title: Obstetric outcome and cytokine levels in threatened miscarriage.
abstract: OBJECTIVE
  To evaluate the proportion of women with threatened miscarriage (TM) who proceed to miscarriage in a population of single ethnicity and to investigate prospectively their risk of adverse pregnancy outcome in relationship with the cytokines levels in their circulation.
  
  
  METHODS
  We conducted a prospective observational study over a period of 1 year of 94 Maltese women presenting with TM at the same hospital and compared their clinical data with those of 564 age-matched controls from the National Obstetric Information System (NOIS) of Malta. Main outcome measures included gestational age and weight at delivery and incidence of adverse pregnancy outcomes. A pilot study was carried out, where in subgroups of 10 women with TM (n=10), non-pregnant women (n=12), normal pregnant controls (n=9) and women presenting with missed-miscarriage (n=11), the plasma levels of β-human chorionic gonadotrophin (β-hCG), tumour necrosis factor α (TNFα), interferon γ (IFNγ), interleukin-6 (IL-6), interleukin-10 (IL-10) and TNF-receptors 1 (R1) and 2 (R2) were measured.
  
  
  RESULTS
  Of the women presenting with TM, 25 (26.6%) proceeded to complete miscarriage. The TM group had also a significantly higher incidence of antepartum haemorrhage (p<0.005), pre-eclampsia (p<0.05), foetal growth restriction (p<0.05), premature labour (p<0.001) and retained placenta (p<0.005). In the pilot biochemical analysis, significantly (p<0.05) higher levels of TNFα and lower levels of TNFR2 were found in the TM subgroup compared to non-pregnant controls. The ratio TNFα/IL-10 was significantly (p<0.05) higher and the β-hCG levels was significantly lower (p<0.01) in missed-miscarriage and non-pregnant subgroups than in TM and normal pregnant controls. The IFNγ/1L-10 and IFNγ/1L-6 ratio were significantly (<0.001) different between the four subgroups with the lowest level found in TM. No similar gradient was found for the TNFα/1L-6 ratio.
  
  
  CONCLUSIONS
  Women presenting with TM are at significantly increased risk of adverse pregnancy outcome and the pathophysiology of these conditions involves a change in the Th1/Th2 balance. Changes in levels of cytokines could help to predict and thus prevent the development of some of these complications.
authors.affiliation: EGA, Institute for Women's Health, Department of Obstetrics and Gynaecology, University College London (UCL), London, United Kingdom. j.calleja-agius@ucl.ac.uk
authors.forename: Jean
authors.initials: J
authors.lastname: Calleja-Agius
authors.forename: Pierre
authors.initials: P
authors.lastname: Schembri-Wismayer
authors.forename: Neville
authors.initials: N
authors.lastname: Calleja
authors.forename: Mark
authors.initials: M
authors.lastname: Brincat
authors.forename: Dorianne
authors.initials: D
authors.lastname: Spiteri
mesh_terms: D000022:Abortion, Spontaneous / Q000097:blood / Q000453:epidemiology; D000033:Abortion, Threatened / Q000097:blood* / Q000453:epidemiology* / Q000628:therapy; D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D036861:Delivery, Obstetric / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D050498:Live Birth / Q000453:epidemiology; D008319:Malta / Q000453:epidemiology; D007744:Obstetric Labor Complications / Q000453:epidemiology; D010865:Pilot Projects; D011247:Pregnancy; D011256:Pregnancy Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma