Zika-related miscarriage or stillbirth may be much higher than previously thought in women infected early in their pregnancies, according to a report today from scientists at six different primate research centers.
All of the teams were monitoring experimentally infected pregnant monkeys to gauge impact on pregnancies and explore damage to different tissues. They were able to control timing and infection method in a way that's not possible in humans.
At a scientific meeting last summer, researchers from different centers were comparing notes about their Zika studies and noticed they were seeing the same patterns. David O'Connor, PhD, professor of pathology at the University of Wisconsin-Madison, said in a press release from the school, "We were sharing our observations that we had seem some of these pregnancies were not going to term."
The decided to pool their data, publishing the findings today in Nature Medicine. Study teams from labs at six National Primate Research Centers were included in the study. The ones in California, Oregon, Wisconsin, and Tulane University used rhesus macaques. Southwest National Primate Research Center used common marmosets, and the Washington National Primate Research Center used pigtail macaques.
Pregnancy losses, even in asymptomatic monkeys
Overall, they found that 26% of pregnancies in monkeys infected with Zika virus during the first trimester ended in miscarriage of stillbirth, about four-fold higher than in unexposed monkeys at the centers. The level they saw is much higher than the 8% rate reported earlier this year in women infected with Zika during the early months of pregnancy. Three more of the baby monkeys died soon after birth.
A recent study estimated that in woman known to be infected, 5.8% miscarried and 1.6% experienced stillbirth during the first trimester. Researchers expect that the true miscarriage and stillbirth rate in humans is less than 26%, but is still much higher than what human studies suggest.
Dawn Dudley, PhD, lead author of the study who is with the University of Wisconsin-Madison department of pathology and laboratory medicine, said pregnancy studies in humans are probably missing half of the people who have Zika, because they rely on symptomatic infections. "Women get enrolled in studies because they have Zika symptoms, but we know that up to half of people who have Zika don't show any symptoms at all," she said. "So the pregnancy studies are probably missing half of the people who have Zika."
Some women may have Zika-related miscarriages before they even know they are pregnant, the team notes, and later-term miscarriages related to the virus may never be known in instances when women don't receive follow-up care. "You could never account for those women having a miscarriage due to Zika virus infection."
During the studies, few monkeys showed symptoms, and when they did, they typically involved rash and conjunctivitis. However, they still uniformly passed the virus to their fetuses. They found that Zika strains involved in recent Asian and American outbreaks damaged tissues connecting mothers to their developing fetuses. Dudley said teams saw evidence of a type of damage to the placenta, which impaired its function. On ultrasound examination, researchers commonly saw increased placental calcification.
Zika as a silently circulating threat
O'Connor said if miscarriages and stillbirths are even more prevalent than birth defects, "we will need to reconsider what we know about Zika virus." He added that it's possible that the virus may have been circulating undetected, quietly doing a great deal of damage by increasing the rate of miscarriage.
He said the situation could be similar to HIV, which when discovered three decades ago had already affected all of Africa. "We need to be open-minded about the possibility that something similar has been happening on a large scale that we simply don't know about."
Lark Coffey, PhD, study coauthor and arbovirologist at the University of California at Davis, said in a media release from the school that for pregnant women in Zika-affected areas who experience spontaneous abortions, health officials may be missing the possible link the Zika. "Our data in monkey indicate that more research is needed so researchers can develop intervention strategies to protect pregnant women and their fetuses from Zika virus," she added.
See also:
Jul 2 Nat Med abstract
Jul 2 UW-Madison press release
Jul 2 UC-Davis press release
