CDC Confirms the link between Zika infection and microcephaly.

Zika has been linked to microcephaly since Brazil reported a sudden increase in number of infants born with microcephaly in September 2015, but causation was not established. CDC today made an important announcement after careful review of all the possible evidence that Zika virus is a cause of microcephaly and other severe fetal brain defects.

The study is published online in the New England Journal of  Medicine today.

“This study marks a turning point in the Zika outbreak.  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,” said Tom Frieden, M.D., M.P.H., director of the CDC. “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.”

The investigators examined the causality evidence in light of Shepard’s criterias, which is set of rules that must be satisfied before labeling  an agent being ‘ teratogenic’  and causing  congenital malformations. According to the Shepard’s criterias, 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.

So, the relationship between Zika infection and microcephaly was termed casual under the rare exposure–rare defect approach as criteria 1, 3 and 4 were fulfilled:

1. Proven exposure must occur at a critical time during prenatal exposure: The microcephaly and other anomalies occur when the exposure occurs during first trimester or early second trimester. 
2. Careful delineation of clinical cases with the finding of a specific defect or syndrome: Infants with Zika infection do have a typical pattern which includes severe microcephaly, intracranial calcifications, and other brain anomalies, sometimes accompanied by eye findings, redundant scalp skin, arthrogryposis, and clubfoot which led the scientist to coin a term “Congenital Zika Syndrome.”
3. Rare exposure and a rare defect: This criterion was met because microcephaly is a rare defect with an incidence of 6 infants per 10,000 liveborn infants in the United States and infection in travelers who spent a limited amount of time in Brazil with active infection, constitute rare exposure for the patients.

Also supportive of causation is lack of alternative explanation for sudden increase in microcephaly cases in Brazil, French Polynesia and Colombia.

But, proving the causation is not enough in the fight against Zika infection. Many key questions are yet to be answered that have important implications.

CDC's director, Tom Frieden, MD said “We are 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," in a statement.

In addition to this researchers are also interested in knowing relative and absolute risk of infection and malformation. At present 1% to 29% of babies are born with microcephaly of all the mothers infected with the virus. They are also looking at other factors that modify the risk and severity of infections, such as gestational week at infection, additional morbidities and co-viral infection like Dengue fever.

CDC has not changed the travel warning or guidelines related to Zika infection after this publication.

Mark S. DeFrancesco, MD, MBA, President of the American College of Obstetricians and Gynecologists (ACOG), released the following statement regarding the U.S. Centers for Disease and Control and Prevention (CDC) paper addressing Zika virus “The message of the CDC paper underscores the importance of ongoing research into this outbreak. We once again encourage Congress to act swiftly to pass emergency funding to enhance our public health preparedness and enable America’s researchers to lead the charge in the development of a vaccine or treatment for this virus. Ongoing support for Zika virus research will protect American families and, indeed, families around the world."

References:

http://www.nejm.org/doi/full/10.1056/NEJMsr1604338?query=featured_home&

http://www.acog.org/About-ACOG/News-Room/Statements/2016/ACOG-Statement-on-the-CDC-Update-on-Zika-Virus

http://www.cdc.gov/media/releases/2016/s0413-zika-microcephaly.html