Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort

Abstract

Background There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes. Methods This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment. Results Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16–33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities. Conclusions Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

Discordant Clinical Outcomes in a Monozygotic Dichorionic-Diamniotic Twin Pregnancy with Probable Zika Virus Exposure. Case Report

“…A series of ZIKV affected twin pregnancies have been reported in the literature, some with concordant and others with discordant outcomes. Twin discordance seems to be a more common finding among dizygotic (DZ) pregnancies, and it can be seen at multiple levels including within clinical and laboratory findings between the twins, between the placentas or the portions of a single placenta, and between the infant and corresponding placenta [ 32 ].…”

“…A further analysis that included in vitro ZIKV infection of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells from three pairs of discordant DZ twins identified a significant difference of NPC survival and viral replication being more severe in samples from the affected twin of each pair [ 34 ]. Most of the reported cases of MZ twin pregnancies with congenital ZIKV infection have concordant clinical outcomes, either having absence of adverse outcomes [ 32 ] or compromise in both fetuses/infants [ 34 , 35 ]. For DZ and MZ pregnancies with concordant fetal and infant outcomes, the extent of the clinical compromise can be variable, including differential findings regarding CNS and eye abnormalities and of neurodevelopmental sequelae such as epilepsy, developmental delay, and hearing loss [ 32 , 34 , 35 ].…”

“…Post-zygotic modification of cells that eventually transform into the placenta, resulting in genetic differences between MZ placentas, has also been documented [ 46 ]. Additionally, discordance for pathologic changes consistent with ZIKV infection was demonstrated in different portions of a monochorionic placenta of twins born to a mother with ZIKV infection during pregnancy [ 32 ]. Thus, both genetic and environmental factors could lead to discordant phenotypes in MZ twins.…”

Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins

“…twin should be evaluated independently for vertical transmission [34]. In this scenario, discordant twins represent a good case-control sample to test for the genetic contribution determining the fetuses' discordant outcome of gestational infection with ZIKV, as they are supposed to have been exposed to ZIKV under similar conditions in the uterus during gestation.…”

“…Indeed, neural progenitor cells (NPCs) from different individuals have been shown to respond differently to ZIKV infection [ 32 , 33 ]. It has recently been shown that infant outcomes can be discordant between twins with prenatal ZIKV exposure, suggesting that each twin should be evaluated independently for vertical transmission [ 34 ]. In this scenario, discordant twins represent a good case–control sample to test for the genetic contribution determining the fetuses’ discordant outcome of gestational infection with ZIKV, as they are supposed to have been exposed to ZIKV under similar conditions in the uterus during gestation.…”