• CostaMaria da Conceição NMDCNCenter of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.Collective Health Institute, Federal University of Bahia, Salvador, Bahia, Brazil., Luciana Lobato Cardim, Cynthia A Moore, Eliene Dos Santos de Jesus, Rita Carvalho-Sauer, Mauricio L Barreto, Laura C Rodrigues, Liam Smeeth, Lavínia Schuler-Faccini, Elizabeth B Brickley, Wanderson K Oliveira, Eduardo Hage Carmo, Julia Moreira Pescarini, Roberto F S Andrade, Moreno M S Rodrigues, Rafael V Veiga, Larissa C Costa, FrançaGiovanny V AGVASecretariat of Health Surveillance, Ministry of Health, Brasilia, Distrito Federal, Brazil., Maria Gloria Teixeira, and Enny S Paixão.
• Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
• PLoS Med. 2023 Feb 1; 20 (2): e1004181e1004181.

BackgroundChildren with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018.Methods And FindingsIn a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls.ConclusionThe sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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