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Colombia confirms first cases of birth defects tied to ZikaWORLDby THE ASSOCIATED PRESS Posted Apr 14, 2016 11:19 am EDT BOGOTA – Colombia is confirming the first two cases of a rare birth defect associated with the spread of Zika. The National Institute of Health on Thursday said that of the 33 cases of microcephaly reported so far this year, two have been confirmed to have been caused by the mosquito-borne virus. The government agency said that one case was in Norte de Santander department near the border with Venezuela and the other in the lowland areas near the capital, Bogota. Zika has been related to a surge in babies born with small heads in Brazil. Despite the virus’ spread across Latin America almost no cases of microcephaly have been discovered elsewhere until now. The Centers for Disease Control on Wednesday confirmed that Zika is a cause of the birth defects. http://www.680news.com/2016/04/14/colombia-confirms-first-cases-of-birth-defects-tied-to-zika/

Colombia confirms two cases of microcephaly associated with Zika virusAPBogotáRelated newsMen zika should wait 6 months to have unprotected sexStudy in Honduras found 11 cases of Guillain-Barre syndrome associated with Zika The Colombian government on Thursday confirmed the first two cases in the country of microcephaly associated with zika. Deputy Health Minister, Fernando Ruiz, told a news conference in Bogota that the cases were reported in women in the departments of Cundinamarca, in the center of the country, and Norte de Santander, in the northeast and on the border with Venezuela . Still in study 15 other cases. (I) http://www.eluniverso.com/noticias/2016/04/14/nota/5523369/colombia-confirma-dos-casos-microcefalia-asociados-virus-zika?utm_source=twitterfeed&utm_medium=twitter

Colombia says two cases of microcephaly linked to Zika virusSource: Reuters - Thu, 14 Apr 2016 15:07 GMT Author: Reuters BOGOTA, April 14 (Reuters) - Colombia's health ministry said on Thursday it had confirmed two cases of the rare birth defect microcephaly are connected to the mosquito-borne Zika virus, after the disease was linked to more than a thousand confirmed cases of microcephaly in Brazil. According to the World Health Organization, there is a strong scientific consensus that Zika can cause microcephaly as well as Guillain-Barre syndrome, a rare neurological disorder that can result in paralysis, though conclusive proof may take months or years. U.S. health officials said on Wednesday that infection with the Zika virus during pregnancy causes microcephaly, a finding experts hope will refocus attention on prevention efforts. (Reporting by Julia Symmes Cobb; Editing by Chizu Nomiyama) http://news.trust.org/item/20160414151037-6vjsl

Map Update https://www.google.com/maps/d/u/0/edit?hl=en&hl=en&authuser=0&authuser=0&mid=zv94AJqgUct4.kT4qLMXp3SLU

Maryland Confirmed Zika Virus Infections (As of April 13, 2016) Travel-AssociatedLocally Acquired Vector-BorneTotal808 http://phpa.dhmh.maryland.gov/Pages/Zika.aspx

Maryland Confirmed Zika Virus Infections (As of April 13, 2016) Travel-AssociatedLocally Acquired Vector-BorneTotal808

Map Update https://www.google.com/maps/d/u/0/edit?hl=en&hl=en&authuser=0&authuser=0&mid=zv94AJqgUct4.kT4qLMXp3SLU

http://epi.publichealth.nc.gov/cd/diseases/zika.html At A Glance - Zika in the U.S. (as of Apr 13, 2016) North CarolinaTravel-associated Zika virus disease cases reported: 9Locally acquired vectorborne cases reported: 0

At A Glance - Zika in the U.S. (as of Apr 13, 2016) North CarolinaTravel-associated Zika virus disease cases reported: 9Locally acquired vectorborne cases reported: 0 U.S. StatesTravel-associated Zika virus disease cases reported: 346Locally acquired vectorborne cases reported: 0 U.S. TerritoriesTravel-associated cases reported: 3Locally acquired vectorborne cases reported: 351

Zika Virus Does Cause Birth DefectsScientists confirm what many suspected, but questions remain. John Tozzi jtozzApril 13, 2016 — 5:00 PM EDTShare on FacebookShare on Twitter Don't Miss Out — Follow Bloomberg OnFacebookTwitterInstagramYouTubeRecommendedWe Applied to Buy a $400,000 Ford GT. Here's What We LearnedU.S. Regulators Request Probes Into Leak of Banks' Living WillsIMF Warns of Possible ‘Spiral’ of Waning Growth, Escalating Debt Thiel: College as Corrupt as Church 500 Years Ago Share on FacebookShare on Twitter After months of mounting evidence, scientists are ready to say definitively that the mosquito-borne Zika virus spreading across the Americas is causing birth defects, a link that the head of the Centers for Disease Control called “unprecedented.” “There is no longer any doubt that Zika causes microcephaly,” CDC Director Tom Frieden declared Wednesday. A spike in microcephaly, when babies are born with abnormally small heads, raised the level of alarm about the disease in Brazil last year. “Never before in history has there been a situation where a bite from a mosquito could result in a devastating malformation.” QUICKTAKEZika VirusZika transmission has been reported in 33 countries and territories in the Americas since it was first detected in Brazil in 2015, according to the World Health Organization. Microcephaly and other birth defects have been linked to the virus in French Polynesia, Brazil, Colombia, Panama, and elsewhere. Zika Virus: What You Need to Know in Two MinutesFrieden said that “no single piece of evidence” proved that the virus causes birth defects. An accumulation of research conducted as the epidemic moved across the continent pointed to the CDC's conclusion, published in the New England Journal of Medicine. That still leaves a long list of urgent questions unanswered, and some may not be answered for years. Among them are what other birth defects might Zika cause? Does it cause developmental problems that aren’t evident at birth but may manifest years later? Are women at risk if they get the Zika virus but don't develop symptoms? Does Zika cause other neurological problems, such as the Guillain-Barré syndrome it’s been linked to? There’s a global public health effort under way to answer these and other questions. But the evidence may be conflicting and slow to point to concrete answers. For example, one analysis of a Zika outbreak in French Polynesia indicated that about 1 percent of women infected with Zika during pregnancy would give birth to children with microcephaly. Another study in Brazil indicated that 30 percent had some kind of abnormality detected in ultrasounds, said Sonja Rasmussen, director of the CDC’s division of public health information and dissemination. The cases of microcephaly caused by Zika appear to be unusually severe, Rasmussen said. And further evidence may indicate a link to other defects or disorders. “We do expect that that’s likely to be the tip of the iceberg,” Rasumussen said. The conclusion affirms the CDC’s earlier advice that pregnant women avoid traveling to areas where Zika is circulating. After evidence was discovered that men infected with the virus can spread it to sex partners, the agency also advised pregnant women to use condoms or abstain from sex. http://www.bloomberg.com/news/articles/2016-04-13/zika-virus-does-cause-birth-defects

CDC Concludes Zika Causes Microcephaly, Other Birth Defects"This study marks a turning point in the Zika outbreak," the CDC's director says U.S. health officials say there's no longer any doubt that the Zika virus causes severe birth defects. Centers for Disease Control and Prevention scientists say in a new study in the New England Journal of Medicine that the virus, which is spreading through much of the Americas, causes microcephaly and other fetal brain defects. Middle School Coach Allegedly Fired for Handing Out FruitEvidence had long pointed to a link between microcephaly, a condition in which babies are born with abnormally small heads, and the mosquito-borne virus. The CDC had not previously said if babies' microcephaly was a result of their mothers being infected with Zika during pregnancy. "This study marks a turning point in the Zika outbreak," CDC Director Tom Frieden said in a statement. "It is now clear that the virus causes microcephaly. We are also launching further studies to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain and other developmental problems." Zika Virus Spreads Across the Americas, May Cause Birth Defects CDC officials said their advice to pregnant women won't change. Pregnant women should avoid traveling to places where the Zika virus is spreading, mostly in Latin America and the Caribbean. Refresh this page for more on this breaking story. http://www.nbcnewyork.com/news/national-international/CDC-Concludes-Zika-Causes-Microcephaly-Other-Birth-Defects-375603241.html

CDC confirms Zika causes severe birth defectsTwitterFacebookLinkedInEmailPrintMARIO TAMA/GETTY IMAGES Nadja Cristina Gomes Bezerra, of Recife, Brazil, displays a photograph of her daughter, who was born with microcephaly. By HELEN BRANSWELL @HelenBranswell APRIL 13, 2016 The Centers for Disease Control and Prevention said Wednesday the time has come to drop the squishy language previously used to describe the Zika virus. It isn’t just suspected of causing birth defects; it does cause birth defects. Senior scientists involved in the agency’s Zika response argue in an articlerushed to print by the New England Journal of Medicine that the virus has met a test used to determine whether an exposure — to a disease agent like a virus or a chemical, for instance — causes birth defects in a developing fetus. The test is called the Shepard criteria, and it lays out seven factors that can be used to determine if an exposure causes birth defects. Zika currently meets four of the seven — and only three are needed to prove causality, the scientists said. ARTICLE CONTINUES AFTER ADVERTISEMENT Scientists at the CDC and the World Health Organization have been clear for weeks that they believed infection during pregnancy was leading in some instances to babies with severe microcephaly — smaller than normal heads — and signs of profound brain damage. But officially, they have avoided saying Zika infection “causes” brain-related birth defects, because in scientific terms there simply wasn’t enough evidence yet to say that definitively. READ MORE5 things the world has learned about Zika so farAt the end of March, however, the WHO took the plunge, saying in a weekly Zika update that “based on observational, cohort and case-control studies there is strong scientific consensus that Zika virus is a cause” of microcephaly and other neurological disorders. Wednesday’s article, however, is the first time scientists have laid out the argument for why Zika can be said to cause birth defects. The lead author of the paper, Dr. Sonja Rasmussen, said it was important to go through that process, both to record the claim in the scientific literature, but also to persuade the public to take the threat seriously. Rasmussen told STAT there continue to be those who doubt the link. CDC wants the public — especially pregnant women — to take the risk seriously, she said, and take the preventive steps it has recommended. “We do these things because we want to be sure that people take action on the recommendations that we make,” said Rasmussen, editor in chief of CDC’s Morbidity and Mortality Weekly Report and an expert in birth defects research. “We really want to do our very best to make sure that pregnant women hear the message that we’re giving them — that if you are thinking about traveling to one of these places where there is Zika virus transmission, please don’t. And if your partner has traveled to one of those places, to take precautions … to prevent sexual transmission.” Subscribe to our Zika updatesEMAIL ADDRESS The Obama administration has been pressing Congress to approve an emergency request for additional funding to research Zika and support a public health response to the virus. Republicans have refused to date to approve the White House’s request for $1.9 million in funding, insisting that money committed but not yet used in the Ebola response be used first. On Wednesday, there was a hint that Republicans may be getting ready to work toward providing additional money. The chairman of the House Appropriations Committee, Representative Hal Rogers of Kentucky, said during a committee hearing that his staff was working on an emergency funding bill that would provide more money in the current fiscal year, which ends in September. But he said his committee needs more information from the administration before it can produce a bill. The administration has already announced, in the meantime, it would divert $500 million from the Ebola fund to the Zika response. Dylan Scott in Washington contributed reporting. Helen Branswell can be reached at [email protected] Follow Helen on Twitter @HelenBranswell https://www.statnews.com/2016/04/13/zika-birth-defects-causes/

It’s confirmed. Zika virus causes microcephaly and other birth defects, CDC says 281 EMAILBY NSIKAN AKPAN April 13, 2016 at 5:00 PM EDT | Updated: Apr 13, 2016 at 5:53 PMCDC director: This study marks a turning point in the Zika outbreak. Photo by Paulo Whitaker/REUTERS Today, the Centers for Disease Control and Prevention definitively confirmed what may have seemed a forgone conclusion: Zika virus causes microcephaly and other neurological birth defects. “This study marks a turning point in the Zika outbreak. It is now clear that the virus causes microcephaly,” CDC director Tom Frieden said in a statement. “We’ve now confirmed what mounting evidence has suggested, affirming our early guidance to pregnant women and their partners to take steps to avoid Zika infection and to health care professionals who are talking to patients every day.” The health agency’s assessment is not based on a single piece of evidence, but rather months of careful evaluation and the growing number of reports of showing a biological connection between the brain disorders. A synopsis of those findings has been published in the New England Journal of Medicine. The researchers reached this conclusion by using Shepard’s criteria — an accepted set of seven rules used to identify causes of birth defects. One sticking point was the abundance of microcephaly observed in fetuses and newborns that had been exposed to the virus in the womb. Shepard’s criteria for proof of Zika-related birth defects in humans as applied to the relationship between Zika virus infection and microcephaly and other brain anomalies. Photo by Rasmussen SA et al., New England Journal of Medicine, (2016) Research into Zika virus has satisfied five of the seven criteria. The missing elements involve tests in animal models, which have not been developed, and the seventh criteria that only apply to chemical agents. For now, the CDC’s guidance for pregnant women remains the same. They recommend that pregnant women avoid travel to Zika-hit regions. Infected men, with or without symptoms, can pass Zika virus to sexual partners. So, the CDC recommends abstinence or condom usage for couples if a male partner has traveled to a Zika-impacted region. The Zika outbreak has afflicted 33 countries and territories in the Americas, according to the World Health Organization. Nsikan AkpanNsikan Akpan is the digital science producer for PBS NewsHour.http://www.pbs.org/newshour/rundown/its-confirmed-zika-virus-causes-microcephaly-and-other-birth-defects-cdc-says/

US health experts confirm that Zika causes birth defects6 minutes ago From the sectionUS & CanadaImage copyrightReutersImage captionBrazil has seen a growing number of cases of microcephaly in recent monthsZika virusZika outbreak: What you need to knowZika outbreak: Travel adviceMothers' fears amid Zika outbreakVideo How mums-to-be are tackling ZikaThe US Centers for Disease Control and Prevention (CDC) has confirmed that the Zika virus causes severe birth defects, including microcephaly. Thousands of babies were born in Brazil last year with microcephaly, a syndrome where children are born with unusually small heads. The defects coincided with a spike in Zika infections, leading experts to suspect the mosquito-borne virus. Growing research has now affirmed those experts' suspicions, the CDC said. "This study marks a turning point in the Zika outbreak. It is now clear that the virus causes microcephaly," said Dr Tom Frieden, the head of the CDC. More on the Zika crisis:Microcephaly: Why it is not the end of the world What you need to know Key questions answered about the virus and its spread Travel advice Countries affected and what you should do The mosquito behind spread of virus What we know about the insect Abortion dilemma Laws and practices in Catholic Latin America On Monday, US health officials warned the Zika outbreak could have more of an effect on the US and called for additional funding to combat the virus. "Everything we know about this virus seems to be scarier than we initially thought," said Dr Anne Schuchat of the CDC. There have been 346 confirmed cases of Zika in the continental United States, according to the CDC, all associated with travel. CDC officials said the findings do not change the agency's earlier guidance to pregnant women. Image copyrightAFPImage captionThe Zika virus can be transmitted via mosquitoThe CDC has discouraged pregnant women from travelling to places where the Zika virus is spreading, mostly in Latin America and the Caribbean. Dr Frieden said intensive research was under way to find out much more about the mosquito-borne virus and to develop a vaccine for it, although he warned that that could still be years away. This is the first time that mosquito bites have caused birth defects, Dr Frieden said. The virus can be transmitted by sexual contact as well. http://www.bbc.com/news/world-us-canada-36040881

CDC Confirms Link Between Zika Virus and Birth DefectsAgency finds enough evidence to conclude it can cause abnormalities in infants of women infected during pregnancy ENLARGECDC Director Tom Frieden said, ‘There is no longer any doubt that Zika causes microcephaly’—in which the head is small for gestational age and sex. PHOTO: ESTEFAN RADOVICZ/XINHUA/ZUMA PRESSBy BETSY MCKAYApril 13, 2016 5:01 p.m. ET2 COMMENTSThe U.S. Centers for Disease Control and Prevention said Wednesday that enough evidence has accumulated for it to conclude that the Zika virus can cause birth defects in the infants of women who are infected during pregnancy. In a paper published in the New England Journal of Medicine, the public health agency said several established criteria to determine a causal relationship have been met, including Zika infection in mothers whose babies developed microcephaly—in which the head is small for gestational age and sex—and other severe brain abnormalities. “There is no longer any doubt that Zika causes microcephaly,” CDC Director Tom Frieden said in a telephone briefing. Most public health officials and scientists have been operating on the assumption that Zika is the cause of a sharp rise in the number of babies born in Brazil over the past six months with these birth defects, as well as an increase in abnormalities in fetuses of pregnant women who have been exposed in other countries where Zika is circulating. Many also assume the virus is behind at least two types of neurological complications in adults, including Guillain-Barre syndrome. The CDC said it is still studying whether Zika causes Guillain-Barre. Zika has been found circulating in 40 countries and territories, according to the CDC. The U.S. Centers for Disease Control and Prevention believes the zika virus has reached 30 states, and urges travelers and expectant mothers to be vigilant. Photo: CDCREAD MOREFollow WSJ Science on Twitter,Facebook and Instagram Couples Should Delay Pregnancy Plans in Event of Zika Symptoms, CDC Says (March 25)Evidence Grows Linking Zika Virus to Birth Defect, Paralysis (March 4)New Study Links Zika Virus to Microcephaly (Feb. 10)Five Things to Know About Zika Virus(Feb. 1)The World Health Organization said in its most recent weekly situation report that “there is scientific consensus that Zika virus is a cause of microcephaly and Guillain-Barre syndrome.” The CDC said its declaration won’t change its current warnings for pregnant women regarding travel to countries where Zika is circulating, or its guidance for preventing the spread of Zika through sexual transmission. But the agency said it hopes that declaring Zika a cause of birth defects in children will help to intensify efforts to raise public awareness of the risks of Zika infection, control the mosquitoes that spread the virus and develop a vaccine against it. A number of vaccine candidates are in development, as are new methods to control or eliminate the Aedes aegypti and Aedes albopictus mosquitoes that spread Zika and other dangerous viruses such as dengue and chikungunya. Many critical questions remain and could take years to answer, Dr. Frieden said. They include what types of and how many birth defects are caused by Zika cause and how common are the defects. One recent study estimated that a woman infected with Zika during her first trimester of pregnancy faces a 1% risk that her baby will develop microcephaly. Another study found abnormalities in 29% of the fetuses of a group of pregnant women who had had the virus. The CDC said it has other studies under way to answer some of these questions. The agency said it based its conclusion on several pieces of evidence. First, in cases the CDC reviewed, exposure to Zika occurred during a critical time in pregnancy: babies with birth defects were born to mothers who were infected with Zika in the first or early second trimester. Second, there was a specific pattern of birth defects, including severe microcephaly and brain lesions, the CDC said. Third, the link between Zika and birth defects involves a rare exposure and a rare birth defect, the CDC said. Infants of pregnant women who have traveled to areas where Zika is circulating have developed microcephaly, a rare condition that normally affects only 6 in 10,000 newborns. Write to Betsy McKay at [email protected] http://www.wsj.com/articles/cdc-confirms-link-between-zika-virus-and-babies-birth-defects-1460581319

U.S. health officials declare Zika cause of severe birth defectsSource: Reuters - Wed, 13 Apr 2016 21:40 GMT Author: Reuters (Repeats with no change to text or headline) April 13 (Reuters) - U.S. health officials have concluded that infection with the Zika virus in pregnant women is a cause of the birth defect microcephaly and other severe brain abnormalities in babies. "It is now clear, the CDC has concluded, that Zika virus does cause microcephaly," Tom Frieden, director of the U.S. Centers for Disease Control and Prevention, said in a conference call with reporters on Wednesday. "There isn't any doubt that Zika causes microcephaly." U.S. and world health officials have been saying for some time that mounting scientific evidence points to the mosquito-born virus as the likely cause of the alarming rise in microcephaly in Zika-hit areas of Brazil. It had not been declared as the definitive cause until now. Never before in history has a bite from a mosquito been seen as the cause of birth defects, Frieden said. (Reporting by Bill Berkrot; Editing by Bernard Orr) http://news.trust.org/item/20160413210451-clmgz

Zika Virus Confirmed as Cause of Rare Microcephaly Birth Defect, CDC SaysBy GILLIAN MOHNEYJULIE BARZILAY Apr 13, 2016, 5:00 PM ET Paulo Whitaker/ReutersWATCH Zika Virus May Cause Paralysis485SHARES EmailThe Zika virus has been confirmed to cause a rare birth defect called microcephaly and other severe problems of the brain, according to a new report from the U.S. Centers for Disease Control and Prevention. Health officials across the globe have suspected for months a link between the virus and the birth defect, characterized by an abnormally small head and brain. Officials said today the evidence is overwhelming that exposure to virus in utero causes the birth defect. CDC Director Dr. Tom Frieden called the news a "turning point" in a fight against the virus that has continued to spread throughout the Americas. “It is now clear that the virus causes microcephaly,” Frieden said. “We’ve now confirmed what mounting evidence has suggested, affirming our early guidance to pregnant women and their partners to take steps to avoid Zika infection and to health care professionals who are talking to patients every day. We are working to do everything possible to protect the American public.” El Salvador Advises Women to Avoid Pregnancy for 2 Years Due to Zika Virus Outbreak Mosquito-Born Zika Virus Linked to Birth Defects Experts Explain Key to Stopping Zika Virus From Spreading The CDC is launching new studies to see if other birth defects are connected to the mosquito-borne virus, Frieden said, calling the link "unprecedented" and pointing out there has never been a mosquito-borne virus that causes birth defects in humans. An increase of the birth defect was first detected in Brazil last September months after a large outbreak of the Zika virus. "We believe microcephaly will be a part of a range of birth defects that may affect women infected at a particular time or at any time during pregnancy," Frieden told reporters. The findings were published today in the New England Journal of Medicine by CDC researchers who did a thorough review of the available scientific evidence linking the Zika virus and the birth defect. Dr. Sonja Rasmussen, lead author and director for the Study Division of Public Health Information and Dissemination at the CDC, told reporters today that scientists found a consistent pattern of defects in infants exposed to the virus in utero. Additionally, she said the virus had been found in brain tissue from deceased infants with microcephaly. Despite the advances that researchers have made in recent months, Rasmussen said “many questions remain,” including how often birth defects occur in fetuses that are exposed to the virus and if a pregnant woman is more at risk during specific stages of pregnancy. "Not all babies born to mothers who are infected with Zika virus during pregnancy will have problems," Rasmussen said. "We need to learn to answer this question -- if a woman is infected during pregnancy, how often will her fetus have birth defects or other problems?" The CDC is also investigating if the virus is linked to an increased likelihood of developingGuillain-Barre syndrome, an immunological reaction that can result in temporarily paralysis in adults. The CDC is not currently changing its recommendations regarding pregnant women or women who may become pregnant. Currently, the CDC advises pregnant women to avoid areas where Zika virus is being transmitted from mosquitoes to people. The agency is also advising men who travel to an area with active Zika transmission and who have a pregnant partner to abstain from sexual activity or use barrier contraception for the duration of the pregnancy. Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical School, said the study is a culmination of months of work and shows the threat to public health. "It brings together the various lines of evidence that in the end provide a very convincing conclusion that the outbreak of microcephaly that we’re seeing Brazil ... is indeed associated with Zika virus, causally," Schaffner said. http://abcnews.go.com/Health/zika-virus-confirmed-rare-microcephaly-birth-defect-cdc/story?id=38370364

Zika Virus Confirmed as Cause of Rare Microcephaly Birth Defect, CDC SaysBy GILLIAN MOHNEYJULIE BARZILAY Apr 13, 2016, 5:00 PM ET Paulo Whitaker/ReutersWATCH Zika Virus May Cause Paralysis485SHARES EmailThe Zika virus has been confirmed to cause a rare birth defect called microcephaly and other severe problems of the brain, according to a new report from the U.S. Centers for Disease Control and Prevention. Health officials across the globe have suspected for months a link between the virus and the birth defect, characterized by an abnormally small head and brain. Officials said today the evidence is overwhelming that exposure to virus in utero causes the birth defect. CDC Director Dr. Tom Frieden called the news a "turning point" in a fight against the virus that has continued to spread throughout the Americas. “It is now clear that the virus causes microcephaly,” Frieden said. “We’ve now confirmed what mounting evidence has suggested, affirming our early guidance to pregnant women and their partners to take steps to avoid Zika infection and to health care professionals who are talking to patients every day. We are working to do everything possible to protect the American public.” El Salvador Advises Women to Avoid Pregnancy for 2 Years Due to Zika Virus Outbreak Mosquito-Born Zika Virus Linked to Birth Defects Experts Explain Key to Stopping Zika Virus From Spreading The CDC is launching new studies to see if other birth defects are connected to the mosquito-borne virus, Frieden said, calling the link "unprecedented" and pointing out there has never been a mosquito-borne virus that causes birth defects in humans. An increase of the birth defect was first detected in Brazil last September months after a large outbreak of the Zika virus. "We believe microcephaly will be a part of a range of birth defects that may affect women infected at a particular time or at any time during pregnancy," Frieden told reporters. The findings were published today in the New England Journal of Medicine by CDC researchers who did a thorough review of the available scientific evidence linking the Zika virus and the birth defect. Dr. Sonja Rasmussen, lead author and director for the Study Division of Public Health Information and Dissemination at the CDC, told reporters today that scientists found a consistent pattern of defects in infants exposed to the virus in utero. Additionally, she said the virus had been found in brain tissue from deceased infants with microcephaly. Despite the advances that researchers have made in recent months, Rasmussen said “many questions remain,” including how often birth defects occur in fetuses that are exposed to the virus and if a pregnant woman is more at risk during specific stages of pregnancy. "Not all babies born to mothers who are infected with Zika virus during pregnancy will have problems," Rasmussen said. "We need to learn to answer this question -- if a woman is infected during pregnancy, how often will her fetus have birth defects or other problems?" The CDC is also investigating if the virus is linked to an increased likelihood of developingGuillain-Barre syndrome, an immunological reaction that can result in temporarily paralysis in adults. The CDC is not currently changing its recommendations regarding pregnant women or women who may become pregnant. Currently, the CDC advises pregnant women to avoid areas where Zika virus is being transmitted from mosquitoes to people. The agency is also advising men who travel to an area with active Zika transmission and who have a pregnant partner to abstain from sexual activity or use barrier contraception for the duration of the pregnancy. Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical School, said the study is a culmination of months of work and shows the threat to public health. "It brings together the various lines of evidence that in the end provide a very convincing conclusion that the outbreak of microcephaly that we’re seeing Brazil ... is indeed associated with Zika virus, causally," Schaffner said. http://abcnews.go.com/Health/zika-virus-confirmed-rare-microcephaly-birth-defect-cdc/story?id=38370364

Statements & ReleasesUNITED STATES VIRGIN ISLANDS DEPARTMENT OF HEALTH _________________________________________________________FOR IMMEDIATE RELEASEApril 12, 2016 Department of Health Confirms a Case of Zika in a Pregnant Woman As reported in today’s Zika surveillance report, the Virgin Islands Department of Health confirmed one additional case of Zika on St. Croix, bringing the total to 14 cases. This is not unexpected, and the Department of Health expects that there will continue to be more positive cases in the future. The Virgin Islands Department of Health is confirming our first Zika case in a pregnant woman residing on the island of St. Croix with no travel history reported.. The patient was 34 weeks pregnant when they were tested for Zika. She has since delivered a healthy baby with normal head circumference, showing no signs of microcephaly. The Department of Health will continue to monitor the mother and child’s progress over the next several weeks. “Both Zika and dengue are potentially dangerous for pregnant women. Zika may be associated with birth defects (microcephaly), and pregnant women are at higher risk of severe complications from dengue fever. Any pregnant woman experiencing symptoms should see their healthcare provider for evaluation. They should also avoid ibuprofen, aspirin, or aspirin-containing drugs until dengue can be ruled out to reduce the risk of hemorrhage. Pregnant women who have a fever should be treated with acetaminophen (Paracetamol or Tylenol®.) as it is not associated with increased risk for hemorrhagic complications,” stated Commissioner Nominee Michelle S. Davis, PhD. Zika has been confirmed to be transmitted sexually, and the CDC now recommends that pregnant women in areas with active Zika transmission, such as in the USVI, should either use condoms the right way every time they have sex or they should not have sex during the pregnancy. Sexual transmission of dengue has not been confirmed, but it is theoretically possible. Since both dengue and Zika cases are currently present in the Territory, all people, but especially pregnant women and their sexual partners, should enhance their efforts to reduce their risk of becoming infected: Use Environmental Protection Agency (EPA)-registered insect repellents containing one of the following:DEET, such as in, Off!, Cutter, Sawyer, and UltrathonPicaridin, such as in Cutter Advanced, Skin So Soft Bug Guard PlusOil of lemon eucalyptus, such as in Repel and Off! BotanicalsIR3535, such as in Skin So Soft Bug Guard Plus Expedition and SkinSmart.Wear long-sleeved shirts and long pantsStay in places with air conditioning or that use window and door screens to keep mosquitoes outsideSleep under a mosquito bed net Treat clothing and gear with permethrin or purchase permethrin-treated itemsCheck around your home and eliminate any standing water, where mosquitoes can breed o Empty and scrub, turn over, cover, or throw out items that hold water, such as tires, buckets, planters, toys, pools, birdbaths, flowerpots, or trash containers. Check inside and outside your homeTightly cover water storage containers (buckets, cisterns, rain barrels) so that mosquitoes cannot get inside to lay eggsFor containers without lids, use wire mesh with holes smaller than an adult mosquito.For more information on what you can do to help control mosquitoes on your property: http://www.cdc.gov/zika/pdfs/control_mosquitoes_chikv_denv_zika.pdfLastly, since people infected with Zika or dengue can be bitten by uninfected mosquitos, that then can become infected and go on to infect other people (including pregnant women), they should follow the recommendations listed above during the first few days of illness to reduce the risk of spreading the disease to others. The Department of Health is continuing to enhance surveillance and lab testing capacity, partner with local healthcare providers, and educate the community about Zika and dengue through public outreach, media and social media. Additionally the Department of Health is offering free inspections at homes with pregnant women. The inspection will look for mosquito breeding containers around the home and presence of mosquito larvae. If the home occupant would like the inspection team can assist with source reduction and treating any mosquito larvae found. For any households with a pregnant woman that would like this free service OR would like additional information about this service, please call the Department of Health Emergency Operations Center at (340) 712-6205. For local information about Zika virus, call the Department of Health Emergency Operations Center at (340) 712-6205. For more general information about the Zika virus call toll free: 1-800-CDC-INFO. If you have symptoms of Zika (fever, rash, joint pain or red eyes) or are pregnant, please see your local Primary Care Provider. The Department of Health has partnered with many clinics so that testing for Zika virus is available free of charge. The Department of Health continues to provide testing for the Zika virus as well. Additional information DOH's Special section on Zika Centers for Disease Control and Prevention: General information about Zika virus and diseaseZika virus information for clinicianProtection against mosquitoesTravel notices related to Zika virusInformation about Zika virus for travelers and travel health providersPan American Health Organization (PAHO) Instructions for Reporting Suspected Zika Cases to USVI Department of Health Dengue, Chikungunya and Zika Reporting Form http://www.healthvi.org/news/press-releases/2016/04/doh-confirms-a-new-case-of-zika.html

REFERENCES 1 Kleber de Oliveira W, Cortez-Escalante J, De Oliveira WT, et al. Increase in reported prevalence of microcephaly in infants born to women living in areas with confirmed Zika virus transmission during the first trimester of pregnancy — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65:242-247 CrossRef | Medline 2 Cauchemez S, Besnard M, Bompard P, et al. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet2016 March 15 (Epub ahead of print) Medline 3 Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med2016;374:1552-1563 4 O’Leary DR, Kuhn S, Kniss KL, et al. Birth outcomes following West Nile Virus infection of pregnant women in the United States: 2003-2004. Pediatrics 2006;117:e537-45 CrossRef | Web of Science | Medline 5 Duffy MR, Chen T-H, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009;360:2536-2543 Free Full Text | Web of Science | Medline 6 Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika virus epidemiology and recent epidemics. Med Mal Infect 2014;44:302-307 CrossRef | Web of Science | Medline 7 Chang C, Ortiz K, Ansari A, Gershwin ME. The Zika outbreak of the 21st century. J Autoimmun 2016;68:1-13 CrossRef | Medline 8 Associated Press-NORC Center for Public Affairs Research. The Zika virus: Americans’ awareness and opinions of the U.S. response. April 2016 (http://www.apnorc.org/PDFs/Zika/2016-04%20Zika%20Virus%20Issue%20Brief%20DTPB_v1r5.pdf). 9 Shepard TH. “Proof” of human teratogenicity. Teratology 1994;50:97-98 CrossRef | Medline 10 Carey JC, Martinez L, Balken E, Leen-Mitchell M, Robertson J. Determination of human teratogenicity by the astute clinician method: review of illustrative agents and a proposal of guidelines. Birth Defects Res A Clin Mol Teratol 2009;85:63-68 CrossRef | Web of Science | Medline 11 Webster WS. Teratogen update: congenital rubella. Teratology 1998;58:13-23 CrossRef | Medline 12 Jones KL, Smith DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet1973;302:999-1001 CrossRef | Medline 13 Lammer EJ, Sever LE, Oakley GP Jr.. Teratogen update: valproic acid. Teratology1987;35:465-473 CrossRef | Medline 14 Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika virus infection in pregnant women in Rio de Janeiro — preliminary report. N Engl J Med. DOI: 10.1056/NEJMoa1602412 Free Full Text | Medline 15 Calvet G, Aguiar RS, Melo AS, et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis2016 February 17 (Epub ahead of print) Medline 16 Driggers RW, Ho CY, Korhonen EM, et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med. DOI: 10.1056/NEJMoa1601824 Free Full Text | Medline 17 Martines RB, Bhatnagar J, Keating MK, et al. Notes from the field: evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65:159-160 CrossRef | Web of Science | Medline 18 Meaney-Delman D, Hills SL, Williams C, et al. Zika virus infection among U.S. pregnant travelers — August 2015–February 2016. MMWR Morb Mortal Wkly Rep 2016;65:211-214 CrossRef | Web of Science | Medline 19 Mlakar J, Korva M, Tul N, et al. Zika virus associated with microcephaly. N Engl J Med2016;374:951-958 Free Full Text | Web of Science | Medline 20 Schuler-Faccini L, Ribeiro EM, Feitosa IM, et al. Possible association between Zika virus infection and microcephaly — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65:59-62 CrossRef | Web of Science | Medline 21 Ventura CV, Maia M, Bravo-Filho V, Góis AL, Belfort R Jr.. Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet 2016;387:228-228 CrossRef | Web of Science | Medline 22 Miranda-Filho Dde B, Martelli CM, Ximenes RA, et al. Initial description of the presumed congenital Zika syndrome. Am J Public Health 2016;106:598-600 CrossRef | Medline 23 Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 2016;47:6-7 CrossRef | Web of Science | Medline 24 Corona-Rivera JR, Corona-Rivera E, Romero-Velarde E, Hernández-Rocha J, Bobadilla-Morales L, Corona-Rivera A. Report and review of the fetal brain disruption sequence. Eur J Pediatr 2001;160:664-667 CrossRef | Web of Science | Medline 25 National Birth Defects Prevention Network. Major birth defects data from population-based birth defects surveillance programs in the United States, 2006-2010. August 2013 (http://www.nbdpn.org/docs/DataDirectory2013_NBDPN_AR.pdf). 26 Bale JF Jr.. Fetal infections and brain development. Clin Perinatol 2009;36:639-653 CrossRef | Web of Science | Medline 27 Dick GW. Zika virus. II. Pathogenicity and physical properties. Trans R Soc Trop Med Hyg1952;46:521-534 CrossRef | Web of Science | Medline 28 Bell TM, Field EJ, Narang HK. Zika virus infection of the central nervous system of mice.Arch Gesamte Virusforsch 1971;35:183-193 CrossRef | Medline 29 Tang H, Hammack C, Ogden SC, et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell2016 March 4 (Epub ahead of print) 30 Public Affairs Committee of the Teratology Society. Causation in teratology-related litigation. Birth Defects Res A Clin Mol Teratol 2005;73:421-423 CrossRef | Web of Science | Medline 31 Teixeira MG, da Conceição N Costa M, de Oliveira WK, Nunes ML, Rodrigues LC. The epidemic of Zika virus-related microcephaly in Brazil: detection, control, etiology, and future scenarios. Am J Public Health 2016;106:601-605 CrossRef | Medline 32 Reefhuis J, Gilboa SM, Johansson MA, et al. Projecting month of birth for at-risk infants after Zika virus disease outbreaks. Emerg Infect Dis (in press). 33 Mitchell AA. Proton-pump inhibitors and birth defects — some reassurance, but more needed. N Engl J Med 2010;363:2161-2163 Full Text | Web of Science | Medline 34 Costa F, Sarno M, Khouri R, et al. Emergence of congenital Zika syndrome: viewpoint from the front lines. Ann Intern Med2016 February 24 (Epub ahead of print) Medline 35 Chan JF, Choi GK, Yip CC, Cheng VC, Yuen KY. Zika fever and congenital Zika syndrome: an unexpected emerging arboviral disease. J Infect2016 March 3 (Epub ahead of print) 36 Abuelo D. Microcephaly syndromes. Semin Pediatr Neurol 2007;14:118-127 CrossRef | Medline 37 Byrd AL, Segre JA. Infectious disease: adapting Koch’s postulates. Science 2016;351:224-226 CrossRef | Web of Science | Medline 38 Fredricks DN, Relman DA. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin Microbiol Rev 1996;9:18-33 Web of Science | Medline 39 Williams JV. Déjà vu all over again: Koch’s postulates and virology in the 21st century. J Infect Dis 2010;201:1611-1614 CrossRef | Web of Science | Medline 40 Hill AB. The environment and disease: association or causation? Proc R Soc Med1965;58:295-300 Medline 41 Frank C, Faber M, Stark K. Causal or not: applying the Bradford Hill aspects of evidence to the association between Zika virus and microcephaly. EMBO Mol Med2016 March 14 (Epub ahead of print) 42 Instituto Nacional de Salud. Boletin Epidemiologico Semanal. April 2016 (http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Boletín%20epidemiológico%20semana%2012.pdf). 43 Hubálek Z, Rudolf I, Nowotny N. Arborviruses pathogenic for domestic and wild animals.Adv Virus Res 2014;89:201-275 CrossRef | Web of Science | Medline 44 Palacios R, Poland GA, Kalil J. Another emerging arbovirus, another emerging vaccine: targeting Zika virus. Vaccine2016 March 23 (Epub ahead of print) Medline

ASSESSMENT OF CRITERIAThus, on the basis of a review of the available evidence, using both criteria that are specific for the evaluation of potential teratogens9 and the Bradford Hill criteria40 as frameworks, we suggest that sufficient evidence has accumulated to infer a causal relationship between prenatal Zika virus infection and microcephaly and other severe brain anomalies. Also supportive of a causal relationship is the absence of an alternative explanation; despite the extensive consideration of possible causes, researchers have been unable to identify alternative hypotheses that could explain the increase in cases of microcephaly that were observed first in Brazil and then retrospectively in French Polynesia, and now in preliminary reports that are being investigated in Colombia.1,2,42 Moving from a hypothesis that Zika virus is linked to certain adverse outcomes to a statement that Zika virus is a cause of certain adverse outcomes allows for direct communications regarding risk, both in clinical care settings and in public health guidance, and an intensified focus on prevention efforts, such as the implementation of vector control, the identification of improved diagnostic methods, and the development of a Zika virus vaccine.44 In addition, after recognizing a causal relationship between Zika virus infection and adverse pregnancy and birth outcomes, we can focus research efforts on other critical issues: First, understanding the full spectrum of defects caused by congenital Zika virus infection; if Zika virus is similar to other teratogens, an expansion of the phenotype would be expected (e.g., with the congenital rubella syndrome, the phenotype was expanded from cataracts to include other findings such as hearing loss, congenital heart defects, and microcephaly).11 Second, quantifying the relative and absolute risks among infants who are born to women who were infected at different times during pregnancy. Third, identifying factors that modify the risk of an adverse pregnancy or birth outcome (e.g., coinfection with another virus, preexisting immune response to another flavivirus, genetic background of the mother or fetus, and severity of infection). Addressing these issues will improve our efforts to minimize the burden of the effects of Zika virus infection during pregnancy. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. This article was published on April 13, 2016, at NEJM.org. SOURCE INFORMATIONFrom the Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services (S.A.R.), Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (D.J.J.), and Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities (M.A.H.), Centers for Disease Control and Prevention, Atlanta; and the Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO (L.R.P.). Address reprint requests to Dr. Rasmussen at the Centers for Disease Control and Prevention, 1600 Clifton Rd., MS E-33, Atlanta, GA 30329, or at [email protected].

OTHER CRITERIAOther criteria can also be used to assess this relationship. Koch’s postulates, developed in the late 19th century, are often cited as necessary to show causation in infectious disease; however, many authors have noted the need for Koch’s postulates to be updated to accommodate modern technologies.37-39 The Bradford Hill criteria40 provide another framework to assess causation; Frank et al. recently used these criteria to assess the relationship between prenatal Zika virus infection and microcephaly and concluded that additional information was needed to assume that the relationship was causal.41 However, several key pieces of evidence have become available since they performed their analysis, including two epidemiologic studies,2,14 a study of the effects of Zika virus on neural progenitor cells,29 and a case report of a fetus with brain anomalies and decreasing head size from whose brain live Zika virus was isolated.16 On the basis of our update of their analysis, which incorporates newly available evidence (Table 2TABLE 2Bradford Hill Criteria for Evidence of Causation as Applied to the Relationship between Zika Virus Infection and Microcephaly and Other Brain Anomalies), nearly all the relevant criteria have been met, with the exception of the presence of experimental evidence. However, Hill emphasizes that meeting all nine criteria is not necessary40; instead, the criteria should serve as a framework to assess when the most likely interpretation of a relationship is causation.

SHEPARD’S CRITERIAIn 1994, Thomas Shepard, a pioneer in the field of teratology, proposed a set of seven criteria for “proof” of human teratogenicity (Table 1TABLE 1Shepard’s Criteria for Proof of Teratogenicity in Humans as Applied to the Relationship between Zika Virus Infection and Microcephaly and Other Brain Anomalies.) that incorporated both approaches.9These criteria were an amalgamation of criteria developed by other teratologists and guided by methods that were used to identify previous teratogens. These criteria have been used to guide discussions about causation in teratology-related litigation30 and to assess other potential teratogens.10 We used Shepard’s criteria9 as a framework to evaluate whether the currently available evidence supports the hypothesis that prenatal Zika virus infection is a cause of microcephaly and other brain anomalies (Table 1). According to these criteria, causality is established when either criteria 1, 3, and 4 (rare exposure–rare defect approach) or criteria 1, 2, and 3 (epidemiologic approach) are fulfilled. The first criterion states that a proven exposure to an agent must occur at a critical time during prenatal development. The severe microcephaly and other brain anomalies that have been observed in many infants are consistent with an infection occurring in the first or early second trimester of pregnancy. Several case reports and studies have shown that women who had fetuses or infants with congenital brain anomalies that were believed, on the basis of the mother’s symptoms or laboratory confirmation, to be due to Zika virus infection were infected in the first or early second trimester of pregnancy, as determined either according to the timing of the symptoms or according to the timing of travel to an area where Zika virus is endemic.14-20 An analysis of the timing of laboratory-confirmed Zika virus transmission in certain states in Brazil and of the increase in the cases of microcephaly identified the first trimester as the critical time period for infection.1 Zika virus infections that occur later in pregnancy have been associated with poor intrauterine growth, fetal death, or in some pregnancies, defects on prenatal imaging that have not yet been confirmed postnatally because the pregnancies are ongoing.14 We conclude that Shepard’s first criterion has been met. Shepard’s second criterion requires that two epidemiologic studies of high quality support the association. Although ecologic data do not necessarily qualify as an epidemiologic study, data from Brazil regarding the temporal and geographic association between Zika virus infection and the later appearance of infants with congenital microcephaly are compelling.1,31,32 Two epidemiologic studies also provide support.2,14 In a study conducted during the outbreak in Brazil, 88 pregnant women who had had an onset of rash in the previous 5 days were tested for Zika virus RNA. Among the 72 women who had positive tests, 42 underwent prenatal ultrasonography, and fetal abnormalities were observed in 12 (29%); none of the 16 women with negative tests had fetal abnormalities. The abnormalities that were observed on ultrasonography varied widely, and some findings lacked postnatal confirmation because the pregnancies were ongoing.14 A retrospective analysis after the 2013–2014 outbreak of Zika virus disease in French Polynesia identified eight cases of microcephaly; the authors used serologic and statistical data and mathematical modeling to estimate that 1% of the fetuses and neonates who were born to mothers who had been infected with Zika virus in the first trimester had microcephaly2 — a prevalence that was approximately 50 times as high as the estimated baseline prevalence. However, this estimate was based on small numbers, confidence intervals were wide, and the risk of other adverse outcomes (e.g., other brain anomalies) was not assessed.2 Although these studies provide important evidence in support of a causal relationship between Zika virus and microcephaly and other brain anomalies, both have limitations as noted by their authors, such as a lack of control for confounding factors and relatively small numbers of cases, and therefore they do not meet the stringent criteria set by Shepard. Thus, we conclude that Shepard’s second criterion has not yet been satisfied. The third criterion, careful delineation of clinical cases with the finding of a specific defect or syndrome, appears to be met. Previous teratogens have caused specific birth defects or syndromes rather than a broad range of birth defects.33 Many fetuses and infants with presumed congenital Zika virus infection have had a typical pattern, including severe microcephaly, intracranial calcifications, and other brain anomalies, sometimes accompanied by eye findings, redundant scalp skin, arthrogryposis, and clubfoot15,20-23; such findings have led authors to use the term “congenital Zika syndrome.”22,34,35 On the basis of clinical details from a limited number of cases, some infants with presumed congenital Zika virus infection have had features that were consistent with fetal brain disruption sequence,24 a phenotype involving the brain that is characterized by severe microcephaly, overlapping cranial sutures, prominent occipital bone, redundant scalp skin, and considerable neurologic impairment.20,22 For example, 11 of 35 infants (31%) with microcephaly whose cases were reported to a Brazil Ministry of Health registry had excessive and redundant scalp skin,20 a finding that is not typically seen in other forms of microcephaly.36 These findings suggest an interruption of cerebral growth, but not in that of the scalp skin, after an injury (e.g., viral infection, hyperthermia, or vascular disruption) that occurred after the initial formation of brain structures, followed by partial collapse of the skull. The fetal brain disruption sequence is rare; only 20 cases were identified in a literature review in 2001.24 Shepard’s fourth criterion refers to the association between a rare exposure and a rare defect; we conclude that this criterion also has been met. The concept behind this criterion is that a rare defect occurring after a rare exposure during pregnancy implies causation because of the unlikelihood of the two rare events occurring together.10 Microcephaly is a rare defect that is estimated to occur in 6 infants per 10,000 liveborn infants in the United States.25 Zika virus would not be a rare exposure among women living in Brazil during the Zika virus outbreak. However, reports of adverse birth outcomes among travelers who spent only a limited time period in an area where there is active Zika virus transmission are consistent with Zika virus being a rare exposure.16,18,19 A recent report is illustrative: a pregnant woman traveled for 7 days to Mexico, Guatemala, and Belize during her 11th week of gestation and had a positive test for Zika virus immunoglobulin M (IgM) antibodies 4 weeks later. On fetal ultrasonography and magnetic resonance imaging performed at 19 to 20 weeks of gestation, severe brain anomalies were diagnosed in the fetus, and the pregnancy was terminated at 21 weeks of gestation. Microcephaly was not present at the time of pregnancy termination, but the head circumference had decreased from the 47th percentile at 16 weeks of gestation to the 24th percentile at 20 weeks of gestation (a finding that is consistent with the timing of diminishing head sizes in previous cases),14 which suggests that microcephaly would have developed in the fetus had the pregnancy continued.16 In this woman, Zika virus would be considered a rare exposure, and her fetus had a rare outcome. The last three criteria are helpful if they are present, but they are not considered to be essential. The fifth criterion, the need for an animal model that shows teratogenicity, has not been met. Although animal models have shown that Zika virus is neurotropic,27,28 no studies that tested for teratogenicity in an animal model have been published, although studies are under way. The sixth criterion, that the association should make biologic sense, is clearly met here. Other viral infections have had similar effects (microcephaly and eye problems).24,26 In addition, pathologic evidence supports this association: Zika virus RNA has been seen in damaged mononuclear cells (presumably glial cells and neurons) in the brains of newborns with microcephaly,17 and the virus appears to be neurotropic.17,19 Live Zika virus has been cultured from the brain of a fetus with severe brain anomalies after maternal infection at 11 weeks of gestation.16 Furthermore, Zika virus efficiently infects neural progenitor cells and produces cell death and abnormal growth, thus providing a possible mechanism for microcephaly.29 The seventh criterion, proof in an experimental system that the agent acts in an unaltered state, is aimed at medications or chemical exposures and does not apply to infectious agents. Thus, given Shepard’s criteria as a framework, criteria 1, 3, and 4 have been satisfied — evidence that is considered sufficient to identify an agent as a teratogen.

POTENTIAL RELATIONSHIP BETWEEN ZIKA VIRUS INFECTION AND BIRTH DEFECTSSince the identification of the Zika virus in Brazil in early 2015, the virus has spread rapidly throughout the Americas (www.cdc.gov/zika/geo/active-countries.html). An increase in the number of infants with microcephaly in Brazil was first noted in September 2015, after the recognition of Zika virus transmission in the country earlier in the year1; this was followed by the recognition of a similar increase in French Polynesia after an outbreak there in 2013 and 2014.2 Despite accumulating evidence that supports the link between Zika virus infection and microcephaly, most experts have taken care not to state that Zika virus infection is causally related to these adverse outcomes.3 This cautious approach toward ascribing Zika virus as a cause of birth defects is not surprising, given that the last time an infectious pathogen (rubella virus) caused an epidemic of congenital defects was more than 50 years ago, no flavivirus has ever been shown definitively to cause birth defects in humans,4 and no reports of adverse pregnancy or birth outcomes were noted during previous outbreaks of Zika virus disease in the Pacific Islands.5,6 On the basis of the available evidence, the public health response to the outbreak of Zika virus disease has moved forward, with the distribution of health messages about the importance of mosquito-bite prevention, recommendations by public health authorities in some of the most severely affected countries to delay pregnancy, and advisories that pregnant women avoid travel to areas with active Zika virus transmission.7 However, communications regarding Zika virus have been challenging: a recent survey showed low levels of knowledge and concern about Zika virus in the United States.8 The recognition of Zika virus as a cause of microcephaly and other serious brain anomalies would allow for more direct communication, which might lead to improved understanding of and adherence to public health recommendations. Therefore, a review of the evidence linking Zika virus infection and adverse pregnancy and birth outcomes is needed. As is typically the case in epidemiology and medicine, no “smoking gun” (a single definitive piece of evidence that confirms Zika virus as a cause of congenital defects) should have been anticipated. Instead, the determination of a causal relationship would be expected to emerge from various lines of evidence, each of which suggests, but does not on its own prove, that prenatal Zika virus infection can cause adverse outcomes. Two approaches have been used to identify potential teratogens (exposures to a mother during pregnancy that have a harmful effect on her embryo or fetus)9: first, the identification of a combination of a rare exposure and a rare defect (sometimes referred to as the astute clinician approach),10 and second, the use of epidemiologic data to confirm an association. Many teratogens were first identified by means of the rare exposure–rare defect approach, including rubella virus, which was identified after an ophthalmologist noted a characteristic form of cataracts in infants whose mothers had rubella during pregnancy,11 and heavy alcohol use, which was identified as a teratogen after the recognition of a characteristic pattern of malformations that became known as the fetal alcohol syndrome.12 In contrast, some teratogens have been identified on the basis of epidemiologic studies (e.g., valproic acid was identified as a teratogen after a case–control study showed an odds ratio of 20 for the association of spina bifida with use of this drug during the first trimester of pregnancy).13

SUMMARYThe Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and birth outcomes, most notably microcephaly and other serious brain anomalies. To determine whether Zika virus infection during pregnancy causes these adverse outcomes, we evaluated available data using criteria that have been proposed for the assessment of potential teratogens. On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this causal relationship included Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants. Given the recognition of this causal relationship, we need to intensify our efforts toward the prevention of adverse outcomes caused by congenital Zika virus infection. However, many questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes. Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy.