Higher Risk of Serious Infection in Offspring of Mothers With Biopsy-Proven MASLD: A Nationwide Cohort Study

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to an increased risk of serious infection, but the impact of in utero exposure to maternal MASLD on the risk of infection in offspring remains unknown.

Methods: This nationwide cohort study included all singleton live born offspring exposed in utero to maternal biopsy-proven MASLD (1992-2017) in Sweden. Offspring born to mothers with MASLD (N = 239) were matched with up to five reference offspring (N = 1131) of mothers without MASLD by maternal age at delivery, calendar year of delivery, and parity. We used multivariable Cox regression to estimate adjusted hazard ratios (aHRs) for incident serious infection up until 2023. Results were also stratified by maternal histological severity of MASLD (simple steatosis vs. severe MASLD including steatohepatitis, any stage of liver fibrosis or cirrhosis).

Results: Over a median of 16.7 years of follow-up, 56 incident serious infections occurred in MASLD offspring (incidence rate [IR] 15.8/1000 person-years) and 140 incident serious infections occurred in reference offspring (IR 7.4/1000 person-years), which corresponded to an aHR of 1.81 (95% CI 1.23-2.68). The aHRs for incident serious infection were similar to offspring of mothers with simple steatosis and severe MASLD (1.97 vs. 1.70). This association was primarily explained by early-life infections (1-year aHR 3.11, 95% CI 1.74-5.58), with severe MASLD potentially being a major factor in the observed association during the first year. Results remained consistent across subgroups.

Discussion: Maternal MASLD, even simple steatosis, is associated with a higher hazard of serious offspring infection, highlighting the need for closer monitoring.

Keywords: MASLD; NAFLD; epidemiology; infections; pediatrics.