Vaginal fluid creatinine in premature rupture of membranes

Abstract

Premature rupture of membranes (PROM) is defined as the rupture of chorioamniotic membranes prior to the onset of labor. There is no gold standard diagnostic test for PROM. The nitrazine paper test, positive ferning pattern, injection of intraamniotic dyes, and estimation of vaginal alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), prolactin, and fibronectin have been used in clinical studies to diagnose PROM. However, these tests have low sensitivity and specificity or they are invasive [1–3]. We hypothesized that vaginal fluid creatinine may be helpful in diagnosing PROM because fetal urine is one of the important sources of amniotic fluid volume. The study group consisted of 54 women in their third trimester of pregnancy with the diagnosis of PROM established by inspection of vaginal pooling and the control group consisted of 34 pregnant women with intact membranes. Criteria for exclusion from the study were placenta previa, vaginal bleeding, and all conditions that may affect fetal urine production. The vagina was washed by injection with a syringe filled with 3 ml of saline solution, and the washing fluid was collected from the posterior vaginal fornix. The collected fluid was promptly quantitatively tested for the presence of creatinine with a creatinine assay (Ektachem Clinical Chemistry Slides, Johnson & Johnson). Descriptive statistical methods and the t-test were performed using the GraphPad Prisma V.3 package program. Roc curve analysis was used to establish an optimal cut-off concentration. The results were evaluated with a significance level of P<0.05. The demographic and clinical characteristics of the two groups are shown in Table 1. Creatinine was detectable in all samples. The mean vaginal fluid creatinine levels in the control and study groups were 0.026±0.029 mg/dl (range, 0.02–0.11 mg/dl) and 0.70±0.55 mg/dl (range, 0.17–2.30 mg/dl), respectively, where the difference was statistically significant (P<0.001). The sensitivity, specificity, positive predictivity, and negative predictivity were all 100% in detecting PROM by evaluation of vaginal fluid creatinine concentration with a cut-off value of 0.12 mg/dl. Our data show that vaginal fluid creatinine is an extremely useful marker in doubtful cases of PROM. In these cases, new methods such as AFP, beta-hCG and fetal fibronectin were investigated. However, they have low specificity owing to overlap between the values of AFP, hCG, and fibronectin in patients with and without intact membranes [1–3]. In conclusion, the creatinine assay is cheaper and faster than other methods, and has higher sensitivity and specificity to establish accurate diagnosis. It is a possible candidate to become a gold standard test for PROM.