Retinol binding protein 4: An adipokine associated with intra-amniotic infection/inflammation

Figures & data

Table I.  Demographic and clinical characteristics of women with normal pregnancies in the mid-trimester and at term, with and without spontaneous labor.

	Mid-trimester (n = 30)	p^a	Term not in labor (n = 31)	p^b	Term in labor (n = 30)	p^c
Maternal age (years)^†	36 (35–38)	<0.001	28 (21.5–33)	<0.001	22 (19–26.2)	<0.001
GA at amniocentesis (weeks)^†	16.2 (16–17)	<0.001	38.5 (37.9–39.6)	NS	38.4 (38–39.2)	<0.001
GA at delivery (weeks)	39 (38–40)	NS	38.5 (37.9–39.6)	NS	38.4 (38–39.2)	NS
Birth weight (grams)	3346 (3218–3671)	NS	3200 (3015–3634)	NS	3295 (3092–3510)	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; Kruskal–Wallis test.

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

	Spontaneous PTL and intact membranes
	Without IAI, term delivery (n = 60)	p^a	Without IAI, preterm delivery (n = 64)	p^b	With IAI, preterm delivery (n = 56)	p^c
Maternal age (years)	23 (18.5–30)	NS	23 (20–30)	NS	23 (20–28.2)	NS
GA at amniocentesis (weeks)^†	32 (30.4–34)	NS	32.2 (30.1–33.4)	<0.001	28.4 (25.1–33.2)	0.001
GA at delivery (weeks)^††	39 (38.1–39.9)	<0.001	34.8 (33.7–35.8)	<0.001	29.5 (25.4–33.4)	<0.001
Birth weight (grams)^††	3240 (2972–3622)	<0.001	2480 (2025–2780)	<0.001	1425 (765–2185)	<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 = 0.001, ^††p < 0.001; Kruskal–Wallis test.

Figure 1.  Amniotic fluid concentrations of retinol-binding protein 4 (RBP4) in normal pregnancies in the mid-trimester and at term, in labor and not in labor. The median amniotic fluid RBP4 concentration was higher in women in the mid-trimester than in those at term not in labor [1861.1 ng/ml, interquartile range (IQR) 1486.2–2034.3 vs. 766.1 ng/ml, IQR 608.5–1154.1; p < 0.0001]. Among women at term, the median amniotic fluid RBP4 concentration did not differ significantly between women in labor and those not in labor (term not in labor: 766.1 ng/ml, IQR 608.5–1154.1 vs. term in labor: 836.8 ng/ml, IQR 589.5–1112.8; p = 0.4). The black lines represent the median and IQR.

Figure 2.  Amniotic fluid concentration of retinol-binding protein 4 (RBP4) among women with spontaneous preterm labor and intact membranes (PTL). The median amniotic fluid RBP4 concentration was higher in patients with intra-amniotic infection/inflammation (IAI) than in women with PTL without IAI who delivered preterm [1268.9 ng/ml, interquartile range (IQR) 900.3–1970.1 vs. 815.8 ng/ml, IQR 592.4–1098.1; p < 0.001], and than those with PTL without IAI who delivered at term (828.7 ng/ml, IQR 499.7–1119.6; p < 0.001). Among women with PTL without IAI, there was no difference in the median amniotic fluid concentration of RBP4 between those who delivered preterm and those who delivered at term (p = 0.7). The black lines represent the median and IQR.

Table III.  A backward stepwise, multivariable logistic regression model including IAI as the dependent variable and maternal age, pre-pregnancy BMI, smoking status, gestational age at amniocentesis and amniotic fluid RBP4 concentration ≥1149.8 ng/ml as covariates.

	Odds ratio	95% CI	p
Maternal age	0.94	0.88–1.01	0.08
Pre-pregnancy BMI	1.17	1.05–1.30	0.004
Smoking status	1.79	0.63–5.09	0.3
GA at amniocentesis	0.91	0.77–1.09	0.3
Amniotic fluid RBP4 concentration ≥ 1149.8 ng/ml	4.6	1.91–11.05	0.001

CI, confidence interval; BMI, body mass index; GA, gestational age; RBP4, retinol binding protein 4.

Figure 3.  Amniotic fluid concentrations of retinol-binding protein 4 (RBP4) among women with spontaneous preterm labor (PTL) and intra-amniotic infection/inflammation (IAI) who delivered within 72 h of amniocentesis and have placental histopathologic diagnosis. The median amniotic fluid RBP4 concentration was significantly higher in patients with IAI and histologic chorioamnionitis than in women with IAI without histologic chorioamnionitis [1901.0 ng/ml, interquartile range (IQR) 1107.3–2492.0 vs. 968.2 ng/ml, IQR 634.7–1396.7; p = 0.01]. The black lines represent the median and IQR.

Figure 4.  The receiver–operating characteristic (ROC) curve of amniotic fluid RBP4 concentration for the identification of IAI among patients with PTL with intact membranes (area under the curve (AUC) 0.71, p < 0.001). Derived from this ROC curve, a cutoff value for amniotic fluid RBP4 concentration of ≥1149.8 ng/ml had a sensitivity of 58.9% and a specificity of 79.8% for the identification of IAI in patients with PTL and intact membranes.