Stillbirth and Zika: A systematic review

Background: In 2015, there were 2.6 million stillbirths, accounting for 4.4% of all global deaths. Despite this burden, global attention to stillbirths has been limited. Evidence has accumulated that Zika virus infection causes multiple adverse outcomes, possibly including fetal demise (stillbirths, miscarriages, abortions), but there has been limited reporting and analysis of these outcomes. We aimed to summarize available data on the fetal demise burden of Zika-affected pregnancies.

Methods: This was a quasi-systematic review (PubMed, Embase, Web of Science; no language limits). Proportions of fetal demise of completed Zika-affected pregnancies were calculated. RRs for fetal demise among completed, Zika-affected versus uninfected pregnancies were estimated from cohort data.

Results: Seventeen reports included 19,928 pregnant women or infants/fetuses with confirmed, probable or suspected Zika infection. Pregnancy outcomes that included fetal demise were known for 23% (4,492). There were 244 cases of fetal demise (5%). 20% of confirmed as compared to 7% of suspected Zika-affected pregnancies ended in fetal demise. Only one cohort study included asymptomatic as well as symptomatic mothers; the crude risk of fetal demise was nearly 13 times higher for Zika-affected as unaffected mothers (RR 12.76, 95% CI 3.94, 41.37, p-value <0.0001), as compared to a crude RR of microcephaly of 6.63 (95% CI 0.78, 57.83, p-value 0.07). Most studies included only symptomatic pregnant women or infants/fetuses with Zika-related anomalies; misclassification of infection status was possible. Conclusions: Available data on fetal demise associated with Zika virus infection is limited, especially in comparison to other outcomes such as microcephaly, yet there is evidence that fetal demise may be a significant burden of Zika virus infection. Studies of Zika infection outcomes should report on fetal demise.