Evaluation of a Novel Diagnostic Kit for the Detection of Placental Alpha-Microglobulin-1 in the Prediction of Preterm Birth in Women Presenting With Signs and Symptoms of Preterm Labor in Comparison to a Control Group of Asymptomatic Women With the Same Gestational Age - a Multicenter Trial

Background

Placental alpha microglobulin-1 (PAMG-1) is a protein found in high concentrations in amniotic fluid but very low concentrations in background levels of cervico-vaginal discharge. In recent years, the medical community has increasingly accepted the widespread use of detecting PAMG-1 to aid the provider in confirming or ruling out rupture of the fetal membranes (ROM). The test used is commercially marketed as the AmniSure® ROM Test, manufactured by AmniSure® International, LLC, Boston, MA, USA.

In one of the original investigations of PAMG-1 for the detection of ROM, Lee et al. noted that in 20 out of the 23 cases where the AmniSure® ROM Test was positive and standard clinical assessment (i.e. nitrazine, ferning and pooling) was negative, the patient was ultimately determined to have been ruptured upon retrospective analysis of their clinical course. It was later reported that for all of the preterm patients in this group that showed signs and symptoms of labor, delivery followed within 7 days. In 2011, the clinical value of a positive AmniSure® ROM Test in the patient presenting with signs and symptoms of preterm labor (PTL) but without membrane rupture was investigated by this same group. The results demonstrated that the AmniSure® ROM Test was highly predictive of delivery of these patients within 48 hours, 7 days and 14 days.

In the patient group on whom the above tests are performed, membrane rupture is excluded as this condition, if present, confirms imminent delivery and dictates a different course of management. It has been demonstrated that the AmniSure® ROM Test can detect PAMG-1 in patients presenting with signs and symptoms of ROM when all other traditional methods are unable to do so. The likelihoods of adverse outcomes associated with these sub-clinical ruptures have been demonstrated to not be statistically different from the adverse outcomes associated with gross or clinically detectable ruptures. The proposed physiological explanation for this phenomenon is that PAMG-1 is released through micro-perforations of the amniotic membranes that more copious amounts of fluid cannot pass through.

The major difference, however, between the patient presenting with signs of preterm labor and those just described above is the presence, or absence, of membrane rupture signs or complaints. Given that the complaints of ROM are typically rooted in an overt episode of suspicious fluid leakage, it is hypothesized that the resulting concentration of PAMG-1 in the vagina of the patient without such overt complaints or signs of ROM will be lower than the current sensitivity threshold of the AmniSure® ROM Test.