Mortality from Congenital Zika Syndrome - Nationwide Cohort Study in Brazil.

BACKGROUND: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. METHODS: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. RESULTS: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. CONCLUSIONS: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.).

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.

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.

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.

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.

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.

Differences in risk factors for incident and recurrent preterm birth: a population-based linkage of 3.5 million births from the CIDACS birth cohort.

BACKGROUND: Preterm birth (PTB) is a syndrome resulting from a complex list of underlying causes and factors, and whether these risk factors differ in the context of prior PTB history is less understood. The aim of this study was to explore whether PTB risk factors in a second pregnancy were different in women with versus without previous PTB. METHODS: We conducted a population-based cohort study using data from the birth cohort of the Center for Data and Knowledge Integration for Health (CIDACS) for the period 2001 to 2015. We used longitudinal transition models with multivariate logistic regression to investigate whether risk factors varied between incident and recurrent PTB. RESULTS: A total of 3,528,050 live births from 1,764,025 multiparous women were analyzed. We identified different risk factors (Pdifference <0.05) between incident and recurrent PTB. The following were associated with an increased chance for PTB incidence, but not recurrent: household overcrowding (OR 1.09), maternal race/ethnicity [(Black/mixed-OR 1.04) and (indigenous-OR 1.34)], young maternal age (14 to 19 years-OR 1.16), and cesarean delivery (OR 1.09). The following were associated with both incident and recurrent PTB, respectively: single marital status (OR 0.85 vs 0.90), reduced number of prenatal visits [(no visit-OR 2.56 vs OR 2.16) and (1 to 3 visits-OR 2.44 vs OR 2.24)], short interbirth interval [(12 to 23 months-OR 1.04 vs OR 1.22) and (<12 months, OR 1.89, 95 vs OR 2.58)], and advanced maternal age (35-49 years-OR 1.42 vs OR 1.45). For most risk factors, the point estimates were higher for incident PTB than recurrent PTB. CONCLUSIONS: The risk factors for PTB in the second pregnancy differed according to women's first pregnancy PTB status. The findings give the basis for the development of specific prevention strategies for PTB in a subsequent pregnancy.

CoronaVac vaccine is effective in preventing symptomatic and severe COVID-19 in pregnant women in Brazil: a test-negative case-control study.

BACKGROUND: More doses of CoronaVac have been administered worldwide than any other COVID-19 vaccine. However, the effectiveness of COVID-19 inactivated vaccines in pregnant women is still unknown. We estimated the vaccine effectiveness (VE) of CoronaVac against symptomatic and severe COVID-19 in pregnant women in Brazil. METHODS: We conducted a test-negative design study in all pregnant women aged 18-49 years with COVID-19-related symptoms in Brazil from March 15, 2021, to October 03, 2021, linking records of negative and positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests to national vaccination records. We also linked records of test-positive cases with notifications of severe, hospitalised or fatal COVID-19. Using logistic regression, we estimated the adjusted odds ratio and VE against symptomatic COVID-19 and against severe COVID-19 by comparing vaccine status in test-negative subjects to test-positive symptomatic cases and severe cases. RESULTS: Of the 19,838 tested pregnant women, 7424 (37.4%) tested positive for COVID-19 and 588 (7.9%) had severe disease. Only 83% of pregnant women who received the first dose of CoronaVac completed the vaccination scheme. A single dose of the CoronaVac vaccine was not effective at preventing symptomatic COVID-19. The effectiveness of two doses of CoronaVac was 41% (95% CI 27.1-52.2) against symptomatic COVID-19 and 85% (95% CI 59.5-94.8) against severe COVID-19. CONCLUSIONS: A complete regimen of CoronaVac in pregnant women was effective in preventing symptomatic COVID-19 and highly effective against severe illness in a setting that combined high disease burden and marked COVID-19-related maternal deaths.

Children living with HIV in Europe: do migrants have worse treatment outcomes?

OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. RESULTS: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96-2.38, p = 0.072). CONCLUSIONS: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring.

Differences in Placental Histology Between Zika Virus-infected Teenagers and Older Women.

In pregnant women, Zika virus (ZIKV) is associated with a congenital syndrome, most frequently involving damage to embryo brain formation and the development of microcephaly. The mechanism(s) by which ZIKV enters the maternal-fetal interface and is transmitted to the fetus remains incompletely determined. We sought to evaluate histologic changes in the placenta of ZIKV-infected pregnant women and to determine if this varied by maternal age. Placental samples were obtained from 66 women, 33 of whom were positive for ZIKV. Histologic evaluations were performed on 4 areas of the placenta: fetal surface, maternal surface, umbilical cord, and membranes. Samples were analyzed by the tissue microarray technique and tested for CD4, CD8, CD20, CD68, FOXP3, and cyclooxygenase-2 expression. Data were evaluated using Fisher exact test. ZIKV infection was more frequent in women less than 18 yr of age (9/11, 81.8%) than in women above 18 yr old (24/55, 43.6%) (P=0.0440). ZIKV detection was associated with neutrophilic chorioamnionitis (P=0.0332) and with septal (P=0.0244) and villous (P=0.0534) calcification. Hofbauer cell hyperplasia (P=0.0260) and cyclooxygenase-2 expression (P=0.0346) were more prevalent in ZIKV-positive women aged 18 yr and below than in the older ZIKV-positive women. ZIKV infection during pregnancy occurs more frequently in adolescents and induces higher rates of damage at the maternal-fetal interface than in older women.

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.

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.

Associations between cesarean delivery and child mortality: A national record linkage longitudinal study of 17.8 million births in Brazil.

BACKGROUND: There is an increasing use of cesarean delivery (CD) based on preference rather than on medical indication. However, the extent to which nonmedically indicated CD benefits or harms child survival remains unclear. Our hypothesis was that in groups with a low indication for CD, this procedure would be associated with higher child mortality and in groups with a clear medical indication CD would be associated with improved child survival chances. METHODS AND FINDINGS: We conducted a population-based cohort study in Brazil by linking routine data on live births between January 1, 2012 and December 31, 2018 and assessing mortality up to 5 years of age. Women with a live birth who contributed records during this period were classified into one of 10 Robson groups based on their pregnancy and delivery characteristics. We used propensity scores to match CD with vaginal deliveries (1:1) and prelabor CD with unscheduled CD (1:1) and estimated associations with child mortality using Cox regressions. A total of 17,838,115 live births were analyzed. After propensity score matching (PSM), we found that live births to women in groups with low expected frequencies of CD (Robson groups 1 to 4) had a higher death rate up to age 5 years if they were born via CD compared with vaginal deliveries (HR = 1.25, 95% CI: 1.22 to 1.28; p < 0.001). The relative rate was greatest in the neonatal period (HR = 1.39, 95% CI: 1.34 to 1.45; p < 0.001). There was no difference in mortality rate when comparing offspring born by a prelabor CD to those born by unscheduled CD. For the live births to women with a CD in a prior pregnancy (Robson group 5), the relative rates for child mortality were similar for those born by CD compared with vaginal deliveries (HR = 1.05, 95% CI: 1.00 to 1.10; p = 0.024). In contrast, for live births to women in groups with high expected rates of CD (Robson groups 6 to 10), the child mortality rate was lower for CD than for vaginal deliveries (HR = 0.90, 95% CI: 0.89 to 0.91; p < 0.001), particularly in the neonatal period (HR = 0.84, 95% CI: 0.83 to 0.85; p < 0.001). Our results should be interpreted with caution in clinical practice, since relevant clinical data on CD indication were not available. CONCLUSIONS: In this study, we observed that in Robson groups with low expected frequencies of CD, this procedure was associated with a 25% increase in child mortality. However, in groups with high expected frequencies of CD, the findings suggest that clinically indicated CD is associated with a reduction in child mortality.

Conditional Cash Transfer Program and Leprosy Incidence: Analysis of 12.9 Million Families From the 100 Million Brazilian Cohort.

Leprosy is a neglected tropical disease predominately affecting poor and marginalized populations. To test the hypothesis that poverty-alleviating policies might be associated with reduced leprosy incidence, we evaluated the association between the Brazilian Bolsa Familia (BFP) conditional cash transfer program and new leprosy case detection using linked records from 12,949,730 families in the 100 Million Brazilian Cohort (2007-2014). After propensity score matching BFP beneficiary to nonbeneficiary families, we used Mantel-Haenszel tests and Poisson regressions to estimate incidence rate ratios for new leprosy case detection and secondary endpoints related to operational classification and leprosy-associated disabilities at diagnosis. Overall, cumulative leprosy incidence was 17.4/100,000 person-years at risk (95% CI: 17.1, 17.7) and markedly higher in "priority" (high-burden) versus "nonpriority" (low-burden) municipalities (22.8/100,000 person-years at risk, 95% confidence interval (CI): 22.2, 23.3, compared with 14.3/100,000 person-years at risk, 95% CI: 14.0, 14.7). After matching, BFP participation was not associated with leprosy incidence overall (incidence rate ratio (IRR)Poisson = 0.97, 95% CI: 0.90, 1.04) but was associated with lower leprosy incidence when restricted to families living in high-burden municipalities (IRRPoisson = 0.86, 95% CI: 0.77, 0.96). In high-burden municipalities, the association was particularly pronounced for paucibacillary cases (IRRPoisson = 0.82, 95% CI: 0.68, 0.98) and cases with leprosy-associated disabilities (IRRPoisson = 0.79, 95% CI: 0.65, 0.97). These findings provide policy-relevant evidence that social policies might contribute to ongoing leprosy control efforts in high-burden communities.

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.

Effect of Early-Life Geohelminth Infections on the Development of Wheezing at 5 Years of Age.

RATIONALE: Exposures to geohelminths during gestation or early childhood may reduce risk of wheezing illness/asthma and atopy during childhood in tropical regions. OBJECTIVES: To investigate the effect of maternal and early childhood geohelminths on development of wheeze/asthma and atopy during the first 5 years of life. METHODS: A cohort of 2,404 neonates was followed to 5 years of age in a rural district in coastal Ecuador. Data on wheeze were collected by questionnaire and atopy was measured by allergen skin prick test reactivity to 10 allergens at 5 years. Stool samples from mothers and children were examined for geohelminths by microscopy. MEASUREMENTS AND MAIN RESULTS: A total of 2,090 (86.9%) children were evaluated at 5 years. Geohelminths were observed in 45.5% of mothers and in 34.1% of children by 3 years. Wheeze and asthma were reported for 12.6% and 5.7% of children, respectively, whereas 14.0% had skin test reactivity at 5 years. Maternal geohelminths were associated with an increased risk of wheeze (adjusted odds ratio, 1.41; 95% confidence interval, 1.06-1.88), whereas childhood geohelminths over the first 3 years of life were associated with reduced risk of wheeze (adjusted odds ratio, 0.70; 95% confidence interval, 0.52-0.96) and asthma (adjusted odds ratio, 0.60; 95% confidence interval, 0.38-0.94) but not skin prick test reactivity. The effects on wheeze/asthma were greatest with later age of first infection, were observed only in skin test-negative children, but were not associated with parasite burden or specific geohelminths. CONCLUSIONS: Although maternal exposures to geohelminths may increase childhood wheeze, childhood geohelminths during the first 3 years may provide protection through a nonallergic mechanism. Registered as an observational study (ISRCTN41239086).

Symptomatic Dengue during Pregnancy and Congenital Neurologic Malformations.

Dengue virus infection during pregnancy increased the risk for any neurologic congenital anomaly in the infant by roughly 50% and for other congenital malformations of brain 4-fold. Our results show an association between dengue during pregnancy and congenital anomalies of the brain, suggesting that flaviviruses other than Zika virus are associated with such malformations.

Seroprevalence of Chikungunya Virus after Its Emergence in Brazil.

Chikungunya has had a substantial impact on public health because of the magnitude of its epidemics and its highly debilitating symptoms. We estimated the seroprevalence, proportion of symptomatic cases, and proportion of chronic form of disease after introduction of chikungunya virus (CHIKV) in 2 cities in Brazil. We conducted the population-based study through household interviews and serologic surveys during October-December 2015. In Feira de Santana, we conducted a serologic survey of 385 persons; 57.1% were CHIKV-positive. Among them, 32.7% reported symptoms, and 68.1% contracted chronic chikungunya disease. A similar survey in Riachão do Jacuípe included 446 persons; 45.7% were CHIKV-positive, 41.2% reported symptoms, and 75.0% contracted the chronic form. Our data confirm intense CHIKV transmission during the continuing epidemic. Chronic pain developed in a high proportion of patients. We recommend training health professionals in management of chronic pain, which will improve the quality of life of chikungunya-affected persons.

Migration and tuberculosis transmission in a middle-income country: a cross-sectional study in a central area of São Paulo, Brazil.

BACKGROUND: Little is known about the impact of growing migration on the pattern of tuberculosis (TB) transmission in middle-income countries. We estimated TB recent transmission and its associated factors and investigated the presence of cross-transmission between South American migrants and Brazilians. METHODS: We studied a convenient sample of cases of people with pulmonary TB in a central area of São Paulo, Brazil, diagnosed between 2013 and 2014. Cases with similar restriction fragment length polymorphism (IS6110-RFLP) patterns of their Mycobacterium tuberculosis complex isolates were grouped in clusters (recent transmission). Clusters with both Brazilian and South American migrants were considered mixed (cross-transmission). Risk factors for recent transmission were studied using logistic regression. RESULTS: Isolates from 347 cases were included, 76.7% from Brazilians and 23.3% from South American migrants. Fifty clusters were identified, which included 43% South American migrants and 60.2% Brazilians (odds ratio = 0.50, 95% confidence interval = 0.30-0.83). Twelve cross-transmission clusters were identified, involving 24.6% of all clustered cases and 13.8% of all genotyped cases, with migrants accounting for either an equal part or fewer cases in 11/12 mixed clusters. CONCLUSIONS: Our results suggest that TB disease following recent transmission is more common among Brazilians, especially among those belonging to high-risk groups, such as drug users. Cross-transmission between migrants and Brazilians was present, but we found limited contributions from migrants to Brazilians in central areas of São Paulo and vice versa.

Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis.

BACKGROUND: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries. METHODS: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories. RESULTS: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases. CONCLUSIONS: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.