Vertical transmission of Zika virus and its outcomes: a Bayesian synthesis of prospective studies

Prospective studies of Zika virus in pregnancy have reported rates of congenital Zika syndrome and other adverse outcomes by trimester. However, Zika virus can infect and damage the fetus early in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. We aimed to provide the first estimates of underlying vertical transmission rates and adverse outcomes due to congenital infection with Zika virus by trimester of exposure. This was a Bayesian latent class analysis of data from seven prospective studies of Zika virus in pregnancy. We estimated vertical transmission rates, rates of Zika-virus-related and non-Zika-virus-related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters and used information from women in comparison groups with no PCR-confirmed infection, where available. The estimated mean risk of vertical transmission was 47% (95% credible interval 26 to 76) following maternal infection in the first trimester, 28% (15 to 46) in the second, and 25% (13 to 47) in the third. 9% (4 to 17) of deliveries following infections in the first trimester had symptoms consistent with congenital Zika syndrome, 3% (1 to 7) in the second, and 1% (0 to 3) in the third. We estimated that in infections during the first, second, and third trimester, respectively, 13% (2 to 27), 3% (−5 to 14), and 0% (−7 to 11) of pregnancies had adverse outcomes attributable to Zika virus infection. Diagnostic sensitivity of markers of congenital infection was lowest in the first trimester (42% [18 to 72]), but increased to 85% (51 to 99) in trimester two, and 80% (42 to 99) in trimester three. There was substantial between-study variation in the risks of vertical transmission and congenital Zika syndrome. This preliminary analysis recovers the causal effects of Zika virus 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 to infection during pregnancy. European Union Horizon 2020 programme.