Updated

Official reports on the impact of Zika virus in Colombia appear to dramatically underestimate the number of infants born there with associated birth defects, a new study suggests.

The actual number may be at least two times higher than the official estimate and perhaps even higher still, according to the study.

The study was published Friday in Morbidity and Mortality Weekly, a journal of the Centers for Disease Control and Prevention. It was conducted by scientists from the CDC and its Colombian equivalent, the National Institute of Health.

The research found there was a fourfold increase in microcephaly cases — babies born with a smaller than normal heads and often under-formed brains — in Colombia from March to November of this year compared with last year. While there were 110 in that period in 2015, there were 476 in 2016.

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Colombia has reported only 60 cases of Zika-linked microcephaly to the World Health Organization.

The peak in affected births came about 24 weeks after the peak in reported infections in pregnant women — and corresponds with the theory that maternal infection in the first trimester or early in the second is the period of highest risk for the developing fetus, said one of the senior authors, Margaret Honein, chief of the CDC’s birth defects branch.

“So we think this is pretty compelling evidence that the increase in microcephaly is linked to the increase in Zika virus disease in these pregnant women,” she said.

Honein suggested Colombia is following a pattern similar to what Brazil saw.

“We expect that every country that has a large Zika virus outbreak will have an increase in microcephaly and severe brain abnormalities following that,” she said.

“So Colombia has experienced a significant increase in microcephaly six months after the peak of Zika virus disease in pregnant women. And that’s what we would anticipate happening.”

Asked why the official microcephaly figure differs from the numbers in the study, Honein deferred to Colombia. But she said researchers there are conducting thorough investigations of each suspected case and reporting on those in which there is strong evidence of maternal Zika infection during pregnancy.

The study noted that samples were not taken for testing in all cases, and even when samples were taken, sometimes they were not taken quickly enough to find evidence of infection.

Neither WHO officials nor Colombian officials responded immediately to requests for comment.

Public health experts studying the Zika outbreak have been puzzled by the fact that Brazil — where the link between the virus and microcephaly was first noted — has seen so many infants with Zika-induced birth defects and other countries have seen, in comparative terms, so few.

A report on Zika released by the WHO on Thursday showed 29 countries have reported a total of 2,436 affected births, with 2,211 of them from Brazil.

The new study noted that between half and three-quarters of Colombia’s population lives in parts of the country where Zika hasn’t been spreading because of the altitude.

In other parts of the country, there has been a definite increase in microcephaly cases. But the condition is difficult to diagnose, and different definitions have been used in different countries, complicating efforts to compare what is happening across borders, Honein said.

Additionally, after Brazil raised the alarm about the potential link between Zika and microcephaly, the government of Colombia advised women to consider delaying pregnancy. The number of live births in the country dropped by approximately 18,000 over a nine-month period after that warning was issued, the study authors reported.