Marxer Carole A, Ebrahimi Fahim, Bergman David, Sun Jiangwei, Hagström Hannes, Thuresson Marcus, Stephansson Olof, Ludvigsson Jonas F
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Gastroenterology and Hepatology, University Digestive Health Care Center Basel - Clarunis, Basel, Switzerland.
Liver Int. 2025 Jul;45(7):e70174. doi: 10.1111/liv.70174.
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.
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).
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).
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.
对于产前暴露于母亲代谢功能障碍相关脂肪性肝病（MASLD）的后代，在成年早期的健康相关结局尚未得到充分研究。我们旨在研究此类后代的死亡风险和癌症风险。
这项全国性队列研究纳入了瑞典所有在产前暴露于母亲经活检证实患有MASLD的单胎活产后代（1992 - 2017年；N = 239）。MASLD后代与最多五名母亲无已知MASLD的对照后代（N = 1131）按母亲分娩年龄、分娩日历年和平产次数进行匹配。我们使用多变量Cox比例风险模型计算截至2021年12月31日的死亡和癌症的调整风险比（aHRs）及95%置信区间（CIs）。对于死亡率，我们按母亲MASLD严重程度分层（仅单纯性脂肪变性与包括脂肪性肝炎、肝纤维化或肝硬化的严重MASLD）。
在中位随访16.9年期间，产前暴露于母亲MASLD的后代中有2例死亡（发病率为0.5/1000人年，95% CI 0.1 - 1.8），对照后代中有7例死亡（发病率为0.4/1000人年，95% CI 0.1 - 0.8），对应的aHR为1.78（95% CI 0.27 - 11.97）。疾病严重程度较高与死亡风险增加无关。我们观察到的癌症事件较少，每1000人年的发病率相似（0.2 [95% CI 0.0 - 1.4] 对比对照后代中的0.3 [0.1 - 0.6]），对应的aHR为0.64（95% CI 0.07 - 5.95）。
我们没有发现证据表明产前暴露于母亲MASLD会影响成年早期的死亡风险或癌症风险，但需要更大规模的研究。
