Liz Szabo

USA TODAY

A new study provides the strongest evidence yet that the Zika virus is the cause of devastating birth defects seen in Brazil, home to the largest outbreak of the disease.

Authors of the new study have followed 88 pregnant women in Brazil to see whether being infected with Zika, which is spread by mosquitoes, increases the rate of birth defects. Seventy-two of the women tested positive for the virus. The women's blood and urine were tested five days or less after they developed an itchy rash, a tell-tale symptom of Zika.

Other symptoms of Zika infection included fever, pink eye, swollen lymph nodes and joint pain. Most people with Zika have no symptoms.

Ultrasounds found major abnormalities in 29% of the fetuses from women who tested positive for Zika, but none of the women without Zika infections, according to the study, published online Friday in The New England Journal of Medicine. Women were exposed to the Zika virus between the sixth and 35th week of pregnancy. A typical pregnancy lasts 40 weeks.

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Those abnormalities included microcephaly, in which babies are born with unusually small skulls, which typically signifies incomplete brain development; restricted growth in the womb; poor development of brain structures; calcifications in the brain, which signal places where tissue has died; abnormal amniotic fluid levels; or abnormal blood flow in the fetal brain, umbilical cord or placenta, according to the study.

"Even if the fetus isn’t affected, the virus appears to damage the placenta, which can lead to fetal death," said study senior author Karin Nielsen, a professor of clinical pediatrics in the division of pediatric infectious diseases at the David Geffen School of Medicine at UCLA.

Two women with Zika infections miscarried early in pregnancy, according to the study, led by doctors at UCLA and Fiocruz, also known as the Oswaldo Cruz Foundation, a large biomedical institute in Rio de Janeiro. Two of the babies were stillborn, dying at 36 weeks and 38 weeks, according to the study.

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Six women have given birth so far. Doctors plan to follow the remaining women through the end of their pregnancies and beyond, Nielsen said.

Two of the babies were born small for their gestational age. One was born with severe microcephaly and eye lesions that could indicate blindness, according to the study.

Doctors delivered one baby by emergency C-section because there was no amniotic fluid left in the uterus, a potentially life-threatening problem. The baby, a boy, recovered and appears to be healthy. His mother was infected with Zika in her 35th week of pregnancy.

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Two infants of mothers with normal ultrasound results appear to be healthy, according to the study.

Ultrasound results were shown to be accurate for the two stillbirths and the six babies born alive, according to the study.

"We're seeing a spectrum of abnormalities," said Nielsen, who referred to the baby's conditions as Zika Virus Congenital Syndrome. "It's not all just microcephaly."

All of the mothers in the study were healthy, with no other risk factors for pregnancy complications.

Babies will need hearing and vision tests, Nielsen said.

Although doctors have been concerned about babies who were infected early in pregnancy, an important time for brain development, the new study suggests that Zika infection later in pregnancy can still have negative effects.

The mothers' Zika symptoms — itchy rash, joint pain and swollen lymph nodes — resemble those of rubella, or German measles, which can cause microcephaly and a range of serious problems for babies. During a rubella pandemic from 1959 to 1965, which led to the birth of 20,000 babies with congenital rubella syndrome, 85% of affected babies had restricted growth in the uterus, according to background information in the study.

The size of that rubella outbreak was limited by the fact that more than 80% of women of childbearing age at the time had been exposed to rubella and had antibodies against it, protecting them and their babies, according to the study.

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Residents of the Americas today have no immunity against the Zika virus, which originated in Africa, because people in this part of the world have never been exposed to it. That lack of immunity helps to explain the virus' explosive spread throughout the Western Hemisphere, said Michael Osterholm,director of the University of Minnesota's Center for Infectious Disease Research and Policy.

Officials at the World Health Organization predict that the Americas could see 4 million cases of Zika virus this year.

Two countries with Zika outbreaks — Brazil and French Polynesia — have seen increases in microcephaly rates. Today, the Nature news site reported that doctors in Colombia are reporting the birth of three babies with Zika infections, one of whom has microcephaly and two of whom have other brain abnormalities.

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Brazil reported 5,909 cases of microcephaly from October through the end of February, according to the World Health Organization. Doctors ruled out more than 1,000 of these cases as not being true incidents of microcephaly; health offiicals are still investigating more than 4,200 cases. Brazil typically reports 163 cases of microcephaly a year, although some have noted that the country may have undercounted these birth defects before the Zika outbreak.

Officials at the World Health Organization have warned that Colombia, whose Zika outbreak started more recently than Brazil's, could see a spike in birth defects this summer, as women infected in early pregnancy give birth.

Experts agreed the new study was significant.

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Nielsen's study, while small, presents "the strongest evidence so far" showing that the Zika virus actually causes birth defects, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Scientifically, the link between Zika and birth defects would be stronger if there were multiple studies with similar results.

Given that only eight women have given birth, the study's conclusions should be seen as preliminary, Fauci said. He notes that Brazilian researchers are currently conducting additional studies that will provide stronger evidence. Doctors there will be comparing the health of infants born to women with and without Zika infections, Fauci said.

Some scientists say the verdict on Zika and birth defects is in.

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The new study "will finally put to rest everyone's questions about whether Zika causes microcephaly," Osterholm said. "This study has given us a very real, very scary view into the future."

The USA needs to "act now as if there were a very clear causal link" between Zika and birth defects, rather than wait for iron-clad proof, said Lawrence Gostin, director of the O’Neill Institute for National and Global Health Law at Georgetown University. Delaying action will only lead to more Zika cases and more injured babies, he said.

Controlling mosquitoes will be crucial this spring and summer, Osterholm said. Communities will need to mount major efforts to clean up trash, which can collect standing water where mosquitoes breed, he said. Communities also will need to put more money into killing mosquitoes with sprays.

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Countries need to make contraception available to women who want to delay pregnancy, Gostin said. That's important, given that birth control is often difficult to access in Latin American and the Caribbean.

Countries also need to make health care and support services available to women and children, particularly babies born with birth defects, who may need lifelong care, Gostin said.

Nielsen said her study also argues against the notion that Brazil's microcephaly cases were caused not by Zika but by pesticides used to kill mosquitoes. Public health experts have dismissed that notion as a myth, with no evidence to back it up, given that babies with birth defects have been born in places where pesticides have not been used. Nielsen said the pesticide myth also could harm efforts to control mosquitoes.

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In other news, researchers at Johns Hopkins University in Baltimore said Friday that they have discovered how the Zika virus causes microcephaly.

The virus selectively infects cells that form the brain's cortex, or outer layer, making them more likely to die and less likely to grow normally, according to a report in Cell Stem Cell. Authors say their findings, based on lab-grown human stem cells, could help scientists screen for drugs that protect brain cells against the Zika virus.

Nielsen notes that previous studies have found the Zika virus in the brains and amniotic fluid of babies and fetuses with microcephaly. Because the Zika virus was found in the brain, but not other organs, Nielsen said the virus appears to target brain tissue.

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