CDC: Zika Virus Definitely Causes Microcephaly

Brenda Goodman, MA

April 13, 2016

Dropping previous caution about the relationship between the Zika virus and the birth defect microcephaly, scientists said Wednesday there is no longer any doubt that Zika causes infants to be born with abnormally small heads and damaged brains.

The announcement marks a "turning point in the Zika outbreak," said CDC Director Tom Frieden, MD, adding that the findings would be published later Wednesday in the New England Journal of Medicine.

"The science now shows what the hundreds of impacted families have suspected all along. Zika virus is the cause of the tragic increase in microcephaly cases and other serious brain defects," Frieden said.

Though the virus had been strongly suspected to cause microcephaly and other serious birth defects, scientists had been careful to say that they didn't yet know whether the appearance of the two things together could be just a coincidence or whether it was a cause-and-effect relationship.

But in a press briefing, experts said there was now enough scientific evidence to prove that Zika causes microcephaly. By clearly laying out that evidence, scientists hope to dispel still-swirling rumors that other agents, such as a chemical that kills mosquito larvae, might be behind the outbreak of microcephaly, which was declared a worldwide public health emergency by the World Health Organization in February.

Experts said they also hoped the strong statement would serve as a wake-up call to Americans who aren't very worried about the Zika infection, at least according to recent surveys.

"My hope is that now that we can be more convincing that Zika virus does cause these severe birth defects in babies, that people will focus on our prevention messages more carefully," said Sonja A. Rasmussen, MD, director of the Division of Public Health Information Dissemination at the CDC.

Scientific Detective Work

The finding isn't based on any single piece of evidence, but on a collection of clues that satisfy two sets of formal scientific rules for determining causality, or whether a given agent causes a condition or disease.

The first set of rules they applied are called Shepard's criteria, after Thomas Shepard, MD, the Seattle pediatrician who first published them in 1994. Shepard's criteria are used to discern whether an agent could be a "teratogen," or something that can disrupt a baby's normal development in the womb.

The CDC scientists said they also met a separate test of causality, outlined by Sir Austin Bradford Hill in 1965.

To satisfy Shepard's criteria, scientists had to prove that at least three out of seven conditions were met.

First, they had to show that exposure happened during a critical window of development. Studies have shown that babies exposed to Zika in the first and second trimesters of pregnancy -- weeks when the brain is still forming -- are at greatest risk for microcephaly.

Second, they had to demonstrate that Zika causes a specific and repeating pattern of birth defects. Indeed, infants who develop microcephaly after Zika infection have distinct damage on brain scans. They also have extra skin on their scalps, eye damage, and their joints may be bent and splayed at odd angles when they're born.

Third, researchers had to show that a rare exposure causes a rare outcome. Rasmussen says this was proven by the rare cases of pregnant travelers who got Zika infections and gave birth to babies with microcephaly, which is a rare birth defect.

On top of that evidence, population studies from Brazil and French Polynesia have shown elevated rates of microcephaly among pregnant women infected with the virus, and more such studies are underway. Zika virus has now been isolated from the amniotic fluid surrounding affected babies, from their brain tissues through autopsy, and from spinal fluid.

An Important Step, But...

Despite the proof they now have in hand, researchers said there were still many key questions left to be answered.

At the top of the list, Rasmussen says, is to try to understand the degree of risk Zika infections might pose to pregnant women. That is, after an infection, how often will a fetus develop birth defects? Current studies suggest that somewhere between 1% and 29% of babies born to infected mothers get microcephaly.

Researchers would also like to know when a developing infant is most vulnerable to the virus, and whether it may cause a spectrum of related problems, ranging from stillbirth and miscarriages on the severe end to learning disabilities on the milder end.

Researchers said they still don't know whether Zika might be acting alone, or whether it only has its worst effects in concert with other agents or infections, like dengue fever.

Though the information is an important scientific step, Rasmussen said it doesn't change CDC recommendations.

"There's no change in our guidance about travel or preventing sexual transmission," she said.

Zika is mainly spread through mosquito bites, but cases in which infected men passed the virus to their sex partners have also been seen.


The New England Journal of Medicine, April 13, 2016.

Press briefing, CDC.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.