1. PRETERM PREMATURE RUPTURE OF MEMBRANE DR.parichehr pooransari Perinatalogist in shohadaye Tagrish hospital

2.  Premature rupture of membranes (PROM) refers to membrane rupture before the onset of uterine contractions (also known as prelabor rupture of membranes); preterm PROM (PPROM) refers to PROM before 37 0/7ths weeks of gestation.

3.  Preterm premature rupture of membranes (PPROM) occurs in 3 percent of pregnancies.  it is responsible for, or associated with, approximately one-third of preterm births.

4.  The strength and integrity of fetal membranes derive from extracellular membrane proteins, including collagens, fibronectin, and laminin. Matrix metalloproteases (MMPs) decrease membrane strength by increasing collagen degradation. Tissue inhibitors of MMPs (TIMMPs) bind to MMPs and shut down proteolysis, thereby helping to maintain membrane integrity. A variety of pathologic events can disrupt this homeostasis and initiate a cascade of biochemical changes that culminate in PROM

5. RISK FACTORS  but most patients have no identifiable risk factors.  A history of PPROM in a previous pregnancy, genital tract infection, antepartum bleeding, and cigarette smoking have a particularly strong association with PPROM  Women with a history of PPROM are at risk for recurrent PPROM or preterm birth without PPROM(13.5% versus 4% without history or about 32% in different studies)

6.  Genital tract infection  more likely pathogenic microorganisms in the amniotic fluid,  significantly higher rate of histologic chorioamnionitis than those who deliver preterm without PPROM  Many of the microorganisms that colonize the lower genital tract have the capacity to produce phospholipases, which can stimulate the production of prostaglandins and thereby lead to the onset of uterine contractions.

7.  Antepartum bleeding — Antepartum bleeding in the first trimester is associated with a small but statistically significant increase in the risk of PPROM. Antepartum bleeding in more than one trimester increases the risk of PPROM three- to seven-fold.  Cigarette smoking — The risk of PPROM among smokers is increased two- to four-fold compared to nonsmokers.  several genetic polymorphisms of genes related to infection, inflammation, and collagen degradation have been identified as potential risk factors for PPROM.

8.  many women describe intermittent or constant leaking of small amounts of fluid or just a sensation of wetness within the vagina or on the perineum.  If amniotic fluid is not immediately visible, the woman can be asked to push on her fundus, Valsalva, or cough to provoke leakage of amniotic fluid from the cervical os.  Findings on ultrasonography — Fifty to 70 percent of women with PPROM have low amniotic fluid volume on initial sonography.

9.  However, the duration of the latency period inversely correlates with gestational age at membrane rupture.  Prematurity-related morbidity varies with gestational age and is higher in the setting of chorioamnionitis. Fetal exposure to intrauterine inflammation has been associated with an increased risk of neurodevelopmental impairmen.

10.  Approximately one-third of women with PPROM develop potentially serious infections, such as intraamniotic infection (chorioamnionitis and funisitis), endometritis, or septicemia. Endometritis is more common after cesarean than vaginal delivery. The incidence of infection is higher at earlier gestational ages.

11.  PPROM is also associated with increased risks of abruptio placentae and prolapse of the umbilical cord. Placental abruption occurs in 2 to 5 percent of pregnancies complicated by PPROM. The risk is increased seven- to nine-fold in PPROM pregnancies in which intrauterine infection or oligohydramnios is present. Placental abruption may be the precipitating event for, or a consequence of, PPROM

12.  Early, severe, prolonged oligohydramnios can be associated with pulmonary hypoplasia, facial deformation, and orthopedic abnormalities. Such complications are most likely when membrane rupture occurs at less than 23 weeks of gestation.  fetal malpresentation is common, given the preterm gestational age and the frequent occurrence of reduced amniotic fluid volume. The risk of cord prolapse is especially high (11 percent in one study in the setting of both nonvertex fetal presentation and PPROM. Non-cephalic presentation may also increase the risk of abruption, infection, and fetal death in utero.

13. DIAGNOSIS  The diagnosis of preterm premature rupture of membranes (PPROM) is clinical, and is generally based on visualization of amniotic fluid in the vagina of a woman who presents with a history of leaking fluid.  Laboratory confirmation of clinically suspected PPROM  Nitrazine and fern tests  Amniotic fluid usually has a pH range of 7.0 to 7.3 compared to the normally acidic vaginal pH of 3.8 to 4.2 and the normal acidic pH of urine of 5.0 to 6.0.

14.  False-negative and false-positive Nitrazine test results occur in up to 5 percent of cases. False negative test results can occur when leaking is intermittent or the amniotic fluid is diluted by other vaginal fluids. False positive results can be due to the presence of alkaline fluids in the vagina, such as blood, seminal fluid, or soap. In addition, the pH of urine can be elevated to near 8.0 if infected with Proteus species.

15.  Well-estrogenized cervical mucus or a fingerprint on the microscope slide may cause a false-positive fern test; false negatives can be due to inadequate amniotic fluid on the swab or heavy contamination with vaginal discharge or blood.

16.  In the United Kingdom, an absorbent pad (AmnioSense) that changes color at pH >5.2 is used as a panty liner and marketed to pregnant women. In a study of 157 pregnant women, the sensitivity and specificity of this device for diagnosis of membrane rupture were 98 and 65 percent,

17. (IGFBP-1 [ACTIM PROM],  AmniSure is a rapid slide test that uses immunochromatography methods to detect trace amounts of placental alpha microglobulin-1 protein in vaginal fluid. An advantage of this test is that it is not affected by semen or trace amounts of blood. placental alpha microglobulin-1 protein assay (PAMG-1 [AmniSure])

18.  A sterile swab is inserted into the vagina for one minute, then placed into a vial containing a solvent for one minute, and then an AmniSure test strip is dipped into the vial. The test result is revealed by the presence of one or two lines within the next 5 to 10 minutes (one visible line means a negative result for amniotic fluid, two visible lines is a positive result, no visible lines is an invalid result). In large studies, sensitivity ranged from 94.4 to 98.9 percent and specificity ranged from 87.5 to 100 percent

19.  Insulin-like growth factor binding protein 1 (Actim PROM) — Identification of insulin-like growth factor binding protein 1 (IGFBP-1), also called placental protein 12 (PP12), may be of value in confirming the diagnosis of PPROM in problematic cases. This protein is secreted by decidual and placental cells and has a very high concentration in amniotic fluid compared to other body fluids

20.  A positive test is denoted by the presence of two blue lines on the dipstick. The test is not affected by the presence of infected vaginal secretions, urine, semen, or small amounts of blood.  The test is most accurate when applied as soon as possible after rupture of membranes. Sensitivity in detecting ruptured membranes ranges from 95 to 100 percent, specificity ranges from 93 to 98 percent, and positive predictive value approaches 98 percent. The test is particularly helpful in identifying those women likely to deliver within seven days.

21.  Placenal protein 12 and alpha-fetoprotein (ROM Plus)  A combination monoclonal/polyclonal antibody test for diagnosis of PPROM detects two protein markers found in amniotic fluid, placental protein 12 (PP12, also called insulin-like growth factor binding protein [IGFBP-1]) and alpha-fetoprotein (AFP). The test is performed by placing the ROM Plus test swab in the vagina for 15 seconds, placing the swab in a diluent, and then placing a sample of the diluent on a special test strip, which develops a line if the proteins are present. Trace amounts of blood do not affect the test.

22. ULTRASOUND EXAMINATION  If the patient has a normal amniotic fluid volume, it is very unlikely that she has experienced rupture of membranes, even with a seemingly convincing history.

23.  Fetal fibronectin — A negative fetal fibronectin result strongly supports absence of membrane rupture  Alpha-fetoprotein — Alpha-fetoprotein (AFP) in vaginal secretions suggestions the presence of amniotic fluid Sensitivity was 96.2 percent and specificity was 100 percent for diagnosis of PROM at an AFP cutoff of 3.88 ng/mL. Measurement of AFP is less costly than other commercially available tests for PROM, but blood in the vagina can give false positive results.  Instillation of dye 1 mL of indigo carmine dye in 9 mL of sterile saline was injected transabdominally into the amniotic fluid, and a tampon was placed in the vagina. Twenty minutes later, the tampon was removed and examined for blue staining, which indicated leakage of amniotic fluid.indigo carmine

24.  Other causes of vaginal/perineal wetness include urinary incontinence, vaginal discharge (normal or related to infection), and perspiration  MANAGEMENT  Gestational age  ●Presence or absence of maternal/fetal infection  ●Presence or absence of labor  ●Fetal presentation  ●Fetal well-being  ●Fetal lung maturity  ●Cervical status (by visual inspection)  ●Availability of neonatal intensive care

25.  Expeditious delivery of women with PPROM is clinically appropriate if  intrauterine infection,  abruptio placentae,  nonreassuring fetal testing, or  a high risk of cord prolapse because of an unstable fetal presentation is present or suspected

26.  Women with penicillin allergy — If the patient's history suggests a "low risk" for anaphylaxis (eg, isolated maculopapular rash without urticaria or pruritus), then we suggest cefazolin 1 g intravenously every 8 hours for 48 hours, followed by cephalexin 500 mg orally four times daily for five days. These drugs provide coverage for both GBS and E Coli, the two major causes of neonatal infection. We also give a single oral dose of azithromycin 1 g.cefazolincephalexin azithromycin

27.  If the patient's history suggests a "high risk" for anaphylaxis (eg, anaphylaxis, angioedema, respiratory distress, urticaria, particularly if these symptoms occurred within 30 minutes of drug administration), we suggest clindamycin 900 mg intravenously every 8 hours for 48 hours plus gentamicin 7 mg/kg ideal body weight for two doses 24 hours apart, followed by oral clindamycin 300 mg every eight hours for five days. We also give a single dose of azithromycin 1 g.clindamycingentamicinazithromycin

28.  In women who are on supplemental progesterone because of a prior pregnancy with preterm delivery related to preterm labor or PPROM, we discontinue the medication upon diagnosis of PPROM  Thromboprophylaxis in the form of sequential compression devices should be provided to all hospitalized pregnant women at bedrest. We also administer prophylactic doses of enoxaparin (1 mg/kg/day) to patients who have additional risk factors for deep vein thrombosis. Ideally, enoxaparin should be discontinued 48 hours prior to anticipated delivery.enoxaparin

29.  Diagnosis of subclinical chorioamnionitis requires amniocentesis to identify microorganisms in the amniotic fluid (gram stain and culture) and document an abnormally low amniotic fluid glucose concentration. A rapid test for interleukin-6 (IL-6), which is perhaps the most sensitive marker for microbial invasion of the amniotic cavity, is available in some countries

30.  Tissue sealants — A variety of tissue sealants (eg, fibrin glue, gelatin sponge) has shown some success in stopping leakage in case reports. Neither the safety nor the efficacy of these sealants has been established.

31. SUMMARY