The Zika virus has been confirmed as a cause of microcephaly and congenital abnormalities, according to an evidence review from CDC scientists published in the New England Journal of Medicine (NEJM).

An additional study published in the BMJ characterizes the brain abnormalities seen in infants with Zika virus congenital syndrome.

Although prenatal Zika virus has been linked to adverse pregnancy and birth outcomes, including microcephaly, a causal relationship had not previously been proven.

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The report published in the NEJM evaluated available data using criteria that have been proposed for the assessment of potential teratogens, including Shepard’s Criteria, Koch’s postulates, and the Bradford Hill criteria. Using these criteria, the researchers determined that sufficient evidence exists to infer a causal relationship between prenatal Zika virus infection and microcephaly and other brain abnormalities. The absence of an alternative explanation for these defects provides additional support.

The researchers used the following evidence to support their determination of a causal relationship:  Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants.

 “[M]any questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes,” wrote Sonja A. Rasmussen, MD, and colleagues in the NEJM report. “Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy.”

To further understand the effects of Zika on infants, a study led by Maria de Fatima Vasco Aragao, MD, PhD, sought to characterize the brain abnormalities seen specifically in Zika-associated microcephaly. The researchers reviewed CT and MRI scans from the first infants with Zika-associated microcephaly in Brazil, including 23 infants who had been diagnosed with microcephaly or craniofacial disproportion at birth. Of these, 15 underwent a CT scan, 1 underwent an MRI scan, and 7 underwent both CT and MRI scans.

Six infants tested positive for IgM antibodies, which are related to the Zika virus; the other 17 were not tested for these antibodies but still met the criteria for congenital infection likely associated with Zika.

All 22 infants who underwent CT scans showed calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. All 8 infants who underwent MRI scans had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven (88%) of these infants had enlarged cisterna magna, 7 (88%) had delayed myelination, and 6 (75%) had a moderate-to-severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases.

These findings distinguish Zika virus congenital syndrome from microcephaly, as this new Zika syndrome includes microcephaly as well as other malformations.


  1. De Fatima Vasco Aragao M, van der Linden V, Brainer-Lima AM, et al. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. BMJ. 2016;353:i1901.
  2. Rasmussen SA, Jamieson DJ, Honein MA, et al. Zika virus and birth defects – reviewing the evidence for causality. N Engl J Med. Published online April 13, 2016. doi:10.1056/NEJMsr1604338.