After months of hesitation, U.S. health officials now say that the Zika virus is indeed the cause of severe brain damage in the infants of some women who were infected with the virus during pregnancy.
A CDC review published online Wednesday in the New England Journal of Medicine describes evidence of what U.S. health officials now call a causal relationship between the virus and a severe form of microcephaly and intracranial calcifications.
The study marks a turning point in the current Zika outbreak, says Dr. Tom Frieden, chief of the CDC. "There's still a lot that we don't know, he says. "But there is no longer any doubt that Zika causes microcephaly."
A causal link between the bite of a mosquito and brain malformations is unprecedented, he says. "And it is because this was so unprecedented that we have until now waited to say that we have concluded that there is a causal link."
There was no single smoking gun, CDC officials say. Dr. Sonja Rasmussen, editor-in-chief of CDC's Morbidity and Mortality Weekly Report and an author on the report, says the conclusion came from looking systematically through the accumulating evidence.
The team used two approaches to confirm the link. The first method involved finding an overlap between a rare exposure and a rare defect. It was the same approach used years ago to confirm the effects of rubella on a pregnancy, and the same used to characterize fetal alcohol syndrome.
The second method looked at the timing of outbreaks in Brazil and French Polynesia and subsequent increases in birth defects. Researchers also looked at rare case reports of pregnant women who traveled to places with Zika virus transmission and subsequently gave birth to babies with microcephaly.
There were other clues. These babies have an unusual and particularly severe form of microcephaly. Plus, the virus has been found in the brain tissue of some babies with microcephaly who died.
Still, a lot of questions remain, the health officials say.
For example, it's unclear whether the baby's risk of brain damage is greater if the mother has symptoms of a viral infection while pregnant, compared with an infected woman who never experiences symptoms. And it's unclear how much that risk changes if a woman is infected early in pregnancy versus late in pregnancy.
Among the most pressing remaining questions, Rasmussen says, are these: "Does Zika cause defects other than those of the brain? Does Zika cause learning problems later in life? Are pregnancy losses, miscarriage, stillbirth among some women infected by Zika virus the result of the infection? And finally, are there other factors involved? For example, has another infection occurred at the same time as the Zika infection that might affect the risk of birth defects?"
Frieden says it could take years to get all those answers.