One of the biggest unknowns about the Zika virus is the extent of damage it causes during pregnancy. Much of the early alarm focused on babies born with abnormally small heads and often underdeveloped brains.

A study released Tuesday by the Centers for Disease Control and Prevention provides disturbing new data about a small group of Zika-infected babies in Brazil, who were born with normal-size heads but developed microcephaly five months to a year after birth.

The report is the first to document infants with laboratory evidence of Zika infection in utero who experienced “poor head growth with microcephaly developing after birth.” Although other researchers have described cases of babies developing microcephaly after birth, they could only presume that those infants had been infected congenitally.

The new study documents that even without microcephaly, Zika-infected babies can have severe neurological damage and other problems. All the infants examined had brain abnormalities, such as decreased brain volume, structures in the brain that were too large and filled with fluid, and decreased brain tissue with a specific pattern of calcium deposits indicating damage.

In a few cases, the mothers had ultrasounds during pregnancy that showed the infants' brain abnormalities. But in other babies, these problems only showed up during CT scans or MRIs conducted after birth.

Along with the lagging rate of head growth, these infants suffered other significant neurological damage. As a result, some have too much muscle tone, which restricts how their bodies can move. Some have muscle weakness on one side or the other. Some have involuntary muscle contractions that cause tremors. Others have difficulty swallowing, as well as seizures and vision problems.

“This is clear evidence that children can be severely affected even if they didn’t have microcephaly at birth,” CDC Director Tom Frieden said. “To me, the major key question we don’t have the answer for is this: How affected will infants be who don’t have microcephaly?”

Because of research into the outbreak in Brazil, a distinct pattern of birth defects from Zika infection during pregnancy is now officially known as congenital Zika syndrome. CDC officials say the latest findings further underscore the importance of screening pregnant women for Zika, conducting comprehensive medical and developmental follow-ups of babies whose mothers were exposed to the virus during pregnancy and following their children after birth.

In addition, early neuroimaging, even among infants with a normal head size, might identify brain abnormalities related to Zika infection during pregnancy, officials said.

“It’s the brain problems, not the size of the head,” said Cynthia Moore, a clinical geneticist and birth-defects expert for the CDC and an author of the study.

Doctors confirmed the link between the Zika virus and microcephaly in April. While the most visible sign of microcephaly is the small size of the head, its actually inside the brain where the most damage occurs. (Whitney Leaming, Julio Negron/The Washington Post)

Denise Jamieson, a clinical obstetrician-gynecologist who is one of the leaders of CDC’s Zika response, said the findings are prompting the agency to review guidance about screening infants born to Zika-infected women.

Some obstetricians such as Jeanne Sheffield, director of maternal-fetal medicine at Johns Hopkins Medicine, said that they already counsel Zika-infected women that normal head circumference at delivery does not mean a child is unaffected. Similar findings about Zika were discussed at a September conference on Zika sponsored by the National Institute of Child Health and Human Development.

The latest report follows the World Health Organization’s decision last week that Zika is no longer a global health emergency but a significant and enduring public health challenge that must be managed with more dedicated resources and expertise.

The CDC study, conducted in collaboration with researchers in Brazil, looked at 13 infants from the states of Pernambuco and Ceara in the country’s northeast, the region hardest hit by Zika. All were born between October 2015 and this past August with a normal head size. Virtually all showed brain abnormalities on CT scans or MRIs, several of them as early as a few days after birth.

The babies underwent extensive imaging and brain, eye, hearing and orthopedic examinations. All 13 showed a slowdown in head growth, and in 11 babies, that decline had slowed to the point where it met the definition of microcephaly, Moore said.

Researchers said they don’t know how Zika infection during pregnancy can lead to an infant’s developing microcephaly after birth. They said the decrease in head size might be the consequence of earlier destruction of critical neural stem cells or other neural cells, a persistent inflammatory response or continued infection of neural cells.

Officials say pregnancy registries in Puerto Rico, where Zika continues to spread rapidly, and on the U.S. mainland are tracking pregnant women with any evidence of Zika. Those surveillance systems will be a critical way to understand the full spectrum of the disease and proportion of infected babies, they say.

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