Even as the Zika virus raged in Brazil, clinicians observed a curious phenomenon: all babies born to mothers infected with the virus during pregnancy were not affected with the characteristic birth anomalies caused by this infection.
Now, a new study shows that this finding is not as straightforward as it seems, however. One in four of these apparently normal babies shows clear signs of defective development, or poor vision and hearing, on later testing.
The Zika virus is an arbovirus spread by certain mosquito breeds, of the genus Aedes, which bite both day and night. The infection readily passes from mother to fetus during pregnancy, and causes birth defects. The most common symptoms include fever, rash, headache, arthralgia and myalgia, and redness of the conjunctiva. However, many cases are completely asymptomatic. During pregnancy, the most common birth defect is microcephaly, or a small head, caused by poor brain development leading to an abnormally small-sized brain.
Zika virus in blood with red blood cells, a virus which causes Zika fever found in Brazil and other tropical countries - Illustration Credit: Kateryna Kon / Shutterstock
The researchers looked at 216 babies born to infected mothers, testing them for their neurodevelopmental status between the ages of 7 and 32 months. All the mothers had a history of symptomatic infection. The study found that almost 30% of babies showed below-par scores in one or more areas of brain development. The tested areas included cognition (including memory and ability to learn), motor skills including both gross and fine movements, and expressive language. The earlier the time of pregnancy at which exposure happened, the greater was the risk that the baby would have developmental, eye and ear abnormalities.
The Zika virus is known to have a predilection for infecting immature nerve cells. This means that even babies who do not suffer from obvious anomalies such as an abnormally small brain (microcephaly) will still be at risk for other issues of nervous system development.
And even if the baby looks and tests normally in early infancy, it’s not yet time to breathe a sigh of relief. Especially important is the fact that almost half of babies who were abnormal at birth later scored normally on testing, during the second or third years of life. Conversely, fully one quarter of babies who tested normally at birth were found, on testing at 32 months, to be subnormal in development or to have defective hearing or vision.
The researchers admit that they do not know what caused the reversion to normality in babies who were sub-par at birth. It could be that they received certain interventions which helped them cope and compensate for their abnormalities, to re-enter the normal functional range. On the other hand, says commentator Sarah Mulkey, “it's quite sobering that babies who appeared normal at birth went on to develop abnormalities due to that early Zika exposure.”
The study also does not allow any direct comparison with Zika infection in pregnant US women, most of whom did not develop any symptoms during their infection. The study was carried out by researchers at the UCLA School of Medicine on more than 200 infants in Rio de Janeiro, Brazil, and published in the journal Nature Medicine on July 8, 2019. The commentary on the findings by Sarah Mulkey et al. was published in the same journal on July 29, 2019.
The commentators go on to add: “"This study adds to the growing body of research that argues in favor of ongoing follow-up for Zika-exposed children, even if their neurologic exams were reassuring at birth. As Zika-exposed children approach school age, it's critical to better characterize the potential implications for the education system and public health.”
In other words, Zika-exposed children need to be reassessed several times as they enter into school age, because a single initial assessment can be misleading and can lead to potentially overlooking the defects in their hearing, vision and brain development which could hinder their adjustment to the school system, without specific interventions. The financial and other resources necessary for this must be calculated and allocated by targeted studies to help proper policies evolve regarding the management and follow-up of these children.
Lessons about early neurodevelopment in children exposed to ZIKV in utero, William J. Muller & Sarah B. Mulkey, Nature Medicine (2019), https://www.nature.com/articles/s41591-019-0540-1