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.

Estimating the real burden of gestational syphilis in Brazil, 2007-2018: a Bayesian modeling study.

Background: Although several studies have estimated gestational syphilis (GS) incidence in several countries, underreporting correction is rarely considered. This study aimed to estimate the level of under-registration and correct the GS incidence rates in the 557 Brazilian microregions. Methods: Brazilian GS notifications between 2007 and 2018 were obtained from the SINAN-Syphilis system. A cluster analysis was performed to group microregions according to the quality of GS notification. A Bayesian hierarchical Poisson regression model was applied to estimate the reporting probabilities among the clusters and to correct the associated incidence rates. Findings: We estimate that 45,196 (90%-HPD: 13,299; 79,310) GS cases were underreported in Brazil from 2007 to 2018, representing a coverage of 87.12% (90%-HPD: 79.40%; 95.83%) of registered cases, where HPD stands for the Bayesian highest posterior density credible interval. Underreporting levels differ across the country, with microregions in North and Northeast regions presenting the highest percentage of missed cases. After underreporting correction, Brazil's estimated GS incidence rate increased from 8.74 to 10.02 per 1000 live births in the same period. Interpretation: Our findings highlight disparities in the registration level and incidence rate of GS in Brazil, reflecting regional heterogeneity in the quality of syphilis surveillance, access to prenatal care, and childbirth assistance services. This study provides robust evidence to enhance national surveillance systems, guide specific policies for GS detection disease control, and potentially mitigate the harmful consequences of mother-to-child transmission. The methodology might be applied in other regions to correct disease underreporting. Funding: National Council for Scientific and Technological Development; The Bill Melinda Gates Foundation and Wellcome Trust.