Giorgio Bedogni1,2, Giuseppe De Matteis1,3, Marta Fabrizi1, Anna Alisi4, Annalisa Crudele4, Fabrizio Pizzolante5, Fabrizio Signore6, Bruno Dallapiccola7, Valerio Nobili8,9, Melania Manco1. 1. Research Area for Multifactorial Disease, Children's Hospital Bambino Gesù, Rome, Italy. 2. Clinical Epidemiology Unit, Liver Research Center, Basovizza, Trieste, Italy. 3. Department of Internal and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 4. Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, Rome, Italy. 5. Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 6. Department of Obstetrics and Gynecology, Misericordia Hospital, Grosseto, Italy. 7. Scientific Directorate, Bambino Gesù Children's Hospital, Rome, Italy. 8. Department of Pediatrics, University La Sapienza, Rome, Italy. 9. Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy.
Abstract
CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is being increasingly diagnosed at younger ages, pointing toward an early-life origin. OBJECTIVE: To evaluate the frequency and risk factors for bright liver (BL) in 1-year-old toddlers. DESIGN: Secondary analysis of the 1-year follow-up of the Feeding Study. Exposures were child PNPLA3 and TM6SF2 gene variants; child anthropometry at birth and at 1 year of follow-up; child subcutaneous, visceral, and epicardial adipose tissue at 1 year of follow-up; maternal anthropometry at the start and at the end of pregnancy; and maternal red blood cell fatty-acid composition at the third trimester of pregnancy. SETTING: General population. PARTICIPANTS: Among 505 mother-toddler pairs, 391 children (77%) underwent liver and abdominal ultrasonography at the 1-year follow-up. MAIN OUTCOME: BL as diagnosed by ultrasonography. RESULTS: Seventeen (4%) of 391 toddlers had BL. Compared with the toddlers with the PNPLA 3 CC genotype, the odds (95% CI) of BL were 3.01 (1.05 to 8.64, P < 0.05) times higher in those with the PNAPLA3 CG genotype and 5.37 (1.12 to 25.77, P < 0.05) higher in those with the PNPLA3 CC genotype. We found no association between BL status and TM6SF2. Body weight, body mass index, and maternal weight gain during pregnancy were higher in BL+ than in BL- children. Visceral adipose tissue was higher but subcutaneous adipose tissue and epicardial adipose tissue were similar in BL+ and BL- children. CONCLUSIONS: Four percent of the Feeding Study children had BL at 1 year of age. In line with expectations, PNAPLA3 was already a predictor of BL at this early age.
CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is being increasingly diagnosed at younger ages, pointing toward an early-life origin. OBJECTIVE: To evaluate the frequency and risk factors for bright liver (BL) in 1-year-old toddlers. DESIGN: Secondary analysis of the 1-year follow-up of the Feeding Study. Exposures were childPNPLA3 and TM6SF2 gene variants; child anthropometry at birth and at 1 year of follow-up; child subcutaneous, visceral, and epicardial adipose tissue at 1 year of follow-up; maternal anthropometry at the start and at the end of pregnancy; and maternal red blood cell fatty-acid composition at the third trimester of pregnancy. SETTING: General population. PARTICIPANTS: Among 505 mother-toddler pairs, 391 children (77%) underwent liver and abdominal ultrasonography at the 1-year follow-up. MAIN OUTCOME: BL as diagnosed by ultrasonography. RESULTS: Seventeen (4%) of 391 toddlers had BL. Compared with the toddlers with the PNPLA 3 CC genotype, the odds (95% CI) of BL were 3.01 (1.05 to 8.64, P < 0.05) times higher in those with the PNAPLA3 CG genotype and 5.37 (1.12 to 25.77, P < 0.05) higher in those with the PNPLA3 CC genotype. We found no association between BL status and TM6SF2. Body weight, body mass index, and maternal weight gain during pregnancy were higher in BL+ than in BL- children. Visceral adipose tissue was higher but subcutaneous adipose tissue and epicardial adipose tissue were similar in BL+ and BL- children. CONCLUSIONS: Four percent of the Feeding Study children had BL at 1 year of age. In line with expectations, PNAPLA3 was already a predictor of BL at this early age.