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ORIGINAL ARTICLE: Activation of the Alternative Pathway of Complement is a Feature of Pre-Term Parturition but not of Spontaneous Labor at Term

Authors

  • Edi Vaisbuch,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Roberto Romero,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
    3. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
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  • Offer Erez,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Shali Mazaki-Tovi,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Juan Pedro Kusanovic,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Eleazar Soto,

    1. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Zhong Dong,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
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  • Tinnakorn Chaiworapongsa,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Sun Kwon Kim,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
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  • Giovanna Ogge,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
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  • Percy Pacora,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
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  • Lami Yeo,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Sonia S. Hassan

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Wayne State University/Hutzel Women’s Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.
E-mail: prbchiefstaff@med.wayne.edu

Abstract

Citation Vaisbuch E, Romero R, Erez O, Mazaki-Tovi S, Kusanovic JP, Soto E, Dong Z, Chaiworapongsa T, Kim SK, Ogge G, Pacora P, Yeo L, Hassan SS. Activation of the alternative pathway of complement is a feature of pre-term parturition but not of spontaneous labor at term. Am J Reprod Immunol 2010; 63: 318–330

Problem  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.

Method of study  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 μg/mL, IQR 0.77–2.16) or without IAI (1.13 μg/mL, IQR 0.92–2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 μg/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).

Conclusion  (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.

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