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May 8, 2016: Thinking on How the Zika Virus Causes Microcephaly

The World Health Organization said in late March that there was “strong scientific consensus” that the Zika virus caused microcephaly, in which infants are born with unusually small heads and damaged brains. In April, the Centers for Disease Control and Prevention went further, declaring, “It is now clear that the Zika virus causes microcephaly.”

Zika-associated microcephaly is a particularly destructive type, the C.D.C. added: The babies’ heads are much smaller than in other types of microcephaly, and even the simplest actions that most newborns master, like swallowing and bending joints, are impaired.

The C.D.C. reached its conclusion not because of a single large study but because of “mounting evidence from many studies,” which collectively satisfied a set of criteria used to test whether a particular threat to a fetus causes a particular birth defect.

Virtually all public health agencies are now giving medical advice based on the belief that the virus is to blame for microcephaly. Here are the lines of evidence they cite.

  1. Cases of microcephaly have surged in Brazil. As early as last August, hospitals in northeast Brazil realized that something unheard of was happening: Neonatal wards that normally saw one or two microcephalic babies a year were seeing five or more at the same time. Doctors learned from the mothers that many had had symptoms of Zika infection months earlier.
  2. On a smaller scale, it seems to have happened in French Polynesia, too. Microcephaly and other fetal malformations that appeared to be associated with maternal Zika infections have been reported in French Polynesia, Colombia, Cape Verde, Martinique and Panama.
The virus crosses the placenta and can reach the fetus. Zika virus has been found in amniotic fluid surrounding microcephalic babies, and autopsies have found it in the brains of fetuses that died in the womb. The virus was discovered in the brain of a microcephalic baby aborted at 32 weeks, six months after the mother recovered from the disease.
  4. Zika also attacks brain cells. Studies in cell cultures and in mice have shown that the virus is “neurotropic” — that is, it targets nerve cells, including the ones that eventually become the baby’s brain. In a study in Cell Stem Cell, researchers exposed fetal stem cells to the virus and found that it particularly attacked cortical neural progenitor cells, which ultimately form the brain’s cortex, the region responsible for many higher functions.
  5. A small study found a big difference in birth defects. A study of 42 pregnant Brazilian women published March 4 found that 29 percent of those who had been infected with Zika virus experienced “grave outcomes” to their pregnancies, while none of the uninfected women did. Those outcomes included fetal death, tiny heads, shrunken placentas and fetal nerve damage that suggested blindness. The most shocking finding was that two babies that had been developing normally died suddenly when their mothers were infected late in pregnancy.
  6. “Shepard’s criteria” have been satisfied, according to the C.D.C. In explaining its April 13 announcement, the C.D.C. said the Zika virus had met four of the seven scientific criteria – so-called Shepard’s criteria, named for the Seattle pediatrician who invented them – needed to determine whether a maternal infection or poisoning in pregnancy directly causes birth defects.

Source: New York Times

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