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

Abstract

Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding European Union Horizon 2020 programme.

Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques

“…Alternatively, the results may suggest immunologic elimination of virus at later gestational ages as previously suggested by a study using direct fetal ZIKV inoculation ( 43 ). Our decision to challenge the animals in this study early in pregnancy (~30 days gestation) was based on findings in humans suggesting that during the first trimester, ZIKV infection is associated with a higher risk of adverse fetal and pregnancy outcomes ( 27 , 43 , 50 – 53 ). In addition, we hypothesized that early pregnancy, possibly before a woman knows she is pregnant, may be a period of especially high risk for sexual transmission of ZIKV because precautions against this transmission route, such as condoms, may not be utilized ( 23 , 24 ).…”

Sexually dimorphic placental responses to maternal SARS-CoV-2 infection

“…Innate immune sensing of SARS-CoV-2 involves the activation of type I and type III interferons and upregulation of ISGs in target cells ( 81 ). Given the relative paucity of SARS-CoV-2 placental infection ( 46 ) in comparison to other pandemic infections such as Zika ( 82 ), the increased ISG production and upregulated IL10 expression in exposed male placentas may be a protective mechanism to prevent direct placental infection and pathology. Indeed, high IFN levels during pregnancy have proven protective against placental HSV infection ( 83 ) and type III IFNs impair ZIKV transplacental transmission ( 84 ).…”

Early embryonic loss following intravaginal Zika virus challenge in rhesus macaques

“…Alternatively, the results may suggest immunologic elimination of virus at later gestational ages as previously suggested by a study using direct fetal ZIKV inoculation (43). Our decision to challenge the animals in this study early in pregnancy (~30 days gestation) was based on findings in humans suggesting that during the first trimester, ZIKV infection is associated with a higher risk of adverse fetal and pregnancy outcomes (27,50-53)( 43) (27,(50)(51)(52)(53). In addition, we hypothesized that early pregnancy, possibly before a woman knows she is pregnant, may be a period of especially high risk for sexual transmission of ZIKV because precautions against this transmission route, such as condoms, may not be utilized (23,24).…”