The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery

Figures & data

Figure 1. Flow chart showing selection of study participants.

Table 1. Maternal and neonatal characteristics in the spontaneous preterm delivery and term delivery groups.

Variable	Spontaneous preterm delivery (n = 19)	Term delivery (n = 118)	p
Gestational age at delivery (weeks + days)	35 + 5 (32 + 4–36 + 5)	40 + 0 (39 + 1–40 + 6)
Maternal age at sampling (years)	38 (36–41)	36 (34–39)	.03
Nulliparous	6 (31.6%)	32 (27.1%)	.78
Maternal BMI at first prenatal visit	24.6 (23.4–26.5)	24.0 (21.9–26.4)	.42
Smoking at first prenatal visit	2 (10.5%)	4 (3.4%)	.20
Previous preterm delivery	3 (15.8%)	6 (5.1%)	.11
Gestational age at sampling (weeks + days)	15 + 5 (15 + 2–16 + 1)	15 + 5 (15 + 2–16 + 1)	.97
Mode of delivery
Vaginal delivery	17 (89.5%)	87 (73.7%)	.16
Caesarean section	2 (10.5%)	25 (21.2%)	.37
Vacuum extraction	0 (0%)	6 (5.1%)	.60
Birth weight (grams)	2483 (2305–2800)	3555 (3240–3843)	<.0001
Gender			.46
Male	8 (42.1%)	63 (53.4%)
Female	11 (57.9%)	55 (46.6%)
Apgar score <7 at 5 min	1 (5.3%)	1 (0.9%)	.26

Continuous variables were compared using a nonparametric Mann–Whitney U Test and presented as the median (IQR). Categorical variables were compared using Fisher’s Exact Test and presented as the number (%).

Bold text indicates statistical significance at p<.05 using a two-sided alternative hypothesis.

Figure 2. Heat map demonstrating the correlation (r) between the log concentrations of the examined candidate proteins. Candidate proteins in bold and italics indicate nominal significance.

Table 2. Number of samples of each of the selected candidate proteins in the mid-trimester amniotic fluid that were below the lowest, respectively, exceeded the highest concentrations in the working range.

Variable	Working range	Samples below the lowest working range (n)	Samples exceeding the highest working range (n)
Adiponectin	977–500,000	0	10
BDNF	20–10,000	0	0
CRP	400–200,000	0	0
GM-CSF	8–4000	0	0
IGFBP-1	195–100,000	0	0
IGFBP-3	195–100,000	0	0
IL-1β	10–5000	1	0
IL-6	39–20,000	0	0
sIL-6RA	39–20,000	0	0
IL-8	5–2500	8	1
IL-10	20–10,000	0	0
IL12A	8–4000	0	0
IL-17	8–4000	1	0
IL-18	20–10,000	56	0
Leptin	195–100,000	0	2
IFN-γ	8–4000	147	0
MCP-1	5–2500	0	0
MIF	98–50,000	0	0
MIP-1-α	78–40,000	0	0
MMP-9	488–250,000	0	0
NT-3	78–40,000	0	0
RANTES	5–2500	6	0
TNF-α	8–4000	15	0
TNF-β	8–4000	0	0
TNF-RI	313–160,000	0	0
TREM-1	195–100,000	0	0

The working range represents the lowest and highest concentrations of the working range. All concentrations are reported in pg/mL.

Table 3. Amniotic fluid levels of selected candidate proteins in relation to spontaneous preterm and term delivery.

Variable	Spontaneous preterm delivery (n = 19)	Term delivery (n = 118)	p*
Adiponectin	130,695 (71,852–199,414)	185,329 (13,5815–290,532)	.033
BDNF	822 (555–1241)	995 (677–1328)	.087
CRP	16,316 (14,504–16,786)	15,573 (12,811–17,368)	.413
GM-CSF	137 (74–156)	176 (111–262)	.049
IGFBP-1	14,346 (10,027–16,871)	12,697 (10,860–16,423)	.910
IGFBP-3	55,761 (39,577–63,997)	59,417 (42,128–71,168)	.320
IL-1β	38 (22–47)	44 (31–64)	.118
IL-6	675 (400–1769)	1048 (511–1700)	.573
sIL-6RA	1976 (1421–2665)	1753 (1431–2271)	.137
IL-8	57 (19–110)	54 (19–125)	.669
IL-10	246 (123–350)	276 (185–392)	.339
IL12A	43 (24–65)	64 (35–102)	.079
IL-17	33 (22–62)	57 (33–88)	.157
IL-18	10 (10–25)	24 (10–33)	.231
Leptin	8789 (4819–10,468)	7526 (4788–10,434)	.757
MCP-1	267 (231–334)	251 (192–344)	.399
MIF	3025 (1885–3891)	3400 (2181–5231)	.042
MIP-1-α	613 (489–961)	776 (575–1157)	.292
MMP-9	6666 (5326–8359)	7358 (6266–9315)	.328
NT-3	3257 (2230–4176)	3578 (2370–4885)	.183
RANTES	12 (10–15)	14 (11–18)	.213
TNF-α	50 (20–96)	85 (40–136)	.055
TNF-β	187 (96–253)	252 (153–433)	.148
TNF-RI	8179 (6165–8916)	7279 (5963–9137)	.724
TREM-1	3206 (2296–6304)	5718 (3630–9307)	.060

All concentrations are reported in pg/mL, based on crude data and presented as median and interquartile range (IQR).

* ANCOVA adjusting for plate effects.

Bold text indicates statistical significance at p<.05 using a two-sided alternative hypothesis.