Zika virus vertical transmission in children with confirmed antenatal exposure

Abstract

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

Fig. 1. Timing of positive and negative ZIKV laboratory results over time by age.

The figure reflects the number of assays performed in each assay category in specimens collected from 130 children. There were 161 serum specimens run for ZIKV PCR and ZIKV IgM and 85 urine specimens run for ZIKV PCR. The vertical line in the box represents the median, the box the interquartile range (10–90% of the data), and the whiskers the 95% confidence interval. The figure represents all the assays performed, not the number of children. All IgM assays were run once and in duplicate and all PCR assays were run once in triplicate. Children can be represented more than once. Error bars represent the standard deviation.

Fig. 2. Infant positive PCR and IgM results by infant age and maternal gestational age of infection.

Panel (a) depicts positive ZIKV PCR results in serum or urine for unique children. Before 90 days of age, 45 children had positive PCR results. After 90 days of age, 17 children had positive PCR results. The difference in distribution of positive PCR results between both age groups was not statistically significant, p = 0.87. Panel (b) depicts positive ZIKV IgM results. Before 90 days of infant age, 29 infants had positive results. After 90 days of age, 13 children had positive IgM results. The difference in distribution of positive IgM results between both age groups was statistically significant, p = 0.03. The statistical test used for comparison was a two-sided hypothesis Student T-test at the alpha 0.05 level. There were no adjustments for multiple comparisons. Error bars represent the standard deviation.