From Pages to Practice

By Lisa Caulley, MD, MPH, FRCSC

Published March 28, 2018


“I just want this baby to be healthy,” said Mrs. Vataire, a 29-year-old woman in her third trimester of pregnancy. She recently immigrated to the United States from French Guiana and was referred for routine prenatal evaluation. Mrs. Vataire had been diagnosed with Zika virus infection in the first trimester. She has read extensively about the congenital neurologic abnormalities associated with Zika virus infection, and asks what the potential effects this infection may have on her child.

Zika virus (ZIKV) emerged as an epidemic in the French Territories of the Americas in early 2016. ZIKV infection during pregnancy has been shown to cause severe birth defects, including microcephaly and neurologic, ocular, and musculoskeletal defects. Although the magnitude of risk is uncertain, studies in women in Brazil and the United States estimate that the risk of Zika-related congenital defects range from 6% to 42%.

In the March 15th issue of NEJM, Hoen et al. reported the effects of ZIKV infection on pregnancy outcomes in women in the French Territories of the Americas. The ZIKA-DFA-FE study prospectively followed 546 pregnant women from diagnosis of symptomatic and PCR-positive ZIKV infection until the end of pregnancy (March 2016 to April 2017). Criteria for symptomatic acute ZIKV infection were at least one symptom of pruritic skin rash, fever, conjunctival hyperemia, arthralgia, or myalgia and 2) a positive result on ZIKV RT-PCR assay in serum or urine. The women underwent monthly clinical and ultrasonographic examinations and live-born infants and fetuses from terminated pregnancies and stillbirths were examined for outcomes that were potentially-associated with ZIKV infection.

Five percent of pregnancies resulted in pregnancy loss and 95% in live births. Neurologic and ocular defects were seen in 7.0% of fetuses and infants, with microcephaly observed in 5.8% of fetuses and infants. The prevalence of neurologic and ocular birth defects was significantly higher when ZIKV infection occurred early in pregnancy: 12.7% in first trimester versus 3.6% in second trimester and 5.3% in third trimester. A neural tube defect was identified in only one patient (0.2%) and was associated with infection during the first trimester.

In an accompanying editorial, Margaret Honein emphasized the higher rate of congenital defects associated with infection during the first trimester and that the risk of severe microcephaly was limited to infections that occurred during the first or second trimester (3.7% and 0.8%, respectively). She notes similarities between the findings in the French Territories of the Americas and in the United States Zika Pregnancy and Infant Registry (a surveillance network that monitors all pregnancies with laboratory evidence of ZIKV infection). Both identified a higher rate of congenital defects with confirmed infections in the first trimester and the finding of only one neural-tube defect in the ZIKA-DFA-FE study confirms “growing evidence that neural-tube defects have not increased in areas with local ZIKV transmission and are most likely not caused by ZIKV infection.”

The results from this study further underscore the serious health threat to pregnant women and their infants posed by congenital ZIKV infection. Longer follow-up of infants is needed to assess possible Zika-related manifestations that were not detected at birth. Mrs. Vataire should be aware that according to the current evidence, birth defects potentially associated with ZIKV infection can occur in up to 7% of fetuses and infants born to pregnant women with symptomatic and PCR-confirmed ZIKV infection in the French Territories of the Americas, and the rate may be higher in mothers infected early in pregnancy.

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Lisa is a 2017-2018 NEJM Editorial Fellow. An otolaryngologist-head and neck surgeon by training, she graduated from the University of Toronto Medical School and completed her residency training at the University of Ottawa. She has a Master's in Public Health from the Harvard T. H. Chan School of Public Health.