2018 Update on infectious disease

Danger for birth defects with maternal Zika infection present in all trimesters, but greatest in first

Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985-994.

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To estimate the risk of congenital neurologic defects associated with Zika virus infection, Hoen and colleagues conducted a prospective cohort study of pregnant women with symptomatic Zika virus infection who were enrolled during March through November 2016 in French Guiana, Guadeloupe, and Martinique. All women had Zika virus infection confirmed by PCR assay.

Details of the study

The investigators reviewed 546 pregnancies, which resulted in the birth of 555 fetuses and infants. Thirty-nine fetuses and neonates (7%; 95% CI, 5.0-9.5) had neurologic and ocular findings known to be associated with Zika virus infection. Of these, 10 pregnancies were terminated, 1 fetus was stillborn, and 28 were live-born.

Microcephaly (defined as head circumference more than 2 SD below the mean) was present in 32 fetuses and infants (5.8%); 9 had severe microcephaly, defined as head circumference more than 3 SD below the mean. Neurologic and ocular abnormalities were more common when maternal infection occurred during the first trimester (24 of 189 fetuses and infants, 12.7%) compared with infection during the second trimester (9 of 252, 3.6%) or third trimester (6 of 114, 5.3%) (P = .001).

Studies report similar rates of fetal injury

Zika virus infection primarily is caused by a bite from the Aedes aegypti mosquito. The infection also can be transmitted by sexual contact, laboratory accident, and blood transfusion. Eighty percent of infected persons are asymptomatic. In symptomatic patients, the most common clinical manifestations are low-grade fever, a disseminated maculopapular rash, arthralgias, swelling of the hands and feet, and nonpurulent conjunctivitis.

The most ominous manifestation of congenital Zika virus infection is microcephaly. Other important manifestations include lissencephaly, pachygyria, cortical atrophy, ventriculomegaly, subcortical calcifications, ocular abnormalities, and arthrogryposis. Although most of these abnormalities are immediately visible in the neonate, some may not appear until the child is older.

The present study is an excellent complement to 2 recent reports that defined the risk of Zika virus-related fetal injury in patients in the United States and its territories. Based on an analysis of data from the US Zika Pregnancy Registry, Honein and colleagues reported an overall rate of congenital infection of 6%.¹² The rate of fetal injury was 11% when the mother was infected in the first trimester and 0% when the infection occurred in the second or third trimester. The overall rate of infection and the first trimester rate of infection were similar to those reported by Hoen and colleagues.

Conversely, Shapiro-Mendoza and colleagues evaluated rates of infection in US territories (American Samoa, Puerto Rico, and the US Virgin Islands) and observed cases of fetal injury associated with second- and third-trimester maternal infection.¹³ These authors reported an overall rate of infection of 5% and an 8% rate of infection with first-trimester maternal infection. When maternal infection occurred in the second and third trimesters, the rates of fetal injury were 5% and 4%, respectively, figures almost identical to those reported by Hoen and colleagues. Of note, the investigations by Honein and Shapiro-Mendoza included women with both symptomatic and asymptomatic infection.

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