Typically, microcephaly occurs in .02 percent to .12 percent of all U.S. births. The prevalence of even more common congenital conditions, such as Down syndrome, is often less than 1 percent. By contrast, the study published in the New England Journal of Medicine found the estimated risk for microcephaly with Zika infections in the first trimester of pregnancy ranged from 1 percent to 13 percent.
The analysis is the first to quantify such risk in pregnant women infected during the current outbreak, which has seen the mosquito-borne virus spread to more than 40 countries and territories in the Americas and beyond. Recent testing showed the same strain is now on the African archipelago of Cape Verde.
"It is an appreciable risk," said Michael Johansson, a CDC biologist and lead author of the study. "We need to do whatever we can to help women avoid Zika virus infections during pregnancy."
The study comes just weeks before the start of summer and mosquito season across the United States. Federal and local public health officials, particularly in the South and Southwest, are highly concerned about many communities' ability to track and prevent spread of the virus.
The CDC and Harvard researchers found a strong association between the risk of microcephaly and infection during the first trimester, but "a negligible association in the second and third trimesters." They were only able to provide a range of risk because of the significant uncertainty about the overall rate of Zika infection in the population studied and the accuracy of the microcephaly cases reported.
Much more research needs to be done about the effects of Zika at all stages of pregnancy, Johansson said, and other studies are now tracking hundreds of Brazilian women and babies.
No other countries where Zika is being transmitted locally have suffered the same spike in microcephaly -- but that could change soon. "If the risk of infection and adverse outcomes is similar in the other geographic areas where Zika virus has since spread, many more cases of microcephaly and other adverse outcomes are likely to occur," the study warned.
It urged health care systems "to prepare for an increased burden of adverse pregnancy outcomes in the coming years."
The CDC is monitoring 279 pregnant women infected with Zika in the United States, while Brazil has recorded nearly 3,600 pregnant women with Zika since January. Since the outbreak began there last year, more than 1,400 cases of microcephaly and other fetal neurological disorders have been confirmed.
Last month, CDC scientists confirmed that the virus causes microcephaly and other severe fetal abnormalities during pregnancy. But researchers don't know the full magnitude of that risk. Some infected women have given birth to healthy babies.
An analysis of a 2013-2014 Zika outbreak in French Polynesia estimated the risk for microcephaly to be around 1 percent for pregnant women infected in their first trimester. But that estimate, from the single outbreak, was based on microcephaly cases identified after the fact.
Researchers in the current study analyzed the approximate number of suspected Zika cases reported in Bahia, Brazil from February 2015 to this past February and the number of reported and estimated microcephaly cases from January 2015 to February. They then calculated the estimated microcephaly risk by comparing estimated infection risk in each trimester to microcephaly incidence. The first trimester of pregnancy was linked with the highest risk, they found.
An earlier study with 88 women at one clinic in Rio de Janeiro found that 29 percent of women who had ultrasounds after testing positive for Zika had fetuses with "grave" complications extending beyond microcephaly to brain calcifications and vision problems. Some fetal problems had not been seen previously, including damage to central nervous systems and a lack of amniotic fluid by late pregnancy.
In the current study, researchers were trying to learn more about the effects of Zika infection in early pregnancy, when women might not even know they were expecting. Hospital or clinic-based studies only capture women with actual viral symptoms, Johansson said.
The CDC and Brazilian researchers are also conducting a case-control investigation involving infected women who have delivered healthy babies and who have given birth to babies with microcephaly. They want to better understand the relative risk the virus is playing in the condition there.