The full scope of Zika-related birth defects may extend far beyond abnormally small heads and brain damage. Research to be presented next week at a teratology conference in San Antonio, Texas, suggests that serious joint problems, seizures, vision impairment, trouble feeding and persistent crying can be added to the list of risks from Zika exposure in the womb.

The new findings confirm doctors’ concerns that even when Zika-exposed babies are born without microcephaly and appear largely normal at birth they can go on to have health issues including seizures and developmental delays that only become apparent in the weeks and months after birth. The new work also reinforces recent findings that suggest the type of outcomes the babies experience also varies by what trimester their mothers were in when they were exposed to Zika—with few cases of microcephaly when mothers were exposed during the third trimester.

The research underscores the steep learning curve that scientists and officials face with this virus, which is transmitted through mosquito bites and sexual contact. Earlier studies chronicling apparent Zika-related damage had also hinted that doctors had much to learn about viral-driven birth defects. In March researchers published findings in the New England Journal of Medicine suggesting that 29 percent of pregnant women who tested positive for Zika had fetuses with abnormalities already apparent via ultrasound. The finding was particularly alarming because doctors knew many more central nervous system issues would likely only be recognizable months or even years after the child’s birth.

Today it remains unclear exactly how many babies born to women infected with Zika during pregnancy will develop birth defects. But the new findings from Brazil do give a better sense of the breadth of obstacles Zika-affected families may face within the first year of their newborns’ lives.

Brazilian researchers followed 83 infants born since August 2015 to mothers believed to have been infected with Zika. The study included families from eight states, mostly in Brazil’s northeast, where birth defects have soared. Because solid testing for Zika was not yet in place last fall, however, only 10 of the 83 mothers were confirmed as Zika-exposed through laboratory testing—a major caveat that applies to most current Zika-outcome studies. That reality leaves open the possibility that the birth defects could be due to other environmental or genetic factors. Still, about 70 percent of the mothers in this study remember experiencing a rash—a known Zika symptom—during their pregnancies, and the researchers eliminated other leading causes of the birth defects including certain toxic exposures and viral infections from cytomegalovirus.

The Brazilian team found that about 10 percent of the 83 babies had knee or elbow joint limitations so severe that the infants cannot fully extend their arms or legs. Another 43 percent of the babies had less-pronounced joint problems that impeded finger or toe motion, or the babies had other limb abnormalities like clubfeet. And half of the babies had seizures and abnormal eye exams.

This study reflects the situation of a relatively small study group—and only included babies with abnormalities. But it does provide some insights, including that birth defects may vary depending on what trimester the mother became infected with the virus. “These findings are in line with our findings about babies exposed to Zika in utero,” says Karin Nielsen-Saines, a pediatric infectious diseases specialist and senior author of the March NEJM research. Still, she cautioned that because this new study only includes babies with abnormalities it does not give a good snapshot of how common birth defects might really be among the Zika-exposed. “You might be missing children who are normal so you may skew your data toward abnormalities,” she says.
Zika has ushered in a number of unwelcome surprises. It is the first insect-borne disease with a proven link to serious birth defects (vision problems have been linked to West Nile Virus but not yet causally verified). Yet infection with several other viruses during pregnancy—in particular toxoplasmosis, rubella or cytomegalovirus—can also lead to microcephaly, vision problems or hearing loss that may not be immediately apparent at birth, so viral-driven birth defects are not unprecedented. CVM and toxoplasmosis can also, rarely, lead to joint issues, says Dee Quinn, director of the Arizona branch of the nonprofit MotherToBaby and a senior genetic counselor on staff at the Colleges of Medicine and Pharmacy at the University of Arizona. 

The new Brazil findings on Zika also echo certain patterns related to those other viral infections. Notably, mothers infected with Zika late in their pregnancies tended to have babies with relatively less-serious side effects: The children more often had developmental delays including trouble sitting up, as well as seizures instead of microcephaly and significant brain calcifications, says Lavinia Schuler-Faccini, the president of the Brazilian Society of Medical Genetics and the scientist presenting the findings next week. Still, that does not mean fetuses exposed during the third trimester are better off. Nielsen-Saines says that in her published work and in ongoing analysis she is seeing that such late exposure is more likely to lead to stillbirths.

Pinning down more concrete answers about how common birth defects may be among pregnant women remains an arduous task, and scientists still do not know if other factors including genetics, exposure to other viruses or how women contracted the virus—via sex or mosquito bite—may play a role. Further complicating efforts to get a handle on the issue: according to the World Health Organization, more pregnant women infected with Zika are now aborting their fetuses.