title: Fetal adrenal gland volume and cortisol/dehydroepiandrosterone sulfate ratio in inflammation-associated preterm birth.
abstract: OBJECTIVE
  Fetal adaptation to stress is regulated in part by the pituitary-adrenocortical system. The stress hormones dehydroepiandrosterone sulfate (DHEAS) and cortisol have opposing effects: cortisol suppresses while DHEAS enhances immune functions. We sought to estimate the impact of intraamniotic inflammation on fetal adrenal gland volume and cortisol-to-dehydroepiandrosterone sulfate ratio (fetal stress ratio) in pregnancies complicated by preterm birth.
  
  
  METHODS
  Fifty-one consecutive singleton fetuses of mothers who had an indicated amniocentesis to rule out infection were analyzed. Intraamniotic inflammation was assessed by proteomic profiling of amniotic fluid for the biomarkers of the Mass Restricted score. The Mass Restricted score ranges from 0 (biomarkers absent) to 4 (all biomarkers present), with Mass Restricted scores of 3 or 4 indicating severe intraamniotic inflammation. Fetal adrenal gland volume was assessed by three-dimensional ultrasonography and corrected for estimated fetal weight. Interleukin-6 (IL-6), cortisol, and DHEAS were measured by immunoassay.
  
  
  RESULTS
  Women with intraamniotic inflammation delivered earlier (27.8+/-3.4 weeks, n=16, compared with 32.3+/-3.0 weeks, n=35, P<.001), and their fetuses had higher cord blood IL-6 (P=.011) and higher corrected adrenal gland volumes (P=.027). Cord blood IL-6 levels were in direct relationship with corrected adrenal volume (r=0.372, P=.019), fetal cortisol (r=0.428, P=.010), and DHEAS (r=0.521, P<.001). However, fetuses exposed to intraamniotic inflammation had an overall lower fetal stress ratio (P=.034). These results maintained after adjusting for gestational age, uterine contractions, and steroid exposure.
  
  
  CONCLUSIONS
  Fetuses exposed to intraamniotic inflammation have higher adrenal gland volumes and lower cortisol-to-DHEAS ratios, suggesting that the fetal adrenocortical axis plays a role in the intrauterine adaptation to inflammation.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA. catalin.buhimschi@yale.edu
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Ozhan M
authors.initials: OM
authors.lastname: Turan
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Funai
authors.forename: Humberto
authors.initials: H
authors.lastname: Azpurua
authors.forename: Mert-Ozan
authors.initials: MO
authors.lastname: Bahtiyar
authors.forename: Sifa
authors.initials: S
authors.lastname: Turan
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Antonette
authors.initials: A
authors.lastname: Dulay
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Copel
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000311:Adrenal Glands / Q000033:anatomy & histology*; D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry; D015415:Biomarkers / Q000032:analysis; D002821:Chorioamnionitis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D009929:Organ Size; D010913:Pituitary-Adrenal System; D011247:Pregnancy; D047928:Premature Birth / Q000503:physiopathology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016216:Ultrasonography, Prenatal
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone