title: Umbilical cord levels of sclerostin, placental weight, and birth weight are predictors of total bone mineral content in neonates.
abstract: BACKGROUND
  During pregnancy, changes occur in the maternal calcium homeostasis to fulfill fetal demand. We hypothesized that the fibroblast growth factor 23 (FGF23) system and Wnt signaling pathway are important for normal skeletal development in the offspring.
  
  
  OBJECTIVE
  Circulating α-klotho, FGF23, sclerostin, and 25-hydroxyvitamin D (25(OH)D) at the fetal and maternal sides of the placenta were measured to investigate associations with newborn bone mass independent of maternal BMI, calcium and phosphate levels, placental weight, and birth weight.
  
  
  METHODS
  In a prospective cohort of healthy pregnant women, the total body bone mineral content (BMC) in 202 newborns was measured by dual-energy X-ray absorptiometry. Maternal circulating levels of the biomarkers were measured at gestational weeks 30-32 and in umbilical cord plasma (UCP) at birth.
  
  
  RESULTS
  Mean α-klotho and sclerostin concentrations in the UCP were significantly higher than maternal levels (3004 vs 1077  pg/ml; P<0.001 and 629 vs 346  pg/ml; P<0.001 respectively), and mean 25(OH)D was lower (31 vs 45  nmol/l; P<0.001). The UCP and maternal FGF23 levels were similar. No significant effects of maternal biomarkers on BMC were found in regression analyses. Among UCP biomarkers, only UCP sclerostin was significantly associated with BMC in univariate analyses, and the effect remained significant after adjustment for birth weight and other confounders.
  
  
  CONCLUSIONS
  We found that UCP sclerostin levels, birth weight, and placental weight were significant predictors of neonatal BMC but found no evidence for a main role of maternal levels of α-klotho, FGF23, sclerostin, or 25(OH)D nor of UCP levels of α-klotho, FGF23, or 25(OH)D.
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, PO Box 4950 Nydalen, Oslo 0424, Norway. kgodang@ous-hf.no
authors.forename: Kristin
authors.initials: K
authors.lastname: Godang
authors.forename: Kathrine Frey
authors.initials: KF
authors.lastname: Frøslie
authors.forename: Tore
authors.initials: T
authors.lastname: Henriksen
authors.forename: Gunhild A
authors.initials: GA
authors.lastname: Isaksen
authors.forename: Nanna
authors.initials: N
authors.lastname: Voldner
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D015502:Absorptiometry, Photon; D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D015519:Bone Density; D001846:Bone Development; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001842:Bone and Bones / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood; D047109:Fetal Development; D000089703:Fibroblast Growth Factor-23; D005819:Genetic Markers; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D000090265:Klotho Proteins; D008297:Male; D009929:Organ Size; D010929:Placentation; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D011446:Prospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; C422903:SOST protein, human; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins