According to the March of Dimes, preterm birth occurs in approximately 10% of U.S. pregnancies. Until recently, cervicovaginal fetal fibronectin (fFN) was the only FDA-approved test for predicting preterm delivery in symptomatic women. We have blogged about fFN previously.
Despite its FDA approval, fFN has limited clinical value. A condition with low prevalence, such as preterm delivery, has a low pre-test probability of occurring, hence a negative test result adds little to the assessment of the patient. Thus, a screening test for a low prevalence condition must demonstrate high positive predictive value (PPV) to be useful. The negative predictive value (NPV) of fFN is 99.5%, meaning a negative result is highly predictive that a woman will NOT deliver soon. However, PPV of fFN is only ~17%, meaning that less than 1 in 5 women with a positive test result will proceed to delivery with 7-14 days. For comparison, the PPV of flipping a coin in this population is 4%. Meta-analyses have supported the lack of utility for fFN.
In April 2018, the FDA approved cervicovaginal placental alpha macroglobulin-1 (PAMG-1), (brand name Parto Sure from QIAGEN) as a test for assessing the risk of spontaneous preterm birth in patients with symptoms of preterm labor.
Several recent studies have evaluated PAMG-1 for its ability to predict preterm birth.
Wing, et al. conducted a prospective study of pregnant women from 15 US sites, with signs or symptoms of preterm labor between 24 and 35 weeks of gestation with intact membranes and cervical dilations less than 3cm (>3 cm generally indicates active labor). They compared the utility of PAMG-1 to fFN. A summary of their key findings are shown in the table below.
| Spontaneous preterm delivery ≤ 7 days | PPV | NPV |
| PAMG-1 | 19.0% | 99.1% |
| fFN | 6.5% | 99.7% |
| Spontaneous preterm delivery ≤ 14 days | ||
| PAMG-1 | 25.0% | 97.7% |
| fFN | 11.1% | 98.7% |
Cervicovaginal PAMG-1 demonstrated similar negative predictive value and improved positive predictive value compared to cervicovaginal fFN.
Similarly, Melchor, et al. conducted a retrospective study of women with preterm contractions presenting to a single maternity hospital in Spain. They compared a one year period during which fFN was used to assess risk of pre-term delivery and a one year period where PAMG-1 was used. Similar to the Melchor study, patients were between 24-34 weeks of gestation with signs or symptoms of preterm labor and had intact membranes and a cervical dilation less than 3cm. A summary of their key findings are shown in the table below.
| Spontaneous preterm delivery ≤ 7 days | PPV | NPV |
| PAMG-1 | 35.3% | 98.3% |
| fFN | 7.9% | 97.9% |
Both studies show improved positive predictive values for PAMG-1 over fFN. However, both studies reported sensitivities for PAMG-1 of 50%. While this test can certainly be viewed as an improvement over fFN, PAMG-1 will only identify half of the women who will deliver within 7 day. Clearly a better marker to predict pre-term delivery is still needed.