A 7-Year Brazilian National Perspective on Plasmid-Mediated Carbapenem Resistance in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii Complex and the Impact of the Coronavirus Disease 2019 Pandemic on Their Occurrence.

BACKGROUND: Carbapenemase production is a global public health threat. Antimicrobial resistance (AMR) data analysis is critical to public health policy. Here we analyzed carbapenemase detection trends using the AMR Brazilian Surveillance Network. METHODS: Carbapenemase detection data from Brazilian hospitals included in the public laboratory information system dataset were evaluated. The detection rate (DR) was defined as carbapenemase detected by gene tested per isolate per year. The temporal trends were estimated using the Prais-Winsten regression model. The impact of COVID-19 on carbapenemase genes in Brazil was determined for the period 2015-2022. Detection pre- (October 2017 to March 2020) and post-pandemic onset (April 2020 to September 2022) was compared using the χ2 test. Analyses were performed with Stata 17.0 (StataCorp, College Station, TX). RESULTS: 83 282 blaKPC and 86 038 blaNDM were tested for all microorganisms. Enterobacterales DR for blaKPC and blaNDM was 68.6% (41 301/60 205) and 14.4% (8377/58 172), respectively. P. aeruginosa DR for blaNDM was 2.5% (313/12 528). An annual percent increase for blaNDM of 41.1% was observed, and a decrease for blaKPC of -4.0% in Enterobacterales, and an annual increase for blaNDM of 71.6% and for blaKPC of 22.2% in P. aeruginosa. From 2020 to 2022, overall increases of 65.2% for Enterobacterales, 77.7% for ABC, and 61.3% for P. aeruginosa were observed in the total isolates. CONCLUSIONS: This study shows the strengths of the AMR Brazilian Surveillance Network with robust data related to carbapenemases in Brazil and the impact of COVID-19 with a change in carbapenemase profiles with blaNDM rising over the years.

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.

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..

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.

Clusters of cause specific neonatal mortality and its association with per capita gross domestic product: A structured spatial analytical approach.

BACKGROUND: Infant mortality rate is a measure of population health and neonatal mortality account for great proportion of these deaths. Underdevelopment might be associated to higher neonatal mortality risk due to assistant related factors. Spatial and temporal distribution of mortality help identifying and developing strategies for interventions. OBJECTIVE: To investigate the cluster areas of asphyxia-associated neonatal mortality and to explore its association with per capita gross domestic product (GDP) in São Paulo State (SP), Brazil. METHODS: Ecological study including live births residents in SP from 2004-2013. Neonatal deaths (0-27 days) with perinatal asphyxia were defined as intrauterine hypoxia, birth asphyxia or meconium aspiration syndrome written in any line of the Death Certificate. Geoprocessing analytical approach included detection of first order effects through quintiles and spatial moving average maps, followed by second order effects by global and local spatial autocorrelation (Moran and LISA, respectively) before and after smoothing with local Bayesian estimates. Finally, Spearman correlation was applied between asphyxia-associated neonatal mortality and mean per capita GDP rates for the municipalities with significant LISA. RESULTS: There were 6,713 asphyxia-associated neonatal deaths among 5,949,267 live births (rate: 1.13/1000) in SP. Spatial moving average maps showed a non-random distribution among municipalities, with presence of clusters (I = 0.048; p = 0.023). LISA map identified clusters of asphyxia-associated neonatal mortality in the south, southeast and northwest. After applying local Bayes estimates, clusters were more pronounced (I = 0.589; p = 0.001). There was a partial overlap of the areas of higher asphyxia-associated neonatal mortality and lower mean per capita GDP. CONCLUSIONS: Spatial analysis identified cluster areas of high asphyxia-associated neonatal mortality and low per capita GDP rates, with a significant negative correlation. This optimized, structured, and hierarchical approach to identify high-risk areas of cause-specific neonatal mortality may be helpful for guiding public health efforts to decrease neonatal mortality.

Operational Challenges in the Use of Structured Secondary Data for Health Research.

Background: In Brazil, secondary data for epidemiology are largely available. However, they are insufficiently prepared for use in research, even when it comes to structured data since they were often designed for other purposes. To date, few publications focus on the process of preparing secondary data. The present findings can help in orienting future research projects that are based on secondary data. Objective: Describe the steps in the process of ensuring the adequacy of a secondary data set for a specific use and to identify the challenges of this process. Methods: The present study is qualitative and reports methodological issues about secondary data use. The study material was comprised of 6,059,454 live births and 73,735 infant death records from 2004 to 2013 of children whose mothers resided in the State of São Paulo - Brazil. The challenges and description of the procedures to ensure data adequacy were undertaken in 6 steps: (1) problem understanding, (2) resource planning, (3) data understanding, (4) data preparation, (5) data validation and (6) data distribution. For each step, procedures, and challenges encountered, and the actions to cope with them and partial results were described. To identify the most labor-intensive tasks in this process, the steps were assessed by adding the number of procedures, challenges, and coping actions. The highest values were assumed to indicate the most critical steps. Results: In total, 22 procedures and 23 actions were needed to deal with the 27 challenges encountered along the process of ensuring the adequacy of the study material for the intended use. The final product was an organized database for a historical cohort study suitable for the intended use. Data understanding and data preparation were identified as the most critical steps, accounting for about 70% of the challenges observed for data using. Conclusion: Significant challenges were encountered in the process of ensuring the adequacy of secondary health data for research use, mainly in the data understanding and data preparation steps. The use of the described steps to approach structured secondary data and the knowledge of the potential challenges along the process may contribute to planning health research.