Causes of death in children with congenital Zika syndrome in Brazil, 2015 to 2018: A nationwide record linkage study

Abstract

Background Children 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 findings In 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. Conclusion The 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. Maria da Conceição Costa and colleagues investigate the sequence of events leading to death of children with Congenital Zika syndrome up to 36 months of age. Author summary Why was this study done? Children with congenital Zika syndrome (CZS) have a broad spectrum of clinical manifestations due to sequelae of central and peripheral nervous system damage that can impair important vital functions and greatly increase the risk of death in affected children. Little is known about the circumstances involved in the death of children affected by this syndrome. Analysis of the sequences of causes attested on the death certificate (DC) can contribute to this understanding and thus support the implementation of health programs and specific postnatal protocols to meet the needs of these children. Brazil was the country with the highest number of live births with CZS. What did the researchers do and find? We linked administrative data of all reporting live births, deaths, and notification of probable and confirmed CZS cases in Brazil in the period from January 1, 2015 to December 31, 2018. We analyzed the proportional mortality of the main underlying, intermediate, immediate, and contributing causes of death of 403 children with CZS up to 36 months age and compared with the same causes of death of 734 children with non-Zika–related CNS congenital anomalies (CA) who died by 36 months of age from the proportional mortality ratio. The leading underlying causes of death for children with CZS were multiple congenital malformations not classified elsewhere and unspecified septicemia. What do these findings mean? The sequence of causes and circumstances involved in the deaths of the CZS children by 36 months age, in Brazil, highlighted the greater vulnerability of these children to infectious and respiratory conditions. It is necessary to develop evidence-based health protocols and raising awareness of conditions associated with high mortality in children affected by congenital Zika virus infection to guide health professionals responsible for caring for these children.