Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation.
OBJECTIVE
Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm) and in the presence of intra-amniotic infection/inflammation (IAI).


METHODS
This cross-sectional study included patients in the following groups: (1) mid-trimester (n = 64); (2) term in spontaneous labor (n = 70); (3) term not in labor (n = 43); (4) spontaneous preterm labor (PTL) who delivered at term (n = 76); (5) PTL without IAI who delivered preterm (n = 73); (6) PTL with IAI (n = 76); (7) preterm prelabor rupture of membranes (PROM) without IAI (n = 71); and (8) preterm PROM with IAI (n = 71). Fragment Bb concentration in AF was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses.


RESULTS
(1) Fragment Bb was detected in all AF samples (n = 544); (2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 microg/ml, interquartile range (IQR) 1.78-3.22 vs. 1.64 microg/ml, IQR 1.06-3.49; p < 0.001]; (3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI, who delivered preterm (4.82 microg/ml, IQR 3.32-6.08 vs. 3.67 microg/ml, IQR 2.35-4.57; p < 0.001) and than that of women with an episode of PTL, who delivered at term (3.21 microg/ml, IQR 2.39-4.16; p < 0.001); (4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 microg/ml, IQR 2.58-5.79 vs. 2.79 microg/ml, IQR 2.09-3.89; p < 0.001). (5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 microg/ml, IQR 1.86-3.22; p = 0.97).


CONCLUSIONS
(1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the AF, and its concentration increases with advancing gestational age; (2) AF concentrations of fragment Bb are higher in pregnancies complicated with IAI; and (3) labor at term is not associated with changes in the AF concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI.
Vaisbuch
Edi
E
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA. evaisbuch@med.wayne.edu
Romero
Roberto
R
Erez
Offer
O
Mazaki-Tovi
Shali
S
Kusanovic
Juan Pedro
JP
Pedro
Kusanovic Juan
KJ
Soto
Eleazar
E
Gotsch
Francesca
F
Dong
Zhong
Z
Chaiworapongsa
Tinnakorn
T
Kim
Sun Kwon
SK
Mittal
Pooja
P
Pacora
Percy
P
Yeo
Lami
L
Hassan
Sonia S
SS
D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism*; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D002821:Chorioamnionitis / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000502:physiology*; D011415:Complement Factor B / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000276:immunology / Q000378:metabolism; D009994:Osmolar Concentration; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000378:metabolism; D011262:Pregnancy Trimester, Second / Q000276:immunology / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D011415:Complement Factor B