Congenital Zika syndrome is associated with higher risk of death

1. Children with congenital Zika syndrome had a higher risk of death throughout the first 3 years of life.

2. Children with congenital Zika syndrome were more likely to suffer from congenital anomalies, nervous system diseases, and infectious diseases than those without the syndrome.

Evidence Rating Level: 2 (Good)

Study Rundown: Prenatal exposure to Zika virus, referred to as congenital Zika syndrome, can have many adverse outcomes, including functional impairments, structural anomalies, and clinical sequelae like epilepsy. Early evidence suggests that affected children have a fatality rate of 10% in the first years of life. However, there is a gap in knowledge as to understanding the relative risk of death among children born with congenital Zika syndrome. This study found that there is a higher risk of death among live-born children with congenital Zika syndrome compared to those without the syndrome and that this risk persists throughout the first 3 years of life. This study was limited by being based on registry data and potential underreporting in the Public Health Event Record. Nevertheless, these study’s findings are significant, as they demonstrate that congenital Zika syndrome is associated with a higher risk of death in the first years of life, promoting the importance of prevention of infection against the Zika virus.

Click to read the study in NEJM

Relevant Reading: Safety and Immunogenicity of an Anti–Zika Virus DNA Vaccine

In-Depth [population-based cohort study]: This population cohort study followed 11,481,215 live-born children for 36 months in Brazil from January 2015 through December 2018. Patients who contributed records during the study period and were singleton live-born children were included in the study. Patients who were ruled out to have congenital Zika syndrome after epidemiologic investigation and records that were classified were excluded from the study. Cases of congenital Zika syndrome were confirmed if there were signs and symptoms consistent with the syndrome or laboratory evidence of ZIKV infection. The primary outcome measured was mortality stratified according to gestational age, birth weight, and status of being small for gestational age. Outcomes in the primary analysis were assessed via Kaplan-Meier curves and survival models for confounding and stratification. Based on the analysis, the overall mortality rate for children with congenital Zika syndrome was 52.6 deaths per 1000 person-years (95% confidence interval [CI], 47.6 to 58.0), compared to 5.6 deaths per 1000 person-years in children without the syndrome (95% CI, 5.6 to 5.7). The mortality rate ratio comparing children with congenital Zika syndrome to those without the syndrome was 11.3 (95% CI, 10.2 to 12.4). When stratifying by weight, infants with a birth weight of 2500 g or greater, children with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) more likely to die than those without the syndrome. In examining causes of death, children with congenital Zika syndrome were twice as likely to suffer from infectious and parasitic diseases, nervous system diseases, and congenital malformations. Overall, this study demonstrated that congenital Zika syndrome leads to a higher risk of death for children throughout the first three years of life, thus highlighting the importance of primary prevention of the Zika virus.

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