Premature rupture of membranes (PROM) refers to rupture of membranes before delivery, which is one of the common complications in obstetrics, with an incidence of 8%-10% . Complications such as infection, trauma increased pressure of amniotic cavity and gestational diabetes may lead to rupture of membranes [2–3]. Preterm premature rupture of the membranes (PPROM) means the rupture of the membranes before labor starts prior to 37 weeks of gestation, which remains a significant obstetric problem that affects 3–4% of all pregnancies and precedes 40–50% of all preterm births . The number of PPROM cases exceeds that of preelampsia and gestational diabetes. According to the report, neonatal death in newborns without chromosomal abnormality or congenital anomaly was mainly caused by prematurity [5–6]. In addition preterm births is also related to a series of long-term effects in survivors, including neurodevelopmental delay, cerebral palsy, blindness, hearing loss, and chronic lung disease [7, 8]. However, the empirical treatment that ignore the complexity and heterogeneity of PPROM pathopHysiology are not satisfactory, antibiotic therapy and antenatal corticosteroid treatment are typically administered to prolong pregnancy, prevent infection, and reduce gestational age dependent morbidities , and the result is futile because probably 90% of pregnant women give birth within one week [10–12].
PPROM results from complex, multifaceted pathways, and precise causes or risk factors of are unknown. Some research showed the etiology of PPROM was multifactorial, such as maternal reproductive tract infections (e.g., bacterial vaginosis BV, trichomoniasis, gonorrhea, Chlamydia, and occult chorioamnionitis), behavioral factors (e.g., cigarette smoking, substance abuse, poor nutritional status, and coitus during pregnancy) and obstetric complications (e.g., multiple gestation, polyhydramnios, incompetent cervix, gestational bleeding, prior cervical surgery, and antenatal trauma) [13, 14]. Among of them, ascending bacterial invasion may lead to intrauterine infection that is the most common risk factor, which account for up to 60% of cases with PPROM [15, 16]. There are some additional risk factors for PPROM, history of PPROM in a previous pregnancy have been proposed [17, 18]. The pathogenesis are still unclear and recent studies have shown both disruption of fetal membrane integrity and activation of uterine contraction can be cauesd by inflammatory mediators. Current study showed inflammation–oxidative stress axis plays a major role in producing pathways that can lead to membrane weakening through a variety of processes. Bacterial products or/and pro-inflammatory cytokines can trigger that the membrane morpHology with PPROM altered. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM . The vaginal microflora of a healthy asymptomatic woman was consisted of a wide variety of anaerobic and aerobic bacterial genera and species dominated include the facultative, microaeropHilic, anaerobic genus Lactobacillus. The activity of Lactobacillus is essential to protect women from genital infections and to maintain the natural healthy balance of the vaginal flora. There is more and more evidence that abnormalities in vaginal flora during pregnancy is associated with preterm labor and delivery with potential neonatal sequelae due to prematurity and poor perinatal outcome pregnancy [20–23].
Early diagnosis of PPROM is necessary and important. It is possible to prevent PROM if treatment can be performed in the early stage of chorionic villous infection, but PROM is inescapable after amniotic layer occurs infection , with the reason that the chorion is thicker than amnion but has less tensile strength  Accurate diagnosis of PROM remains a frequent clinical problem in obstetrics. At present, there are only several tests to confirm a diagnosis of PPROM post-facto, including microfetal cell identification, amniotic fluid crystallization and intra-amniotic dye injection. The disadvantages of intra-amniotic injection are invasive, which increases the risk of infection and premature delivery. The inadequacy of microfetal cell identification or amniotic fluid crystallization is the long detection period and the high false positive rate, and not any method to reliably predict PPROM . It is the lack of a non-invasive gold standard for the diagnosis of PROM that led to the appearance of several tests based on alternative biochemical markers . The diagnostic performance of traditional indicators reflecting inflammation or infection includes leucocytes, IL-6, C-reactive protein (CRP), and procalcitonin (PCT), vaginal prolactin, alpHa-feto-protein (AFP), fetal fibronectin and insulin-like growth factor binding protein-1 (IGFBP-1), whcih need to be improved [28, 29] As a result, the biomolecular markers with high sensitivity and specifificity that can predict PPROM plays a very important role, which is the key of early clinical diagnosis .
Recent studies suggested that urine test is helpful for timely screening of high-risk pregnant women with PPROM. Urine test is a routine process for the hospitalized patients, which has good operability, low cost and non-invasiveness. It includes 20 important indicators, named leukocytes; (BLD): occult blood; (PRO): protein; (GLU): glucose; (KET): ketone bodies; (UBG): urobilinogen; (BIL): urobilirubin; pH; (SG): urine specific gravity; (NIT): nitrite; (WBCs): white blood cells; (RBCs): red blood cells; (EC): epithelial cell count; Cast; (P.CAST): pathological cast; (BAC): bacteria; (SRC): small round cells; (BYST): yeast; Crystals; (Cond): electrical conductivity. The aim of this study was designed to investigate the value of urine test in diagnosis and prediction of PPROM.