Abstract
Congenital Zika virus infection causes a spectrum of adverse birth outcomes, including severe birth defects of the central nervous system. The association of prenatal ultrasonographic findings with adverse neonatal outcomes, beyond structural anomalies such as microcephaly, has not been described to date. To determine whether prenatal ultrasonographic examination results are associated with abnormal neonatal outcomes in Zika virus-affected pregnancies. A prospective cohort study conducted at a single regional referral center in Rio de Janeiro, Brazil, from September 1, 2015, to May 31, 2016, among 92 pregnant women diagnosed during pregnancy with Zika virus infection by reverse-transcription polymerase chain reaction, who underwent subsequent prenatal ultrasonographic and neonatal evaluation. Prenatal ultrasonography. The primary outcome measure was composite adverse neonatal outcome (perinatal death, abnormal finding on neonatal examination, or abnormal finding on postnatal neuroimaging). Secondary outcomes include association of specific findings with neonatal outcomes. Of 92 mother-neonate dyads (mean [SD] maternal age, 29.4 [6.3] years), 55 (60%) had normal results and 37 (40%) had abnormal results on prenatal ultrasonographic examinations. The median gestational age at delivery was 38.6 weeks (interquartile range, 37.9-39.3). Of the 45 neonates with composite adverse outcome, 23 (51%) had normal results on prenatal ultrasonography. Eleven pregnant women (12%) had a Zika virus-associated finding that was associated with an abnormal result on neonatal examination (adjusted odds ratio [aOR], 11.6; 95% CI, 1.8-72.8), abnormal result on postnatal neuroimaging (aOR, 6.7; 95% CI, 1.1-38.9), and composite adverse neonatal outcome (aOR, 27.2; 95% CI, 2.5-296.6). Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities (aOR, 12.8; 95% CI, 2.6-63.2), postnatal neuroimaging abnormalities (aOR, 8.8; 95% CI, 1.7-45.9), and composite adverse neonatal outcome (aOR, 20.5; 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings on prenatal ultrasonography had a sensitivity of 48.9% (95% CI, 33.7%-64.2%) and a specificity of 68.1% (95% CI, 52.9%-80.1%) for association with composite adverse neonatal outcomes. For a Zika virus-associated abnormal result on prenatal ultrasonography, the sensitivity was lower (22.2%; 95% CI, 11.2%-37.1%) but the specificity was higher (97.9%; 95% CI, 88.7%-99.9%). Abnormal results on prenatal ultrasonography were associated with adverse outcomes in congenital Zika infection. The absence of abnormal findings on prenatal ultrasonography was not associated with a normal neonatal outcome. Comprehensive evaluation is recommended for all neonates with prenatal Zika virus exposure.
Highlights
The rate of abnormal perinatal outcomes after maternal Zika virus infection has been estimated to be from 6% to 55% for infections acquired in the first trimester and from 3% to 29% for infections acquired in the third trimester.[1]
Eleven pregnant women (12%) had a Zika virus–associated finding that was associated with an abnormal result on neonatal examination, abnormal result on postnatal neuroimaging, and composite adverse neonatal outcome
Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities, postnatal neuroimaging abnormalities, and composite adverse neonatal outcome
Summary
The rate of abnormal perinatal outcomes after maternal Zika virus infection has been estimated to be from 6% to 55% for infections acquired in the first trimester and from 3% to 29% for infections acquired in the third trimester.[1] The spectrum of anomalies associated with maternal Zika virus infection is still being characterized, and most information to date has been gleaned from retrospective cohorts and case-control studies.[2,3,4,5,6,7,8,9,10] Recent reports evaluating the predictive value of prenatal ultrasonography are limited because they included cohorts identified prenatally or postnatally with microcephaly alone and did not include all pregnant women infected with Zika virus.[11,12] variation in the case definition of Zika virus infection by different groups, the reliance on serologic diagnosis in endemic areas, complicates the interpretation of results owing to the cross-reactivity of antibodies with other common flaviviruses, such as dengue virus.[13,14] microcephaly was among the birth defects initially associated with congenital Zika virus, additional brain abnormalities have been identified in its absence, and the spectrum of postnatal abnormalities is not yet fully characterized.[10,15,16,17,18,19] Reports have primarily focused on the predictive value of prenatal ultrasonography in identifying microcephaly among affected neonates.[20] it is likely that not all Zika virus–infected fetuses will be affected to the same degree, such as with cytomegalovirus infection[21]; focusing prenatal diagnosis on the detection of microcephaly will fail to identify all infants at risk for adverse outcome
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