Mortality and Cancer in Offspring of Mothers With Biopsy-Proven MASLD During Pregnancy: A Nationwide Cohort Study.

BACKGROUND & AIMS: Health-related outcomes through early adulthood among offspring prenatally exposed to maternal metabolic dysfunction-associated steatotic liver disease (MASLD) are insufficiently investigated. We aimed to study the risk of mortality and cancer in such offspring.

METHODS

This nationwide cohort study included all singleton live born offspring with prenatal exposure to maternal biopsy-proven MASLD (1992-2017; N = 239) in Sweden. MASLD offspring were matched with up to five reference offspring (N = 1131) of mothers without known MASLD by maternal age at delivery, calendar year of delivery, and parity. We used a multivariable Cox proportional hazard model to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for mortality and cancer up until 31 December 2021. For mortality, we stratified by maternal MASLD severity (simple steatosis alone vs. severe MASLD comprising steatohepatitis, liver fibrosis or cirrhosis).

RESULTS

Over a median follow-up of 16.9 years, two deaths occurred in offspring prenatally exposed to maternal MASLD (IR 0.5/1000 person-years, 95% CI 0.1-1.8) and seven deaths in reference offspring (IR 0.4/1000 person-years, 95% CI 0.1-0.8), which corresponded to an aHR of 1.78 (95% CI 0.27-11.97). Higher disease severity was not associated with an increased risk of death. We observed few cancer events with similar IR/1000 person-years (0.2 [95% CI 0.0-1.4] vs. 0.3 [0.1-0.6] in reference offspring), which corresponded to an aHR of 0.64 (95% CI 0.07-5.95).

CONCLUSIONS

We found no evidence that prenatal exposure to maternal MASLD affects the risk of death or cancer through early adulthood but larger studies are needed.