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Severity of Zika outbreak explains microcephaly rate in Northeast Brazil

In 2015, Northeast Brazil experienced a disproportionately higher rate of microcephaly than anywhere else in the country. Researchers explained that this is because the region had been hardest hit by the Zika virus outbreak, with 94% of an estimated 8.5 million total cases.

Specifically, they found that women infected during early pregnancy were 17 times more likely to have a child with microcephaly.

Oliver J. Brady, DPhil, assistant professor and Henry Wellcome Fellow at the London School of Hygiene and Tropical Medicine, and colleagues wrote that “an abnormally high rate” of microcephaly was reported in Northeast Brazil near the end of 2015. This rate — reaching 56.7 per 10,000 births — has not been documented in other Brazilian states or South American countries since Zika virus began to spread in the Americas. This originally suggested that “alternate causes or the involvement of arboviral cofactors” were to blame for the high rates of microcephaly in the region, researchers said.

Brady and colleagues collected data from Brazilian national databases to estimate exposure to different types of known or suspected causes of microcephaly — including Zika virus, dengue, chikungunya, bovine viral diarrhea virus infection, Zika coinfection and water toxins — for every live birth in Brazil reported between Jan. 1, 2015, and May 23, 2017. The researchers identified between 3.6 million and 5.4 million cases of microcephaly during the study period.

They said they found no evidence to support anything other than Zika as the source of the microcephaly outbreak. In addition, they said concurrent exposure to arbovirus infection or previous yellow fever vaccination did not alter the risk for microcephaly.

 
Researchers suggest that 94% of an estimated 8.5 million total cases of Zika virus infection occurred in Northeast Brazil. They credit the this to the disproportionate rate of infants affected by microcephaly.
Source: Shutterstock

The researchers estimated an absolute risk for microcephaly of 40.8 cases (95% CI, 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI, 3.2-369.1) — that is, if Zika infection occurred in the first or second trimester of pregnancy.

However, Brady and colleagues cautioned that because the rate of Zika infection among pregnant women was “highly variable,” most pregnant women in Brazil would have had a lower risk for infection during the outbreak.

Although infants born to mothers infected with Zika were at significantly higher risk for other types of birth defects, the RR for Zika-attributable microcephaly was much higher (1.1-1.5 vs. 4.1), the researchers said.

“Recent evidence suggests that up to 24% of microcephaly may only be diagnosable postnatally and that further developmental abnormalities may also occur,” Brady and colleagues wrote. “Further longer term studies are needed in children born to Zika virus-infected (and noninfected) mothers to describe and measure the full lifetime burden of Zika virus.” – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

In 2015, Northeast Brazil experienced a disproportionately higher rate of microcephaly than anywhere else in the country. Researchers explained that this is because the region had been hardest hit by the Zika virus outbreak, with 94% of an estimated 8.5 million total cases.

Specifically, they found that women infected during early pregnancy were 17 times more likely to have a child with microcephaly.

Oliver J. Brady, DPhil, assistant professor and Henry Wellcome Fellow at the London School of Hygiene and Tropical Medicine, and colleagues wrote that “an abnormally high rate” of microcephaly was reported in Northeast Brazil near the end of 2015. This rate — reaching 56.7 per 10,000 births — has not been documented in other Brazilian states or South American countries since Zika virus began to spread in the Americas. This originally suggested that “alternate causes or the involvement of arboviral cofactors” were to blame for the high rates of microcephaly in the region, researchers said.

Brady and colleagues collected data from Brazilian national databases to estimate exposure to different types of known or suspected causes of microcephaly — including Zika virus, dengue, chikungunya, bovine viral diarrhea virus infection, Zika coinfection and water toxins — for every live birth in Brazil reported between Jan. 1, 2015, and May 23, 2017. The researchers identified between 3.6 million and 5.4 million cases of microcephaly during the study period.

They said they found no evidence to support anything other than Zika as the source of the microcephaly outbreak. In addition, they said concurrent exposure to arbovirus infection or previous yellow fever vaccination did not alter the risk for microcephaly.

 
Researchers suggest that 94% of an estimated 8.5 million total cases of Zika virus infection occurred in Northeast Brazil. They credit the this to the disproportionate rate of infants affected by microcephaly.
Source: Shutterstock

The researchers estimated an absolute risk for microcephaly of 40.8 cases (95% CI, 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI, 3.2-369.1) — that is, if Zika infection occurred in the first or second trimester of pregnancy.

However, Brady and colleagues cautioned that because the rate of Zika infection among pregnant women was “highly variable,” most pregnant women in Brazil would have had a lower risk for infection during the outbreak.

Although infants born to mothers infected with Zika were at significantly higher risk for other types of birth defects, the RR for Zika-attributable microcephaly was much higher (1.1-1.5 vs. 4.1), the researchers said.

“Recent evidence suggests that up to 24% of microcephaly may only be diagnosable postnatally and that further developmental abnormalities may also occur,” Brady and colleagues wrote. “Further longer term studies are needed in children born to Zika virus-infected (and noninfected) mothers to describe and measure the full lifetime burden of Zika virus.” – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Kristina M. Adams Waldorf

    Kristina M. Adams Waldorf

    The unusual geographic concentration of microcephalic neonates attributed to Zika virus infections has remained a mystery and triggered many alternative theories as to the underlying cause in this region. This study provides a geospatial analysis using Brazilian national registries to capture Zika virus infections and cases with microcephaly and/or fetal brain anomalies. This work is likely to provide the most accurate estimate that we will ever obtain for the RR of microcephaly due to Zika virus infection in the first and second trimesters. This study also provides a model for future efforts to estimate the relationships between a new viral outbreak and the incidence of birth defects. 

    • Kristina M. Adams Waldorf, MD
    • Professor of obstetrics and gynecology
      Professor of global health
      University of Washington

    Disclosures: Infectious Diseases in Children was unable to confirm relevant financial disclosures prior to publication.

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