Premature rupture of membranes (PROM) is defined as the rupture of the foetal amniotic membranes before the onset of labour [1–3]. It occurs in 10% of all term pregnancies, and is associated with a number of complications which include infection and preterm birth .
Rupture of foetal membranes occurs as a result of apoptosis, activation of some enzymes such as collagenase at 37weeks and mechanical forces . PROM most likely occurs due to a premature initiation of these pathways . Early PROM could also occur as a result of inflammation with or without infection of the membranes . Studies have also suggested that membrane rupture could also be due to a number of factors such as defects in collagen structure and production as well as increased oxidative stress. Another factor implicated in PROM is a mismatch between production and breakdown of collagen in the extracellular matrix of the foetal membranes brought about by an increase in the activity of a number of matrix metalloproteins . Several risk factors have been implicated in PROM and they include a low body mass index, urinary tract infections, a low socioeconomic status, vaginal bleeding and invasive procedures like amniocentesis [4, 5].
The correct diagnosis of PROM is essential. A wrong or missed diagnosis can lead to unnecessary interventions and delivery, as well as other adverse complications like infections to both mother and foetus [4, 6]. Routinely the diagnosis of PROM depends on a combination of an accurate history of a drainage or continuous trickle of fluid per vaginam. An examination findings of a pooling of clear fluid in the posterior fornix of the vagina, associated egress of fluid from the cervical canal, with a positive confirmatory test, for example Nitrazine test or Amnisure [7–10]. In indeterminate cases of PROM, these routine methods can lead to high false positive and false negative results. False positive Nitrazine test could be as a result of any lower genital tract infections or possible contamination of samples by semen, urine, and blood .
Many biochemical diagnostic modalities for PROM have been described. These include measurement of biomarkers with high concentrations in foetal amniotic fluid rather than other kinds of vaginal secretions, e.g. vaginal human chorionic gonadotropin (HCG), vaginal PH, vaginal fluid insulin growth factor binding protein-1, foetal fibronectin tests, vaginal fluid prolactin levels, urea, alpha fetoprotein (AFP) and creatinine [1, 11–16]. Even though these markers could improve the diagnosis of PROM, they have not become popular due to the complex nature of the tests and high cost .
Amnisure® is a newly developed easy to use, non-invasive diagnostic test of PROM and PPROM that combines both high sensitivity with low false positive results, it is designed as a dipstick format highly sensitive for detecting presence of placental alpha macroglogulin-1 (PAMG-1), a specific protein present in the amniotic fluid . PAMG-1 was selected as a marker to use in Amnisure due to its unique characteristic presence in high levels in amniotic fluid, low level in blood, and extremely low in cervico-vaginal secretions, the test contains highly sensitive monoclonal antibodies that is designed to detect as low as 5ng/ml of PAMG-1 in cervico-vaginal secretion after a rupture of membranes .
There is a paucity of studies on the use of vaginal fluid urea and creatinine in the diagnosis of PROM in this environment. This study is apt because, measurement of urea and creatinine in vaginal washing for the detection of PROM is based on the concept that in the second half of a pregnancy, the major component of amniotic fluid is the urine of the foetus [1, 18]. Most of the current diagnostic tests for PROM have high sensitivity and specificity. Vaginal fluid urea and creatinine has values closest to Amnisure, clinical assessment, ferning test and Nitrazine test have a sensitivity of 85%, 97% and 93% respectively, and a specificity of 98%, 72%, and 85% respectively. Vaginal fluid urea and creatinine in diagnosis of PROM has a sensitivity of 98% and specificity of 100% .
In comparison to the Amnisure test, Urea and creatinine assay is readily available in most centres, is much cheaper to assay than the Amnisure test which costs $59.9 (#21000) per test kit , with no need for extra equipment and reagents, making introduction of this method into routine use feasible and practical. However, a major advantage the Amnisure test has over the urea and creatinine assay is that, the Amnisure test is a bedside test with results available in 10mins, while the urea and creatinine needs to be sent to the laboratory for assay and takes 1–2 hours to get the results. This study showed that vaginal fluid urea and creatinine was an effective and cheaper alternative to the Amnisure test.