Infectious Disease

Children with congenital Zika syndrome 11 times more likely to die, large study finds

February 24, 2022

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Please see the study for all authors’ relevant financial disclosures.

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Maternal Zika virus infection during pregnancy places a developing fetus at risk for a suite of severe birth defects and disabilities, including microcephaly, one of the most visible tolls of the Zika virus epidemic in the Americas.

In the United States, among children born to mothers with Zika virus infection, the incidence of congenital Zika syndrome is about one in 20 infants, according to recently published estimates.

Source: CDC.gov/Misty Ellis

Infection with Zika virus during pregnancy can cause a pattern of fetal and infant birth defects, including microcephaly. Source: CDC.gov/Misty Ellis

Even exposed infants who do not develop congenital Zika syndrome have been shown to be at a higher risk for abnormal development.

Now, a new study from Brazil — the country at the center of the 2015-2016 epidemic — has helped clarify on a large scale the increased risk for mortality that infants born with congenital Zika syndrome face.

According to a review of all singleton live births that occurred in Brazil from 2015 through 2018, the risk for death among children born with congenital Zika syndrome was around 11 times higher than it was for children born without the syndrome, researchers reported this week in The New England Journal of Medicine.

The researchers followed more than 11.4 million Brazilian children through their first 3 years of life, including more than 3,300 with congenital Zika syndrome, and calculated mortality rates of 52.6 deaths (95% CI, 47.6-58) per 1,000 person-years among children with the syndrome and 5.6 deaths (95% CI, 5.6-5.7) per 1,000 person-years among other children.

The mortality rate ratio among children with congenital Zika syndrome was 11.3 (95% CI, 10.2-12.4) compared with those without the syndrome. Mortality rates were similar among children born before 32 weeks’ gestation but increased after that. Children born at term with a normal birth rate were 12.9 times (95% CI, 10.9-15.3) more likely to die, the researchers found.

“This study showed a higher risk of death among live-born children with congenital Zika syndrome than among those without the syndrome, and the risk persisted throughout the first 3 years of life,” the researchers wrote. “These findings draw attention to the importance of primary prevention of infection in women of childbearing age against Aedes aegypti bites.”

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Sarah B. Mulkey, MD, PhD

Sarah B Mulkey

Children born with congenital Zika syndrome face enormous challenges because of birth defects, neurological conditions and abnormalities of their neurosensory systems of vision and hearing. Depending upon the trimester of maternal Zika virus infection, the risk for having a baby with congenital Zika syndrome is about 5% to 12%. This article reported by Paixao and colleagues is really the first large study to focus on child mortality from congenital Zika syndrome. The methods of combining data sources on live births, public health reported congenital Zika syndrome and death-related information enabled a countrywide view of child mortality since the Zika virus epidemic in Brazil. The study’s finding of children born with congenital Zika syndrome having 11.3 times the risk for mortality is high but is an expected finding given the serious nature of the neurological impact from the congenital infection.

The global brain abnormalities caused by the Zika virus in children with congenital Zika syndrome can affect everything that the brain does. Children can have impaired mobility, not be able to orally eat, can have epilepsy, may have impaired ability to communicate needs and can have abnormalities in vision or hearing to varying degrees. We know from other childhood neurological conditions, such as severe perinatal brain injury or other global brain malformations, that life expectancy can be reduced when a child cannot ambulate, has epilepsy, is nonverbal, is tube fed and has blindness and deafness. The mortality rate for these children with congenital Zika syndrome was even higher after the first year of age and not restricted to infancy, showing that the neurological condition can have increasing risk of mortality over time. Leading causes of death were reported due to infections, cerebral palsy and epilepsy. Children with impaired mobility and feeding can have aspiration pneumonia, which can be a serious infection in a child with significant neuromotor disability.

This study shows the unfortunate effects of life expectancy from congenital Zika syndrome and that the risk will likely continue to be high as surviving children age. This is an important study for providers who care for children with the complex medical needs of congenital Zika syndrome and the children’s families. A discussion about life expectancy is important to have with families caring for a medically complex child but is a hard conversation to have. Further studies to better understand the mortality risk level for individual children are needed given the wide spectrum of brain abnormalities and functional impairments in children with congenital Zika syndrome.

Sarah B. Mulkey, MD, PhD

Prenatal-neonatal neurologist

Co-director, Congenital Infection Program

Children’s National Hospital

Washington, D.C

Disclosures: Mulkey reports receiving funding from NIH and the Thrasher Research Fund and having a contract with the CDC for Zika studies.

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