Babies exposed to Zika in a Brazilian city did not have microcephaly

A research group monitored 55 women with a confirmed diagnosis of Zika during pregnancy. Some 28% of the babies were born with mild neurological alterations, but no cases of microcephaly were identified.

By Karina Toledo, in São José do Rio Preto  |  Agência FAPESP – For about a year, researchers at the São José do Rio Preto Medical School (FAMERP) in São Paulo, Brazil, have been monitoring a group of 55 women with a confirmed diagnosis of Zika virus infection during pregnancy.

All the women took their pregnancies to term. The babies were born alive and no cases of microcephaly or any severe neurological alterations were identified. 

The study was presented by Maurício Lacerda Nogueira, a professor at FAMERP, on May 31 during the São Paulo School of Advanced Science in Arbovirology, a program that took place with FAPESP’s support between May 29 and June 9.

“About 28% of the infants were found to have some kind of alteration at birth, such as minor brain calcifications, small lesions in brain blood vessels, unilateral hearing loss or retina damage. Some only had the virus in their organisms and displayed no symptoms. No serious neurological alterations were observed,” Nogueira said in an interview with Agência FAPESP.

All the children included in the study would have been considered normal by health services and would not have been diagnosed as victims of Zika if they had not taken part in a research protocol, he added. The pattern observed in São José do Rio Preto, according to Nogueira, contrasts strongly with that observed in several states in Brazil’s Northeast region and in Rio de Janeiro.

A study published in the New England Journal of Medicine by researchers affiliated with the Oswaldo Cruz Foundation (FIOCRUZ) found that 39.2% of 125 pregnant women with a confirmed diagnosis of Zika virus infection in Rio de Janeiro had babies with major neurological alterations and that 7.2% did not take the pregnancy to term, resulting in a total of 46.4% with negative outcomes. Four infants were born with microcephaly, corresponding to just over 3% of the study sample.

“The Rio de Janeiro study was the first description of Zika in pregnant women,” Nogueira said. “We’re now adding a new population in a new environment, and the results are very different. We’re showing a different pattern of outcomes for Zika infection during pregnancy.”

Data from the city of Salvador, the capital of Bahia State, were also presented during the São Paulo School of Advanced Science in Arbovirology by Dr. Albert Icksang Ko, a researcher affiliated with Yale University in the United States. Ko has been working in partnership with a group at FIOCRUZ in Bahia.

Ko and collaborators monitored all births occurring at a public hospital in Salvador during November and December 2015, when the Zika epidemic peaked in the state. The study therefore also included women without a confirmed diagnosis of Zika virus infection.

“We found a completely different pattern of outcomes from that observed in São José do Rio Preto. In our study, some 10% of infants were born with severe congenital alterations, including microcephaly,” Ko said.

In search of answers

According to Nogueira, the first hypothesis suggested to explain such contrasting gestational outcomes was the existence of genetically different populations of Zika virus in Brazil.

“This hypothesis has been refuted by recent studies showing that the diversity of Zika is still negligible in the Americas,” he said. “The virus that’s circulating here in São José do Rio Preto is basically the same as the virus found in Bahia or Rio de Janeiro. So, if the difference isn’t in the virus, then it must be in the human host. Some genetic factor must be protecting certain people, or it may be prior exposure to other viruses.”

Data from Ko’s study in Bahia suggest that the presence of antibodies against dengue virus in the pregnant women who took part in the study was associated with a lower risk of microcephaly in their offspring. Further studies are needed to confirm this preliminary finding.

For Paolo Zanotto, a researcher affiliated with the University of São Paulo’s Biomedical Science Institute (ICB-USP), one of the possibilities to be investigated is the occurrence of maternal co-infection as a risk factor for microcephaly and other severe congenital alterations. 

“Pathogens such as syphilis, rubella and toxoplasmosis, among others, are known to cause congenital malformations,” Zanotto said. “Fetal damage may be favored if a pregnant woman is infected by one of these pathogens and Zika at the same time.”

According to Zanotto, who also coordinates the Zika Virus Research Network (Rede Zika) in São Paulo, it will not be possible to reach a conclusion until the total number of people infected in the various locations is determined.

“In order to know whether there has been proportionally more microcephaly in the Northeast of Brazil than in Colombia, Central America or São José do Rio Preto, we have to determine these denominators, and to do that, we need extremely reliable serological tests,” he said. Serological tests are designed to detect antibodies against a virus in the bloodstream even after the acute phase of an infection is over.

For Nogueira, at some point it will also be necessary to unify the data obtained in São Paulo, Rio de Janeiro and the Northeast to compare them more comprehensively. “All this still has to be evaluated with care and in a large number of patients so that we can obtain more precise answers,” he said.

The study performed at FAMERP was supported by FAPESP through a Thematic Project for which Nogueira is the principal investigator.

The group now plans to continue monitoring the babies to see whether any late developmental alterations arise. This research will be part of another project supported by a grant awarded under the program Research in Public Policies for the Unified Health System (PPSUS).