1. Zika Virus Response: Pregnancy and Birth Defects Task Force
Scott Grosse, PhD
National Center on Birth Defects and Developmental Disabilities
Centers for Disease Control and Prevention
Good morning. Thank you for this opportunity to speak with you today on behalf of CDC’s Pregnancy and Birth Defects Task Force. The Zika outbreak is a rapidly evolving situation, and CDC is actively engaged on many fronts.

2. Zika is a Cause of Microcephaly
Zika virus was discovered in 1947, but was not originally linked to birth defects. Before 2015, Zika virus disease (Zika) outbreaks occurred in areas of Africa, Southeast Asia, and the Pacific Islands. Because the symptoms of Zika are similar to those of many other diseases, many cases may not have been recognized. However, over the past several months, medical and public health professionals gathered and reviewed mounting evidence of the link between Zika virus infection during pregnancy and microcephaly.
On April 13th of this year, building on the hard work of many scientists, CDC concluded that Zika virus is a cause of microcephaly and other brain anomalies.
To reach this conclusion, CDC conducted a systematic evaluation of the evidence, which showed that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies.

3. Congenital Zika Syndrome
Congenital Zika syndrome is a recently recognized pattern of congenital anomalies associated with Zika virus infection during pregnancy that includes:
Microcephaly
Intracranial calcifications
Other brain anomalies
Zika virus also linked to:
Eye anomalies
Hearing loss
Limb abnormalities
Impaired growth
Congenital Zika syndrome is a recently recognized pattern of congenital anomalies associated with Zika virus infection during pregnancy that includes microcephaly, intracranial calcifications and other brain anomalies, eye anomalies, and others (such as clubfoot and contractures). Research is ongoing to further define the spectrum of anomalies associated with congenital Zika syndrome.
All reports of microcephaly so far have been congenital microcephaly, meaning the microcephaly occurred before birth.

4. Many Questions Remain
What is the full range of potential health problems that Zika virus infection may cause?
What is the level of risk from a Zika virus infection during pregnancy?
When during pregnancy does Zika virus infection poses the highest risk to the fetus?
What are other factors (e.g., co-occurring infection, nutrition, symptomatic vs. asymptomatic) that might affect the risk for birth defects?
This response continues to evolve. Although we have learned about the association of Zika and poor pregnancy outcomes in a short amount of time, many questions remain.
For example, we’re still investigating:
What is the full range of potential health problems that Zika virus infection may cause (Does Zika cause other defects)? For example, does Zika cause learning problems later in life? Are pregnancy losses among some women infected by Zika virus caused by the infection? etc.), and
What is the level of risk from a Zika infection during pregnancy (that is, if a woman is infected, how often will her fetus have Zika-associated problems),
When during pregnancy does Zika virus infection pose the highest risk to the fetus?
What are other factors (such as other infections occurring at the same time) that might affect the risk for birth defects.
Answering these critical questions is a focus of our ongoing research and may help improve our prevention efforts and ultimately help reduce the effects of Zika infection during pregnancy.

5. How CDC is Collecting Data for Action
Surveillance of Pregnant Women, Fetuses, & Infants
Zika Active Pregnancy Surveillance System (Puerto Rico)
Proyecto Vigilancia de Embarazadas con Zika (Colombia)
U.S. Zika-Related Birth Defects Surveillance
US Zika Pregnancy
Registry
This slide lists some of the activities that CDC is doing to learn more about Zika infection during pregnancy.
We are collecting data for action.
CDC established the US Zika Pregnancy Registry. We are working in collaboration with state, tribal, local and territorial health departments to collect information about women with laboratory evidence of possible Zika virus infection during pregnancy in the United States and their infants.
We have helped develop a similar system in Puerto Rico, the Zika Active Pregnancy Surveillance System in Puerto Rico.
And we have established enhanced surveillance of pregnant women with Zika in Colombia.
CDC also recently funded 45 jurisdictions to establish or enhance Zika-related birth defects surveillance systems that monitor brain abnormalities, including microcephaly, and central nervous system defects, to better understand Zika exposure during pregnancy and adverse outcomes.
Data collected will be used to update recommendations for clinical care, plan for services for pregnant women, their infants and families affected by Zika, and improve prevention of Zika infection during pregnancy.

6. Number of Pregnant Women with Lab Evidence of Zika
837 *
1,638 **
Pregnant women with any laboratory evidence of possible Zika virus infection in the 50 US States and DC
Pregnant women with any laboratory evidence of possible Zika virus infection in US Territories
*Includes aggregated data reported to the US Zika Pregnancy Registry as of September 29, 2016
As of September 29, we have worked with state, local, tribal, and territorial health departments to identify 837 pregnant women with any laboratory evidence of possible Zika virus infection, with or without symptoms, in the United States and DC. And 1638 pregnant women in the US territories, including Puerto Rico, US Virgin Islands, and American Samoa.
**Includes aggregated data from the US territories reported to the US Zika Pregnancy and data from Puerto Rico reported to the Zika Active Pregnancy Surveillance as of September 29, 2016

7. Reporting Poor Outcomes
As of September 29, 2016 in US states and the District of Columbia, there were
22 live-born infants with birth defects*
5 pregnancy losses with birth defects**
As of September 29,2016 in US territories, there were
1 live-born infant with birth defects*
1 pregnancy loss with birth defects**
* Includes microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from damage to the brain that affects nerves, muscles and bones, such as clubfoot or inflexible joints, and confirmed hearing loss.
**Includes miscarriage, stillbirths, and terminations with evidence of the birth defects mentioned above
These numbers reflect the number of poor outcomes among pregnancies with laboratory evidence of possible Zika virus infection that have been reported to the pregnancy surveillance systems.
As of September 29, 2016 in US states and the District of Columbia, there were
22 live-born infants with birth defects*
5 pregnancy losses with birth defects**
This includes aggregated data reported to the US Zika Pregnancy Registry
As of September 29,2016 in US territories, there were
1 live-born infant with birth defects*
1 pregnancy loss with birth defects**
This includes aggregated data reported to the US Zika Pregnancy Registry and data from the Puerto Rico reported to the Zika Active Pregnancy Surveillance System
The poor birth outcomes reported include those that have been detected in infants infected with Zika before or during birth, including microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from damage to brain that affects nerves, muscles and bones, such as clubfoot or inflexible joints, and confirmed hearing loss
These numbers are not real time estimates. They will reflect the outcomes of pregnancies reported with any laboratory evidence of possible Zika virus infection as of 12 noon every Thursday the week prior; numbers will be delayed one week.

8. Primary focus: protect pregnant women and their pregnancies
Future Directions
Enhance ability to protect pregnant women and their fetuses/infants from Zika virus infection
Define the full clinical spectrum of Congenital Zika Syndrome, including through US birth defects surveillance
Strengthen surveillance and reporting of cases through the three pregnancy surveillance systems
Improve diagnostic testing for pregnant women and infants
Promote personal protection measures
Continue to update clinical guidance for pregnant women, evaluation of infants, and couples trying to conceive as new data emerge
Assist with efforts to develop a safe and effective vaccine by leveraging CDC collaborations in areas with active Zika virus transmission
Primary focus: protect pregnant women and their pregnancies
Continue to define clinical spectrum of Zika virus disease
Strengthen surveillance and reporting of cases
Follow up cases through pregnancy registries
Improve laboratory diagnostics and expand speed and access to testing
Promote personal protection measures
Issue new and revised clinical / public health guidance
Assisting with efforts to develop and deploy safe and effective vaccines and other medical countermeasures

9. More information on Zika: www.cdc.gov/zika
Thank you!
More information on Zika:
Questions about CDC’s work related to Zika and unintended pregnancy: contact CDC-INFO at or
All of this is the work of many people. Many thanks to all of our collaborators, and thank you all for listening today.

10. Extra Slides

11. First Time in History…
“Never before in history has there been a situation where a bite from a mosquito could result in a devastating malformation.” – Dr. Tom Frieden, CDC Director Fortune, April 13, 2016
Today’s Zika outbreak is unprecedented. Although Zika was first identified almost 70 years ago, the newly recognized potentially devastating effects on pregnancy are a new phenomenon. We are literally learning more about Zika and what it means for pregnant women every day. CDC’s top priority for this public health response is pregnant women and their fetuses.

12. Where is Zika now?
59 countries and territories worldwide, including 49 countries and territories in the Americas, reporting active Zika virus transmission
Before 2015, Zika outbreaks occurred in areas of Africa, Southeast Asia, and the Pacific Islands. Currently, outbreaks are occurring in many countries or territories in the Americas and worldwide, including the Commonwealth of Puerto Rico, a U.S territory, the U.S. Virgin Islands, and Miami-Dade, Florida in the continental U.S.
CDC recommends that pregnant women not travel to areas with active Zika transmission.
As of September 23, 2016

13. Tools for Healthcare Providers and Information for Patients
*Free materials available in English, Spanish and other languages
CDC has also developed a number of communications materials for healthcare providers and their patients.
We are also translating our clinical guidance into tools and materials for healthcare providers to use. These are available on the website.

14. Pediatric Evaluation and Follow-up Tools: Initial Evaluation and Outpatient Management During the First 12 Months of Life for Infants with Possible Congenital Zika Virus Infection
Download at:
This guidance on evaluation and outpatient management has also been summarized in a tool or pocket guide for clinicians. The tool can be downloaded from the CDC’s website (link to the right).

15. CDC and AAP Collaboration
On July 21–22, CDC sponsored a meeting in collaboration with American Academy of Pediatrics (AAP), entitled “Clinical Evaluation and Management of Infants with Congenital Zika Virus Infection” involving:
Specialties
Audiology, clinical genetics, critical care, developmental and behavioral pediatrics, endocrinology, hospitalist medicine, infectious disease, lactation and infant feeding, maternal-fetal medicine, neonatology, neurology, nutrition, ophthalmology, orthopedics, pediatrics, physical medicine and rehabilitation
Principal partners
AAP, AAP Puerto Rico chapter, American Academy of Family Physicians, American Congress of Obstetricians and Gynecologists, Association of Maternal and Child Health Programs, Family Voices, March of Dimes, Parent to Parent, and the National Association of Pediatric Nurse Practitioners
Other federal agencies
Administration for Children and Families, Office of the Assistant Secretary for Preparedness and Response, Maternal & Child Health Bureau of the Health Resources and Services Administration, and National Institute of Child Health and Human Development, National Institutes of Health
On July 21st and 22nd, CDC sponsored a meeting in collaboration with the American Academy of Pediatrics, entitled “Clinical Evaluation and Management of Infants with Congenital Zika Virus Infection”
Multiple pediatric specialties, partner organizations and other federal agencies were represented.

16. Updated Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection — United States, August 2016

17. Interim Guidance for Evaluation and Testing: Infants with Possible Congenital Zika Virus Infection

18. Zika Virus in Pregnancy
No evidence of increased susceptibility
Infection can occur in any trimester
Incidence of Zika virus infection in pregnant women is not known
No evidence of more severe disease compared with non-pregnant people
Centers for Disease Control and Prevention, CDC Health Advisory: Recognizing, Managing, and Reporting Zika Virus Infections in Travelers Returning from Central America, South America, the Caribbean and Mexico, 2016.
Besnard, M., et al., Evidence of Perinatal Transmission of Zika Virus, French Polynesia, December 2013 and February Euro Surveill, (14): p. 1-5.
Oliveira Melo, A., et al., Zika Virus Intrauterine Infection Causes Fetal Brain Abnormality and Microcephaly: Tip of the Iceberg? Ultrasound in Obstetrics & Gynecology, (1): p. 6-7.
Recognizing that Zika is a cause of microcephaly and has been associated with certain other birth defects does not mean that every pregnant woman infected with Zika will have a baby with a birth defect. It means that infection with Zika during pregnancy increases the chances for these problems.
No evidence of increased susceptibility to Zika virus in pregnant women.
Zika virus infection can occur in any trimester, but the incidence of Zika virus infection in pregnant women is not known.
There is no evidence that pregnant women have more severe disease compared with non-pregnant people.
Based on the available evidence, we think that Zika virus infection in a woman who is not pregnant would not pose a risk for birth defects in future pregnancies after the virus has cleared from her blood

19. Diagnostic Testing for Zika Virus
Molecular method
Real-time reverse transcriptase-polymerase chain reaction (rRT- PCR) for viral RNA in body fluids or tissues
Serologic method
Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay
Plaque reduction neutralization test (PRNT) to detect neutralizing antibodies in serum
Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods.
Real time reverse transcriptase-polymerase chain reaction or real-time RT-PCR is the molecular method and it detects viral RNA in body fluids such as serum, urine, cerebrospinal fluid or tissues such as placenta. Anytime RNA is detected it provides a definitive diagnosis of Zika virus infection.
Serologic tests include the Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay to detect [anti-Zika virus] IgM antibodies in serum [or CSF] and plaque reduction neutralization test or PRNT which measures virus-specific neutralizing antibody titers.

20. Symptomatic Pregnant Women
Evaluated <2 weeks after symptom onset
Should receive Zika virus rRT-PCR testing of serum and urine
Evaluated 2–12 weeks after symptom onset
Should first have a Zika virus immunoglobulin (IgM) test
If positive or equivocal, serum and urine rRT-PCR should be performed
Updated guidance for health care providers caring for pregnant women with possible Zika exposure was released on July 29.
Symptomatic pregnant women who are being evaluated <2 weeks after symptom onset should receive Zika virus rRT-PCR testing of serum and urine.
However, if evaluation is occurring 2–12 weeks after symptom onset, Zika virus immunoglobulin (IgM) testing should be performed first. THEN, if this result is positive or equivocal, serum and urine rRT-PCR should be performed. Of note, if the rRT-PCR ends up being negative, then PRNT should be performed.

21. Asymptomatic Pregnant Women
Who live in areas without active Zika virus transmission, evaluated <2 weeks after their last possible exposure
rRT-PCR testing should be performed
If the rRT-PCR test is negative, a Zika IgM test should be performed 2–12 weeks after the exposure
Who live in an area without active Zika virus transmission, evaluated 2–12 weeks after their last possible exposure
Should receive a Zika virus IgM antibody test
If positive or equivocal, serum and urine rRT-PCR should be performed
Who live in areas with active Zika virus transmission
Should receive Zika virus IgM antibody testing as part of routine obstetric care during the 1st and 2nd trimesters, with immediate rRT-PCR testing of women who are IgM-positive or equivocal
For asymptomatic women
Who live in areas without active Zika virus transmission, but had an exposure, and are being evaluated <2 weeks after their last possible exposure,
rRT-PCR testing should be performed on both serum and urine. If the rtRT-PCR test is negative, a Zika IgM test should be performed 2–12 weeks after the exposure.
For those Who live in an area without active Zika virus transmission but had an exposure, and are being evaluated 2–12 weeks after their last possible exposure
Zika virus IgM antibody test should be performed. If this test is positive or equivocal, serum and urine rRT-PCR should be performed.
And finally, for those pregnant women who live in areas with active Zika virus transmission, Zika virus IgM antibody testing should be performed as part of routine obstetric care during the 1st and 2nd trimesters, with immediate rRT-PCR testing of women who are IgM-positive or equivocal.