Neurological and ocular birth defects possibly associated with Zika virus infection were present in 7% of fetuses and infants of pregnant women who had symptomatic, confirmed infection in France's territories in the Americas, researchers for the prospective ZIKA-DFA-FE study reported.
Birth defects occurred more often in fetuses and infants whose mothers had been infected early in pregnancy, reported Bruno Hoen, MD, PhD, of the University Medical Center of Guadeloupe in Pointe-a-Pitre, France, and colleagues, in the New England Journal of Medicine.
"Zika virus infection during pregnancy has been identified only recently to cause severe birth defects, including microcephaly, other brain defects, and the congenital Zika syndrome," Hoen told MedPage Today. "However, the magnitude of this risk was not clearly defined, with discrepancies between observational data from Brazil and the U.S. Zika pregnancy registry."
In Brazil, birth defects from Zika virus were estimated to be higher than 40% according to a prospective observational study. In the United States, percentages have ranged from 5% to 10%.
In French territories of the Americas -- French Guiana, Guadeloupe, and Martinique -- the Zika virus epidemic began in early 2016. ZIKA-DFA-FE used several recruitment methods to enroll women whose pregnancies overlapped with the epidemic period. In each territory, pregnant women with suspected infection went to a prenatal diagnosis center for Zika infection testing and were asked to join the study.
Only pregnant women with clinical symptoms consistent with acute Zika virus infection and laboratory confirmation of recent infection with a positive result on a molecular testing of blood or urine samples were included. The researchers considered the date of the first Zika virus-related symptom onset as the date of infection.
Of 555 fetuses and infants in the 546 pregnancies included in the ZIKA-DFA-FE study, 28 were not carried to term or were stillborn, and 527 were born alive. Neurologic and ocular defects possibly associated with Zika virus infection were present in 39 fetuses and infants (7.0%; 95% CI 5.0%-9.5%). Microcephaly was detected in 32 fetuses and infants (5.8%), of whom 9 (1.6%) had severe microcephaly, and congenital Zika syndrome was identified in 17 (3.1%).
"Whichever endpoint was considered -- neurologic and ocular defects, microcephaly, or Zika congenital syndrome -- abnormalities were more common when Zika infection occurred during the first trimester than when it occurred during the second or third trimester of pregnancy," Hoen said. For example, neurologic and ocular defects were 12.7% when Zika virus infection occurred in the first trimester, 3.6% when it occurred in the second trimester, and 5.3% when it occurred in the third trimester.
These findings are remarkably similar to ones in the U.S. Zika Pregnancy and Infant Registry, wrote Margaret Honein, PhD, MPH, of the Centers for Disease Control and Prevention in Atlanta in an accompanying editorial. In the U.S., approximately 5% of pregnancies with possible Zika virus infection and 10% of the subset of pregnancies with laboratory-confirmed Zika virus infection resulted in a Zika virus-associated birth defect, she noted; the risk estimate was 15% when the confirmed infection occurred in the first trimester.
"Although there is growing clarity about the magnitude of the risk of serious birth defects associated with Zika virus infection detected during the newborn period, the full range of disabilities, including the possible effect on neurodevelopment, remains unknown," she noted.
And while studies of pregnant women with symptomatic Zika virus infections are important, they don't provide information about the estimated 80% of pregnant women with Zika virus infections who have no reported symptoms, she added: "Population level increases in Zika virus-associated birth defects are unlikely to be recognized without ongoing timely and comprehensive surveillance of birth defects that captures all affected fetuses and infants regardless of whether maternal Zika virus exposure or infection was identified."
The difference between these rates and those observed in Brazil is not attributable to the percentage of infants and fetuses with microcephaly, but to the percentage with wider neurologic birth defects, Hoen and colleagues noted. The clinical implications of Brazil findings are not yet known and may be determined through longer-term follow-up.
"The Zika virus should definitely be added to the list of infectious agents that can cause severe birth defects, as are rubella virus, cytomegalovirus, and others," Hoen said.
To protect fetal health in the future, Zika virus serology should be included in initial pregnancy work-ups for women in endemic areas, and fetal ultrasound monitoring should be enhanced when Zika virus infection has been diagnosed, he added.
This study was supported by the French Ministry of Health, by a grant from Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases project, by the ZIKAlliance Consortium (the European Union's Horizon 2020 Research and Innovation Program), and by INSERM.
The study authors and editorialist reported no conflicts of interest.
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