POCT PROM

Purpose:
Premature rupture of the membranes (PROM) at term occurs in 5 to 10% of pregnancies and pre-term PROM (PROM<37 weeks’ gestation) occurs in approximately a third of all premature births and is associated with significant neonatal morbidity and mortality. Without clear evidence of amniotic fluid loss observed by speculum examination, the diagnosis of PROM can be uncertain and complementary diagnostic tests are recommended [NG25]. Amniotic fluid specific biomarkers tests from PROM commercially available in the UK include insulin-like growth factor binding protein-1 (IGFBP-1 - Actim® PROM) and placental alpha microglobulin-1 (PAMG-1 - AmniSure®).

NICE guideline [NG25] Preterm labour and birth (last updated June 2022).
1.3          Diagnosing preterm prelabour rupture of membranes (P-PROM)
if pooling of amniotic fluid is not observed, perform an IGFBP-1 or PAMG-1 test of vaginal fluid.

1.3.2          If the result of the test is positive, do not use the test results alone to decide what care to offer the woman, but also take into account her clinical condition, medical and pregnancy history and gestational age, and either: offer care consistent with the woman having P PROM or re-evaluate the woman’s diagnostic status at a later time point.

1.3.3          If the results of the IGFBP-1 or PAMG-1 test is negative and no amniotic fluid is observed:
do not offer antenatal prophylactic antibiotics, explain to the woman that it is unlikely she has P–PROM, but that she should return for reassessment if there are any further symptoms suggestive of P–PROM or preterm labour.

IGFBP-1 is a 25kD protein synthesized in the decidual cells and foetal liver and is secreted into amniotic fluid. Amniotic fluid is normally not found in the vagina, but when foetal membranes rupture, amniotic fluid leaks into the vagina and the IGFBP-1 concentration quickly rises and remains high until delivery.

PAMG-1 is a protein found in very high levels in amniotic fluid (2,000–25,000 ng/ml) and at extremely low background levels in normal vaginal discharge (0.05–0.2 ng/ml). The test is set to a cutoff of 5 ng/ml to identify microscopic leaks of amniotic fluid while avoiding false positives from intact membranes.

Scope:
Weqas offers 2 separate programmes, one for qualitative assessment of IGFBP-1 (Actim® PROM) and one for qualitative PAMG-1 (Amnisure®). For IGFBP-1, Purified human IGFBP-1 is added to an artificial amniotic fluid buffer base to produce a high positive base. The high positive base is further diluted with the negative base to create a series of samples spanning the analytical range. Each of the samples are distributed on 2-3 occasions to allow for the assessment of between batch variability. Two samples are distributed bi-monthly, providing 12 samples over the year. The programme assesses the diagnostic accuracy of the test, specificity and sensitivity at a range of IGFBP-1 concentrations including the diagnostic threshold.

For PAMG-1, material is sourced from a third-party supplier and currently not produced in house. Two samples are distributed bi-monthly, providing 12 samples over the year. The programmes assesses both site and device performance, including bias, within and between batch imprecision for the quantitative analytes. Challenging samples are distributed at or near the limit of detection and diagnostic thresholds for the qualitative analytes.

Key Features:

Liquid stable samples are supplied ready to use; no pre-analytical preparation is required.
Qualitative reporting available, with interpretations based on recommended cut-offs.
Linear related panel distributed covering the clinically relevant range.
Programme assesses diagnostic accuracy at a range of concentrations including near the diagnostic threshold.