Three ultrasounds done in the early weeks of pregnancy in a Finnish woman living in the United States infected by Zika failed to show signs of brain damage in a fetus later diagnosed with the birth defect microcephaly, U.S. researchers said in a study published on Wednesday.
The woman was not identified but she was infected while traveling on vacation in Mexico, Guatemala and Belize in November 2015. The exact location of transmission was not known.
It was not until the 19th week of her pregnancy that signs of the birth defect first showed up on an ultrasound. A follow up study using magnetic resonance imaging or MRI showed extensive brain abnormalities.
Studies showed that the fetal brain had shrunken from a normal head circumference in the 47th percentile during week 16 to the 24th percentile in week 20. Even so, the head circumference was still not small enough to be classified as microcephaly, the researchers reported.
But given the extent of the damages seen on the MRI, the woman elected to terminate the pregnancy in the 21st week.
"What our paper suggests is that physicians should use caution in reassuring patients who have normal fetal ultrasound examinations early in their pregnancies," said Adre du Plessis, Director of the Fetal Medicine Institute at Children's National Health System in Washington, D.C., a coauthor of the study published on Wednesday in the New England Journal of Medicine
Du Plessis said single ultrasounds may not capture infection-associated fetal brain abnormalities that may worsen over the course of the pregnancy.
"There is an enormous amount we don't know about this current strain and outbreak of Zika virus. It seems to be behaving differently than in the past," du Plessis said in a conference call with reporters.
"What we do know for sure is if the fetal brain is affected this appears to be a very bad situation," he said.
Zika to date has not been proven to cause microcephaly in babies, but there is growing evidence that suggests a link. The condition is defined by unusually small heads that can result in developmental problems. Brazil — hardest hit by the virus — said it has confirmed more than 900 cases of microcephaly, and considers most of them to be related to Zika infections in the mothers. Brazil is investigating nearly 4,300 additional suspected cases of microcephaly.
In the paper, scientists examined the case of the woman who is from Washington, D.C. She became infected with Zika during her 11th week of pregnancy.
Although Zika infections typically remain present in the blood for 5 to 7 days, the virus in this patient remained present in this woman's blood until 10 days after the fetus was aborted.
Dr. Cheng-Ying Ho, a neuropathologist at Children's National, said the finding raises questions about whether there is a correlation between the duration of virus infection in the mother and the severity of the brain injuries in the fetus.
An autopsy of the fetus showed high concentrations of the virus in the brain, placenta and umbilical cord. Virus isolated from the brain showed it was still infectious, growing easily in lab dishes of human nerve cells, the study reported.
Study co-author Dr. Roberta DeBiasi, an infectious disease expert at Children's National, called the high levels of virus in the fetal brain and placenta "concerning and suggests that the virus may be able to hide from the immune system there."
The study authors believe the findings call into question current recommendations for Zika testing in pregnant women, which only recommend testing for presence of the virus within two weeks of an infection. Subsequent tests look for antibodies of the virus but not the virus itself.
Current recommendations do not include the use of MRI imaging tests, which are much more costly than ultrasounds and may not be accessible to pregnant women in countries with Zika transmission.
"What really matters is whether there is evidence of changes in the brain to suggest injury in the context of a proven viral infection in the mother," du Plessis said.
"That is where MRI is the gold standard for picking up changes in the brain, even though it has limitations in terms of availability and cost," du Plessis said.