Category Archives: Premature Rupture of Membranes

Premature Rupture of Membranes

Placental Alpha-Microglobulin-1 as a Marker of Membrane Rupture

Preterm babyPremature rupture of membranes (PROM) is spontaneous rupture of fetal membranes before the onset of uterine contractions. Preterm PROM, which is PROM before 37 weeks is a major cause of preterm birth.

Previously, we have blogged about the cervicovaginal markers IGFBP1 and AFP to diagnose PROM. In recent years, a number of studies have reported on the utility of cervicovaginal placental alpha-microglobulin-1 (PAMG-1) as a marker of Rupture of Membranes.

PAMG-1 is present in blood, amniotic fluid (AF), and cervicovaginal fluid of pregnant women. The concentration of PAMG-1 in AF (2,000–25,000 ng/mL) is several thousand times higher than that in cervico-vaginal discharge when the fetal membranes are intact (0.05–0.2 ng/mL). The high concentration of PAMG-1 in AF makes it potentially a good marker to detect the presence of AF in the vaginal canal.

In one of the largest studies, Lee et al examined 184 women with symptoms or signs of PROM. 159 were later confirmed to have PROM. In this population, PAMG-1 demonstrated a sensitivity of 98.7%, specificity of 87.5%, positive predictive value of 98%, and a negative predictive value of 91.3%. In contrast, Nitrazine in the same patients demonstrated a sensitivity of 88.1%, specificity of 87.5%, positive predictive value of 97.9%, and a negative predictive value of 52.5%. This performance is supported by several other studies as well.

Diagnostic Utility of PAMG-1







Lee et al. 2007 Obstet Gynecol






Cousins et al.2005 Am J Perinatol






Ng et al. 2013 BioMed Res Intern






Abdelazim et al. 2013 J Obstet Gyneacol Res





In summary, PAMG-1 appears to be a viable method to detect PROM in cervicovaginal fluid and appears to be superior to conventional methods.

Laboratory testing for premature rupture of membranes

This post is by a guest author, Douglas Stickle, Ph.D.  Dr. Stickle is a professor in the Department of Pathology at Thomas Jefferson University and the director of chemistry and point-of-care testing at Jefferson University Hospitals in Philadelphia, PA.

Rupture of membranes (ROM) is the term used to describe the breaking of the amniotic sac, as normally occurs before the onset of labor. If this happens earlier than the 37th week of pregnancy it is called preterm ROM (PROM). It’s a condition that can lead to a preterm birth, or, if very early, a preterm, premature birth.

Preterm baby 2When PROM happens, there is an increased risk of complications due to intrauterine infection, umbilical cord compression, and the neurodevelopmental disorders that are associated with a preterm delivery. Diagnosis of PROM is particularly important when the gestational age is incompatible with a viable birth, often considered to be a fetal age less than 24 weeks. In such cases, medical intervention is necessary to preserve the chances for a live birth.

Suspected cases of PROM are often investigated by laboratory analysis of fluid obtained from the vagina to detect properties or substances that should otherwise not be present unless the fluid contains amniotic fluid due to PROM. The simplest forms of testing are measurement of acidity (pH) of the fluid, or a test called "fern" testing. Fern testing refers to the fern-like appearance of amniotic fluid when it is dried on a glass slide. Both of these tests aren’t very accurate and so other tests have been developed to better identify patients with ruptured membranes.

These other tests are designed to detect molecules that are normally present in amniotic fluid but not vaginal fluid. For example, tests have been developed that detect alpha-fetoprotein (AFP) or insulin-like growth factor binding protein-1 (IGFBP-1). The presence or absence of these molecules in the specimen are determined by a lateral flow immunoassay. The assay works like commonly performed tests for human chorionic gonadotropin (hCG) (aka pregnancy tests).

These tests are highly sensitive to low concentrations of these molecules, which is both good and bad. It’s good because they can detect small amounts of the molecules and lead to a more accurate diagnosis. It’s bad because these two molecules are also present in maternal blood which means that if a sample is contaminated with blood, the certainty of a positive test to detect amniotic fluid is called into question.

From the doctor’s perspective, a practical advantage of the immunoassays is that their results are binary – the result is either positive or negative — whereas the pH test and the fern test are more subjective and difficult to interpret definitively. However, the AFP and IGFBP-1 tests may be subject to false-positive results as the gestational age of the fetus approaches term. This suggests that, at later stages of pregnancy, these biomarkers may signify imminence of delivery.

The gold standard, or best test, to diagnose rupture of membranes is a dye test, in which a colored fluid is injected into the amniotic fluid followed by direct observation to see if the dye subsequently appears in the vaginal pool fluid. Also, ultrasound imaging of the amniotic fluid volume may also assist in diagnosis of PROM, but in individual cases such imaging may be difficult to interpret. Given the low but finite risk of complications of the dye test, the AFP and IGFBP-1 tests are often preferred as first-line tests for preterm premature rupture of membranes.