title: Obstetric Obesity is Associated with Neonatal Hyperbilirubinemia with High Prevalence in Native Hawaiians and Pacific Island Women.
abstract: Obesity and pregnancy both place the liver under metabolic stress, but interactions between obstetric obesity and bilirubin metabolism have not been studied. We determined associations between obesity, maternal/neonatal bilirubin levels, and uridine 5'diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme that eliminates bilirubin. Adult livers were analyzed for UGT1A1 expression, activity, and bilirubin clearance by pharmacokinetic modeling. Then, matched maternal and neonatal sera (N = 450) were assayed for total and unconjugated bilirubin. Associations between obesity, UGT1A1, maternal and neonatal hyperbilirubinemia were determined statistically through correlation analysis (Pearson's test) as well as binned categories (one-way ANOVA). Morbid obesity decreased hepatic UGT1A1 protein levels, activity, and bilirubin clearance (P< .001). Increasing obesity corresponded to elevated maternal unconjugated bilirubin (P< .05). Maternal obesity was also significantly positively correlated with elevated neonatal bilirubin levels (P< .01, N = 450) and this was strongest in Native Hawaiians and Pacific Islander (NHPI) women (P< .01, n = 150). Obstetric obesity is associated with maternal and neonatal hyperbilirubinemia, likely through inhibition of hepatic UGT1A1. The NHPI cohort was the most obese and had the highest levels of maternal and neonatal unconjugated bilirubin. Neonates from obese mothers may be more susceptible to jaundice and side effects from parenteral nutrition.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology; John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (LRAR, SJM, ACC).
authors.forename: Luc Ra
authors.initials: LR
authors.lastname: Rougée
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology; John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (LRAR, SJM, ACC).
authors.forename: Shogo J
authors.initials: SJ
authors.lastname: Miyagi
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology; John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (LRAR, SJM, ACC).
authors.forename: Abby C
authors.initials: AC
authors.lastname: Collier
mesh_terms: D000328:Adult; D015992:Body Mass Index; D005260:Female; D014453:Glucuronosyltransferase / Q000032:analysis / Q000378:metabolism; D006254:Hawaii / Q000208:ethnology; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000209:etiology*; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism; D044468:Native Hawaiian or Pacific Islander / Q000208:ethnology / Q000706:statistics & numerical data; D009765:Obesity / Q000150:complications*; D011247:Pregnancy; D015995:Prevalence; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: bilirubin; developmental pharmacology; glucuronidation; jaundice