title: Fetal and maternal Doppler velocimetry and cytokines in high-risk pregnancy.
abstract: OBJECTIVE
  Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies.
  
  
  METHODS
  TNF-alpha and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-a and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score.
  
  
  RESULTS
  TNF-alpha levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-alpha and IL-6 levels, P < 0.0001 and P < 0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-alpha and IL-6 levels. Abnormal uterine artery PI and the presence of a "notch" were also highly significantly related to TNF-alpha and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a "notch". Abnormal cerebro/placental ratios showed significant correlations to TNF-alpha and IL-6 levels.
  
  
  CONCLUSIONS
  The present results suggest a strong correlation between levels of TNF-alpha and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.
authors.affiliation: University School of Medical Sciences, Department of Perinatology and Gynecology, University Hospital, Poznan, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Dubiel
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Seremak-Mrozikiewicz
authors.forename: Grzegorz H
authors.initials: GH
authors.lastname: Breborowicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Drews
authors.forename: Marek
authors.initials: M
authors.lastname: Pietryga
authors.forename: Saemundur
authors.initials: S
authors.lastname: Gudmundsson
mesh_terms: D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply* / Q000196:embryology*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D020768:Middle Cerebral Artery / Q000196:embryology / Q000502:physiology*; D011237:Predictive Value of Tests; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D011446:Prospective Studies; D011673:Pulsatile Flow; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D018615:Ultrasonography, Doppler, Color; D016216:Ultrasonography, Prenatal; D014469:Umbilical Arteries / Q000502:physiology; D014599:Uterus / Q000098:blood supply
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha