Gestational diabetes mellitus and development of intergenerational non-alcoholic fatty liver disease (NAFLD) after delivery: a systematic review and meta-analysis

Background It is known that gestational diabetes mellitus (GDM)-complicated pregnancies could affect maternal cardiometabolic health after delivery, resulting in hepatic dysfunction and a heightened risk of developing nonalcoholic fatty liver disease (NAFLD). Hence, this study aims to summarise existing literature on the impact of GDM on NAFLD in mothers and investigate the intergenerational impact on NAFLD in offspring. Methods Using 4 databases (PubMed, Embase, Web of Science and Scopus) between January 1980 and December 2023, randomized controlled trials and observational studies that assessed the effect of maternal GDM on intergenerational liver outcomes were extracted and analysed using random -effects meta -analysis to investigate the effect of GDM on NAFLD in mothers and offspring. Pooled odds ratio (OR) was calculated using hazards ratio (HR), relative risk (RR), or OR reported from each study, with corresponding 95% con fi dence intervals (CI), and statistical heterogeneity was assessed with the Cochran Q -test and I 2 statistic, with two-sided p values. The study protocol was pre -registered on PROSPERO (CRD42023392428). Findings Twenty studies pertaining to mothers and offspring met the inclusion criteria and 12 papers were included further for meta -analysis on intergenerational NAFLD development. Compared with mothers without a history of GDM, mothers with a history of GDM had a 50% increased risk of developing NAFLD (OR 1.50; 95% CI: 1.21 - 1.87, over a follow-up period of 16 months - 25 years. Similarly, compared with offspring born to non-GDMcomplicated pregnancies, offspring born to GDM-complicated pregnancies displayed an approximately two -fold elevated risk of NAFLD development (2.14; 1.57 - 2.92), over a follow-up period of 1 - 17.8 years. Interpretation This systematic review and meta -analysis suggests that both mothers and offspring from GDMcomplicated pregnancies exhibit a greater risk to develop NAFLD. These fi ndings underline the importance of early monitoring of liver function and prompt intervention of NAFLD in both generations from GDM-complicated pregnancies.