Prolonged Zika viremia in mothers a significant risk factor for birth defects
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Prolonged viremia in Zika-infected mothers is associated with a sevenfold higher risk for neonatal or fetal adverse outcomes compared with pregnancies without prolonged viremia, researchers reported.
Study results published in Emerging Infectious Diseases also showed that prolonged maternal viremia is associated with a twofold higher risk for congenital infection compared with mothers with Zika virus who do not experience prolonged viremia.
“In the case of Zika infection during pregnancy, the duration of maternal viremia should be followed, as it may represent an important risk factor for maternal-fetal transmission and subsequent adverse outcomes if it lasts longer than 30 days,” Léo Pomar, PhD, from Lausanne University Hospital in Switzerland, told Healio.
Pomar and colleagues enrolled pregnant women with Zika virus and noninfected pregnant women in a prospective cohort study at a hospital in French Guiana during the early months of the Zika epidemic, between January and July 2016.
They included 33 infected and 326 noninfected women who were tested during each trimester and at delivery. The researchers defined prolonged viremia as ongoing virus detection at 30 days or longer following infection and adverse outcomes as fetal loss or neurologic anomalies.
They found that adverse outcomes were more common among neonates and fetuses from the 14 mothers with prolonged viremia (40%) than those from the 19 infected mothers who did not experience prolonged viremia (5.3%; adjusted RR = 7.2; 95% CI, 0.9-57.6) or neonates and fetuses from uninfected mothers (6.6%; aRR = 6.7; 95% CI, 3-15.1). They also found that congenital infections were more common in neonates and fetuses born to mothers with prolonged viremia compared with the other two cohorts, respectively (60% vs. 26.3% vs. 0%; aRR = 2.3; 95% CI, 0.9-5.5).
“Our results are not surprising; they confirm the hypothesis that was put forward at the beginning of the pandemic,” Pomar said. “The limitations of our study are mainly the low proportion of patients with prolonged viremia included, preventing the association with more subtle signs and symptoms and a possible selection bias inherent to Zika cohorts, as mothers of fetuses and neonates with adverse outcomes underwent systematic reverse transcription-PCR testing, which could lead to an overestimation of the rate of adverse outcomes. This would not bias the comparison with the control groups.”
Perspective
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This study’s key message is that a pregnant woman with Zika virus infection and prolonged viremia — Zika PCR test positive for 30 days or more from discovery of symptoms or the initial detection of the virus — is at a significantly increased risk for having a baby with congenital Zika syndrome and the associated abnormal neurologic outcomes. Sequential testing for ongoing viremia may be able to provide further information on risk to the fetus for women infected with Zika virus. The study by Driggers and colleagues referenced in the paper was the first report of concern that prolonged viremia could be more likely associated with abnormal fetal outcomes because in that case, the fetus had significant cerebral abnormalities and the mother had prolonged viremia. This case report in The New England Journal of Medicine from 2016 was from my colleagues at Children’s National Hospital. However, the presence of prolonged viremia does not necessarily indicate that the fetus or infant will have Zika-related birth defects, but it is a laboratory assessment that can be used as a marker for an increase in risk.
This study may support an addition to current clinical guidelines for the evaluation of pregnant women with Zika virus infection, that Zika PCR tests should be followed serially every 2 to 4 weeks until negative, along with serial imaging to assess for fetal abnormalities. The presence of prolonged viremia may heighten the clinical concern for possible risk for infection to the fetus.
Other Zika pregnancy cohorts with Zika PCR data available should assess for similar findings if data are available. In a future Zika-virus outbreak, serial Zika PCR tests should be performed in pregnant women to better correlate duration of viremia with pregnancy and infant outcomes.
Reference:
Driggers RW, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1601824.
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