Fetal adrenal gland volume and cortisol/dehydroepiandrosterone sulfate ratio in inflammation-associated preterm birth.
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.
Buhimschi
Catalin S
CS
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA. catalin.buhimschi@yale.edu
Turan
Ozhan M
OM
Funai
Edmund F
EF
Azpurua
Humberto
H
Bahtiyar
Mert-Ozan
MO
Turan
Sifa
S
Zhao
Guomao
G
Dulay
Antonette
A
Bhandari
Vineet
V
Copel
Joshua A
JA
Buhimschi
Irina A
IA
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
D015415:Biomarkers; D015850:Interleukin-6; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone