Zika Virus Infection in Pregnant Women in Rio de Janeiro

Abstract

Background: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants.

Methods: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes.

Results: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester).

Conclusions: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

Figure 1. Prospective Maternal Cohort and Pregnancy Outcomes

Among 134 ZIKV-positive women, 9 were lost to follow-up before delivery and 125 had outcomes that could be evaluated; 116 of these pregnancies resulted in 117 live-born babies (there was one set of twins); 9 pregnancies ended in fetal death. One ZIKV-positive mother who had a miscarriage was coinfected with chikungunya virus; two ZIKV-negative mothers whose pregnancies ended in fetal death were infected with chikungunya virus. Three infants of ZIKV-negative mothers were small for gestational age at birth (listed as “abnormalities on examination”); one was born to a mother with confirmed chikungunya virus infection.

Figure 2. Pregnancy and Infant Outcomes According to the Week of Gestation at the Time of ZIKV Infection

Adverse outcomes included 9 cases of fetal death in 125 pregnancies (7.2%) and 49 abnormal clinical findings, imaging findings, or both during the newborn period in 117 infants (42%) born from 116 pregnancies. Adverse outcomes occurred in women who were infected during the period from 6 to 39 weeks of gestation. Abnormalities are detailed in Table S2 in the Supplementary Appendix.

Figure 3. Fetal Biometric Variables as Measured on Ultrasonography

Fetal measurements of biparietal diameter (Panel A), head circumference (Panel B), and estimated fetal weight (Panel C), plotted according to gestational age, are shown for each fetus of ZIKV-positive women who had ultrasonography performed during pregnancy. Dotted lines show the 10th and 90th percentiles for gestational age, based on established nomograms from www.perinatology.com. Fetal weight curves are based on the Hadlock formula, in which a measurement of less than the 10th percentile is considered to indicate fetal growth restriction. Microcephaly was defined as a head circumference of more than 2 standard deviations below the mean expected for gestational age. Symbols denote the trimester of PCR-documented infection (first trimester, <14 weeks; second trimester, 14 to 28 weeks; third trimester, ≥29 weeks). Repeat measurements for the same fetus are connected with a solid line to show growth trajectory. Results for fetuses with abnormal findings are denoted in color and labeled with maternal patient number. Not all measurements were obtained for every fetus at each ultrasound examination.

Figure 4. Infant Anthropometric Measures at Birth

Shown are measurements of head circumference at birth in infant boys (Panel A) and girls (Panel B) and estimated birth weight in infant boys (Panel C) and girls (Panel D), according to gestational age at birth. A total of 117 live infants were born to women in our cohort who had positive results for ZIKV on polymerase-chain-reaction (PCR) assays, and 57 were born to women who had negative PCR results for ZIKV. Small for gestational age was defined as a z score for birth weight of less than −1.28. Microcephaly was defined as a z score of less than −2 (moderate) and less than −3 (severe).