Mortality 12 Times Higher in Children With Congenital Zika

Mônica Tarantino

February 23, 2022

About 80% of people infected with Zika virus show no symptoms, and that's particularly problematic during pregnancy. The infection can cause birth defects and is the origin of numerous cases of microcephaly and other neurologic impairments.

The large amount of Aedes aegypti mosquitos in Brazilian cities, in addition to social and political problems, facilitated the spread of Zika to the point that the country recorded its highest number of congenital Zika syndrome notifications from 2015 to 2018. Since then, researchers have investigated the extent of the problem.

One of the most compelling findings about the dramatic legacy of Zika in Brazil was recently published in The New England Journal of Medicine: after tracking a total of 11,481,215 children born alive in Brazil up to 36 months of age between the years 2015 and 2018, the researchers found that the mortality rate was about 12 times higher among children with congenital Zika syndrome in comparison to children without the syndrome. The study is the first to follow children with congenital Zika syndrome for 3 years and to report mortality in this group.

"This difference persisted throughout the first 3 years of life," Enny Cruz Paixão, PhD, from the London School of Hygiene and Tropical Medicine, in London, and Fiocruz-Bahia's Instituto Gonçalo Moniz, in Brazil, commented in an interview with Medscape Medical News.

A total of 11,481,215 children were followed up to 36 months of age. At the end of the study period, the mortality rate was 52.6 deaths (95% CI, 47.6 – 58.0) per 1000 person-years among children with congenital Zika syndrome and 5.6 deaths (95% CI, 5.6 – 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among children with congenital Zika syndrome, as compared with those without it, was 11.3 (95% CI, 10.2 – 12.4). Data analysis also showed that the 3308 children with the syndrome were born to mothers who were younger and had fewer years of study when compared to the mothers of their 11,477,907 counterparts without the syndrome.

"If the children survived the first month of life, they had a greater chance of surviving during childhood, because the mortality rates drop," said Paixão. "In children with congenital Zika syndrome, this rate also drops, but slowly. The more we stratified by period ― neonatal, post neonatal, and the period from the first to the third year of life ― the more we saw the relative risk increase. After the first year of life, children with the syndrome were almost 22 times more likely to die compared to children without it. It was hard to believe the data." Paixão added that the mortality observed in this study is comparable with the findings of previous studies.

In addition to the large sample size ― more than 11 million children ― another unique aspect of the work was the comparison with healthy live births. "Previous studies didn't have this comparison group," said Paixão.

Perhaps the major challenge of the study, Paixão explained, was the fragmentation of the data. "In Brazil we have high-quality data systems, but they are not interconnected. We have a database with all live births, another with mortality records, and another with all children with congenital Zika syndrome. The first big challenge was putting all this information together."

The solution found by the researchers was to use data linkage ― bringing information about the same person from different data banks to create a richer dataset. Basically, they linked the data from the live births registry with the deaths that occurred in the studied age group plus around 18,000 children with congenital Zika syndrome. This was done, said Paixão, by choosing some identifying variables (such as mother's name, address, and age) and using an algorithm that evaluates the probability that the "N" in one database is the same person in another database.

"This is expensive, complex, [and] involves super-powerful computers and a lot of researchers," she said.

The impressive mortality data for children with congenital Zika syndrome obtained by the group of researchers made it inevitable to think about how the country should address this terrible legacy.

"The first and most important recommendation is that the country needs to invest in primary care, so that women don't get zika during pregnancy and children aren't at risk of getting the syndrome," said Paixão.

As for the affected population, she highlighted the need to deepen the understanding of the syndrome's natural history to improve survival and quality of life of affected children and their families. One possibility that was recently discussed by the group of researchers is to carry out a study on the causes of hospitalization of children with the syndrome to develop appropriate protocols and procedures that reduce admissions and death in this population.

This news was originally published on Medscape in Portuguese.

N Engl J Med. 2022;386:757-767. Full text

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.