All-Cause and Cause-Specific Mortality in Children With Congenital Zika Syndrome in Brazil.

IMPORTANCE: Congenital Zika syndrome (CZS) can lead to a range of developmental and neurological issues, which increases the risk of early death. However, the all-cause and cause-specific mortality in children with CZS in the first 5 years of life remain unknown.

OBJECTIVE: To compare the hazard of all-cause and cause-specific mortality before age 5 years among children with and without CZS in Brazil.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used nationwide linked routine data including all children born from January 2015 to December 2018 in Brazil. They were followed-up until age 5 years, death, or December 2020, whichever occurred first. All analysis were conducted in May 2024.

EXPOSURES: Confirmed or probable cases of CZS.

MAIN OUTCOMES AND MEASURES: All-cause and cause-specific deaths from respiratory, infectious and parasitic, and nervous system diseases were the outcomes. Hazard ratios (HRs), comparing children with and without CZS, for all and cause-specific mortality were estimated using Cox proportional hazard models adjusted for region and year of birth, maternal characteristics (age, education, race and/or ethnicity, and marital status), and sex of the newborn. The analysis was conducted in May 2024.

RESULTS: In total, there were 11 387 431 live births (5 832 594 male newborns [51.2%]). Of 3080 children notified as CZS cases, 444 (14.4%) died, including 154 (34.7%) from respiratory diseases, 152 (34.2%) from infectious and parasitic diseases, and 82 (18.5%) from nervous system diseases. Children with CZS were predominantly preterm (596 newborns [20.0%] vs 1 122 378 newborns [10.1%]) and had low birth weight (1095 newborns [35.7%] vs 805 373 newborns [7.1%]), compared with children without CZS. After controlling for confounders, children with CZS were 13.10 (95% CI, 11.86-14.46) times more likely to die in the first 5 years of life compared with those without the syndrome. The cause-specific mortality HRs were 30.28 (95% CI, 25.59-35.83) for respiratory diseases, 28.26 (95% CI, 23.85-33.48) for infectious and parasitic diseases, and 57.11 (95% CI, 45.23-72.11) for nervous system diseases. After excluding newborns who were preterm, low birth weight, and/or small for gestational age, the HRs for all-cause and cause-specific deaths were even higher.

CONCLUSIONS AND RELEVANCE: In this cohort study, children born with CZS had strikingly higher risk of overall and cause-specific mortality. These findings may support the development of clinical protocols to prevent early mortality and improve survival in these children.