Study supports Zika link to microcephaly

About one in 100 women infected by the Zika virus in early pregnancy may be at risk of having a baby with microcephaly, according to a new study of an epidemic that occurred in French Polynesia.

The study, published in the Lancet medical journal, offers further evidence that the virus is implicated in microcephaly – a condition in which babies’ brains do not develop properly, resulting in abnormally small heads.

“Our analysis strongly supports the hypothesis that Zika virus infection during the first trimester of pregnancy is associated with an increased risk of microcephaly,” says Dr Simon Cauchemez, co-author of the study from the Institut Pasteur in Paris. “We estimated that the risk of microcephaly was 1 in 100 women infected with Zika virus during the first trimester of pregnancy. The findings are from the 2013-14 outbreak in French Polynesia and it remains to be seen whether our findings apply to other countries in the same way.”

Although the risk that they calculate through mathematical modelling – 1% – is low by comparison with a virus such as rubella which causes birth defects in 50% of women infected in early pregnancy, the attack rate of the Zika virus itself is very high. There may be other co-factors in Brazil, where the rise in cases of microcephaly has triggered an international alert from the World Health Organisation. But if the findings from French Polynesia are applicable, “in Latin America right now we are speaking about relatively small risks which apply to a very large population of pregnant women,” said Professor Arnaud Fontanet, co-author of the study, from the Institut Pasteur in Paris.

The rate of 1% is lower than that found by a previous study earlier this month. Researchers in Rio de Janeiro, Brazil, enrolled 72 women who had a rash – the most identifiable symptom – and who tested positively for Zika. Out of 42 healthy women who agreed to an ultrasound examination, 29% had a foetus with microcephaly or some other sort of congenital malformation.

The Institut Pasteur scientists, however, were searching past data from the French Polynesia Zika outbreak in 2013-14 specifically for microcephaly – a small head accompanied by evidence of calcifications in the brain. Their study, they say, had the advantage of very good, complete data. Congenital abnormalities were always reported. They found eight microcephaly cases in the two years, seven of which followed the Zika epidemic. The other they consider their baseline – one case a year would have been the norm for the French Polynesian population and is the equivalent of two per 10,000 live births, a similar prevalence to that of Europe.

They constructed a number of mathematical models to attempt to explain the increase during the Zika epidemic. The best fit was with infection of the mother by the virus in the first trimester of pregnancy.

The researchers set out to look at microcephaly and not the larger number of congenital malformations that were reported during the epidemic in French Polynesia. “It may well be that infection during the second trimester or the third trimester could lead to a different type of congenital malformation,” Fontanet told the Guardian. The first trimester is crucial for the development of the brain, “but if you infect later you can imagine there might be other malformations”. That would fit with the study of pregnant women in Rio de Janeiro.

Writing in a linked comment, Dr Laura Rodrigues from the London School of Hygiene and Tropical Medicine, said: “The finding that the highest risk of microcephaly was associated with infection in the first trimester of pregnancy is biologically plausible, given the timing of brain development and the type and severity of the neurological abnormalities.”

More research is needed however, she said. “Further data will soon be available from Pernambuco, Colombia, Rio de Janeiro, and maybe other sites … The fast production of knowledge during this epidemic is an opportunity to observe science in the making: from formulation of new hypotheses and production of new results that will provide confirmations and contradictions to the refinement of methods and the gradual building of consensus.”

Dr Melissa Gladstone, senior lecturer in paediatric neurodisability at the University of Liverpool, welcomed the research, but cautioned: “Unless direct links are made and/or full investigations of babies are undertaken to exclude other causes and to identify Zika infection in infants, it will be difficult to entirely link Zika with microcephaly,” she said. “Furthermore, we may have a long way to go in terms of knowing whether there are more subtle effects of Zika virus on infants and children in the long term which span beyond microcephaly to developmental and learning difficulties.”

Dr Derek Gatherer, a lecturer in biomedical and life sciences at Lancaster University, said the study helped scientists begin to think about defining a risk period during pregnancy, with major implications likely for travel advice for pregnant women travelling to affected areas.