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Asymptomatic maternal Zika infection doesn’t dampen birth defect risk


 

EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017

 

– One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.

This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.

“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”

She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.

Just how serious is the global threat of Zika virus infection?

On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.

“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
 

What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?

The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.

The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
 

When during pregnancy does maternal Zika infection pose the highest risk to the fetus?

Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.

“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
 

What is the full range of potential health problems Zika infection can cause?

“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”

Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.

Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.

“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”

Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.

“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
 

How long does Zika virus persist in the body?

The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.

“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.

It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.

“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
 

Resources

In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).

Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at ZikaMCH@cdc.gov.

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