C-reactive protein in preterm premature rupture of the membranes

Summary The usefulness of maternal C-reactive protein (CRP) measurements in the diagnosis of chorioamnionitis and puerperal and neonatal infectious morbidity was studied among 147 patients with preterm rupture of the membranes (PROM). Thirty-three patients developed chorioamnionitis, 10 patients developed puerperal endometritis, and 21 newborn infants developed neonatal infections. There was no difference in the highest antepartum CRP between patients with or without chorioamnionitis. The overall test performance for CRP was poor suggesting that elevated antepartum CRP may be misleading in the diagnosis of chorioamnionitis. However, use of serial CRP measurements increases the test performance. The high negative predictive value suggests that CRP is useful in predicting the absence of chorioamnionitis.     

Serum highly sensitive C-reactive protein in preterm premature rupture of membranes

OBJECTIVE: Low-grade inflammation may raise serum C-reactive protein (CRP) concentrations. We studied whether serum CRP is altered in preterm premature rupture of membranes (PPROM), which is frequently associated with an asymptomatic intrauterine infection. STUDY DESIGN: CRP was quantitated with highly sensitive immunofluorometric (IFMA) and immunoenzymometric (IEMA) assays in 32 women with PPROM at 30.7+/-0.4 gestational weeks (mean+/-standard error of the mean) and in 27 gestational age-matched healthy women. The results were compared to those obtained by the conventional immunoturbidimetric method. RESULTS: Twenty-three PPROM patients had a normal CRP value (相似文献   

Antibiotics after preterm premature rupture of the membranes

Preterm premature rupture of the membranes remains a common cause of preterm deliveries and neonatal morbidities. The goal of this study is to review the evidence with regard to the antibiotic treatment after preterm premature rupture of the membranes, long-term outcomes related to antibiotic treatment, and possible complications with treatment. Future research goals are also discussed.     

Fetal behavior in preterm premature rupture of the membranes

Although the subject has been the focus of a large body of obstetric literature, premature rupture of the membranes and its pathogenesis, management, and incidence of sequelae remain confused and controversial. The origins of this disquieting state of affairs can be traced to the lack of a specific, narrow definition of the condition, and resultant variations both in gestational age and maternal epidemiology in the populations assessed.     

Oral ritodrine and preterm premature rupture of membranes

A prospective randomized study was performed to determine whether or not oral ritodrine therapy significantly prolonged the latent period in patients with prematurely ruptured membranes. Compared with a control group of similar patients, those treated had a significantly prolonged mean latent period. In addition, 47.6% of the treatment group versus 14.2% of the control group had a latent period of more than one week.     

Is C-reactive protein really useful in preterm premature rupture of the membranes?

Summary. In a prospective blind study 380 daily serum samples from 55 women with preterm premature rupture of the membranes were analysed for C-reactive protein (CRP). Although the last CRP before delivery was higher in patients with histological chorioamnionitis ( P = 0.007), considerable overlap between infected and non-infected pregnancies occurred, precluding the use of CRP as a diagnostic test if published normal levels were used. When upper limits were set at 30, 35, or 40 mg/1, the last CRP before delivery proved 90, 95 and 100% specific and 88, 92 and 100% positively predictive of infection in singleton pregnancies. Such high specificities are needed to prevent inappropriate intervention based on false positive results. We therefore propose upper limits for single estimations of 30, 35, or 40 mg/1 depending on the relative risks of preterm delivery versus infection at various gestational ages. In addition, consecutive values <20 mg/1 appeared highly predictive of infection.     

Transabdominal amnioinfusion in preterm premature rupture of membranes

Objective

To evaluate the effect of transabdominal amnioinfusion on prolongation of pregnancy, and maternal and neonatal outcomes in preterm premature rupture of membranes (pPROM).

Methods

We conducted a prospective randomized controlled study of women with pPROM during singleton live pregnancy—between 26 and 33 + 6 weeks—whose amniotic fluid index (AFI) was less than the 5th percentile. The study group underwent transabdominal amnioinfusion at admission and then weekly if their AFI fell below the 5th percentile again. The control group received expectant management.

Results

The difference in the mean interval from pPROM to delivery between the groups was not statistically significant. Neonatal and maternal outcomes were significantly improved in the study group compared with the control group (fetal distress [10% vs 37%]; early neonatal sepsis [17% vs 63%]; neonatal mortality [17% vs 63%]; spontaneous delivery [83% vs 53%]; and postpartum sepsis [7% vs 33%]).

Conclusion

Transabdominal amnioinfusion reduced fetal distress, early neonatal sepsis, and neonatal mortality. In the study group, more participants delivered spontaneously and there were fewer cases of postpartum sepsis, although the pPROM-delivery interval was not increased.     

Is C-reactive protein really useful in preterm premature rupture of the membranes?

In a prospective blind study 380 daily serum samples from 55 women with preterm premature rupture of the membranes were analysed for C-reactive protein (CRP). Although the last CRP before delivery was higher in patients with histological chorioamnionitis (P = 0.007), considerable overlap between infected and non-infected pregnancies occurred, precluding the use of CRP as a diagnostic test if published normal levels were used. When upper limits were set at 30, 35, or 40 mg/l, the last CRP before delivery proved 90, 95 and 100% specific and 88, 92 and 100% positively predictive of infection in singleton pregnancies. Such high specificities are needed to prevent inappropriate intervention based on false positive results. We therefore propose upper limits for single estimations of 30, 35, or 40 mg/l depending on the relative risks of preterm delivery versus infection at various gestational ages. In addition, consecutive values greater than 20 mg/l appeared highly predictive of infection.     

Symptoms that precede preterm labor and preterm premature rupture of the membranes

Great emphasis has been placed on recognition of the early warning symptoms of preterm labor by both pregnant women and health care providers. In addition to the expected increase in both painless and painful uterine contractions, several symptoms have been commonly cited in textbooks and patient educational materials as preceding preterm labor including menstrual-like cramps, backache, pelvic pressure, and an increased amount of vaginal discharge. We interviewed 107 women with preterm labor, 102 women with preterm prematurely ruptured membranes, and 106 ambulatory normal pregnant women to ascertain the frequency of each of eight putative warning symptoms of preterm labor in each group. Preterm labor patients were distinguished as expected from both normal women and amniorrhexis patients by a greater frequency of painful and painless contractions. Menstrual cramps, backache, and increased vaginal discharge, symptoms often said to be normally present in pregnancy, were also significantly more common in preterm labor patients than in women with preterm membrane rupture and in normal subjects.     

Maturity testing with preterm premature rupture of the membranes

The presence or absence of fetal pulmonary maturity as assessed by amniotic fluid analysis and the role of fetal maturity tests in the management of premature rupture of the membranes are addressed. The hazards of the high falsely immature test are carefully explored. A management scheme based on the results of amniotic fluid analysis is also described.     

C-reactive protein in vaginal fluid of patients with preterm premature rupture of membranes

OBJECTIVE: To assess whether C-reactive protein (CRP) concentrations in cervical amniotic fluid reflect the condition of the intrauterine environment in patients with preterm premature rupture of membranes (PROM) before 35 weeks of gestation. METHODS: Amniotic fluid was obtained in 29 consecutive patients admitted with the diagnosis of preterm PROM earlier than 35 weeks of gestation either by amniocentesis or by collecting cervical fluid. CRP was measured in maternal blood, amniotic fluid, vaginal fluid and in cord blood obtained at delivery. Intraamniotic infection was defined as a positive amniotic fluid for aerobic or anaerobic bacteria, or Mycoplasma. The placentas and umbilical cords were examined for the presence of chorioamnionitis and funisitis. RESULTS: A significant correlation was found between vaginal fluid CRP concentrations and both amniotic fluid (r = 0.95, p < 0.001) and umbilical cord levels (r = 0.47, p < 0.05). No correlation was found between maternal blood and vaginal fluid CRP concentrations. The proportion of patients with intraamniotic infection was 37.9% (11/29). The median (range) vaginal fluid CRP concentration was higher in patients with intraamniotic infection than in those with sterile amniotic fluid [901 (0-1354) vs. 507 (0-798) ng/mL, p < 0.001]. The median (range) vaginal fluid CRP concentration was higher in fetuses with (n = 12) than in those without funisitis (n = 17) [901 (598-1354) vs. 487 (0-1115) ng/mL, p < 0.01]. After adjustment for gestational age, vaginal fluid CRP concentration > 800 ng/mL remained a predictor of intraamniotic infection and funisitis. CONCLUSIONS: Increased vaginal fluid CRP concentration is associated with intraamniotic infection and funisitis. As CRP is produced by hepatocytes and does not cross the placenta, its measurement in vaginal fluid might be an additional parameter for the assessment of fetal well-being in patients with premature PROM.     

Uterine activity after preterm premature rupture of the membranes

Preterm premature rupture of the membranes complicates few pregnancies but is a major contributor to overall perinatal morbidity and mortality. Although a reduced incidence of preterm premature rupture of fetal membranes has been reported in women who had antepartum uterine activity monitoring, there are few data regarding uterine activity after preterm premature rupture of fetal membranes. Therefore daily uterine activity monitoring was performed in 101 consecutive women with preterm premature rupture of fetal membranes between 26 and 34 weeks' gestation. The mean gestational ages at rupture and delivery were 31.4 +/- 2.3 and 33.7 +/- 4.5 weeks, respectively. A significant increase in contraction frequency was identified within 24 hours of onset of preterm labor (p less than 0.005). A contraction frequency of four or more per hour predicted the onset of labor within 24 hours with a sensitivity of 72%, a specificity of 90%, a positive predictive value of 54%, and a negative predictive value of 95%. These results indicate that most women with preterm premature rupture of fetal membranes exhibit a baseline contraction frequency that is similar to that of women with intact membranes and premature labor. An abrupt increase in contraction frequency is a warning of impending labor.     

Etiology and epidemiology of preterm premature rupture of the membranes

Preterm premature rupture of membranes continues to be a common complication of pregnancy with significant implications for perinatal outcome. Unfortunately, given the multiple risk factors that have been presented, which are reportedly associated with PPROM, attempts to reduce the incidence of this clinical event may seem daunting to the clinician. Despite this, one should attempt to address the potential risk factors that avail themselves to change. Unfortunately, although many risk factors have been identified, there are few randomized intervention trials for PPROM prevention. Examples of interventions documented to be beneficial include smoking cessation and screening for and treatment of chlamydial infections. These seem to be reasonable and logical interventions to consider in general, and may potentially have an effect on various causal agents of PPROM.     

Prevention of preterm labor and premature rupture of the membranes

Preterm delivery is currently the leading cause of perinatal morbidity and mortality. PROM is the most common easily identifiable cause of preterm delivery, present in 20-30% of preterm births. The conflicting results of success in prematurity prevention programs obtained by different investigators probably reflect the populations that were studied. Meis and colleagues divided the etiologies of low birth weight into four categories: 1) Low birth weight in infants greater than 37 weeks' gestation, 2) PROM, 3) birth weight caused by medical complications, and 4) idiopathic premature labor (IPL). In patients seen in the county health department clinic (1,529 births), IPL accounted for 25% of birth weights less than 2,500 g. In contrast, patients seen in a large private obstetric practice (1,327 births), IPL was the etiology of low birth weight in 47% of patients. Not surprisingly, a prematurity prevention program has not reduced the rate of low birth weight for the public patients but has resulted in decreases of low birth weight for the private patients. Paramount in the prevention of preterm birth is physician education regarding known risk factors, signs and symptoms of preterm labor, and the role of close follow-up in the patients identified as high risk. Papiernik's success with limitation of physical efforts and work leave, when appropriate, in high-risk patients is laudable and, many feel, should be emulated. Prenatal care must include for each woman education concerning the signs and symptoms of preterm labor and PROM. Individual risk factors must be ascertained and followed with appropriate observation, therapy, and/or modification plans. Finally, the early detection of preterm labor will expedite prompt treatment and so increase chances of postponing delivery.     

Treatments of preterm premature rupture of the membranes: a meta-analysis

The objective of this overview was to critically evaluate published randomized controlled trials on treatments in preterm premature rupture of the membranes. The Oxford data base on perinatal trials, MEDLINE, Excerpta Medica, and Index Medicus were searched. Through primary and secondary review with preset inclusion criteria, two independent judges identified 27 randomized controlled trials, of which 13 met inclusion criteria. The quality of these randomized controlled trials was scored. Five randomized controlled trials regarding antenatal use of corticosteroids to prevent respiratory distress syndrome could be combined meta-analytically and showed a reduction in respiratory distress syndrome in the treatment group (p = 0.001). However, no significant reduction in respiratory distress syndrome (p = 0.286) was found after one study, with the lowest quality score, was excluded. A significant increase in endometritis and a trend toward an increase in neonatal infections and cesarean section rates were noted with treatment. Tocolysis, prophylactic antibiotics, and other interventions studied were not found to be of proved benefit and therefore should not be used outside of a randomized controlled trial.     

Maternal serum cytokines in preterm premature rupture of membranes

OBJECTIVE: To estimate whether maternal serum interleukin (IL)-6 or granulocyte colony-stimulating factor (G-CSF) obtained daily are elevated in women with preterm premature rupture of membranes who develop funisitis. METHODS: Daily blood samples were obtained from women with preterm premature rupture of membranes and analyzed for IL-6 and G-CSF by enzyme-linked immunosorbent assay. Funisitis was determined by placental examination. Observations were stratified based on the presence or absence of funisitis and analyzed. Proportional hazards models were used to evaluate time-to-delivery on the basis of diagnostic IL-6 and G-CSF levels, determined by receiver operating characteristic curve analysis. RESULTS: Of the 107 patients available for analysis, 54 (50%) had evidence of funisitis after delivery. Patients with funisitis were more likely to deliver at an earlier gestational age (28.5 weeks compared with 31.5 weeks, P<.001) and have Medicaid insurance (57% compared with 39%, P=.04). Serum IL-6 and G-CSF were elevated 24 to 48 hours before delivery in women with preterm premature rupture of membranes with funisitis compared with those without funisitis (IL-6, 7.5 compared with 2.8 pg/mL, P<.001; G-CSF, 121.7 compared with 56.9 pg/mL, P=.002). Using values identified by the receiver operating characteristic curve, elevated serum IL-6 in the interval 24-72 hours before delivery was significantly associated with funisitis (P<.03), even after controlling for gestational age and insurance status. CONCLUSION: Maternal serum IL-6 and G-CSF appear to be biomarkers in the identification of women with preterm premature rupture of membranes likely to develop funisitis. LEVEL OF EVIDENCE: II.     

Apoptosis in the chorion of fetal membranes in preterm premature rupture of membranes

We sought to determine if apoptosis in the chorion of fetal membranes was increased in patients with preterm premature rupture of membranes (PPROM) with histological chorioamnionitis. Using the TUNEL (terminal uridine deoxynucleotidyl transferase dUTP nick-end labeling) method (ApopTag Plus kit; Oncor, Gaithersburg, MD), apoptosis was quantified. Of the 47 subjects with PPROM, 18 lacked sufficient chorion for quantification (confirmed by cytokeratin staining). In the remaining 30 subjects, fetal membranes with and without chorioamnionitis were examined and apoptosis was quantified. There were no differences in maternal age, race, insurance, cesarean rate, or gestational age between groups. The chorion of fetal membranes from PPROM patients with chorioamnionitis had significantly more apoptotic nuclei than those without chorioamnionitis (19.1 versus 0.8; P= .005). Of the 17 subjects excluded for absence of chorion, 16 (94%) had at least moderate chorioamnionitis. This investigation suggests that apoptosis is accelerated in the chorion of PPROM subjects with chorioamnionitis. Absence of the chorion in 37% of subjects is supportive of the hypothesis that inflammation accelerates cell death and destruction of the chorion.