More Than Microcephaly: Congenital Zika Syndrome

Laura A. Stokowski, RN, MS; William B. Dobyns, MD


September 21, 2016

In This Article

The Zika virus might have been just another mosquito-borne infection—only on our radar if we lived in or planned to visit a tropical setting, much like yellow fever, dengue fever, or Chikungunya—if not for the completely unexpected and tragic effects on unborn infants. When reports of microcephaly first began to surface from Brazil, many people were in disbelief, speculating that it was not the Zika virus that caused the dramatic rise in neurodevelopmental disorders in that country. Instead, they tried to blame some unidentified culprit, such as larvicide added to drinking water, vaccines, or the genetically modified mosquitoes released to control dengue fever. But it soon became clear that the virus was, indeed, the cause of a surge in infants born with microcephaly in regions affected by Zika.

In a review of the evidence supporting the role of the Zika virus as a human teratogen published in April,[1] scientists from the Centers for Disease Control and Prevention (CDC) affirmed that congenital brain anomalies are the result of maternal Zika infection during the first or early second trimester of pregnancy. The relative and absolute risks to infants of mothers who were infected later in pregnancy are still unquantified. A recent case report[2] described an infant with prolonged Zika virus shedding whose mother became overtly symptomatic and tested positive for Zika virus during the third trimester of pregnancy. The newborn had a normal head circumference and normal results on neurologic examination, but by 6 months of age, he was showing signs of neuropsychomotor developmental delay, global hypertonia, and spastic hemiplegia.

William B. Dobyns, MD

Recently, reports of newborns without microcephaly at birth but with abnormal results on neurologic exams have surfaced. Ventura and colleagues[3] concluded that "microcephaly should not be a required criterion for congenital Zika virus infection diagnosis." The prognosis for infants without microcephaly at birth and the correlation between this condition and the timing of maternal Zika infection are areas of great interest, although few data are available. In a media briefing, the CDC reported that babies with so-called late-onset microcephaly have been born to mothers infected during the third trimester of their pregnancies.[4]

Medscape spoke with William B. Dobyns, MD, professor in the Departments of Pediatrics and Neurology at the University of Washington in Seattle and principal investigator at the Seattle Children's Research Institute, about the known spectrum of neurodevelopmental effects of congenital Zika infection and the significance of the range of phenotypes now being reported.

Congenital Zika Syndrome

Medscape: What do we know about neonatal neurodevelopmental effects when the mother is infected with Zika during pregnancy?

William B. Dobyns, MD: We know a lot about the children who have clear-cut microcephaly at birth, but less about children who have a normal head size at birth and then develop microcephaly. I'll start with the former.

Late last year, reports started appearing from Brazil about an increase in the frequency of babies with microcephaly at birth, particularly in northeastern Brazil, where the Zika virus was spreading in an epidemic fashion. The Brazilian Ministry of Health clearly demonstrated that there was an increased rate of microcephaly. After that, we got a few scattered reports of what the babies looked like through photographs and some prenatal studies. The reports, which continued well into 2016, persistently talked about microcephaly as if that was the diagnosis.

But that was just scratching the surface. The physicians who were initially writing about the affected Brazilian infants had no background in pediatric developmental disorders. Reports gradually appeared over the next couple of months from expert Brazilian specialists, and they started to describe the problem more accurately. With a group of doctors, including some from Brazil, I have submitted a paper on 57 children with very detailed evaluations of what the kids look like clinically and radiologically, on brain scans.

In infants with a small head size at birth, we are now able to recognize a congenital Zika syndrome, the preferred diagnostic label that is now being substituted for the very inadequate designation of microcephaly. Babies with congenital Zika syndrome have multiple other features.

...the preferred diagnostic label that is now being substituted for the very inadequate designation of microcephaly.

When you examine the babies, their head sizes vary, but they are often very small. In our 57 children with microcephaly, head circumferences ranged from 2 standard deviations below the mean to 7 standard deviations below the mean(and 85%–90% were more than 3 SDs below the mean). This means that the head sizes of a large majority of these children are not even borderline; they are very small. There is a spectrum. Although we do see children whose head sizes are only slightly small, most are very small.

Small head size is the first of multiple features. Clinically, these babies all have marked developmental delays and very abnormal neurologic exams. Very early on, they are spastic and stiff—that's cerebral palsy—and they tend to be very irritable and tremulous. Most have significant feeding problems.

These abnormalities don't take months to show up, as in some other neurodevelopmental disorders. The neurologist was able to describe abnormalities on his first examination of these babies.


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