Burden of hepatitis E virus infection in pregnancy and maternofoetal outcomes: a systematic review and meta-analysis

BACKGROUND: There is still a dearth of knowledge on the burden of HEV infection in the global population of pregnant women. Therefore, we conducted a systematic review and meta-analysis to estimate the global burden of HEV infection in pregnancy. METHODS: We searched PubMed, Embase, Web of Knowledge, and Global Index Medicus to identify articles published until January 26, 2020. We considered cross-sectional, case-control, and cohort studies reporting the immunoglobulins M HEV seroprevalence in asymptomatic and symptomatic (jaundice or elevated transaminases) pregnant women or investigating the association between HEV infection and maternofoetal outcomes. We used a random-effects model to pool studies. This review was registered with PROSPERO, CRD42018093820. RESULTS: For HEV prevalence estimates, we included 52 studies (11,663 pregnant women). The seroprevalence was 3.5% (95% confidence interval: 1.4–6.4) in asymptomatic women (most of whom from high endemic areas). The prevalence in symptomatic women was 49.6% (42.6–56.7) with data only from HEV high endemic countries. In the multivariable meta-regression model, the prevalence was higher in symptomatic women compared to asymptomatic (adjusted prevalence odds ratio [aPOR]: 1.76; 95%CI: 1.61–1.91) and decreased with increasing year of publication (by 10-year) (aPOR: 0.90; 95%CI: 0.84–0.96). The proportion of HEV vertical transmission was 36.9% (13.3–64.2). Risk of bias was low, moderate and high respectively in 12 (23%), 37 (70%), and 4 studies (7%) addressing HEV prevalence estimation. HEV infection was associated with maternal deaths (pooled OR 7.17; 3.32–15.47), low birth weight (OR: 3.23; 1.71–6.10), small for gestational age (OR: 3.63; 1.25–10.49), preterm < 32 weeks (OR: 4.18; 1.23–14.20), and preterm < 37 weeks (OR: 3.45; 2.32–5.13), stillbirth (OR: 2.61; 1.64–4.14), intrauterine deaths (OR: 3.07; 2.13–4.43), and not with miscarriage (OR: 1.74; 0.77–3.90). All studies which assessed the association between HEV infection and maternofoetal outcomes had a moderate risk of bias. CONCLUSIONS: Findings from this study are suggestive of a high burden of HEV infection in pregnancy in high endemic countries, its association with poor maternofoetal outcomes, and a high rate of vertical transmission. This study supports the need for specific strategies to prevent exposure of pregnant women to HEV infection, especially in high endemic areas.