Maternal Early-Pregnancy Glucose Concentrations and Liver Fat Among School-Age Children

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Background and Aims: Gestational diabetes seems to be associated with offspring NAFLD. We hypothesized that maternal glucose concentrations across the full range may have persistent effects on offspring liver fat accumulation. Approach and Results: In a multiethnic, population-based, prospective cohort study among 2,168 women and their offspring, maternal early-pregnancy glucose concentrations were measured at a median of 13.1 weeks’ gestation (95% CI, 9.6-17.2). Liver fat fraction was measured at 10 years by MRI. NAFLD was defined as liver fat fraction ≥5.0%. We performed analyses among all mothers with different ethnic backgrounds and those of European ancestry only. The multiethnic group had a median maternal early-pregnancy glucose concentration of 4.3 mmol/L (interquartile range, 3.9-4.9) and a 2.8% (n = 60) prevalence of NAFLD. The models adjusted for child age and sex only showed that in the multiethnic group, higher maternal early-pregnancy glucose concentrations were associated with higher liver fat accumulation and higher odds of NAFLD, but these associations attenuated into nonsignificance after adjustment for potential confounders. Among mothers of European ancestry only, maternal early-pregnancy glucose concentrations were associated with increased odds of NAFLD (OR, 1.95; 95% CI, 1.32; 2.88, after adjustment for confounders) per 1-mmol/L increase in maternal early-pregnancy glucose concentration. These associations were not explained by maternal prepregnancy and childhood body mass index, visceral fat, and metabolic markers. Conclusions: In this study, maternal early-pregnancy glucose concentrations were only among mothers of European ancestry associated with offspring NAFLD. The associations of higher maternal early-pregnancy glucose concentrations with offspring NAFLD may differ between ethnic groups.

Original languageEnglish
Pages (from-to)1902-1913
Number of pages12
Issue number4
Early online date18 May 2021
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
The general design of the Generation R Study was made possible by financial support from the Erasmus University Medical Center, the Netherlands Organization for Health Research and Development, and the Ministry of Health, Welfare, and Sport. The study was supported, in part, by the European Research Council (Consolidator Grant ERC‐2014‐CoG‐648916; to V.W.V.J.); the European Union’s Horizon 2020 Research and Innovation programme LifeCycle (733206; to V.W.V.J.); the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, and ZonMw the Netherlands project [529051022; to J.F.F.] and Precise project [529051023; to J.F.F.]); the Dutch Heart Foundation (2017T013; to R.G.); the Dutch Diabetes Foundation (2017.81.002; to R.G.); and the Netherlands Organisation for Health Research and Development (NWO, ZonMw; 543003109; to R.G.).

Publisher Copyright:
© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

Research programs

  • EMC MM-04-54-08-A


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