Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation

Figures & data

Table I.  Demographic and clinical characteristics of patients with a normal pregnancy in the mid-trimester and those at term, with and without spontaneous labor.

	Mid-trimester (n = 64)	p^a	Term not in labor (n = 43)	p^b	Term in labor (n = 70)	p^c
Maternal age (years)^†	37 (35–38)	<0.001	27 (21–32)	<0.001	22 (20–27)	<0.001
GA at amniocentesis (weeks)^†	16 (16–17)	<0.001	39 (38–40)	NS	39 (38–40)	<0.001
GA at delivery (weeks)^††	39.5 (38–40)	NS	39 (38–40)	NS	39 (38–40)	NS
Birth weight (g)^††	3343 (3015–3616)	NS	3250 (3030–3580)	NS	3330 (3100–3680)	NS

Values expressed as median (interquartile range). GA, gestational age; NS, not significant.

p^a between mid-trimester and term not in labor.

p^b between term not in labor and term in labor.

p^c between mid-trimester and term in labor.

^†p < 0.001, ^††p = NS, Kruskal–Wallis test with Bonferroni correction.

Table II.  Demographic and clinical characteristics of patients presenting with spontaneous preterm labor (PTL) and intact membranes.

	PTL without IAI, term delivery (n = 76)	p^a	PTL without IAI, preterm delivery (n = 73)	p^b	PTL with IAI, preterm delivery (n = 76)	p^c
Maternal age (years)	23 (20–27)	NS	23 (20–29.5)	NS	23 (20–28.2)	NS
GA at amniocentesis (weeks)^†	30.7 (28.6–32.3)	NS	29.3 (26.4–32.4)	<0.001	27.4 (24.7–32.5)	<0.001
GA at delivery (weeks)^††	38.7 (37.9–39.9)	<0.001	33.0 (28.9–34.8)	<0.001	27.6 (25.0–32.6)	<0.001
Birth weight (g)^††	3100 (2778–3387)	<0.001	1956 (1080–2940)	<0.001	1068 (647–1990)	<0.001

Values expressed as median (interquartile range).

GA, gestational age; PTL, preterm labor; IAI, intra-amniotic infection/inflammation; NS, not significant.

p^a between PTL without IAI who delivered at term and PTL without IAI who delivered preterm.

p^b between PTL without IAI who delivered preterm and PTL with IAI who delivered preterm.

p^c between PTL without IAI who delivered at term and PTL with IAI who delivered preterm.

^†p = 0.006, ^††p < 0.001, Kruskal–Wallis test with Bonferroni correction.

Table III.  Demographic and clinical characteristics of patients presenting with preterm prelabor rupture of membranes (preterm PROM).

	Preterm PROM without IAI (n = 71)	Preterm PROM with IAI (n = 71)	p*
Maternal age (years)	24 (20–31)	28 (22–33)	0.03
GA at amniocentesis (weeks)	31.4 (27.6–32.7)	29.7 (26.6–32.0)	0.03
GA at delivery (weeks)	32.6 (30.3–33.7)	30.1 (28.0–32.1)	<0.001
Birth weight (g)	1835 (1435–2160)	1480 (1134–1810)	<0.001

Values expressed as median (interquartile range).

GA, gestational age; IAI, intra-amniotic infection/inflammation; PROM, prelabor rupture of the membranes.

*Mann–Whitney U-test.

Figure 1. Amniotic fluid concentration of fragment Bb in normal pregnancies in the mid-trimester and at term, with and without spontaneous labor: The median amniotic fluid concentration of fragment Bb was higher in women at term not in labor than in those in the mid-trimester [term not in labor: 2.42 μg/ml, IQR 1.78–3.22 vs. mid-trimester: 1.64 μg/ml, IQR 1.06–3.49; p < 0.001]. Among women at term, the median amniotic fluid fragment Bb concentration did not differ between patients with spontaneous labor and those not in labor (term in labor: 2.47 μg/ml, IQR 1.86–3.22; p = 0.97).

Figure 2. Amniotic fluid concentration of fragment Bb in women with spontaneous preterm labor and intact membranes: The median amniotic fluid concentration of fragment Bb was higher in patients with IAI than in those without IAI who delivered preterm (PTL 4.82 μg/ml, IQR 3.32–6.08 vs. 3.67 μg/ml, IQR 2.35–4.57; p < 0.001), as well as than that of those who delivered at term (3.21 μg/ml, IQR 2.39–4.16; p < 0.001). Among women with PTL without IAI, there was no significant difference in the median amniotic fluid fragment Bb concentration between patients who delivered preterm and those who delivered at term (p = 0.4).

Figure 3. Amniotic fluid concentration of fragment Bb in women with preterm prelabor rupture of membranes (preterm PROM): The median amniotic fluid concentration of fragment Bb was higher in patients with IAI than in those without IAI (4.24 μg/ml, IQR 2.58–5.79 vs. 2.79 μg/ml, IQR 2.09–3.89; p < 0.001).

Figure 4. Receiver–operating characteristic (ROC) curve of amniotic fluid fragment Bb concentration of patients with PTL and intact membranes for the identification of IAI (n = 225, area under the curve 0.72, p < 0.001).

Table IV.  Diagnostic indices and likelihood ratios of amniotic fluid fragment Bb concentration for the detection of intra-amniotic infection/inflammation in patients presenting with spontaneous preterm labor with intact membranes (n = 225).

Cutoff (μg/ml)	OR (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)	+LR (95% CI)	+LR (95% CI)
≥4.31	5.1 (2.8–9.2)	61.8% (53.0–69.8)	75.8% (71.3–79.9)	2.56 (1.85–3.48)	0.50 (0.38–0.66)

Figure 5. Amniotic fluid concentration of fragment Bb in women with spontaneous PTL, intact membranes and IAI who delivered within 72 h of amniocentesis and have placental histopathologic diagonsis: Among women with IAI, the median amniotic fluid concentration of fragment Bb was higher in patients with histologic chorioamnionitis than in those without (5.25 μg/ml, IQR 3.97–11.27 vs. 4.48 μg/ml, IQR 2.80–5.29; p = 0.025).