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<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) in pregnancy may disrupt physiological maternal immune adaptations, thereby altering fetal immune programming and increasing the long-term risk of autoimmune diseases (ADs) in offspring. This is a pressing public health concern, as both maternal MASLD and childhood-onset ADs are rising in prevalence worldwide. This nationwide cohort study included all singleton live-born offspring of mothers with biopsy-proven MASLD diagnosed in Sweden between 1992 and 2017. We matched the 239 identified MASLD offspring with up to 5 reference offspring (<i>n</i> = 1,131) of mothers without known MASLD by maternal age at delivery, calendar year of delivery, and parity. We used multivariable Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) for any AD up until 2023. We performed stratified analyses by histological stage of maternal MASLD (simple steatosis versus severe MASLD defined as either steatohepatitis, any stage of liver fibrosis, or cirrhosis). During a median of 18.4 years of follow-up (interquartile range [IQR] 13.2–23.8), 15 exposed offspring (incidence rate [IR] 3.4/1000 person-years) vs. 40 reference offspring (IR 1.9/1000 person-years) were diagnosed with AD. This corresponded to an aHR of 1.20 (95% CI 0.57–2.53). The risk of AD remained unchanged among 175 offspring born to mothers with simple steatosis (aHR 0.84, 95% CI 0.29–2.45), and was higher, but not significant, in 64 offspring of mothers with severe MASLD (aHR 1.98, 95% CI 0.67–5.84). We did not identify an association of maternal MASLD with AD in offspring. Larger studies with follow-up extending beyond early adulthood are, however, needed.</p>

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Autoimmune disease in offspring of mothers with metabolic dysfunction-associated steatotic liver disease (MASLD): a nationwide cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Carole A. Marxer,
  • Fahim Ebrahimi,
  • David Bergman,
  • Jiangwei Sun,
  • Hannes Hagström,
  • Marcus Thuresson,
  • Olof Stephansson,
  • Jonas F. Ludvigsson

摘要

Metabolic dysfunction-associated steatotic liver disease (MASLD) in pregnancy may disrupt physiological maternal immune adaptations, thereby altering fetal immune programming and increasing the long-term risk of autoimmune diseases (ADs) in offspring. This is a pressing public health concern, as both maternal MASLD and childhood-onset ADs are rising in prevalence worldwide. This nationwide cohort study included all singleton live-born offspring of mothers with biopsy-proven MASLD diagnosed in Sweden between 1992 and 2017. We matched the 239 identified MASLD offspring with up to 5 reference offspring (n = 1,131) of mothers without known MASLD by maternal age at delivery, calendar year of delivery, and parity. We used multivariable Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) for any AD up until 2023. We performed stratified analyses by histological stage of maternal MASLD (simple steatosis versus severe MASLD defined as either steatohepatitis, any stage of liver fibrosis, or cirrhosis). During a median of 18.4 years of follow-up (interquartile range [IQR] 13.2–23.8), 15 exposed offspring (incidence rate [IR] 3.4/1000 person-years) vs. 40 reference offspring (IR 1.9/1000 person-years) were diagnosed with AD. This corresponded to an aHR of 1.20 (95% CI 0.57–2.53). The risk of AD remained unchanged among 175 offspring born to mothers with simple steatosis (aHR 0.84, 95% CI 0.29–2.45), and was higher, but not significant, in 64 offspring of mothers with severe MASLD (aHR 1.98, 95% CI 0.67–5.84). We did not identify an association of maternal MASLD with AD in offspring. Larger studies with follow-up extending beyond early adulthood are, however, needed.