Is routine sampling of fetal fibronectin justified?

Because the Goldenberg study was a large multicenter trial that included women across a broad spectrum of age, race, and socioeconomic status, its results could be applied to all US women. Indeed, this study provided a compelling incentive to use fetal fibronectin sampling as a screening test for risk of preterm delivery.

Other studies^6-8 corroborated the landmark Lockwood and Goldenberg studies, providing an affirmative answer to the question “Can we screen for preterm delivery?”

Some experts argue that a negative fibronectin test is useful in identifying those at low risk of delivery, thereby avoiding tocolysis and hospitalization.

TABLE 1

Fetal fibronectin as a predictor of spontaneous preterm delivery: Detection at 22-24 weeks’ gestation

Does fibronectin sampling meet the standard for screening?

Significant burden. There is no question that preterm birth represents a significant burden.^9,10 For one, it is common. Recent data indicate that approximately 10% of deliveries in the United States occur before 37 weeks of gestation, which translates to more than 400,000 preterm births annually. Of these, 2% to 3% occur before 32 weeks’ gestation.

Preterm infants are at a greatly increased risk of serious complications (eg, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage) and death.¹¹ In fact, preterm delivery is perhaps the most common cause of neonatal death.

Good marks for accuracy, cost, ease of use, safety, acceptability. As noted, a positive result is strongly associated with preterm birth. Further, this noninvasive test poses little to no threat to women, is simple for the clinician to perform, is economical, and is well received by patients.

Availability of effective treatment. Of the 5 conditions a widely used screening test must possess, this is the only one in which fetal fibronectin sampling is lacking. No effective interventions exist to decrease preterm birth in women with positive tests.

Antibiotic therapy fails to reduce preterm births

In May 2003, Andrews et al12 published the results of a multicenter, double-blind, placebo-controlled trial in which asymptomatic women with fetal fibronectin levels over 50 ng/mL (6.6% of the 16,317 women screened) received antibiotic therapy.

The final study population included 347 women given a 10-day course of metronidazole (250 mg 3 times daily) plus erythromycin (250 mg once daily) and 356 women taking placebo. The 2 groups were well matched for age, ethnicity, marital status, education, average gestational age, and incidence of bacterial vaginosis.

Treatment did not reduce the rate of spontaneous preterm birth. No differences were seen in the incidence of delivery before 32, 35, or 37 weeks, or in birth weight (TABLE 2). Nor was there improvement in any health parameters in the infants delivered by women in the antibiotic group.

TABLE 2

Effect of antibiotic therapy on spontaneous preterm delivery

Was the study flawed?

One could argue that the Andrews study had some limitations. First, it is possible that the sample size was too small to detect differences between the treatment groups. Second, screening was performed at a mean gestational age of 23 weeks (range, 21 to 26 weeks), which may not have been early enough. Third, patient compliance was poor (only about 50% of the antibiotic group took all of their medication); thus, treatment efficacy may have been inadequately assessed. In addition, the 10-day treatment regimen may have been too brief.

Could other agents yield better results?

It is possible that metronidazole and erythromycin were not the appropriate antibiotics for treating the subclinical infection associated with preterm delivery. In fact, an entirely different class of agents may be needed.

Is inflammation a factor? If inflammation rather than subclinical infection is the primary precipitant of fetal fibronectin release into the cervix and vagina prior to preterm labor, antiinflammatory therapy may have a role in its prevention.

Clinical experience

We do not use fetal fibronectin as a screening test in asymptomatic women since there is no established intervention. There is more debate about whether it can be used as a diagnostic test. Some experts argue that, in patients with “threatened” preterm labor, a negative fetal fibronectin test may be useful in identifying those at low risk of delivery, thereby avoiding tocolysis and hospitalization.

However, since this benefit has not been demonstrated in clinical trials or observational studies, it should not alter our practice. Until it has been proven, we will continue to manage women with symptoms of preterm labor without the use of fetal fibronectin.