title: Association of maternal diabetes/glycosuria and pre-pregnancy body mass index with offspring indicators of non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Little is known about early life determinants of non-alcoholic fatty liver disease (NAFLD). We examined associations of maternal pregnancy diabetes/glycosuria and pre-pregnancy body mass index (BMI) with offspring markers of NAFLD and liver pathology and examined mediation by birthweight and concurrent offspring adiposity.
  
  
  METHODS
  We used data from a UK prospective pregnancy cohort. Offspring underwent abdominal ultrasonography (USS) at mean age 17.8 years. Outcomes included USS-assessed fatty liver, estimated liver volume and shear velocity, a variant of elastography (a marker of liver fibrosis) (N = 1 215) and blood-based markers of liver pathology [alanine amino transferase, aspartate amino transferase, gamma- glutamyltransferase and haptoglobin] (N = 2 359).
  
  
  RESULTS
  2.1 % (N = 25) of participants had USS-assessed fatty liver [maternal diabetes/glycosuria (N = 7) and no diabetes/glycosuria (N = 18)]. Maternal diabetes/glycosuria was associated with greater odds of offspring USS fatty liver in confounder adjusted models [adjusted odds ratio (aOR) 6.74 (95 % confidence interval (CI) 2.47, 18.40)] and higher shear velocity [adjusted ratio of geometric mean (aRGM):1.10 (95 % CI 1.05, 1.15)]. These associations were not mediated by offspring birthweight or concurrent adiposity. Maternal diabetes/glycosuria was not associated with liver volume or blood-based outcomes. Greater maternal pre-pregnancy BMI was associated with greater odds of offspring USS fatty liver [aOR 2.72 (95 % CI: 1.20, 6.15)], higher liver volume [aRGM 1.03 (95 % CI 1.00, 1.07)] and shear velocity [aRGM1.03 (95 % CI: 1.01, 1.06)] in confounder adjusted models. These associations were largely mediated by offspring adiposity. Maternal pre-pregnancy BMI was not consistently associated with blood-based outcomes.
  
  
  CONCLUSIONS
  Results suggest that maternal pregnancy diabetes/glycosuria is associated with offspring NAFLD through mechanisms other than offspring's own adiposity.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Road, Bristol, UK.
authors.forename: Sumaiya
authors.initials: S
authors.lastname: Patel
authors.affiliation: School of Social and Community Medicine, University of Bristol, UK & MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Callaway
authors.affiliation: School of Social and Community Medicine, University of Bristol, UK & MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
authors.forename: Corrie
authors.initials: C
authors.lastname: Macdonald-Wallis
authors.affiliation: Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.affiliation: School of Social and Community Medicine, University of Bristol, UK & MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. Abigail.Fraser@bristol.ac.uk.
authors.forename: Abigail
authors.initials: A
authors.lastname: Fraser
mesh_terms: D050154:Adiposity; D000293:Adolescent; D001724:Birth Weight; D015992:Body Mass Index; D005260:Female; D006029:Glycosuria; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000209:etiology*; D016017:Odds Ratio; D011247:Pregnancy; D011248:Pregnancy Complications; D011254:Pregnancy in Diabetics; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000209:etiology*; D011446:Prospective Studies; D012307:Risk Factors
keywords: ALSPAC; Fetal overnutrition; Glycosuria; NAFLD; Obesity; Pregnancy diabetes