Large numbers of babies with borderline normal head sizes were born in Brazil as far back as 2012, two years before the Zika virus is thought to have entered the country, say researchers searching for answers to urgent questions.
Pediatric cardiologist Dr. Sandra Mattos had been collecting data on 100,000 newborns in the Brazilian state of Paraiba as part of her work studying and treating congenital heart disease.
The microcephaly fears linked to the Zika virus drove her team to check back into hospital records for head circumferences of more than 1,600 babies born in the state in the last four years.
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"We were very, very surprised," Mattos said. Babies with mild microcephaly were present in the population dating back to at least 2012.
Having a head slightly smaller than the limit doesn't mean there's neurological disease. "Borderline cases seem to be present all along," she said.
Brazilian authorities set the criterion for microcephaly, a measurement of head size, at 32 centimetres for full-term births. Doctors were asked to report babies at or below that level for further investigation.
Mattos said the data analysis also confirmed the number of severe microcephaly cases increased starting in October or November of 2014.
Scientists think the original reports of 4,700 suspected cases were inflated by over-reporting that didn't stand up when specialists examined the babies. Brazil's Ministry of Health said Tuesday that 404 cases have been confirmed as involving microcephaly or other nervous system disorders and 709 have been ruled out. The other cases remain under investigation.
'We have to deal with an unknown enemy.' - Dr. Sandra Mattos
Lingering questions remain, including why more than 80 per cent of suspected microcephaly cases are confined to Brazil's northeast region. And why has microcephaly not appeared in other Latin American countries with similar climates, such as among the 2,100 pregnant women infected with Zika in Colombia?
In her research paper submitted to the Bulletin of the World Health Organization, Mattos and her colleagues suggest other potential factors need to be considered.
These include boosting effects from other infections, exposure to teratogens or agents that cause birth defects, such as drugs, and malnutrition, which could have "an intensifying effect."
In Berlin, epidemiologist Dr. Christoph Zink has been charting publicly available data from the Zika virus outbreak in terms of when cases appeared, the geographic distribution and the continuous microcephaly epidemic.
"I soon got the idea that blaming the Zika virus for this epidemic does not really get to the point," Zink said.
Zink suspects there was massive under-reporting of microcephaly in Brazil in the last five years. He proposes another potential explanation for the recent concentration of severe microcephaly cases in the northeast.
"I would ask my toxicological colleagues in Brazil to please look very closely into the practical application of agrochemicals in their country," Zink said.
Pressing needs of pregnant women
Mattos said pesticides have been raised as a potential factor by her colleagues in Brazil.
At this point, there's more speculation than answers or enough data to draw conclusions.
"I think we jumped a little bit too fast into Zika. It may be well. Not saying it isn't. But just saying there are a few things that don't seem to kind of match very easily in this picture and that we may need to investigate a bit further," Mattos said.
On Thursday, Mattos will present her data to officials with the U.S. Centers for Disease Control and Prevention.
"We have to deal with an unknown enemy, a big problem, a major disease, a new disease that has changed, an environmental problem we don't know," Mattos said. "At the same time, we need time for science to run its routines … we have tremendous pressing needs of the population, pregnant women, women of reproductive age, for quick answers."
This week, Canadian health officials released recommendations on prevention and treatment of Zika virus, including how to evaluate pregnant women with a travel history and followup screening for infants.
One of the challenges of events like the Zika outbreak is how they are defined by a high level of scientific uncertainty, said Prof. Joshua Greenberg, who researches risk communication in public health at Carleton University in Ottawa.
"I think the World Health Organization, the CDC, the Public Health Agency of Canada are doing the best they possibly can to communicate what they know and don't know about the virus and the links it has to the microcephaly cases. And that's a really difficult thing for public health officials to do, because of the expectation or the desire among the scientific community, but I think among the population as well, to have a higher degree of certainty about what's going on, to provide reassurance, to express confidence," Greenberg said.
Researchers expect it will take months before the questions about the association between microcephaly and the Zika virus are answered. For her part, Mattos is now checking to see if there is evidence of microcephaly in Brazil as early as 2010.