The report, published Wednesday in the New England Journal of Medicine, provides troubling new information about the capacity of the virus to infect a fetus and cause serious harm. The case also indicates that Zika may remain in the blood for a long time: The 33-year-old woman still tested positive for Zika 10 weeks after she likely was infected during a trip to Guatemala – far beyond what scientists have thought is the case.
"This helps put more pieces together in the puzzle because we know so little about how this virus acts and when and how long it stays in your blood after you have symptoms," said Laura Riley, vice chair of obstetrics and gynecology at Massachusetts General Hospital in Boston, who was not part of the study. Even though the study only involves one patient, "it's very important because she was followed so closely and there is so much detailed information. "
While the case offers important details to researchers and obstetricians-gynecologists counseling pregnant women who may have been exposed to the virus, "we're going to need to study this with a large number of patients to provide guidance for women," said Catherine Spong, acting director for the National Institute of Child Health and Human Development.
The woman and her husband traveled on vacation to Mexico, Guatemala and Belize in late November when she was 11 weeks pregnant. The couple told researchers they had been bitten by mosquitoes during their trip, particularly in Guatemala. After returning home, the woman developed eye and muscle pain, fever and a rash. A series of ultrasounds that began one week after her symptoms subsided -- at 13, 16 and 17 weeks of pregnancy -- showed none of the characteristic problems linked to Zika. The most prominent in utero are an abnormally small head and brain calcifications, bright, white spots that indicate something is amiss. Both are key to a diagnosis of a rare condition called microcephaly.
Yet on the ultrasound at 19 weeks, significant brain abnormalities appeared: The baby's brain was small and contained an unusual amount of fluid. The cerebral cortex, its outer layer, was very thin. By the 20th week, a fetal MRI showed severe atrophy, especially in the front and top brain areas that are involved in decision-making, learning, vision, hearing, touch and taste. The fetus did not meet the threshold to be diagnosed with microcephaly.
In the initial ultrasounds, "they only looked at the size of the head and looked for brain calcifications to make sure she didn't have microcephaly and reassured her that everything looks okay," said Rita Driggers, one of the study's lead authors and medical director of Sibley Memorial Hospital’s maternal-fetal medicine division. Driggers, an assistant professor of gynecology and obstetrics at Johns Hopkins University School of Medicine, was involved in the patient's care.
The takeaway for clinicians, she and others said, is to make sure during ultrasounds to look for other brain changes beyond microcephaly and intracranial calcifications.
Adre du Plessis, director of Children's National Health System's Fetal Medicine Institute and another study author, said Wednesday that the lack of those markers in the earlier ultrasounds may have led to "false reassurances" for the mother. What's more, he said, such delayed diagnosis of brain infection in the fetus may put women who'd opt to terminate a pregnancy "outside the legal limits" of an abortion.
Forty-three states prohibit abortions after a specified point in pregnancy -- most often the point of fetal viability -- except when necessary to protect the woman’s life or health.
Researchers said they are not recommending that all pregnant women infected with Zika uniformly seek out fetal MRIs, which are expensive and not readily available in many of the countries in Central and South America that have been hardest hit by the Zika epidemic. In the United States, the technology is available at most major medical centers.
It's possible that researchers might be able to develop other markers to predict whether babies will become infected and develop abnormalities, du Plessis said.
The study also provides new information about how long the virus persists in the blood of an infected person. The common thinking has been that the virus is only present for seven days to about two weeks at the outer limits. But this patient had virus in her blood from the time she became infected, when she was about 11 weeks pregnant, up until the time of her abortion, at 21 weeks.
"That's a very novel finding and important for future study," said Roberta DeBiasi, Children's chief of infectious disease division and another study author.
It's possible that the woman's persistent infection was the result of the virus replicating in the fetus or placenta, the researchers said.
Researchers also found "significant" cell death of neurons in the part of the brain that plays a role in sight, hearing and language, researchers said.