Strongest evidence yet to be found for Zika’s role in birth defects

Zika virus was found in the brain of a fetus, the strongest evidence yet that the virus causes abnormally small heads and incomplete brain development, according to an article in The New England Journal of Medicine. This is the first documented case of virus transmission from mother to child, though it is not a definitive link between Zika and fetal abnormalities — a connection first suggested by the Brazilian minister of health.

The Zika virus appeared to particularly favor neurons, today’s case report found. Damage from the virus may have halted brain development at 20 weeks, though it’s not clear how the virus was infecting nerve cells. Some structures found at autopsy showed that the virus was reproducing in the fetus’s brain.

In early 2015, a Zika outbreak was identified in northern Brazil, where other viruses spread by mosquitoes (like dengue) were circulating. By September, doctors began reporting an unusual number of babies born with microcephaly, a condition where infants are born with unusually small heads and underdeveloped brains. Zika has spread to many countries in the Americas, though Brazil bears the heaviest caseload, with estimates of 440,000 to 1.3 million infected as of December.

The number of newborns with microcephaly has increased twentyfold in the northern part of Brazil, the health minister has said. That led to the suspected link — and five public health agencies in multiple countries have advised women not to get pregnant as a result. Until now, though, there was no evidence of virus transmission from a pregnant woman to her fetus.

“This is the critical point: you have a mother who’s infected, a fetus that’s abnormal, and in the fetus, you have the genetic signature of the virus,” says Andrew Pekosz, director of the Center for Emerging Viruses and Infectious Diseases at Johns Hopkins Bloomberg School of Public Health. “This is clear data showing Zika can infect the fetus.” Today’s case report isn’t proof that Zika is causing microcephaly, but it makes the link much likelier, Pekosz says.

The woman was a 25-year-old European volunteer who had been working in Natal, Brazil, on the country’s northeast tip. She got pregnant in February 2015; at the 13th week of pregnancy, she had a fever and rash consistent with Zika infection. Ultrasounds at 14 weeks and 20 weeks were normal.

Then, she returned to Europe at 28 weeks pregnant. An ultrasound in her 29th week showed the first signs of abnormalities. At 32 weeks, an ultrasound showed that the fetus was abnormally small — in the third percentile for fetal weight — and its head was below the second percentile for circumference. There were calcium buildups in the brain and placenta.

The woman chose to get an abortion, and doctors performed an autopsy, where they found viral replication of Zika in the fetus’s brain. The fetus was negative for 13 other viruses that may cause fetal abnormalities; the woman had no history of genetic abnormalities in her family.

The autopsy also showed severe structural abnormalities in the fetus’s brain, said study author Tatjana Avšič Županc, a microbiologist at the University of Ljubljana in Slovenia. There was a total absence of brain folds; fluid had also built up in the brain. “Our evidence means a certain danger to pregnant women, especially those in the first trimester,” Županc says. “Particularly for those who reside in or visit areas with highly endemic Zika virus.”

There are still a lot of questions to be answered about Zika’s effects on fetuses. For instance, about 80 percent of infections are asymptomatic, says Nikos Vasilakis, a pathologist at the University of Texas Medical Branch.

No one yet knows if asymptomatic infections can cause fetal abnormalities. Animal models could provide hints about these questions — but there are no animal models for Zika, says Johns Hopkins’ Pekosz.

Studies proving causality and allowing doctors to begin assessing risks of birth defects will take years, Vasilakis says. And no one knows if infection in the first trimester — a crucial developmental period — is more dangerous than in later trimesters. “It’s quite a challenge to figure out what happens,” Vasilakis says. “It’s going to take a lot of money and scientific discipline.”