Hepatitis E during pregnancy: Maternal and foetal case‐fatality rates and adverse outcomes—A systematic review

Abstract

Abbreviations: CFR, case-fatality rate; FHF, fulminant hepatic failure; HEV, hepatitis E virus; IQR, interquartile range; LBW, low birth weight; NOS, Newcastle-Ottawa Scale;PRISMA, preferred reporting items for systematic reviews and meta-analysis; PROM, premature rupture of membranes. AbstractHepatitis E virus infection during pregnancy can have severe consequences for mother and child, such as vertical transmission, fulminant hepatic failure, even foetal or maternal mortality. The aim of this systematic review is to describe maternal, foetal and neonatal case-fatality rates as well as the prevalence of adverse outcomes in relation to hepatitis E virus infection during pregnancy. A systematic literature search was performed in Pubmed, Embase, Cochrane and CINAHL. Search terms included Pregnant, Women, Maternal, Infant, Foetal, Neonatal and Hepatitis E virus.Data were extracted using predefined data collection forms. All studies were quality assessed, either by the Newcastle-Ottawa Scale or by an adapted assessment scale for cross-sectional studies. We found 23 eligible studies, all observational, which were included in this systematic review with a total of 1338 cases. The median maternal, foetal and neonatal case-fatality rates were 26% (IQR 17%-41%), 33% (IQR 19%-37%) and 8% (IQR 3%-20%), respectively. Adverse outcomes such as fulminant hepatic failure, preterm labour, postpartum haemorrhage, low birth weight and vertical transmission were reported. The two studies that reported the highest prevalence of fulminant hepatic failure also reported the highest case-fatality rates. The median prevalence of fulminant hepatic failure was 45.3%. This systematic review found a high case-fatality rate among pregnant women infected with hepatitis E virus and a high rate of adverse outcomes among these women and their children. The results from this review mainly apply to hospital settings and symptomatic pregnant women from endemic countries. K E Y W O R D Sfoetus, hepatitis E virus, mortality, pregnant women, systematic review |

Innate Immune Responses to Acute Viral Infection During Pregnancy

“…A 2019 systematic review including a total of 1,338 pregnant women with hepatitis E showed a 45% risk of fulminant hepatic failure, a median maternal CFR of 26% and a median fetal CFR of 33%. Other obstetric complications were not consistently reported in the included articles but data from four studies suggest an increased risk of postpartum hemorrhage, ranging from 13.6 to 30% ( 28 ). There are no proven drug therapies for hepatitis E (ribavirin, which has shown equivocal benefits in small case series, is contraindicated in pregnancy) and the only available vaccine for prevention of hepatitis E is not manufactured or licensed outside China ( 28 ).…”

“…The World Health Organization estimates that sepsis accounts for 10.7% of maternal deaths globally ( 33 ) and there is evidence of a particular vulnerability to acute viral infection. For example, pregnant women suffered disproportionately high mortality rates in the influenza pandemics of 1918, 1957, and 2009 ( 34 – 36 ), and hepatitis E, typically a mild and self-limiting illness, has a 26% case-fatality rate in pregnant women ( 28 ). These disparities are likely to arise from a combination of immunological, hormonal, and physiological adaptations that are specific to pregnancy ( 37 – 39 ).…”

HEV study protocol : design of a cluster-randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh

“…Our study is not powered to directly evaluate perinatal and maternal death, because of the low rates of these outcomes in Matlab. However, given the substantial evidence linking maternal and perinatal mortality to HEV disease in pregnancy,2 demonstration of vaccine protection against confirmed HEV disease in pregnancy will provide strong evidence that vaccination is likely to prevent maternal and perinatal deaths.…”

“…Hepatitis E virus (HEV) is an enteric RNA virus causing outbreaks or endemics in developing countries with poor sanitation and is one of the leading causes of acute hepatitis worldwide 1. Pregnant women are particularly vulnerable to HEV infection, with a high rate of maternal mortality, miscarriage, premature delivery and stillbirth 2…”

Viral Hepatitis in pregnancy

“…Meta-analysis shows that the pooled case-fatality risk for pregnant mothers can be as high as 26 % for acute HEV infection [109]. Other pregnancy complications include preterm labour (50 %) and prelabour rupture of membranes (10 %), while postpartum haemorrhage was reported in 13.6-30 % [112].…”