The association of cytokines and micronutrients with hepatitis e virus infection during pregnancy and the postpartum period in rural Bangladesh

Hepatitis E virus (HEV) infection is severe during pregnancy, with a pregnant case fatality rate around 30%. In Bangladesh, plasma samples from 1,100 women during the first trimester (TM) and third TM of pregnancy and 3 months postpartum (PP) were tested for anti-HEV IgG. During this time, 40 women developed antibody responses to HEV. These seroconverters are classified as the cases (incidence = 46 infections per 1,000 personyears). All except one seroconversion occurred between the third TM and 3 months PP. The cases and 40 matched non-seroconverters (controls) underwent analysis of a panel of 10 cytokines, 12 vitamins and minerals, and two markers of inflammation. Throughout pregnancy, seroconverting cases displayed higher concentrations of both pro-and anti-inflammatory cytokines compared with the non-seroconverting controls, even prior to infection. In the first TM, seroconverters had lower circulating zinc concentrations (P = 0.03), an increased prevalence of vitamin D deficiency (25-hydroxy vitamin D [25(OH)2D] < 50 nmol/L, P = 0.08), and anemia (hemoglobin < 110 g/L, P = 0.05) compared with controls. There were no differences in C-reactive protein or á-1-acid glycoprotein. Antecedent micronutrient deficiencies may lead to dysregulated cytokine expression and immunologic compromise, increasing the risk of HEV infection, especially during pregnancy. This exploratory analysis reveals potential novel associations that deserve further study.