IMMUNOLOGIC DYSREGULATION AND MICRONUTRIENT DEFICIENCIES ASSOCIATED WITH RISK OF INTRAPARTUM HEPATITIS E INFECTIONS IN PREGNANT BANGLADESHI WOMEN

Abstract

Hepatitis E is the leading cause of acute hepatitis globally, causing death (15–40%CFR) in pregnant women. We analyzed serial sera from two prospective cohorts totaling 110,473 pregnancies from Bangladesh, between 2001–2007(A) and 2007–2010(B). We tested anti‐HEV IgG status twice in pregnancy and at 3 months postpartum. From 1,127 specimens in cohort A, 63 women seroconverted‐ an incidence of 56 per 1000 person‐years. In cohort B, in 1100 women, 40 seroconverters revealed a lower incidence of 46 per 1000 person‐years. Cytokine and micronutrient analysis across pregnancy compared host risk factors and immunologic trajectories between seroconverters and age‐, parity‐ and GA‐matched controls using multiplex Th1/Th2 cytokine assays. Seroconverters (98% after 3rd trimester) had higher concentrations of IFN‐gamma, IL‐2, IL‐12, IL‐8, IL‐4, IL‐5, IL‐10, and TNF‐alpha than controls during the 1st trimester and 3 months postpartum (p<0.05), long before their infections occurred, suggesting immunologic dysregulation associated with risk of future infection. Future cases also had lower circulating Zn at pregnancy onset (749±113 versus 814±151 μg/L, p=0.03), perhaps increasing HEV susceptibility through compromised gut immunity. VitD and Cu levels were also lower. Differences in Zn, Hb, and VitD at the outset of pregnancy may predispose women to HEV infection through immunomodulation. Supported by NIH/NIAID.