title: Fetal programming of children's obesity risk.
abstract: OBJECTIVE
  Childhood obesity affects nearly 17% of children and adolescents in the United States. Increasing evidence indicates that prenatal maternal stress signals influence fetal growth, child obesity, and metabolic risk. Children exhibiting catch-up growth, a rapid and dramatic increase in body size, within the first two years of life are also at an increased risk for developing metabolic disorder and obesity. We evaluate the potential role of the maternal hypothalamic-pituitary-adrenal (HPA) and placental axis in programming risk for child obesity.
  
  
  METHODS
  This prospective longitudinal study measured placental corticotropin-releasing hormone (pCRH) and maternal plasma cortisol at 15, 19, 25, 30, and 37 gestational weeks and collected child body mass index (BMI) at birth, 3, 6, 12, and 24 months. Participants included 246 mothers and their healthy children born full term. Each child's BMI percentile (BMIP) was determined using World Health Organization (WHO) standards based on age and sex. Child BMIP profiles from birth to two years of age were characterized using general growth mixture modeling (GGMM). We evaluated whether fetal exposure to placental CRH and maternal cortisol are associated with BMIP profiles.
  
  
  RESULTS
  Placental CRH at 30 gestational weeks was highly associated with both BMIP (p<.05) and weight (p<.05) at birth when accounting for gestational age at birth and used as a predictor in modeling BMIP profiles. Maternal cortisol was not associated with child BMIP. GGMM analyses identified four distinct BMIP profiles: typical, rapid increase, delayed increase, and decreasing (See Fig. 2). The typical profile comprised the majority of the sample and maintained BMIP across the first two years. The rapid and delayed increase profiles each exhibit a period of reduced body size followed by BMI catch-up growth. The rapid increase profile exhibited catch-up within the first 12 months while the delayed group showed an initial decrease in BMIP at 3 months and a dramatic increase from 12 to 24 months. The decreasing profile exhibited normal birth weight and BMIP followed by persisting, low BMIP. The members of the rapid and delayed increase profiles were exposed to the highest concentrations of placental CRH at 30 gestational weeks compared to those in the typical profile group (Fig. 3).
  
  
  CONCLUSIONS
  Exposure to elevated placental CRH concentrations during the third trimester is associated with catch-up growth. An early period of small body size followed by rapid catch-up growth is a profile associated with increased metabolic risk and increased obesity risk. Our findings suggest that placental CRH exposure makes a unique contribution to fetal programming of obesity risk.
authors.affiliation: Department of Psychology, University of Denver, United States.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Stout
authors.affiliation: Department of Psychology, University of Denver, United States.
authors.forename: Emma V
authors.initials: EV
authors.lastname: Espel
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, United States.
authors.forename: Curt A
authors.initials: CA
authors.lastname: Sandman
authors.affiliation: Department of Psychology, Chapman University, United States.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Glynn
authors.affiliation: Department of Psychology, University of Denver, United States; Department of Psychiatry and Human Behavior, University of California, Irvine, United States. Electronic address: Elysia.Davis@du.edu.
authors.forename: Elysia Poggi
authors.initials: EP
authors.lastname: Davis
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D047109:Fetal Development; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D009765:Obesity / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone
keywords: BMI; CRH; Early childhood; Fetal programming; Obesity; Prenatal