Congenital Zika Syndrome: A Nationwide Cohort Study in Brazil, 2015-2018

BACKGROUND: Prenatal exposure to ZIKV has potential teratogenic effects with a wide spectrum of clinical presentation called congenital Zika syndrome (CZS). There are limited data on survival of children with CZS, we estimated mortality comparing live births with and without CZS. METHODS: A population-based cohort study using linked routinely collected data in Brazil, from January 2015 to December 2018. Kaplan-Meier and survival analyses were performed adjusted for confounding and stratified by gestational age, birth weight and small for gestational age. RESULTS: We followed 11,737,554 live births for up to 36 months. The mortality rate among live births with CZS was 52.6 (95% confidence interval [CI] 47.6-58.0) and among those without CZS it was 5.6 (5.6-5.7) per 1000 person-years. The mortality rate ratio was 11.3 (95%CI 10.2-12.4) times higher among live births with CZS than those without CZS up to the age of 36 months. For infants born before 32 weeks' gestation or with birth weight less than 1500g, the risk of death was similar regardless of CZS. Infants with CZS born at term (mortality rate with and without CZS—38.4 vs 2.7) or with birth weight greater than 2499g (mortality rate with and without CZS—32.6 vs 2.5) were 14.3 (95%CI 12.4-16.4) and 12.9 (95%CI 10.9-15.3) times more likely to die than those without CZS. The burden of congenital anomalies, diseases of the nervous system and infectious diseases, as recorded causes of deaths, were higher among the CZS group. CONCLUSION: There is a higher mortality risk in live births with CZS than live births without CZS that persists throughout the first three years of life.