the outcome in terms of time to death and the status of each subject (death or censorship) in the neonatal period (0-27 days). Survival functions were calculated using the Kaplan-Meier method stratified according to the adequacy of birth weight into three groups (normal, very small, or very large). We used multivariate Cox regression to adjust for proportional hazard ratios (HRs). Results: The neonatal death rate during the study period was 12.03/10,000 live births. We found 1.8% newborns with VSGA and 2.7% with VLGA. The adjusted analysis showed a significant increase in mortality risk for VSGA infants (HR = 4.25; 95% CI: 3.89-4.65), independent of sex, 1-min Apgar score, and five maternal factors. Discussion: The risk of neonatal death in full-term live births was approximately four times greater in those with birth weight restriction. The development of strategies to control the factors that determine fetal growth restriction through planned and structured prenatal care can substantially reduce the risk of neonatal death in full-term live births, especially in developing countries such as Brazil.

Risk factors for insufficient weight and height gain in children with congenital heart disease followed up at a nutrition outpatient clinic.

OBJECTIVE: To describe weight and height evolution and to identify risk factors for insufficient anthropometric growth in children with congenital heart disease. METHODS: Historical cohort study including 131 children with congenital heart disease, followed up at a nutrition outpatient clinic. The anthropometric indices over time (initial score, after 12 and 24 months of follow-up) were analyzed using generalized estimating equations. The outcome was 'insufficient weight-height gain', defined as an increase of ≤0.5 in the z-score of weight-for-age (W/A), height-for-age (H/A) or body mass index-for-age (BMI/A) after 12 months of follow-up. Multiple logistic regression models were applied to identify risk and confounding factors. RESULTS: The z-scores of W/A (p<0.001) and BMI/A (p<0.001) improved after 12 months, as well as the three indexes after 24 months (p<0.001). At the end of this period, 55.7% of the patients did not achieve an increase of >0.5 in the Z score of W/A; 77.1%, of H/A; and 45.8%, of BMI/A. A follow-up of less than five appointments was associated with insufficient gain in W/A (OR 7.78; 95%CI 3.04-19.88), H/A (OR 10.79; 95%CI 2.22-52.45) and BMI/A (OR 2.54; 95%CI 1.12-5.75). Not having undergone cardiac surgery and being aged ≥12 months were factors associated with insufficient W/A gain (OR 3.95; 95%CI 1.38-11.29/OR 3.60; 95%CI 1.33-9.72) and BMI/A (OR 2.81; 95%CI 1.08-7.28/OR 3.39; 95%CI 1.34-8.56). Low income was associated with insufficient H/A gain (OR 4.11; 95%CI 1.25-13.46). CONCLUSIONS: Being aged less than or 12 months, the lowest number of appointments, absence of surgical treatment and low family income were risk factors for insufficient weight and height gain in children with congenital heart disease.