5 years later, researchers assess how children exposed to Zika are developing
5 years later, researchers assess how children exposed to Zika are developing
When Yariel turned 5 in November, he had a pandemic birthday party, like most school-age kids these days. It was a karaoke party at home with family and one neighbor and a cake decorated with Roblox action figures.
"It was a Dominican cake," his mom, Yaritza Martinez, explains — a layer cake covered in meringue icing. She also put up balloons and silver streamers and a big Roblox banner.
But unlike a lot of American kids, this isn't Yariel's first pandemic. When Martinez was pregnant with him in 2016, she traveled to her home country of the Dominican Republic for a few weeks — and then came home to the Washington, D.C., suburbs.
"As soon I came here, the next day, I went to the hospital," she says, describing how tired she felt. "After two days, I [got] the test for Zika."
The test was positive.
She was referred to the Congenital Zika Program at Children's National Hospital, a regional hub for Zika virus treatment, and enrolled in a study. Researchers monitored her baby's brain as it developed using MRIs of her pregnant belly.
"It was a lot. It was stressful," she says. "I [got] depressed at that time, because we never [knew] what is going on."
Thankfully, throughout the pregnancy it seemed like her baby's head was growing normally. There were no signs of microcephaly, the unusually small head that is the hallmark birth defect of Zika infection during pregnancy.
After birth, everything changed, Martinez says. She stopped feeling so anxious.
"I always pay attention, if I see something different, comparing to my other two kids — but no." She smiles, watching him tumble around the living room and play with the car he got for his birthday. "He's a healthy boy."
Zika isn't completely out of their lives, though. Mother and son are still involved in research to help scientists understand whether there are more subtle differences from Zika that can appear as children grow up.
Long-term Zika research yields some answers
A few years before COVID-19 became the current public health emergency of international concern, the Zika virus swept through Latin America. Dramatic photos of babies born with small heads filled newspapers. Scientists didn't understand why it was happening or how common it was — or what prenatal Zika exposure might mean for these children as they grew older. According to the Centers for Disease Control and Prevention, 1,000 babies were born to women in the U.S. who had Zika during their pregnancies in 2016.
Now that some years have passed, more is becoming clear about Zika and its impact on children. Researchers have been assessing groups of these children as they get older and comparing them to children with no exposure to Zika.
About a year after the emergency was declared, researchers found that in the U.S., about 94% of babies born to women infected with Zika appeared to be normal at birth with no signs of microcephaly.
Then last year, Dr. Sarah Mulkey, a child neurologist in the Prenatal Pediatrics Institute at Children's National, published a study that found even among these babies that appeared normal at birth, there did seem to be some developmental differences.
"A baby doesn't have to do a lot of things — they have to eat and make lots of diapers for their parents and all that," Mulkey explains. "It's not until they get older and they're starting to get to school age that we can really assess more and more very important areas of development: Are they learning how to speak normally — learning their vocabulary? Can they run and jump and clear off the ground? Can they balance? These are things we can assess once they get older."
In late September, a few weeks before his fifth birthday, Yariel went to see Dr. Mulkey, as he has many times before. During his assessment, he strung beads and showed off his vocabulary and threw beanbags and walked along a line of yellow tape. Yariel remembers putting coins through a slot. "The coins — I was doing faster," he says. He also remembers eating pizza and getting a gift card.
"He [told] Dr. Mulkey he [would] go to Target to buy toys with that gift card," Martinez says, laughing. "He always [enjoys] that time with Dr. Mulkey."
Teasing out the effects of Zika and the coronavirus
From Mulkey's perspective, Yariel's doing very well, although there are a few areas where he needs more practice.
"He probably needs to work on some of his fine motor skills," she says. "I counseled the mom that we should try getting some pasta out and stringing it on some yarn and working with some coins and putting it in a piggy bank and working on our tracing letters — to try and work on that fine motor control."
Mulkey is finishing her analysis and writing up the most recent results from the children she and her collaborators have been following, both in the U.S. and in Colombia. They're looking out for severe neurological issues, like autism, but also for more subtle differences.
"The complicated part now is that we're studying children with an in-utero exposure to Zika, but also in the face of a pandemic that is affecting child exposures and development," Mulkey says.
The coronavirus pandemic has made the world very different for children. Many are socializing less with other children, staying home from school, and more. Separating those effects from the effects of Zika exposure is challenging. "Right now, we're still trying to kind of understand where our data is going to lead us," she says.
Although their analysis hasn't been completed or peer reviewed, it does seem as though Yariel isn't alone — that the difficulty with fine motor skills seems to be a common issue among children exposed to Zika.
"It seems to be an area that they are having some more struggles with, whereas the bigger motor functions of running and jumping seem to be a little bit better," she says.
Although drawing outside the lines might not sound like a serious problem, "things that might seem like they're just minor developmental issues can get magnified and have lots of consequences," says Dr. Karen Puopolo, a neonatologist at the University of Pennsylvania and Children's Hospital of Philadelphia.
As an example: "Say you're in third grade and you're really frustrated by not being able to [play] the recorder, and so you start misbehaving during music class," Puopolo explains. "Now the school labels you as a misbehaving child, so when we make the placement for you for fourth grade, maybe we're not going to put you in the advanced class because you seem like you're a fidgety misbehaving child."
For decades, neonatologists have been doing the kind of neurodevelopmental follow-up that Mulkey is doing with Yariel, Puopolo says, and they've shown "that identifying potential developmental deficits early on and intervening was really important to [children's] long-term development, especially when they got to school age."
Mulkey's research on Zika and development — which includes Yariel — will continue for a few more years. "We're going to be getting MRIs in the children once they get to age 7," she says. She'll be looking for any brain structural differences between the children who had Zika exposure and those who didn't — both in the U.S. and in Colombia. She believes it may be some of the longest-term follow-up for Zika-exposed children in the world.
Puopolo says that kind of long-term research is rare because it's expensive, time-consuming and requires a lot from the parents and children who are participating. "Really good longitudinal data — let's see how they are when they're 5, let's see how they are when they're 7, let's see how they are when they go to middle school — is unusual," she says. "You learn a lot from that type of follow-up, though."
Lessons for babies with COVID-19 exposure
There might be lessons in this work for the pandemic currently underway.
When a pregnant woman gets sick with fever and inflammation, "these kinds of things can affect early brain development," Mulkey explains. "A mom that has COVID during pregnancy and has a fever, or viral flu during pregnancy — we could potentially see these same kinds of effects long-term" in their children, as well.
CDC estimates there have been more than 150,000 COVID-19 cases in pregnant people so far — more than a hundred times the number of babies born to mothers with Zika in the U.S. And Mulkey is following about 50 children through Children's Congenital Infection Program who were born to a mother that had COVID-19 during pregnancy or who caught it within the first few weeks after birth.
There are important differences here, though. One of the major adverse outcomes of Zika infection is microcephaly, a severe birth defect. So far, there's no signal that COVID-19 infection is leading to a specific birth defect, Puopolo says. But having COVID-19 during pregnancy has been shown to increase the risk of the baby being born prematurely, which is associated with a lot of health problems, from cerebral palsy to hearing or vision problems.
What is the impact on an infant, Puopolo asks, of "your mother getting COVID in your first trimester when all of your organs are developed, or in the second or third trimester, where there's a lot of brain growth? Or what if she's sick at the time of delivery and the baby gets it as well? Does any of that mean anything when the baby is 5 years old?" she says. "We have no idea." Only long-term research can answer those questions.
Mulkey says one lesson from Zika is that it will be essential to follow groups of children exposed to COVID-19 in utero long term — even after COVID-19 has fallen out of the headlines. For a lot of researchers who studied groups of children exposed to Zika, she says, "once it was no longer a public health emergency, funding was withdrawn."
"Child development occurs over many years and there are stages of development that could be affected from an early exposure," she explains. "We need to follow all of the kids born during this pandemic whose mothers were sick during pregnancy or who were babies who had the early infection and see if there's any differences in long-term outcomes — we can't stop at one year," she says. "We really need to follow them up until school age."
Yariel will keep coming in for assessments for several years to come. In the meantime, he'll keep growing up — celebrating New Year's with his parents and siblings, watching My Little Pony: A New Generation (his favorite movie), playing with his toy race cars — and next year, starting school for the first time.
He says he's ready.
ARI SHAPIRO, HOST:
Before COVID-19, there was Zika. The virus swept through Latin America in 2016. Some babies were born with small heads. Scientists didn't understand why or how common it was. Since then, they've learned that most kids whose mothers had Zika during pregnancy were not born with any visible birth defects. In 2017, Selena Simmons-Duffin met one of those children named Yariel. At the time, he was a curly haired 1-year-old. She went with him to Children's National Hospital here in Washington, D.C.
YARITZA MARTINEZ: (Speaking Spanish). Up, up, up.
SELENA SIMMONS-DUFFIN, BYLINE: At this moment, he's gazing up at his mom, Yaritza Martinez, in an exam room chair, pondering a move to stand.
MARTINEZ: Up - good job. Bravo.
SHAPIRO: Well, now Yariel is 5 years old, and Selena went back to check in on him and bring us up to date on what scientists know about the long-term impact of Zika exposure.
SIMMONS-DUFFIN: Yariel has spent a lot of this pandemic year in his family's cozy apartment just north of Washington, D.C. He's a bit shy. His long, curly hair is pulled into a ponytail.
You don't remember me.
MARTINEZ: He was too little (laughter).
SIMMONS-DUFFIN: His mom, Yaritza Martinez, says he's doing great. His older brother and sister, Dylan and Angie (ph), clearly adore him, enough to turn up the volume of "My Little Pony: A New Generation," which they say they have watched a thousand times.
YARIEL: More. More. I can't hear it.
SIMMONS-DUFFIN: A few months ago, Yariel went back to Children's National Hospital for his five-year-assessment - no more baby stuff like standing up. This time, he showed off his vocabulary and threw bean bags and walked along a line of yellow tape. Yariel remembers putting coins through a slot.
MARTINEZ: The coins - do you remember?
YARIEL: The coins - I was doing it faster.
MARTINEZ: You had fun that day, right?
MARTINEZ: At Children's National, Dr. Sarah Mulkey says from her perspective, Yariel is doing very well.
SARAH MULKEY: He certainly knew a lot of words on his vocabulary test. We were quite impressed with him. He probably needs to work on some of his fine motor skills. When he was doing his drawing assessment, he went over the lines a couple times too much, so his score wasn't the best.
SIMMONS-DUFFIN: That's something he can work on before he goes to school next year, she says. Her analysis of the data from her assessment of Yariel and the other children in this group isn't complete yet. She says it's a challenge to tease apart the effects of Zika exposure from the effects of living through the coronavirus pandemic, which has meant fewer chances to play with other kids, for instance. But so far, it seems like Yariel isn't alone and that fine motor skills is an area that Zika-exposed children struggle with more than children who were not exposed.
MULKEY: That seems to be an area that they are having some more struggles with, whereas kind of the bigger motor functions of running and jumping seem to be doing a little bit better.
SIMMONS-DUFFIN: Drawing outside the lines might not sound like a serious problem, but it does matter. Dr. Karen Puopolo is a neonatologist at Pennsylvania Hospital in Philadelphia. She explains...
KAREN PUOPOLO: Say you're in third grade and you're really frustrated by not being able to do the recorder, and so you start misbehaving during music class. And so when we make the placement for you for fourth grade, maybe we're not going to put you in the advanced class because, you know, you seem like you're a fidgety, misbehaving child.
SIMMONS-DUFFIN: That's why it's so important to identify these subtle differences and intervene early, she says. This kind of research, following groups of children from before birth through school age, is unusual. Mulkey has images of Yariel's brain from before he was born, MRIs of Martinez's pregnant belly, and she'll have images of his brain again when he's 7 years old. This is expensive and time-consuming work that requires a lot from the participants, but it's also really important, Mulkey says.
MULKEY: A baby doesn't have to do a lot of things. They need to eat and make lots of diapers for their parents and all that kind of thing. But it's not until they get older and they're starting to go to school age that we can really assess executive function, language development, emotional development.
SIMMONS-DUFFIN: Things that may affect their success later in life. This isn't just about Zika. Getting sick during pregnancy with any virus can affect fetal development, says Puopolo, including perhaps coronavirus.
PUOPOLO: Currently, we do not have evidence that having COVID during pregnancy leads to any specific impact on the infant, other than the fact that there is an increased risk that the baby will be born preterm.
SIMMONS-DUFFIN: However, she says, COVID-19 has already affected a lot of pregnant people - more than 150,000 in the U.S., according to the CDC. That's more than 100 times the number affected by Zika in the U.S., and there's still a lot unknown about COVID-19's long-term effects.
PUOPOLO: I don't want to, like, scare the world and suggest that there's any reason to worry about that, but clearly it's a novel virus, and it's a novel situation. And so there is reason to be thoughtful about how we might approach understanding any potential impact that might come down the line.
SIMMONS-DUFFIN: Mulkey is following a group of children affected by COVID-19, and she hopes she can do long-term research with them as well.
For his part, Yariel will keep going in for assessments for several more years. That's OK with him and his mom, Yaritza.
MARTINEZ: Even now, they don't know everything about Zika, so they still investigate.
SIMMONS-DUFFIN: His older sister Angie, who's 16, has already started drawing with him so he can work on his fine motor skills.
YARIEL: Practice, writing and, you know, holding, like, a pencil. And, like, he's kind of getting the hang of it there, so...
SIMMONS-DUFFIN: He's working at it so next fall, when it's time to start kindergarten, he'll be ready. Selena Simmons-Duffin, NPR News.
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