The clinical significance of a positive Amnisure test in women with preterm labor and intact membranes

Figures & data

Table I.  Characteristics of study population.

Characteristics	Negative Amnisure (n = 73)	Positive Amnisure (n = 17)	p value
Maternal age (years)^†	30 ± 4	32 ± 3	NS
Nulliparity (n)	41 (56%)	8 (47%)	NS
Gestational age at test (week)^†	28.0 ± 4.0	27.1 ± 4.7	NS
Cervical dilatation (cm)^†	1 ± 1	2 ± 1	< 0.05
Antenatal corticosteroids (n)	45 (62%)	14 (82%)	NS

Note: ^†values are given as mean ± standard deviation.

Table II.  The result of AF analysis and pregnancy outcomes.

Pregnancy characteristics/outcomes	Negative Amnisure (n = 73)	Positive Amnisure (n = 17)	p value
Positive AF culture (n)	1 (1%)	2 (12%)	0.092
Intra-amniotic infection and/or inflammation (n)	17 (24%)	10 (59%)	< 0.01^a
Gestational age at delivery (week) ^b	34.8 ± 4.9	29.8 ± 6.1	< 0.005
Test-to-delivery interval
≤ 48 h	5 (7%)	7 (41%)	< 0.005^a
≤ 7 days	13 (18%)	11 (65%)	< 0.001 ^a
≤ 2 week	16 (22%)	13 (77%)	< 0.001 ^a
≤ 4 week	23 (32%)	13 (77%)	< 0.005 ^a
Preterm delivery
< 35 week	26 (36%)	12 (71%)	< 0.05 ^a
< 37 week	40 (55%)	15 (88%)	< 0.05 ^a
Birth weight (g)^b	2399 ± 926	1609 ± 981	< 0.01
1-min Apgar score < 7	21/56 (38%)	12/17 (71%)	< 0.05 ^a
5-min Apgar score < 7	8/56 (14%)	9/17 (53%)	< 0.005 ^a
Perinatal death	4 (6%)	2 (12%)	NS
Admission to neonatal intensive care unit^c	20/62 (32%)	11/15 (73%)	< 0.01 ^a
Significant neonatal morbidity^c	6/62 (10%)	8/15 (53%)	< 0.005 ^a

Note: ^asignificant after adjustment for gestational age at test;

^bvalues are given as mean ± standard deviation;

^cThirteen infants were excluded from the analysis, because they died shortly after delivery as a result of extreme prematurity or were delivered at another institution, and thus, could not be evaluated with respect to the presence or absence of neonatal complications.

Figure 1.  The AF MMP-8 concentrations according to the presence or absence of clinical evidence of ROM and the result of Amnisure test (a negative Amnisure test: median, 1.2 ng/mL [range: 0.3–2109.1 ng/mL]; a positive Amnisure test: median, 49.3 ng/mL [range: 0.3–5304.8 ng/mL]).

Figure 2.  Kaplan–Meier survival distribution function by test result. [The median test-to-delivery duration and hazard ratio (95% confidence interval) for each group adjusted for gestational age at test, cervical dilatation, and intra-amniotic infection and/or inflammation are as follows: Amnisure (+) fFN (+): 9.7 days, 3.8 (1.1–12.8); Amnisure (+) fFN (−): 5.3 days, 5.0 (1.4–18.0); Amnisure (−) fFN (+): 25.7 days, 3.4 (1.3–8.5); Amnisure (−) fFN (−): 53.7 days, 1 (reference).]

Table III.  Logistic regression analysis of Amnisure and Fibronectin tests in predicting time-to-spontaneous delivery in patients with preterm labor and intact membranes.

Test result			Test-to-spontaneous delivery duration
			< 48 h (n = 10)^a		< 7 days (n = 22)^b		<14 days (n = 27)^c
			OR	CI	OR	CI	OR	CI
Amnisure test (n = 90)		(+)	9.7	2.2–43.3	7.0	2.0–24.1	9.4	2.4–36.4
		(−)	1		1		1
Fibronectin test (n = 64)		(+)	1.8	0.3–9.9	3.2	0.9–11.7	5.2	1.4–19.8
		(−)	1		1		1
Fibronectin test (+) (n = 28)	Aminsure test	(+)	1.6	0.2–15.1	1.4	0.2–8.4	1.7	0.3–9.7
		(−)	1		1		1
Fibronectin test (−) (n = 36)	Aminsure test	(+)	35.6	1.1–>999	365.1	4.0–>999	365.1	4.0–>999
		(−)	1		1		1

Note: All models adjusted for gestational length at time of test and cervical dilatation except those stratified by fibronectin result due to sample size restrictions. ^aTwo patients who delivered preterm within 48 h by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded from this analysis; ^btwo patients who delivered preterm within 7 days by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded from this analysis; ^ctwo patients who delivered preterm within 14 days by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded from this analysis

Table IV.  Logistic regression analysis of Amnisure and fibronectin tests in predicting intra-amniotic infection and/or inflammation and sPTB in patients with preterm labor and intact membranes.

Test result			Intra-amniotic infection and/or inflammation (n = 27)		Spontaneous preterm delivery
					< 35 weeks ^a (n = 34)		< 37 weeks ^b (n = 46)
			OR	CI	OR	CI	OR	CI
Amnisure test (n = 90)		(+)	3.9	1.01–15.1	2.7	0.7–10.3	3.6	0.6–20.6
		(−)	1		1		1
Fibronectin test (n = 64)		(+)	8.5	1.6–46.9	7.3	1.8–29.5	9.8	2.2–43.5
		(−)	1		1		1
Fibronectin test (+) (n = 28)	Aminsure test	(+)	0.5	0.06–5.3	0.4	0.1–2.2	2.3	0.2–28.1
		(−)	1		1		1
Fibronectin test (−) (n = 36)	Aminsure test	(+)	25.2	1.7–363.8	66.7	2.8–>999	10.7	0.97–117.9
		(−)	1		1		1

Note: All models adjusted for gestational length at time of test and cervical dilatation except those stratified by fibronectin result due to sample size restrictions. ^aFour patients who delivered preterm (before 35 weeks) by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded from this analysis; ^bnine patients who delivered preterm before 37 weeks by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded from this analysis.

Table V.  Amnisure and fibronectin test time-to-delivery screening performance metrics overall and stratified by fibronectin test result

Outcome	Metric	Amnisure test (n = 90)	Fibronectin test (n = 64)	Amnisure Among
				fFN (−) (n = 36)	fFN(+) (n = 28)
Test-to-spontaneous delivery < 48 h^a	Prevalence	11.4%	12.7%	8.6%	17.9%
	PPV	37.5%	17.9%	40.0%	28.6%
	NPV	94.4%	91.4%	96.7%	85.7%
	LR+*	9.71^†	1.79	35.6^†	1.62
	LR−*	0.10^†	0.56	0.03^†	0.62
	Sensitivity	60.0%	62.5%	66.7%	40.0%
	Specificity	87.2%	58.2%	90.6%	78.3%
Test-to-spontaneous delivery < 7 days^b	Prevalence	25.0%	23.8%	14.3%	35.7%
	PPV	62.5%	35.7%	80.0%	42.9%
	NPV	83.3%	85.7%	96.7%	66.7%
	LR+*	6.97^†	3.18	365.1^†	1.41
	LR−*	0.14^†	0.31	0.003^†	0.71
	Sensitivity	45.5%	66.7%	80.0%	30.0%
	Specificity	90.9%	62.5%	96.7%	77.8%
Test-to-spontaneous delivery < 14 days^c	Prevalence	30.7%	28.6%	14.3%	46.4%
	PPV	75.0%	46.4%	80.0%	57.1%
	NPV	79.2%	85.7%	96.7%	57.1%
	LR+*	9.41^†	5.23^†	365.1^†	1.69
	LR−*	0.11^†	0.19^†	0.003^†	0.59
	Sensitivity	44.4%	72.2%	80.0%	30.8%
	Specificity	93.4%	66.7%	96.7%	80.0%

Note: fFN = fetal Fibronectin; AUC = area under receiver operating characteristic curve;

*adjusted for gestational length at time of test and cervical dilatation except those stratified by fibronectin result due to sample size restrictions;

^†significant after adjustment;

^atwo patients who delivered preterm within 48 h by augmentation of labor/cesarean delivery due to maternal-fetal indications were excluded;

^btwo patients who delivered at preterm within 7 days by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded;

^ctwo patients who delivered at preterm within 14 days by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded.

Table VI.  Amnisure and fibronectin test sPTB screening performance metrics overall and stratified by fibronectin test result.

Outcome	Metric	Amnisure test (n = 90)	Fibronectin test (n = 64)	Amnisure Among
				fFN (−) (n = 36)	fFN (+) (n = 28)
Intra-amniotic infection/and/or inflammation	Prevalence	30.7%	28.1%	16.7%	42.9%
	PPV	58.8%	42.9%	60.0%	28.6%
	NPV	76.1%	83.3%	90.3%	52.4%
	LR+*	3.91†	8.55†	25.2†	0.54
	LR−*	0.26†	0.12†	0.04†	1.84
	Sensitivity	37.0%	66.7%	50.0%	16.7%
	Specificity	88.5%	65.2%	93.3%	68.8%
sPTB <35 weeksa	Prevalence	39.5%	39.7%	22.9%	60.7%
	PPV	68.8%	60.7%	80.0%	42.9%
	NPV	67.1%	77.1%	86.7%	33.3%
	LR+*	2.71	7.35†	66.7†	0.38
	LR−*	0.37	0.14†	0.02†	2.62
	Sensitivity	32.4%	68.0%	50.0%	17.6%
	Specificity	90.4%	71.1%	96.3%	63.6%
sPTB <37 weeksb	Prevalence	56.8%	54.1%	35.3%	77.8%
	PPV	86.7%	77.8%	80.0%	83.3%
	NPV	50.0%	64.7%	72.4%	23.8%
	LR+*	3.59	9.83†	10.7	2.26
	LR−*	0.28	0.10†	0.1	0.44
	Sensitivity	28.3%	63.6%	33.3%	23.8%
	Specificity	94.3%	78.6%	95.5%	83.3%

Note: ^fFN = fetal Fibronectin;

*adjusted for gestational length at time of test and cervical dilatation except those stratified by fibronectin result due to sample size restrictions;

^†significant after adjustment;

^afour patients who delivered preterm before 35 weeks by augmentation of labor or cesarean delivery due to maternal-fetal indications were excluded from this analysis;

^bnine patients who were delivered at preterm before 37 weeks by augmentation

Table VII.  The clinical course of women with a positive Amnisure test.

Case	GA at test (wks)	GA at delivery (wks)	AF culture	AF MMP-8	Cervical dilatation at test	Delivery mode	Clinical course
1	29.9	29.9	(−)	0.3	0	C/S	Placenta previa and massive vaginal bleeding with labor pain and fetal distress
2	25.9	25.9	(−)	918.4	1	VD	Clinical chorioamnionitis and spontaneous labor progression
3	25.6	25.7	(−)	5304.8	2	VD	Spontaneous labor progression
4	25	25	(−)	7.0	2	C/S	Spontaneous labor progression and breech presentation
5	28.4	28.6	(−)	7.9	2	C/S	Spontaneous labor progression and placenta previa
6	19.3	19.4	(−)	49.3	5	VD	Bag bulging and labor progression
7	26.3	26.6	(+)	1574.3	0	VD	Induction of labor because of suspicion of chorioamnionitis
8	33.6	34	(−)	9.1	1	VD	Spontaneous labor progression
9	26.6	27.1	(−)	1988.9	1	VD	Spontaneous labor progression
10	25	25.7	(−)	744.1	2	C/S	Spontaneous labor progression and breech presentation
11	28.3	29	(−)	900.4	2	C/S	Spontaneous labor progression and previous C/S
12	21.9	23	(+)	3522.4	3	VD	Spontaneous labor progression
13	33.9	35.3	(−)	3.7	2	VD	Spontaneous ROM at 35 + 1 weeks and induction of labor
14	31	35	(−)	43.5	2	VD	Spontaneous ROM at 35weeks and subsequent spontaneous labor progression
15	32.7	41.3	(−)	0.5	0	VD	Term delivery
16	30.3	40.1	(−)	0.8	1	VD	Term delivery
17	17.4	35.1	(−)	1815.6	1	VD	Induction of labor at 35 weeks because of suspicion of chorioamnionitis

Note: GA: gestational age, AF: amniotic fluid, MMP-8: matrix metalloproteinase-8, NA: not available, VD: vaginal delivery, C/S: cesarean section, ROM: rupture of membranes.