Zika Virus: Questions Remain


Does late-pregnancy or early-infancy infection cause abnormalities? Are symptomatic & asymptomatic maternal infections equally likely to cause defects?

Although the World Health Organization declared the end of the Public Health Emergency of International Concern regarding Zika virus and associated neurological disorders, questions about the infection and its consequences remain.

One question is the effect of timing of infection on the prevalence of birth defects in infants of infected mothers. Timing of viral infection is well known to affect clinical outcomes, for example, in case of rubella virus, but the effect of timing is unclear for Zika virus. Honein, et al. attempted to answer this and other questions in a recent study published in JAMA.1

The authors analyzed data from the US Zika Pregnancy Registry on the outcomes of 442 completed pregnancies with confirmed maternal Zika virus infection. They found that the timing of infection affects the proportion of infants with birth defects. The proportion of pregnancies with birth defects was higher if infection occurred during the first trimester (11%, 95% confidence interval [CI], 6%-19%) than second (0%; 95% CI, 0%-5%) or third trimester (0%; 95% CI, 0%-11%). Imprecision of these data is evidenced by the large confidence intervals and insufficient group size. It remains unclear whether infection late in pregnancy or early in infancy causes abnormalities. This question requires further investigation.

Most of the fetuses/infants with birth defects (85%) had brain abnormalities. Zika virus infection-related brain abnormalities may include early brain malformations, such as neural tube defects, brain abnormalities with or without microcephaly, eye abnormalities, and congenital contractures and deafness.

Another important question addressed in the study was whether symptomatic and asymptomatic maternal Zika virus infections are equally likely to result in birth defects. Symptomatic course of infection was found equally likely to cause birth defects as asymptomatic infection: brain abnormalities were observed in 6% of completed pregnancies, regardless of the presence of the symptoms. Microcephaly was observed in 4% of the pregnancies. (For comparison, its prevalence in the US was 7 per 10,000 live births in 2009-2013.)

These findings support the Centers for Disease Control and Prevention recommendations to:

1) Screen all pregnant women for Zika virus infection.

2) Test all newborns whose mothers were found positive for Zika virus infection or newborns with abnormalities consistent with congenital Zika syndrome. Serologic and polymerase chain reaction testing of infant serum is recommended in this setting.2

3) Counsel all individuals at risk of exposure on preventative measures. In addition to traditional measures of prevention, abstinence or the use of barrier contraception with exposed partner should be recommended as well as delay in conception after exposure of either male or female partner or both.3

Limitations of the study include unknown exact timing of gestational exposure to Zika virus, greater likelihood of identifying infection in pregnancies with abnormalities and in women with symptomatic Zika virus infection during pregnancy, incomplete reporting of cases to the registry, inability to identify viral infection that occurred early in pregnancy but was tested for late in pregnancy, and limitations in accounting for other risk factors for birth defects.

While Zika virus vaccine is still in development and treatment of infected individuals is symptomatic, this study advances our understanding of Zika virus infection, its consequences, and management.


1. Honein MA, et al. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA. 2016 Dec 15. [Epub ahead of print]

2. Clinical Guidance for Healthcare Providers Caring for Infants & Children. Centers for Disease Control and Prevention website. https://www.cdc.gov/zika/hc-providers/infants-children.html Accessed December 15, 2016.

3. Clinical Guidance for Healthcare Providers for Prevention of Sexual Transmission of Zika Virus. Centers for Disease Control and Prevention website. https://www.cdc.gov/zika/hc-providers/clinical-guidance.html Accessed December 15, 2016.

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