Hepatitis Delta in Pregnancy Linked to Higher Stillbirth Risk in Nationwide US Study

Hepatitis delta virus, the most severe form of viral hepatitis, has long been recognized as a formidable pathogen in the general population, yet its behavior during pregnancy has remained largely uncharted territory. A new nationwide analysis of hospitalizations across the United States, spanning nearly a quarter century from 1998 to 2022, now offers one of the clearest pictures to date of what happens when pregnant women carry both hepatitis B and its satellite companion, hepatitis delta. The findings, published in BMC Infectious Diseases, suggest that while delta infection is rare among expectant mothers, it carries a measurable burden of liver disease and, most strikingly, a roughly fourfold increase in the risk of stillbirth compared with hepatitis B infection alone.

The study, led by Paul Wasuwanich of Mount Carmel Health System and the University of Florida College of Medicine, together with maternal-fetal medicine specialist Tony S. Wen and pediatric hepatologist Wikrom Karnsakul of Johns Hopkins University School of Medicine, drew on the National Inpatient Sample, the largest publicly available database of hospital discharges in the United States. Using standardized ICD-9 and ICD-10 diagnostic codes, the researchers extracted records of pregnant women hospitalized with hepatitis B and hepatitis delta over the 24-year study window. They then compared demographic characteristics, comorbid conditions, pregnancy complications, fetal outcomes, and mortality between two cohorts: women infected with hepatitis B virus alone and women co-infected with hepatitis B and hepatitis delta viruses.

The virology underlying this comparison is central to why the question matters. Hepatitis delta virus is a defective RNA virus that cannot complete its life cycle without hepatitis B virus, which supplies the envelope proteins the delta virion needs to assemble and spread. Because of this absolute dependence, delta infection occurs only in people who already harbor hepatitis B, either as a simultaneous co-infection or as a superinfection laid on top of chronic hepatitis B. Superinfection in particular is notorious for driving fulminant hepatitis in acute settings and for accelerating the progression of chronic liver disease toward cirrhosis and hepatocellular carcinoma. Despite this severity, pregnant patients with delta infection have been so scarcely studied that no specific clinical guidance exists for managing the combination during gestation.

From the nationwide dataset, the investigators identified 390 pregnancies affected by hepatitis delta co-infection and 127,332 pregnancies with hepatitis B alone. The delta cohort was young, with a median age of 30 years, and the predominant racial and ethnic group was Asian or Pacific Islander, accounting for 27.4 percent of cases, a distribution consistent with the global epidemiology of hepatitis B, which is endemic across much of Asia and the Pacific islands. Notably, there were no maternal deaths recorded in the delta group during the study period, a reassuring finding given the virus’s fearsome reputation in nonpregnant populations.

When the researchers examined liver-related comorbidities, the differences between the cohorts became apparent. Hepatitis C co-infection was roughly three times more common among women with delta infection, occurring in 12.1 percent of the delta cohort versus 4.1 percent of the hepatitis B-only group, a difference that was highly statistically significant. Cirrhosis, the advanced scarring of the liver that represents the end stage of chronic viral hepatitis, was also significantly more frequent in the delta cohort, affecting 1.3 percent of these pregnant women compared with just 0.2 percent of those with hepatitis B alone. These figures, though small in absolute terms, align with the established biology of delta superinfection, which is known to accelerate hepatic fibrosis and push patients toward cirrhosis at younger ages than hepatitis B alone.

Not every measured variable diverged between the groups. Rates of diabetes, obesity, HIV infection, intravenous drug use, coagulopathy, and thrombocytopenia were statistically similar across both cohorts, suggesting that the excess liver disease seen in the delta group was not simply a reflection of a generally sicker patient population. This pattern of findings strengthens the interpretation that the delta virus itself, rather than confounding comorbidities, drives the additional hepatic burden observed in these pregnancies.

The fetal outcomes formed the most consequential part of the analysis. Of the 390 pregnancies in the delta cohort, 318, or 81.5 percent, had a known delivery outcome recorded. Among these, stillbirth occurred in 2.8 percent of delta-affected pregnancies, compared with 0.7 percent of pregnancies with hepatitis B alone, a difference that reached statistical significance. In other words, women carrying both viruses faced roughly a fourfold higher rate of stillbirth than women carrying hepatitis B alone. By contrast, the rates of preterm birth and post-term birth did not differ significantly between the two groups, indicating that the adverse effect of delta co-infection on fetal outcomes was concentrated in fetal loss rather than in altered timing of delivery.

The authors conclude that hepatitis delta remains uncommon in pregnancy but is likely under-recognized, and that pregnancies affected by concurrent hepatitis B and delta infection may carry a higher risk of adverse fetal outcomes, particularly stillbirth, compared with hepatitis B alone. The under-recognition point deserves emphasis: because delta testing is not routinely performed in all hepatitis B-positive pregnant patients, the true prevalence of co-infection in this population may exceed what hospital discharge data capture, and the 390 identified cases likely represent a floor rather than a ceiling.

The study’s methodology carries both strengths and limitations worth noting. The National Inpatient Sample offers an unmatched scale for studying rare conditions, pooling discharge data from thousands of hospitals to assemble a cohort large enough for meaningful statistical comparison. However, the database relies on administrative coding, which can miss diagnoses, and it captures only hospitalized patients, meaning milder cases managed in outpatient settings would not appear. The researchers analyzed the data using chi-square tests for categorical comparisons and logistic regression to adjust for potential confounders, and the study was approved as exempt by the institutional review board of the University of Florida College of Medicine under the Declaration of Helsinki.

For clinicians, the practical message is that hepatitis B-positive pregnant women, particularly those from regions where delta virus is endemic or those with risk factors such as injection drug use, may warrant screening for hepatitis delta so that heightened surveillance of fetal well-being can be considered. For researchers, the findings open a clear agenda: prospective studies with virologically confirmed delta infection, detailed gestational timing of infection, and longitudinal follow-up of offspring are needed to confirm the stillbirth signal and to establish whether antiviral strategies targeting hepatitis B, which would also suppress the delta helper virus, can mitigate the fetal risk. In the meantime, this 24-year nationwide analysis stands as the most comprehensive portrait yet of a neglected intersection between severe viral hepatitis and pregnancy.

Subject of Research: Outcomes of hepatitis B and hepatitis delta co-infection in hospitalized pregnant women in the United States

Article Title: Outcomes of hepatitis B and hepatitis delta infection in hospitalized pregnant women in the United States: a nationwide study, 1998–2022

Article References: Wasuwanich, P., Wen, T. S., & Karnsakul, W. (2026). Outcomes of hepatitis B and hepatitis delta infection in hospitalized pregnant women in the United States: a nationwide study, 1998–2022. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14406-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14406-z

Keywords: hepatitis B, hepatitis delta, pregnancy, stillbirth, cirrhosis, viral hepatitis, National Inpatient Sample, hepatitis C, fetal outcomes, maternal health, liver disease, epidemiology