The trajectories of CD4 T lymphocytes over time in patients who have defaulted on treatment for tuberculosis in a cohort of people living with HIV, Recife/PE.

BACKGROUND: The CD4 T lymphocyte count in people living with HIV (PLHIV) is a predictor for the progression of the disease (AIDS), survival and response to antiretroviral treatment (ART). A CD4 T lymphocyte count of less than 200 cells/mm3 is indicative of a greater risk for the onset of opportunistic diseases and death. Defaulting on treatment for tuberculosis (TB) may impact immune recovery in PLHIV who are taking ART. The aim of this study was to investigate an association of the CD4 lymphocyte with TB treatment Trajectory and with death. METHODS: A cohort of PLHIV over eighteen years of age and who were taking ART and who had defaulted on pulmonary TB treatment. Latent Class analysis was used to identify different trajectories of CD4 T lymphocyte counts over time. RESULTS: Latent class 1 (High CD4 trajectory) grouped individuals together who were characterized as maintaining a low probability (0 to 29%) of a CD4 count ≤ 200 cells/mm3over time, while latent class 2 (Low CD4 trajectory) grouped individuals together with a high probability (93% to 60%), and latent class 3 (Fluctuating CD4 trajectory), grouped individuals with a fluctuating probability (66% to 0%). The chance of defaulting on treatment earlier (≤ 90 days) was four times higher in latent class 2 (Low CD4 trajectory). Although there was no statistical significance, there was a higher frequency of deaths in this same latent class. CONCLUSION: Individuals with a high probability of a CD4 count ≤ 200 cells/ mm3 should be monitored in order to avoid treatment default and thereby prevent death. New studies should be conducted with a larger sample size and a longer follow-up time in PLHIV who initiated ART treatment early so as to support clinical decisions for a better understanding of immune behavior.

Evaluating the relationship between conditional cash transfer programme on preterm births: a retrospective longitudinal study using the 100 million Brazilian cohort.

BACKGROUND: Preterm births increase mortality and morbidity during childhood and later life, which is closely associated with poverty and the quality of prenatal care. Therefore, income redistribution and poverty reduction initiatives may be valuable in preventing this outcome. We assessed whether receipt of the Brazilian conditional cash transfer programme - Bolsa Familia Programme, the largest in the world - reduces the occurrence of preterm births, including their severity categories, and explored how this association differs according to prenatal care and the quality of Bolsa Familia Programme management. METHODS: A retrospective cohort study was performed involving the first live singleton births to mothersenrolled in the 100 Million Brazilian Cohort from 2004 to 2015, who had at least one child before cohort enrollment. Only the first birth during the cohort period was included, but born from 2012 onward. A deterministic linkage with the Bolsa Familia Programme payroll dataset and a similarity linkage with the Brazilian Live Birth Information System were performed. The exposed group consisted of newborns to mothers who received Bolsa Familia from conception to delivery. Our outcomes were infants born with a gestational age < 37 weeks: (i) all preterm births, (ii) moderate-to-late (32-36), (iii) severe (28-31), and (iv) extreme (< 28) preterm births compared to at-term newborns. We combined propensity score-based methods and weighted logistic regressions to compare newborns to mothers who did and did not receive Bolsa Familia, controlling for socioeconomic conditions. We also estimated these effects separately, according to the adequacy of prenatal care and the index of quality of Bolsa Familia Programme management. RESULTS: 1,031,053 infants were analyzed; 65.9% of the mothers were beneficiaries. Bolsa Familia Programme was not associated with all sets of preterm births, moderate-to-late, and severe preterm births, but was associated with a reduction in extreme preterm births (weighted OR: 0.69; 95%CI: 0.63-0.76). This reduction can also be observed among mothers receiving adequate prenatal care (weighted OR: 0.66; 95%CI: 0.59-0.74) and living in better Bolsa Familia management municipalities (weighted OR: 0.56; 95%CI: 0.43-0.74). CONCLUSIONS: An income transfer programme for pregnant women of low-socioeconomic status, conditional to attending prenatal care appointments, has been associated with a reduction in extremely preterm births. These programmes could be essential in achieving Sustainable Development Goals.

Association of interpregnancy interval with adverse pregnancy outcomes according to the outcomes of the preceding pregnancy: a longitudinal study with 4.7 million live births from Brazil.

Background: Earlier studies have proposed a link between the Interpregnancy Interval (IPI) and unfavorable birth outcomes. However, it remains unclear if the outcomes of previous births could affect this relationship. We aimed to investigate whether the occurrence of adverse outcomes-small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW)-at the immediately preceding pregnancy could alter the association between IPI and the same outcomes at the subsequent pregnancy. Methods: We used a population-based linked cohort from Brazil (2001-2015). IPI was measured as the difference, in months, between the preceding birth and subsequent conception. Outcomes included SGA (<10th birthweight percentile for gestational age and sex), LBW (<2500 g), and PTB (gestational age <37 weeks). We calculated risk ratios (RRs), using the IPI of 18-22 months as the reference IPI category, we also stratified by the number of adverse birth outcomes at the preceding pregnancy. Findings: Among 4,788,279 births from 3,804,152 mothers, absolute risks for subsequent SGA, PTB, and LBW were higher for women with more adverse outcomes in the preceding delivery. The RR of SGA and LBW for IPIs <6 months were greater for women without previous adverse outcomes (SGA: 1.44 [95% Confidence Interval (CI): 1.41-1.46]; LBW: 1.49 [1.45-1.52]) compared to those with three previous adverse outcomes (SGA: 1.20 [1.10-1.29]; LBW: 1.24 [1.15-1.33]). IPIs ≥120 months were associated with greater increases in risk for LBW and PTB among women without previous birth outcomes (LBW: 1.59; [1.53-1.65]; PTB: 2.45 [2.39-2.52]) compared to women with three adverse outcomes at the index birth (LBW: 0.92 [0.78-1.06]; PTB: 1.66 [1.44-1.88]). Interpretation: Our study suggests that women with prior adverse outcomes may have higher risks for adverse birth outcomes in subsequent pregnancies. However, risk changes due to differences in IPI length seem to have a lesser impact compared to women without a prior event. Considering maternal obstetric history is essential in birth spacing counseling. Funding: Wellcome Trust225925/Z/22/Z.

Perinatal health outcomes of international migrant women in Brazil: A nationwide data linkage study of the CIDACS birth cohort (2011-2018).

BACKGROUND: We investigated perinatal outcomes among live births from international migrant and local-born mothers in a cohort of low-income individuals in Brazil. METHODS: We linked nationwide birth registries to mortality records and socioeconomic data from the CIDACS Birth Cohort and studied singleton live births of women aged 10-49 years from 1st January 2011 to 31st December 2018. We used logistic regressions to investigate differences in antenatal care, adverse pregnancy outcomes, and neonatal (i.e., ≤28 days) mortality among international migrants compared to non-migrants in Brazil; and explored the interaction between migration, race/ethnicity and living in international border municipalities. RESULTS: We studied 10,279,011 live births, of which 9469 (0.1 %) were born to international migrants. Migrant women were more likely than their Brazilian-born counterparts to have a previous foetal loss (ORadj: 1.16, 1.11-1.22), a delayed start of antenatal care (i.e., beyond 1st trimester) (1.22, 95%CI:1.16-1.28), a newborn who is large for gestational age (1.29, 1.22-1.36), or a newborn with congenital anomalies (1.37, 1.14-1.65). Conversely, migrant women were less likely to deliver prematurely (0.89, 0.82-0.95) or have a low birth weight infant (0.74, 0.68-0.81). There were no differences in neonatal mortality rates between migrants and non-migrants. Our analyses also showed that, when disparities in perinatal outcomes were present, disparities were mostly concentrated among indigenous mothers in international borders and among live births of Black mothers in non-borders. CONCLUSION: Although live births of international migrants generally have lower rates of adverse birth outcomes, our results suggest that indigenous and Black migrant mothers may face disproportionate barriers to accessing antenatal care.

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.

Participation in Conditional Cash Transfer Program During Pregnancy and Birth Weight-Related Outcomes.

Importance: There is limited evidence of the association of conditional cash transfers, an important strategy to reduce poverty, with prevention of adverse birth-related outcomes. Objective: To investigate the association between receiving benefits from the Bolsa Família Program (BFP) and birth weight indicators. Design, Setting, and Participants: This cohort study used a linked data resource, the Centro de Integracao de Dados e Conhecimentos Para Saude (CIDACS) birth cohort. All live-born singleton infants born to mothers registered in the cohort between January 2012 and December 2015 were included. Each analysis was conducted for the overall population and separately by level of education, self-reported maternal race, and number of prenatal appointments. Data were analyzed from January 3 to April 24, 2023. Exposure: Live births of mothers who had received BFP until delivery (for a minimum of 9 months) were classified as exposed and compared with live births from mothers who did not receive the benefit prior to delivery. Main Outcomes and Measures: Low birth weight (LBW), birth weight in grams, and small for gestational age (SGA) were evaluated. Analytical methods used included propensity score estimation, kernel matching, and weighted logistic and linear regressions. Race categories included Parda, which translates from Portuguese as "brown" and is used to denote individuals whose racial background is predominantly Black and those with multiracial or multiethnic ancestry, including European, African, and Indigenous origins. Results: A total of 4 277 523 live births (2 085 737 females [48.8%]; 15 207 among Asian [0.4%], 334 225 among Black [7.8%], 29 115 among Indigenous [0.7%], 2 588 363 among Parda [60.5%], and 1 310 613 among White [30.6%] mothers) were assessed. BFP was associated with an increase of 17.76 g (95% CI, 16.52-19.01 g) in birth weight. Beneficiaries had an 11% lower chance of LBW (odds ratio [OR], 0.89; 95% CI, 0.88-0.90). BFP was associated with a greater decrease in odds of LBW among subgroups of mothers who attended fewer than 7 appointments (OR, 0.85; 95% CI, 0.84-0.87), were Indigenous (OR, 0.73; 95% CI, 0.61-0.88), and had 3 or less years of education (OR, 0.76; 95% CI, 0.72-0.81). There was no association between BFP and SGA, except among less educated mothers, who had a reduced risk of SGA (OR, 0.83; 95% CI, 0.79-0.88). Conclusions and Relevance: This study found that BFP was associated with increased birth weight and reduced odds of LBW, with a greater decrease in odds of LBW among higher-risk groups. These findings suggest the importance of maintaining financial support for mothers at increased risk of birth weight-related outcomes.

Maternal and congenital syphilis attributable to ethnoracial inequalities: a national record-linkage longitudinal study of 15 million births in Brazil.

BACKGROUND: This study estimated ethnoracial inequalities in maternal and congenital syphilis in Brazil, understanding race as a relational category product of a sociopolitical construct that functions as an essential tool of racism and its manifestations. METHODS: We linked routinely collected data from Jan 1, 2012 to Dec 31, 2017 to conduct a population-based study in Brazil. We estimated the attributable fraction of race (skin colour) for the entire population and specific subgroups compared with White women using adjusted logistic regression. We also obtained the attributable fraction of the intersection between two social markers (race and education) and compared it with White women with more than 12 years of education as the baseline. FINDINGS: Of 15 810 488 birth records, 144 564 women had maternal syphilis and 79 580 had congenital syphilis. If all women had the same baseline risk as White women, 35% (95% CI 34·89-36·10) of all maternal syphilis and 41% (40·49-42·09) of all congenital syphilis would have been prevented. Compared with other ethnoracial categories, these percentages were higher among Parda/Brown women (46% [45·74-47·20] of maternal syphilis and 52% [51·09-52·93] of congenital syphilis would have been prevented) and Black women (61% [60·25-61·75] of maternal syphilis and 67% [65·87-67·60] of congenital syphilis would have been prevented). If all ethnoracial groups had the same risk as White women with more than 12 years of education, 87% of all maternal syphilis and 89% of all congenital syphilis would have been prevented. INTERPRETATION: Only through effective control of maternal syphilis among populations at higher risk (eg, Black and Parda/Brown women with lower educational levels) can WHO's global health initiative to eliminate mother-to-child transmission of syphilis be made feasible. Recognising that racism and other intersecting forms of oppression affect the lives of minoritised groups and advocating for actions through the lens of intersectionality is imperative for attaining and guaranteeing health equity. Achieving health equality needs to be addressed to achieve syphilis control. Given the scale and complexity of the problem (which is unlikely to be unique to Brazil), structural issues and social markers of oppression, such as race and education, must be considered to prevent maternal and congenital syphilis and improve maternal and child outcomes globally. FUNDING: Wellcome Trust, CNPq-Brazil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Cesarean sections and early-term births according to Robson classification: a population-based study with more than 17 million births in Brazil.

BACKGROUND: Cesarean section (CS) rates are increasing worldwide and are associated with negative maternal and child health outcomes when performed without medical indication. However, there is still limited knowledge about the association between high CS rates and early-term births. This study explored the association between CSs and early-term births according to the Robson classification. METHODS: A population-based, cross-sectional study was performed with routine registration data of live births in Brazil between 2012 and 2019. We used the Robson classification system to compare groups with expected high and low CS rates. We used propensity scores to compare CSs to vaginal deliveries (1:1) and estimated associations with early-term births using logistic regression. RESULTS: A total of 17,081,685 live births were included. Births via CS had higher odds of early-term birth (OR 1.32; 95% CI 1.32-1.32) compared to vaginal deliveries. Births by CS to women in Group 2 (OR 1.50; 95% CI 1.49-1.51) and 4 (OR 1.57; 95% CI 1.56-1.58) showed the highest odds of early-term birth, compared to vaginal deliveries. Increased odds of an early-term birth were also observed among births by CS to women in Group 3 (OR 1.30, 95% CI 1.29-1.31), compared to vaginal deliveries. In addition, live births by CS to women with a previous CS (Group 5 - OR 1.36, 95% CI 1.35-1.37), a single breech pregnancy (Group 6 - OR 1.16; 95% CI 1.11-1.21, and Group 7 - OR 1.19; 95% CI 1.16-1.23), and multiple pregnancies (Group 8 - OR 1.46; 95% CI 1.40-1.52) had high odds of an early-term birth, compared to live births by vaginal delivery. CONCLUSIONS: CSs were associated with increased odds of early-term births. The highest odds of early-term birth were observed among those births by CS in Robson Groups 2 and 4.

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020).

OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Mortality in children under 5 years of age with congenital syphilis in Brazil: A nationwide cohort study.

BACKGROUND: Congenital syphilis (CS) is a major and avoidable cause of neonatal death worldwide. In this study, we aimed to estimate excess all-cause mortality in children under 5 years with CS compared to those without CS. METHODS AND FINDINGS: In this population-based cohort study, we used linked, routinely collected data from Brazil from January 2011 to December 2017. Cox survival models were adjusted for maternal region of residence, maternal age, education, material status, self-declared race and newborn sex, and year of birth and stratified according to maternal treatment status, non-treponemal titers and presence of signs and symptoms at birth. Over 7 years, a total of 20 057 013 live-born children followed up (through linkage) to 5 years of age, 93 525 were registered with CS, and 2 476 died. The all-cause mortality rate in the CS group was 7·84/1 000 person-years compared with 2·92/1 000 person-years in children without CS, crude hazard ratio (HR) = 2·41 (95% CI 2·31 to 2·50). In the fully adjusted model, the highest under-five mortality risk was observed among children with CS from untreated mothers HR = 2·82 (95% CI 2·63 to 3·02), infants with non-treponemal titer higher than 1:64 HR = 8·87 (95% CI 7·70 to 10·22), and children with signs and symptoms at birth HR = 7·10 (95% CI 6·60 to 7·63). Among children registered with CS, CS was recorded as the underlying cause of death in 33% (495/1 496) of neonatal, 11% (85/770) of postneonatal, and 2·9% (6/210) of children 1 year of age. The main limitations of this study were the use of a secondary database without additional clinical information and the potential misclassification of exposure status. CONCLUSIONS: This study showed an increased mortality risk among children with CS that goes beyond the first year of life. It also reinforces the importance of maternal treatment that infant non-treponemal titers and the presence of signs and symptoms of CS at birth are strongly associated with subsequent mortality. TRIAL REGISTRATION: Observational study.

Understanding and controlling asthma in Latin America: A review of recent research informed by the SCAALA programme.

Asthma is an important health concern in Latin America (LA) where it is associated with variable prevalence and disease burden between countries. High prevalence and morbidity have been observed in some regions, particularly marginalized urban populations. Research over the past 10 years from LA has shown that childhood disease is primarily non-atopic. The attenuation of atopy may be explained by enhanced immune regulation induced by intense exposures to environmental factors such as childhood infections and poor environmental conditions of the urban poor. Non-atopic symptoms are associated with environmental and lifestyle factors including poor living conditions, respiratory infections, psychosocial stress, obesity, and a diet of highly processed foods. Ancestry (particularly African) and genetic factors increase asthma risk, and some of these factors may be specific to LA settings. Asthma in LA tends to be poorly controlled and depends on access to health care and medications. There is a need to improve management and access to medication through primary health care. Future research should consider the heterogeneity of asthma to identify relevant endotypes and underlying causes. The outcome of such research will need to focus on implementable strategies relevant to populations living in resource-poor settings where the disease burden is greatest.

Mortality among over 6 million internal and international migrants in Brazil: a study using the 100 Million Brazilian Cohort.

Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98-0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03-1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09-1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80-0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40-0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17-4.05). Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants. Funding: The Wellcome Trust.

Association of Conditional Cash Transfers With Maternal Mortality Using the 100 Million Brazilian Cohort.

Importance: Conditional cash transfers (CCTs) have been consistently associated with improvements to the determinants of maternal health, but there have been insufficient investigations regarding their effects on maternal mortality. Objective: To evaluate the association between being a Bolsa Família program (BFP) beneficiary and maternal mortality and to examine how this association differs by duration of BFP receipt, maternal race, living in rural or urban areas, the Municipal Human Development Index (MHDI), and municipal primary health care coverage. Design, Setting, and Participants: This cross-sectional analysis was nested within the 100 Million Brazilian Cohort. Girls and women aged 10 to 49 years (hereinafter referred to as women) who had at least 1 live birth were included, using data from Brazilian national health databases linked to the 100 Million Brazilian Cohort (January 1, 2004, to December 31, 2015). Propensity score kernel weighting was applied to control for sociodemographic and economic confounders in the association between BFP receipt and maternal mortality, overall and stratified by different subgroups (race, urban or rural area, and MHDI), and duration of BFP receipt. Data were analyzed from July 12, 2019, to December 31, 2022. Main Outcome(s) and Measures: Maternal death. Results: A total of 6 677 273 women aged 10 to 49 years were included in the analysis, 4056 of whom had died from pregnancy-related causes. The risk of maternal death was 18% lower in women who received BFP (weighted odds ratio [OR], 0.82 [95% CI, 0.71-0.93]). A longer duration receiving BFP was associated with an increased reduction in maternal mortality (OR for 1-4 years, 0.85 [95% CI, 0.75-0.97]; OR for 5-8 years, 0.70 [95% CI, 0.60-0.82]; OR for ≥9 years, 0.69 [95% CI, 0.53-0.88]). Receiving BFP was also associated with substantial increases in the number of prenatal appointments and interbirth intervals. The reduction was more pronounced in the most vulnerable groups. Conclusions and Relevance: This cross-sectional analysis nested within the 100 Million Brazilian Cohort found an association between BFP receipt and maternal mortality. This association was of greater magnitude in women with longer exposure to BFP and in the most vulnerable groups. These findings reinforce evidence that programs such as BFP, which have already proven effective in poverty reduction, have great potential to improve maternal survival.

Causes of death in children with congenital Zika syndrome in Brazil, 2015 to 2018: A nationwide record linkage study.

BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

Socioeconomic risk markers of congenital Zika syndrome: a nationwide, registry-based study in Brazil.

While it is well known that socioeconomic markers are associated with a higher risk of arbovirus infections, research on the relationship between socioeconomic factors and congenital Zika syndrome (CZS) remains limited. This study investigates the relationship between socioeconomic risk markers and live births with CZS in Brazil. We conducted a population-based study using data from all registered live births in Brazil (Live Births Information System) linked with the Public Health Event Record from 1 January 2015 to 31 December 2018. We used logistic regression models to estimate the OR and 95% CIs of CZS based on a three-level framework. In an analysis of 11 366 686 live births, of which 3353 had CZS, we observed that live births of self-identified black or mixed race/brown mothers (1.72 (95% CI 1.47 to 2.01) and 1.37 (95% CI 1.24 to 1.51)) were associated with a higher odds of CZS. Live births from single women compared with married women and those from women with less than 12 years of education compared with those with more than 12 years of education also had higher odds of CZS. In addition, live births following fewer prenatal care appointments had increased odds of CZS in the nationwide data. However, in the analyses conducted in the Northeast region (where the microcephaly epidemic started before the link with Zika virus was established and before preventive measures were known or disseminated), no statistical association was found between the number of prenatal care appointments and the odds of CZS. This study shows that live births of the most socially vulnerable women in Brazil had the greatest odds of CZS. This disproportionate distribution of risk places an even greater burden on already socioeconomically disadvantaged groups, and the lifelong disabilities caused by this syndrome may reinforce existing social and health inequalities.

Ethnoracial inequalities and child mortality in Brazil: a nationwide longitudinal study of 19 million newborn babies.

BACKGROUND: Racism is a social determinant of health inequities. In Brazil, racial injustices lead to poor outcomes in maternal and child health for Black and Indigenous populations, including greater risks of pregnancy-related complications; decreased access to antenatal, delivery, and postnatal care; and higher childhood mortality rates. In this study, we aimed to estimate inequalities in childhood mortality rates by maternal race and skin colour in a cohort of more than 19 million newborns in Brazil. METHODS: We did a nationwide population-based, retrospective cohort study using linked data on all births and deaths in Brazil between Jan 1, 2012, and Dec 31, 2018. The data consisted of livebirths followed up to age 5 years, death, or Dec 31, 2018. Data for livebirths were extracted from the National Information System for livebirths, SINASC, and for deaths from the Mortality Information System, SIM. The final sample consisted of complete data for all cases regarding maternal race and skin colour, and no inconsistencies were present between date of birth and death after linkage. We fitted Cox proportional hazard regression models to calculate the crude and adjusted hazard ratios (HRs) and 95% CIs for the association between maternal race and skin colour and all-cause and cause-specific younger than age 5 mortality rates, by age subgroups. We calculated the trend of HRs (and 95% CI) by time of observation (calendar year) to indicate trends in inequalities. FINDINGS: From the 20 526 714 livebirths registered in SINASC between Jan 1, 2012, and Dec 31, 2018, 238 436 were linked to death records identified from SIM. After linkage, 1 010 871 records were excluded due to missing data on maternal race or skin colour or inconsistent date of death. 19 515 843 livebirths were classified by mother's race, of which 224 213 died. Compared with children of White mothers, mortality risk for children younger than age 5 years was higher among children of Indigenous (HR 1·98 [95% CI 1·92-2·06]), Black (HR 1·39 [1·36-1·41]), and Brown or Mixed race (HR 1·19 [1·18-1·20]) mothers. The highest hazard ratios were observed during the post-neonatal period (Indigenous, HR 2·78 [95% CI 2·64-2·95], Black, HR 1·54 [1·48-1·59]), and Brown or Mixed race, HR 1·25 [1·23-1·27]) and between the ages of 1 year and 4 years (Indigenous, HR 3·82 [95% CI 3·52-4·15]), Black, HR 1·51 [1·42-1·60], and Brown or Mixed race, HR 1·30 [1·26-1·35]). Children of Indigenous (HR 16·39 [95% CI 12·88-20·85]), Black (HR 2·34 [1·78-3·06]), and Brown or Mixed race mothers (HR 2·05 [1·71-2·45]) had a higher risk of death from malnutrition than did children of White mothers. Similar patterns were observed for death from diarrhoea (Indigenous, HR 14·28 [95% CI 12·25-16·65]; Black, HR 1·72 [1·44-2·05]; and Brown or Mixed race mothers, HR 1·78 [1·61-1·98]) and influenza and pneumonia (Indigenous, HR 6·49 [95% CI 5·78-7·27]; Black, HR 1·78 [1·62-1·96]; and Brown or Mixed race mothers, HR 1·60 [1·51-1·69]). INTERPRETATION: Substantial ethnoracial inequalities were observed in child mortality in Brazil, especially among the Indigenous and Black populations. These findings demonstrate the importance of regular racial inequality assessments and monitoring. We suggest implementing policies to promote ethnoracial equity to reduce the impact of racism on child health. FUNDING: MCTI/CNPq/MS/SCTIE/Decit/Bill & Melinda Gates Foundation's Grandes Desafios Brasil, Desenvolvimento Saudável para Todas as Crianças, and Wellcome Trust core support grant awarded to CIDACS-Center for Data and Knowledge Integration for Health.

Vaccine effectiveness of CoronaVac against COVID-19 among children in Brazil during the Omicron period.

Although severe COVID-19 in children is rare, they may develop multisystem inflammatory syndrome, long-COVID and downstream effects of COVID-19, including social isolation and disruption of education. Data on the effectiveness of the CoronaVac vaccine is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. We conducted a test-negative design to estimate vaccine effectiveness using 197,958 tests from January 21, 2022, to April 15, 2022, during the Omicron dominant period in Brazil among children aged 6 to 11 years. The estimated vaccine effectiveness for symptomatic infection was 39.8% (95% CI 33.7-45.4) at ≥14 days post-second dose. For hospital admission vaccine effectiveness was 59.2% (95% CI 11.3-84.5) at ≥14 days. Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness.

Population-based surveillance for congenital zika virus syndrome: a latent class analysis of recorded cases from 2015-2018.

OBJECTIVE: This study aims to describe clinical findings and determine the medium-term survival of congenital zika syndrome (CZS) suspected cases. METHODS: A retrospective cohort study using routine register-based linked data. It included all suspected cases of CZS born in Brazil from January 1, 2015, to December 31, 2018, and followed up from birth until death, 36 months, or December 31, 2018, whichever came first. Latent class analysis was used to cluster unconfirmed cases into classes with similar combinations of anthropometry at birth, imaging findings, maternally reported rash, region, and year of birth. Kaplan-Meier curves were plotted, and Cox proportional hazards models were fitted to determine mortality up to 36 months. RESULTS: We followed 11,850 suspected cases of CZS, of which 28.3% were confirmed, 9.3% inconclusive and 62.4% unconfirmed. Confirmed cases had almost two times higher mortality when compared with unconfirmed cases. Among unconfirmed cases, we identified three distinct clusters with different mortality trajectories. The highest mortality risk was observed in those with abnormal imaging findings compatible with congenital infections (HR = 12.6; IC95%8.8-18.0) and other abnormalities (HR = 11.6; IC95%8.6-15.6) compared with those with normal imaging findings. The risk was high in those with severe microcephaly (HR = 8.2; IC95%6.4-10.6) and macrocephaly (HR = 6.6; IC95%4.5-9.7) compared with normal head size. CONCLUSION: Abnormal imaging and head circumference appear to be the main drivers of the increased mortality among suspected cases of CZS. We suggest identifying children who are more likely to die and have a greater need to optimise interventions and resource allocation regardless of the final diagnoses.

Relationship between the Bolsa Família national cash transfer programme and suicide incidence in Brazil: A quasi-experimental study.

BACKGROUND: Socioeconomic factors have been consistently associated with suicide, and economic recessions are linked to rising suicide rates. However, evidence on the impact of socioeconomic interventions to reduce suicide rates is limited. This study investigates the association of the world's largest conditional cash transfer programme with suicide rates in a cohort of half of the Brazilian population. METHODS AND FINDINGS: We used data from the 100 Million Brazilian Cohort, covering a 12-year period (2004 to 2015). It comprises socioeconomic and demographic information on 114,008,317 individuals, linked to the "Bolsa Família" programme (BFP) payroll database, and nationwide death registration data. BFP was implemented by the Brazilian government in 2004. We estimated the association of BFP using inverse probability of treatment weighting, estimating the weights for BFP beneficiaries (weight = 1) and nonbeneficiaries by the inverse probability of receiving treatment (weight = E(ps)/(1-E(ps))). We used an average treatment effect on the treated (ATT) estimator and fitted Poisson models to estimate the incidence rate ratios (IRRs) for suicide associated with BFP experience. At the cohort baseline, BFP beneficiaries were younger (median age 27.4 versus 35.4), had higher unemployment rates (56% versus 32%), a lower level of education, resided in rural areas, and experienced worse household conditions. There were 36,742 suicide cases among the 76,532,158 individuals aged 10 years, or older, followed for 489,500,000 person-years at risk. Suicide rates among beneficiaries and nonbeneficiaries were 5.4 (95% CI = 5.32, 5.47, p < 0.001) and 10.7 (95% CI = 10.51, 10.87, p < 0.001) per 100,000 individuals, respectively. BFP beneficiaries had a lower suicide rate than nonbeneficiaries (IRR = 0.44, 95% CI = 0.42, 0.45, p < 0.001). This association was stronger among women (IRR = 0.36, 95% CI = 0.33, 0.38, p < 0.001), and individuals aged between 25 and 59 (IRR = 0.41, 95% CI = 0.40, 0.43, p < 0.001). Study limitations include a lack of control for previous mental disorders and access to means of suicide, and the possible under-registration of suicide cases due to stigma. CONCLUSIONS: We observed that BFP was associated with lower suicide rates, with similar results in all sensitivity analyses. These findings should help to inform policymakers and health authorities to better design suicide prevention strategies. Targeting social determinants using cash transfer programmes could be important in limiting suicide, which is predicted to rise with the economic recession, consequent to the Coronavirus Disease 2019 (COVID-19) pandemic.