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All-Cause and Cause-Specific Mortality in Children With Congenital Zika Syndrome in Brazil
Luciana Lobato Cardim1, Maria da Conceição Nascimento Costa1,2, Laura Cunha Rodrigues1,3
1Center of Data and Knowledge Integration for Health, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
Insights
Children with Congenital Zika syndrome (CZS) face a significantly higher risk of death within their first five years. This includes increased mortality from respiratory, infectious, and nervous system diseases, highlighting the need for targeted interventions.
Area of Science:
- Public Health
- Pediatrics
- Infectious Diseases
Background:
- Congenital Zika syndrome (CZS) is associated with severe developmental and neurological deficits.
- The impact of CZS on all-cause and cause-specific mortality in early childhood remains largely unquantified.
- Understanding mortality risks is crucial for developing effective interventions and improving outcomes for affected children.
Purpose of the Study:
- To compare the hazard of all-cause and cause-specific mortality before age 5 years among children with and without CZS in Brazil.
- To identify specific causes of death associated with CZS in early childhood.
Main Methods:
- A nationwide cohort study in Brazil linked routine data for children born between January 2015 and December 2018.
- Children were followed until age 5, death, or December 2020, with confirmed or probable CZS cases identified as the exposure.
- Cox proportional hazard models were used to estimate adjusted hazard ratios for all-cause and cause-specific mortality, controlling for demographic and maternal factors.
Main Results:
- Children with CZS exhibited a 13.10-fold increased risk of all-cause mortality by age 5 compared to children without CZS.
- Significantly higher mortality risks were observed for respiratory diseases (HR=30.28), infectious/parasitic diseases (HR=28.26), and nervous system diseases (HR=57.11).
- The increased mortality risk associated with CZS persisted and was even higher when excluding preterm, low birth weight, or small-for-gestational-age newborns.
Conclusions:
- Children born with Congenital Zika syndrome face a substantially elevated risk of premature death from various causes.
- These findings underscore the critical need for enhanced clinical management and support systems for children with CZS.
- Implementing targeted clinical protocols may improve survival rates and long-term outcomes for this vulnerable population.
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.
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