Researchers reported on Wednesday new evidence firming the association between Zika virus and a spike in birth defects, referring to the presence of the virus in the brain of an aborted fetus of a European woman who became pregnant while living in Brazil.

An autopsy of the fetus showed microcephaly or small head size, as well as severe brain injury and high levels of the Zika virus in fetal brain tissues, surpassing levels of the virus usually found in blood samples, researchers in Slovenia from the University Medical Center in Ljubljana reported in the New England Journal of Medicine.

The findings help “strengthen the biologic association” between Zika virus infection and microcephaly, researchers from the Harvard School of Public Health and Massachusetts General Hospital in Boston, wrote in an editorial that accompanied the paper.

Researchers in Brazil are scrambling to determine whether the arrival of the Zika virus in that country has caused a major rise in microcephaly, with more than 4,000 suspected cases of the condition reported to date. Brazil has confirmed more than 400 of those cases as microcephaly, and identified the presence of Zika in 17 babies, but a link has yet to be proven.

The virus is transmitted by mosquitoes. There is no treatment or vaccine.

Professor Tatjana Aviupanc, who led the researchers in Slovenia, said in an email her team’s findings “may present the most compelling evidence to date” that birth defects associated with Zika infection in pregnancy may be caused by replication of the virus in the brain.

She said more studies are needed for definitive proof.

In the NEJM paper, the mother showed signs of Zika infection during her 13th week of pregnancy, but ultrasounds during her 14th and 20th week were normal.

It was not until the woman went back to Europe that researchers found ultrasound evidence of severe fetal abnormalities during an ultrasound in her 29th week.

That suggests that ultrasounds may pick up signs of severe fetal abnormalities “only very late in gestation – in many cases too late to terminate the pregnancy,” Drs. Eric Rubin, Michael Green and Lindsey Baden wrote in the editorial.
In the Slovenian case, the woman also detected reduced fetal movement and was told the fetus had a poor prognosis. She requested an abortion, which was approved by state and hospital ethics boards and performed at 32 weeks gestation. A normal pregnancy lasts 40 weeks.

Aside from obvious microcephaly, the fetus showed no other deformities. The woman had no family history of genetic abnormalities that could have caused the microcephaly.

Researchers did an autopsy, and instead of normal grooves formed in the brain during growth, the surface of the brain was smooth and there were numerous calcifications, which are suggestive of inflammation.

Zika virus tested positive in brain samples but no other defects were found in any other fetal organs. Form the brain samples, the team was able to identify the complete genetic sequence of the Zika viral genome, which most closely matched a Zika virus strain isolated from a patient from French Polynesia in 2013 and a Zika virus strain isolated in Sao Paulo, Brazil, in 2015.

Importantly, the tests suggest that the virus selectively attacks nerve tissue, but doesn’t clearly show how it does.

In January, a team of researchers at the U.S. Centers for Disease Control and Prevention reported that they, too, found evidence of Zika virus in brain samples from Brazil taken from two miscarriages and two newborns who died shortly after birth.

CDC published full results of their findings earlier on Wednesday.

In an advice to women on Wednesday, the World Health Organization (WHO) guided women on how to protect themselves from Zika, particularly if pregnant, but also reassured them that most women in areas affected by the mosquito-borne virus will give birth to ‘normal infants.’

WHO called on pregnant women in general, including those who develop symptoms of Zika infection, to visit their health care provider for close monitoring.