A direct causal link between Zika virus infection in pregnant women and the brain damaging birth defect has been registered by a study.
But while preliminary findings from the first 32 cases involved in the study confirm causality, the researchers said, the true size of the effect will become clear only after full analysis of all 200 cases and 400 controls.
The study, published in The Lancet Infectious Diseases journal, was requested by the Brazilian health ministry to investigate the causes of the microcephaly epidemic that the World Health Organization (WHO) declared an international public health emergency earlier this year.
The outbreak of Zika, a mosquito-borne disease, was detected last year in Brazil, where it has been linked to more than 1,700 cases of microcephaly, a birth defect marked by small head size that can lead to severe developmental problems. The virus has since spread rapidly through the Americas and Caribbean.
While the WHO and other disease experts had said there was strong scientific consensus that Zika and microcephaly were linked, evidence until now has been largely circumstantial.
MISSING PIECE OF JIGSAW
Laura Rodrigues, a professor at the London School of Hygiene and Tropical Medicine who worked on this study, said its results were "the missing pieces in the jigsaw" proving the link.
The research followed and compared pregnancies that resulted in healthy babies with those that resulted in cases of microcephaly - looking for signs that the Zika virus is passed onto fetuses who develop the defect.
It covered all babies born with microcephaly delivered in eight public hospitals in Brazil's north-eastern Pernambuco State between January 15 and May 2 this year. For each case, two controls were added. These were the first two babies born the following morning without microcephaly in one of the hospitals.
After taking samples and conducting brain scans, the researchers found that 41 percent of mothers of babies with microcephaly tested positive for Zika infection in blood or cerebrospinal fluid samples, compared with none of those whose babies did not have microcephaly.
A high proportion of mothers of both microcephaly and non-microcephaly babies also tested positive for another mosquito-borne virus, dengue fever, as well as other infections such as herpes, rubella and toxoplasma.
"Our findings suggest Zika virus should be officially added to the list of congenital infections," said Thália Velho Barreto de Araújo of Brazil's Pernambuco University, who also worked on the research team. "However, many questions still remain to be answered - including the role of previous dengue infection."
Rodrigues warned that preliminary analyses should be viewed with some caution, since they can overestimate the strength of a link. "When complete, the study, along with other ongoing research, will provide vital information on any role co-factors might have in the epidemic," she said.