In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.
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It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.
The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.
Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.
“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”
Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.
“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”
Early evidence
Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.
Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.
“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.
“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”
Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.
The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.
As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.