title: Activation of the alternative pathway of complement is a feature of pre-term parturition but not of spontaneous labor at term.
abstract: OBJECTIVE
  Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre-term delivery <34 weeks of gestation. The aim of this study was to determine whether spontaneous pre-term labor (PTL) with intact membranes, intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations.
  
  
  METHODS
  This cross-sectional study included women in the following groups: (i) non-pregnant (n = 40); (ii) normal pregnancy (gestational age range 20-36, 6/7 weeks, n = 63); (iii) women at term not in labor (n = 70); (iv) women at term in spontaneous labor (n = 59); (v) patients with an episode of PTL who delivered at term (n = 62); (vi) PTL without IAI who delivered pre-term (n = 30); and (vii) PTL with IAI who delivered pre-term (n = 67). Maternal plasma FBb concentrations were determined by ELISA.
  
  
  RESULTS
  (i) Among patients with PTL, those who had a pre-term delivery either with IAI (1.21 microg/mL, IQR 0.77-2.16) or without IAI (1.13 microg/mL, IQR 0.92-2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 microg/mL, IQR 0.64-1.57; P = 0.007 and P = 0.026, respectively); (ii) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered pre-term (P = 0.9); (iii) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (P = 0.8); (iv) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls (P = 0.8) and were not correlated with advancing gestational age (r = -0.28, P = 0.8).
  
  
  CONCLUSIONS
  (i) Pre-term parturition is associated with activation of the alternative complement pathway in maternal circulation; (ii) such activation is not detectable in spontaneous labor at term; (iii) IAI does not explain the activation of the alternative pathway of complement in PTL. Collectively, these observations suggest that pre-term and term labors have fundamental differences in the regulation of innate immunity.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA.
authors.forename: Edi
authors.initials: E
authors.lastname: Vaisbuch
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
authors.forename: Shali
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Eleazar
authors.initials: E
authors.lastname: Soto
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Sun Kwon
authors.initials: SK
authors.lastname: Kim
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ogge
authors.forename: Percy
authors.initials: P
authors.lastname: Pacora
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
mesh_terms: D000328:Adult; D003170:Complement Pathway, Alternative / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000276:immunology; D036801:Parturition; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D047928:Premature Birth / Q000276:immunology*; D047929:Term Birth / Q000276:immunology; D055815:Young Adult
chemical_list: D003165:Complement System Proteins