Vertical Transmission of Zika Virus and Its Outcomes: A Bayesian Synthesis of Prospective Studies

Abstract

Background: Prospective studies of Zika virus (ZIKV) in pregnancy have reported rates of Congenital Zika Syndrome (CZS) and other adverse outcomes by trimester. However, ZIKV may infect and damage the fetus in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. Methods: We applied Bayesian latent class analysis to data from 7 prospective studies, in order to simultaneously estimate: vertical transmission (VT) rates, rates of ZIKV-related and non-ZIKV related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters, and utilised information from women in comparison groups with no PCR-confirmed infection, where available. Findings: Following maternal infection in the 1st, 2nd, and 3rd trimesters, the estimated average risks of VT were 46%, 28% and 25%; 8.5%, 2.9%, and 0.8% deliveries had symptoms consistent with Congenital Zika Syndrome (CZS). We estimated that in 1st, 2nd, and 3rd trimesters respectively 13.4%, 3.3% and 0.3% of pregnancies had adverse outcomes attributable to ZIKV in pregnancy. Diagnostic sensitivity of markers of congenital infection is lowest in the 1st trimester (42%) but about 80% subsequently. There was substantial between-study variation in the risks of VT and CZS. Interpretation: This preliminary analysis recovers the causal effects of ZIKV from disparate study designs. Higher transmission in the first trimester is unusual with congenital infections but accords with laboratory evidence of decreasing susceptibility of placental cells over pregnancy. Funding Statement: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 734857. Declaration of Interests: CT and CP report that this work was partly supported by the National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre. CT received funding from AbbVie and the Penta Foundation during the period of the study, outside the submitted work. All authors are members of the ZIKAction consortium. Ethics Approval Statement: Not required.