Preterm birth (PTB) is a major public health burden, affecting >12% of all births in the United States, the majority of which are attributable to spontaneous preterm labor. Despite efforts to reduce the prevalence of PTB, its rate continues to rise. Recent studies have demonstrated that administration of progestins to women at risk of PTB provides an effective reduction in the rate of its occurrence. Although these trials provide hope for the identification of interventions that may ultimately reduce the overall rate of PTB in the United States, the at-risk populations identified as candidates for intervention comprise only a small proportion of the total number of cases of spontaneous preterm birth. It is estimated that of all cases of PTB, only 8.7% and 1.7-2.3% of women, respectively, have the risk factors of prior PTB or significant cervical shortening in the midtrimester and would benefit from prophylactic therapy.

Spontaneous preterm labor comprises the majority of cases of PTB. Historically, prediction of spontaneous PTB has not been very successful using the classic criteria for the diagnosis of preterm labor of regular uterine contractions with concomitant cervical change. Using these criteria, >70% of patients diagnosed and treated for preterm labor ultimately deliver at term. One of the limitations of any screening approach for preterm labor is that preterm labor is an intermediate diagnosis as there is no gold standard test considering that the ultimate outcome that would define true preterm labor is subsequent PTB. Recently, employment of biomarker results such as fetal fibronectin (fFN) in the diagnostic cascade of preterm labor has yielded sensitivity and specificity for the prediction of PTB of >80%. Therefore, employment of these techniques in the evaluation of threatened preterm labor could ultimately lead to the avoidance of unnecessary interventions to women at low risk and, more importantly, implementation of therapy to those women most likely to deliver preterm.

Our aim is to review the current medical literature to summarize the various published methods of fFN plus cervical length (CL) screening utilized to predict PTB risk. Furthermore, we will quantify the screening efficacy of fFN plus CL testing to predict PTB at various pregnancy endpoints.

Materials and Methods

Data sources and study selection

We searched PubMed and Cochrane databases without date criteria in October 2012 using the key words “fibronectin” and “cervical length” with restriction to English language and human studies. These search criteria yielded 85 studies. In all, 29 review articles were excluded, as were 6 articles on unrelated topics. Of the remaining 50 studies, 39 were excluded because they did not report the association between the combination of fFN and CL in symptomatic women and their association with PTB. A bibliographic review of selected articles was also performed to search for additional studies that may have been missed with the original search terms. One additional study was identified, yielding 12 total studies for review ( Figure ).

Study inclusion flow diagram

FFN, fetal fibronectin; NPV, negative predictive value; PPV, positive predictive value; PTB, preterm birth.

DeFranco. Combination of fFN and cervical length for preterm labor screening. Am J Obstet Gynecol 2013.

Of these 12 studies, 7 reported sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) for PTB. Two studies provided sufficient data for these values to be calculated by one of the authors of this review (E.A.D.). The remaining 3 studies did not report sensitivity, specificity, PPV, NPV, or sufficient data for these values to be calculated, therefore they were also excluded. Therefore, 9 studies were included in the final review ( Table 1 ).

TABLE 1

Overview of published studies reporting PTB risk associated with both fFN positivity and shortened cervix in symptomatic women

	Study	Design	Sample size	Singletons or twins	Criteria for short cervix, mm	Outcome PTB	Overall rate of PTB	Screen+ rate of PTB a	PPV, %	NPV, %	Sensitivity, %	Specificity, %
1	Hincz et al, 2002	Prospective cohort	82	Singletons	21-31	≤28 d	17.1% (≤28 d) 25.6% (<37 wk)	63% (≤28 d)	63 b	97 b	86 b	90 b
2	Rozenberg et al, 1997	Prospective cohort	76	Singletons	≤26	<37 wk	26.3% (<37 wk)	55%	52	84	55	82
3	Gomez et al, 2005	Prospective cohort	215	Singletons	<15 <30	<35 wk	16% (<35 wk)	81% (<35 wk) 47% (<35 wk)	81 47	89 91	38 53	98 89
4	Schmitz et al, 2006	Prospective cohort	359	Singletons	16-30	<35 wk	13.4% (<35 wk)	35%	35	94	67	81
5	Eroglu et al, 2007	Prospective cohort	51	Singletons	<20 <25	≤7 d c	11.7% (<7 d) 19.6% (<35 wk)	— d	80 80	97.2 97.0	80 80	97.2 97.0
6	Ness et al, 2007	RCT	100	Both	<20	<37 wk <34 wk	24.7% (<37 wk) 9.3% (<34 wk)	42.9% (<37 wk) 28.6% (<34 wk)	43 29	77 92	13 22	94 94
7	Asakura et al, 2009	Retrospective cohort	108	Both	<20	<37 wk <34 wk	37% (<37 wk) 14.8% (<34 wk)	44.4% (<37 wk) 37% (<34 wk)	44 37	65 93	30 62	78 82
8	Audibert et al, 2010	Prospective cohort	62	Both	<25	<37 wk <34 wk ≤14 d	23% (<37 wk) 14% (<34 wk) 6% (≤14 d)	54.2% (<37 wk) 39.1% (<34 wk) 12.5% (≤14 d)	56 39 13	74 87 92	56 64 50	74 71 64
9	Rose et al, 2010	Retrospective cohort	141	Both	16-29 ≤15	<37 wk <14 d <7 d	17% (<37 wk) 2.1% (<14 d) 0.7% (<7 d)	— d 0 0	— 0 0	— 97.8 99.3	— 0 0	— 96.4 96.4

 

fFN, fetal fibronectin; NPV, negative predictive value; PPV, positive predictive value; PTB, preterm birth; RCT, randomized controlled trial.

DeFranco. Combination of fFN and cervical length for preterm labor screening. Am J Obstet Gynecol 2013.

a Combined screening with fFN and cervical length test positive;

b Delivery ≤28 d;

c Primary outcome PTB <35 wk, but only sufficient data to calculate “n’s” from delivery within 7 d as outcome;

d Data not reported.

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