In the Journals

CDC: ‘No longer any doubt’ Zika causes microcephaly, other birth defects

CDC officials recently confirmed that a causal relationship exists between Zika virus infection during pregnancy and microcephaly and other serious birth defects.

“It is now clear that Zika does cause microcephaly,” Thomas R. Frieden, MD, MPH, director of the CDC, said during a news conference. “This confirmation is based on a thorough review of the best scientific evidence, conducted by the CDC and other experts in maternal and fetal health and mosquito-borne diseases. There is still a lot that we don’t know, but there is no longer any doubt that Zika causes microcephaly.”

Thomas Frieden, MD

Thomas R. Frieden

The confirmation announcement by the CDC coincided with the publication of a special report in the New England Journal of Medicine that detailed the confirmation process. According to Sonja A. Rasmussen, MD, director of the CDC’s Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services, and colleagues, the evidence used to support this connection included observations of Zika virus infection at times during pregnancy that were consistent with the apparent birth defects, observation of a rare phenotype involving microcephaly and other brain defects in fetuses with congenital Zika infection. The evidence also included further data that strongly support the biological link, including the presence of Zika in brain tissue of affected fetuses and infants.

“There is no single piece of evidence that provides conclusive proof of this connection,” Frieden said. “Rather, mounting evidence from many studies and a careful review of causal criteria were needed to determine that Zika causes microcephaly and other birth defects.”

Sonja Rasmussen

Sonja A. Rasmussen

According to Rasmussen, two different scientific criteria were used to establish a framework for assessing causation. They included the Thomas Shepard criteria and the Bradford Hill criteria. The Shepard criteria involve seven individual criteria, five of which have been at least partially met. The unsatisfied criteria included identifying teratogenicity in experimental animals. The remaining unsatisfied criterion only applies to evaluation of causation for medication or chemical exposure and does not apply to infection-related teratogenicity. Likewise, of the eight applicable criteria within the Hill criteria, each, with the exception of observed causation in experimental animals, was met.

“Our evaluation of the evidence using both of these sets of criteria yielded the same conclusion. Zika is a cause of microcephaly and other severe brain abnormalities,” Rasmussen said during the news conference.

Figure 1. A comparison of a typical head size for a baby and a baby with microcephaly.

Source: CDC

According to Rasmussen, the full spectrum of other birth defects caused by Zika remains unknown, but currently includes intracranial calcification and other severe brain defects. Rasmussen also said the type of microcephaly being observed in connection with Zika is a very severe form of the condition. Further, CDC officials stated they are still unable to positively confirm an association between Zika virus infection and Guillain-Barré syndrome.

“This is an unprecedented association,” Frieden said. “Never before in history has there been a situation where a bite from a mosquito could result in devastating malformations, and it is because this was so unprecedented that we have waited until now [to confirm] that there is a causal link.” – by Dave Costill

Disclosures: Frieden and Rasmussen are employed by the CDC.

CDC officials recently confirmed that a causal relationship exists between Zika virus infection during pregnancy and microcephaly and other serious birth defects.

“It is now clear that Zika does cause microcephaly,” Thomas R. Frieden, MD, MPH, director of the CDC, said during a news conference. “This confirmation is based on a thorough review of the best scientific evidence, conducted by the CDC and other experts in maternal and fetal health and mosquito-borne diseases. There is still a lot that we don’t know, but there is no longer any doubt that Zika causes microcephaly.”

Thomas Frieden, MD

Thomas R. Frieden

The confirmation announcement by the CDC coincided with the publication of a special report in the New England Journal of Medicine that detailed the confirmation process. According to Sonja A. Rasmussen, MD, director of the CDC’s Division of Public Health Information Dissemination, Center for Surveillance, Epidemiology, and Laboratory Services, and colleagues, the evidence used to support this connection included observations of Zika virus infection at times during pregnancy that were consistent with the apparent birth defects, observation of a rare phenotype involving microcephaly and other brain defects in fetuses with congenital Zika infection. The evidence also included further data that strongly support the biological link, including the presence of Zika in brain tissue of affected fetuses and infants.

“There is no single piece of evidence that provides conclusive proof of this connection,” Frieden said. “Rather, mounting evidence from many studies and a careful review of causal criteria were needed to determine that Zika causes microcephaly and other birth defects.”

Sonja Rasmussen

Sonja A. Rasmussen

According to Rasmussen, two different scientific criteria were used to establish a framework for assessing causation. They included the Thomas Shepard criteria and the Bradford Hill criteria. The Shepard criteria involve seven individual criteria, five of which have been at least partially met. The unsatisfied criteria included identifying teratogenicity in experimental animals. The remaining unsatisfied criterion only applies to evaluation of causation for medication or chemical exposure and does not apply to infection-related teratogenicity. Likewise, of the eight applicable criteria within the Hill criteria, each, with the exception of observed causation in experimental animals, was met.

“Our evaluation of the evidence using both of these sets of criteria yielded the same conclusion. Zika is a cause of microcephaly and other severe brain abnormalities,” Rasmussen said during the news conference.

Figure 1. A comparison of a typical head size for a baby and a baby with microcephaly.

Source: CDC

According to Rasmussen, the full spectrum of other birth defects caused by Zika remains unknown, but currently includes intracranial calcification and other severe brain defects. Rasmussen also said the type of microcephaly being observed in connection with Zika is a very severe form of the condition. Further, CDC officials stated they are still unable to positively confirm an association between Zika virus infection and Guillain-Barré syndrome.

“This is an unprecedented association,” Frieden said. “Never before in history has there been a situation where a bite from a mosquito could result in devastating malformations, and it is because this was so unprecedented that we have waited until now [to confirm] that there is a causal link.” – by Dave Costill

Disclosures: Frieden and Rasmussen are employed by the CDC.

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