Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

BACKGROUND: Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. METHODS: We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. CONCLUSION: Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes

Risk factors for atopic and non-atopic asthma in a rural area of Ecuador

Background: Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children. Methods: A cross-sectional study was conducted among 3960 children aged 6–16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity. Results: A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/day)) but inversely associated with age and birth order. Conclusions: The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze

Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population.

Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA) and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children's guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was defined by the presence of positive serologic test results for IgG to seven pathogens (Toxocara spp, Toxoplasma gondii, Helicobacter pylori, and hepatitis A, herpes simplex, herpes zoster and Epstein-Barr viruses) and the presence of intestinal helminth eggs in stool samples (Ascaris lumbricoides and Trichiuris trichiura). African ancestry was negatively associated with maternal education and household income and positively associated with infections and variables, indicating poorer housing and living conditions. The self-reported skin colour was associated with infections only. In stratified analyses, the proportion of African ancestry was associated with most of the outcomes investigated, particularly among admixed individuals. In conclusion, BGA was associated with socioenvironmental conditions and infections even in a low-income and highly admixed population, capturing differences that self-reported skin colour miss. Importantly, our findings suggest caution in interpreting significant associations between BGA and diseases as indicative of the genetic factors involved

CIDACS-RL: a novel indexing search and scoring-based record linkage system for huge datasets with high accuracy and scalability

Background: Record linkage is the process of identifying and combining records about the same individual from two or more different datasets. While there are many open source and commercial data linkage tools, the volume and complexity of currently available datasets for linkage pose a huge challenge; hence, designing an efficient linkage tool with reasonable accuracy and scalability is required. Methods: We developed CIDACS-RL (Centre for Data and Knowledge Integration for Health – Record Linkage), a novel iterative deterministic record linkage algorithm based on a combination of indexing search and scoring algorithms (provided by Apache Lucene). We described how the algorithm works and compared its performance with four open source linkage tools (AtyImo, Febrl, FRIL and RecLink) in terms of sensitivity and positive predictive value using gold standard dataset. We also evaluated its accuracy and scalability using a case-study and its scalability and execution time using a simulated cohort in serial (single core) and multi-core (eight core) computation settings. Results: Overall, CIDACS-RL algorithm had a superior performance: positive predictive value (99.93% versus AtyImo 99.30%, RecLink 99.5%, Febrl 98.86%, and FRIL 96.17%) and sensitivity (99.87% versus AtyImo 98.91%, RecLink 73.75%, Febrl 90.58%, and FRIL 74.66%). In the case study, using a ROC curve to choose the most appropriate cut-off value (0.896), the obtained metrics were: sensitivity = 92.5% (95% CI 92.07–92.99), specificity = 93.5% (95% CI 93.08–93.8) and area under the curve (AUC) = 97% (95% CI 96.97–97.35). The multi-core computation was about four times faster (150 seconds) than the serial setting (550 seconds) when using a dataset of 20 million records. Conclusion: CIDACS-RL algorithm is an innovative linkage tool for huge datasets, with higher accuracy, improved scalability, and substantially shorter execution time compared to other existing linkage tools. In addition, CIDACS-RL can be deployed on standard computers without the need for high-speed processors and distributed infrastructures

Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study.

BACKGROUND: Indirect financial costs and barriers to health-care access might contribute to leprosy treatment non-adherence. We estimated the association of the Brazilian conditional cash transfer programme, the Programa Bolsa Família (PBF), on leprosy treatment adherence and cure in patients in Brazil. METHODS: In this quasi-experimental study, we linked baseline demographic and socioeconomic information for individuals who entered the 100 Million Brazilian Cohort between Jan 1, 2007, and Dec 31, 2014, with the PBF payroll database and the Information System for Notifiable Diseases, which includes nationwide leprosy registries. Individuals were eligible for inclusion if they had a household member older than 15 years and had not received PBF aid or been diagnosed with leprosy before entering the 100 Million Brazilian Cohort; they were excluded if they were partial receivers of PBF benefits, had missing data, or had a monthly per-capita income greater than BRL200 (US$50). Individuals who were PBF beneficiaries before leprosy diagnosis were matched to those who were not beneficiaries through propensity-score matching (1:1) with replacement on the basis of baseline covariates, including sex, age, race or ethnicity, education, work, income, place of residence, and household characteristics. We used logistic regression to assess the average treatment effect on the treated of receipt of PBF benefits on leprosy treatment adherence (six or more multidrug therapy doses for paucibacillary cases or 12 or more doses for multibacillary cases) and cure in individuals of all ages. We stratified our analysis according to operational disease classification (paucibacillary or multibacillary). We also did a subgroup analysis of paediatric leprosy restricted to children aged up to 15 years. FINDINGS: We included 11?456 new leprosy cases, of whom 8750 (76·3%) had received PBF before diagnosis and 2706 (23·6%) had not. Overall, 9508 (83·0%) patients adhered to treatment and 10?077 (88·0%) were cured. After propensity score matching, receiving PBF before diagnosis was associated with adherence to treatment (OR 1·22, 95% CI 1·01-1·48) and cure (1·26, 1·01-1·58). PBF receipt did not significantly improve treatment adherence (1·37, 0·98-1·91) or cure (1·12, 0·75-1·67) in patients with paucibacillary leprosy. For patients with multibacillary disease, PBF beneficiaries had better treatment adherence (1·37, 1·08-1·74) and cure (1·43, 1·09-1·90) than non-beneficiaries. In the propensity score-matched analysis in 2654 children younger than 15 years with leprosy, PBF exposure was not associated with leprosy treatment adherence (1·55, 0·89-2·68) or cure (1·57, 0·83-2·97). INTERPRETATION: Our results suggest that being a beneficiary of the PBF, which facilitates cash transfers and improved access to health care, is associated with greater leprosy multidrug therapy adherence and cure in multibacillary cases. These results are especially relevant for patients with multibacillary disease, who are treated for a longer period and have lower cure rates than those with paucibacillary disease. FUNDING: CONFAP/ESRC/MRC/BBSRC/CNPq/FAPDF-Doenças Negligenciadas, the UK Medical Research Council, the Wellcome Trust, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)

A completeness indicator of gestational and congenital syphilis information in Brazil

OBJECTIVE: To evaluate the quality of information on gestational syphilis (GS) and congenital syphilis (CS) on the Sistema de Informação de Agravos de Notificação (SINAN-Syphilis Brazil – Notifiable Diseases Information System) by compiling and validating completeness indicators between 2007 and 2018. METHODS: Overall, care, and socioeconomic completeness scores were compiled based on selected variables, by using ad hoc weights assigned by experts. The completeness scores were analysed, considering the region and area of residence, the pregnant woman’s race/colour, and the year of case notification. Pearson’s correlation coefficients were used to validate the scores obtained by the weighted average method, compared with the values obtained by principal component analysis (PCA). RESULTS: Most selected variables presented a good or excellent degree of completeness for GS and CS, except for clinical classification, pregnant woman’s level of education, partner’s treatment, and child’s race/colour, which were classified as poor or very poor. The overall (89.93% versus 89.69%) and socioeconomic (88.71% versus 88.24%) completeness scores for GS and CS, respectively, were classified as regular, whereas the care score (GS-90.88%, and CS-90.72%) was good, despite improvements over time. Differences in the overall, care and socioeconomic completeness scores according to region, area of residence, and ethnic-racial groups were reported for syphilis notifications. The completeness scores estimated by the weighted average method and PCA showed a strong linear correlation (> 0.90). CONCLUSION: The completeness of GS and CS notifications has been improving in recent years, highlighting the variables that form the care score, compared with the socioeconomic scores, despite differences between regions, area of residence, and ethnic-racial groups. The weighted average was a viable methodological alternative easily operationalised to estimate data completeness scores, allowing routine monitoring of the completeness of gestational and congenital syphilis records

Factors associated with small- and large-for-gestational-age in socioeconomically vulnerable individuals in the 100 Million Brazilian Cohort.

BACKGROUND: Evidence points to diverse risk factors associated with small- (SGA) and large-for-gestational-age (LGA) births. A more comprehensive understanding of these factors is imperative, especially in vulnerable populations. OBJECTIVES: To estimate the occurrence of and sociodemographic factors associated with SGA and LGA births in poor and extremely poor populations of Brazil. METHODS: The study population consisted of women of reproductive age (14-49 y), whose last child was born between 2012 and 2015. INTERGROWTH 21st consortium criteria were used to classify weight for gestational age according to sex. Multinomial logistic regression modeling was performed to investigate associations of interest. RESULTS: Of 5,521,517 live births analyzed, SGA and LGA corresponded to 7.8% and 17.1%, respectively. Multivariate analysis revealed greater odds of SGA in children born to women who self-reported as black (OR: 1.21; 95% CI: 1.19, 1.22), mixed-race (parda) (OR: 1.08; 95% CI: 1.07, 1.09), or indigenous (OR: 1.11; 95% CI: 1.06, 1.15), were unmarried (OR: 1.08; 95% CI: 1.07, 1.08), illiterate (OR: 1.47; 95% CI: 1.42, 1.52), did not receive prenatal care (OR: 1.57; 95% CI: 1.53, 1.60), or were aged 14-20 y (OR: 1.21; 95% CI: 1.20, 1.22) or 35-49 y (OR: 1.12; 95% CI: 1.10, 1.13). Considering LGA children, higher odds were found in infants born to women living in households with ≥3 inadequate housing conditions (OR: 1.11; 95% CI: 1.10, 1.12), in indigenous women (OR: 1.22; 95% CI: 1.19, 1.25), those who had 1-3 y of schooling (OR: 1.18; 95% CI: 1.17, 1.19), 1-3 prenatal visits (OR: 1.16; CI 95%: 1.14, 1.17), or were older (OR: 1.26; 95% CI: 1.25, 1.27). CONCLUSIONS: In poorer Brazilian populations, socioeconomic, racial, and maternal characteristics are consistently associated with the occurrence of SGA births, but remain less clearly linked to the occurrence of LGA births

Postnatal growth in small vulnerable newborns: a longitudinal study of 2 million Brazilians using routine register-based linked data

Background: Preterm, low–birth weight (LBW) and small-for-gestational age (SGA) newborns have a higher frequency of adverse health outcomes, including linear and ponderal growth impairment. Objective: To describe the growth trajectories and to estimate catch-up growth during the first 5 y of life of small newborns according to 3 vulnerability phenotypes (preterm, LBW, SGA). Methods: Longitudinal study using linked data from the 100 Million Brazilian Cohort baseline, the Brazilian National Live Birth System (SINASC), and the Food and Nutrition Surveillance System (SISVAN) from 2011 to 2017. We estimated the length/height-for-age (L/HAZ) and weight-for-age z-score (WAZ) trajectories from children of 6–59 mo using the linear mixed model for each vulnerable newborn phenotype. Growth velocity for both L/HAZ and WAZ was calculated considering the change (Δ) in the mean z-score between 2 time points. Catch-up growth was defined as a change in z-score > 0.67 at any time during follow-up. Results: We analyzed 2,021,998 live born children and 8,726,599 observations. The prevalence of at least one of the vulnerable phenotypes was 16.7% and 0.6% were simultaneously preterm, LBW, and SGA. For those born at term, all phenotypes had a period of growth recovery from 12 mo. For preterm infants, the onset of L/HAZ growth recovery started later at 24 mo and the growth trajectories appear to be lower than those born at term, a condition aggravated among children with the 3 phenotypes. Preterm and female infants seem to experience slower growth recovery than those born at term and males. The catch-up growth occurs at 24–59 mo for males preterm: preterm + AGA + NBW (Δ = 0.80), preterm + AGA + LBW (Δ = 0.88), and preterm + SGA + LBW (Δ = 1.08); and among females: term + SGA + NBW (Δ = 0.69), term + AGA + LBW (Δ = 0.72), term + SGA + LBW (Δ = 0.77), preterm + AGA + LBW (Δ = 0.68), and preterm + SGA + LBW (Δ = 0.83). Conclusions: Children born preterm seem to reach L/HAZ and WAZ growth trajectories lower than those attained by children born at term, a condition aggravated among the most vulnerable

Conditional cash transfer program and child mortality: A cross-sectional analysis nested within the 100 Million Brazilian Cohort.

BACKGROUND: Brazil has made great progress in reducing child mortality over the past decades, and a parcel of this achievement has been credited to the Bolsa Família program (BFP). We examined the association between being a BFP beneficiary and child mortality (1-4 years of age), also examining how this association differs by maternal race/skin color, gestational age at birth (term versus preterm), municipality income level, and index of quality of BFP management. METHODS AND FINDINGS: This is a cross-sectional analysis nested within the 100 Million Brazilian Cohort, a population-based cohort primarily built from Brazil's Unified Registry for Social Programs (Cadastro Único). We analyzed data from 6,309,366 children under 5 years of age whose families enrolled between 2006 and 2015. Through deterministic linkage with the BFP payroll datasets, and similarity linkage with the Brazilian Mortality Information System, 4,858,253 children were identified as beneficiaries (77%) and 1,451,113 (23%) were not. Our analysis consisted of a combination of kernel matching and weighted logistic regressions. After kernel matching, 5,308,989 (84.1%) children were included in the final weighted logistic analysis, with 4,107,920 (77.4%) of those being beneficiaries and 1,201,069 (22.6%) not, with a total of 14,897 linked deaths. Overall, BFP participation was associated with a reduction in child mortality (weighted odds ratio [OR] = 0.83; 95% CI: 0.79 to 0.88; p < 0.001). This association was stronger for preterm children (weighted OR = 0.78; 95% CI: 0.68 to 0.90; p < 0.001), children of Black mothers (weighted OR = 0.74; 95% CI: 0.57 to 0.97; p < 0.001), children living in municipalities in the lowest income quintile (first quintile of municipal income: weighted OR = 0.72; 95% CI: 0.62 to 0.82; p < 0.001), and municipalities with better index of BFP management (5th quintile of the Decentralized Management Index: weighted OR = 0.76; 95% CI: 0.66 to 0.88; p < 0.001). The main limitation of our methodology is that our propensity score approach does not account for possible unmeasured confounders. Furthermore, sensitivity analysis showed that loss of nameless death records before linkage may have resulted in overestimation of the associations between BFP participation and mortality, with loss of statistical significance in municipalities with greater losses of data and change in the direction of the association in municipalities with no losses. CONCLUSIONS: In this study, we observed a significant association between BFP participation and child mortality in children aged 1-4 years and found that this association was stronger for children living in municipalities in the lowest quintile of wealth, in municipalities with better index of program management, and also in preterm children and children of Black mothers. These findings reinforce the evidence that programs like BFP, already proven effective in poverty reduction, have a great potential to improve child health and survival. Subgroup analysis revealed heterogeneous results, useful for policy improvement and better targeting of BFP

Factors associated with low birth weight at term: a population-based linkage study of the 100 million Brazilian cohort.

BACKGROUND: Factors associated with low birth weight at term (TLBW), a proxy for intrauterine growth restriction (IUGR), are not well-elucidated in socioeconomically vulnerable populations. This study aimed to identify the factors associated with TLBW in impoverished Brazilian women. METHODS: Records in the 100 Million Brazilian Cohort database were linked to those in the National System of Information on Live Births (SINASC) to obtain obstetric, maternal, birth and socioeconomic data between 2001 and 2015. Multivariate logistic regression was performed to investigate associations between variables of exposure and TLBW. RESULTS: Of 8,768,930 term live births analyzed, 3.7% presented TLBW. The highest odds of TLBW were associated with female newborns (OR: 1.49; 95% CI: 1.47-1.50), whose mothers were black (OR: 1.20; 95% CI: 1.18-1.22), had a low educational level (OR: 1.57; 95% CI: 1.53-1.62), were aged ≥35 years (OR: 1.44; 95% CI: 1.43-1.46), had a low number of prenatal care visits (OR: 2.48; 95% CI: 2.42-2.54) and were primiparous (OR: 1.62; 95% CI: 1.60-1.64). Lower odds of TLBW were found among infants whose mothers lived in the North, Northeast and Center-West regions of Brazil compared to those in the South. CONCLUSION: Multiple aspects were associated with TLBW, highlighting the need to comprehensively examine the mechanisms underlying these factors, especially in more vulnerable Brazilian populations, in order to contribute to the elaboration of health policies and promote better conditions of life for poor and extremely poor mothers and children