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

Abstract

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.

Fig 1. Underlying cause of deaths using ICD-10 codes by age group and CS status.

Among children with CS, infections specific to the perinatal period and hematological disorders were more than twice as common as they were among children without CS during the neonatal period. During the postneonatal period, HIV, noxious substances transmitted via placenta or breast milk, anemia, and specific external causes were more than twice as common as they were among children without CS. Among children 1 year or older, bacterial meningitis and paralytic ileus and intestinal obstruction were more than twice as common as they were among children without CS. Similar to the postneonatal period, among older children with CS, specific external causes (events of undetermined intent and accidental threats to breathing) were more than twice as common as they were among children without CS (S2 Fig). CS, congenital syphilis; ICD, International Classification of Diseases.