Management of preterm premature rupture of the membranes

In many cases, the management of preterm PROM will be dictated by the presence of advanced labor, intrauterine infection, placental abruption, or nonreassuring fetal testing. These patients should be delivered expeditiously, with group B streptococcus prophylaxis given where possible, and cesarean delivery reserved for routine obstetric indications. The stable patient with PPROM and documented fetal pulmonary maturity is best treated by early induction. Alternatively, the patient with PPROM remote from term can benefit from conservative treatment. Adjunctive antibiotic treatment and serial evaluation of maternal and fetal well-being offer significant potential for the reduction of perinatal morbidity. Although corticosteroid and tocolytic administration remain controversial, there is a theoretical benefit to their administration, particularly if concurrent antibiotic treatment is given to treat subclinical intrauterine infection.     

Antenatal corticosteroids in preterm premature rupture of membranes

It is clear that there is no unequivocal indication for the use of antenatal corticosteroids in the preterm gestation with PROM. Extrapolating the effects seen in gestations with intact membranes, however, there are potential benefits in reduction of neonatal respiratory disease and intracranial hemorrhage at the expense of increased risks of maternal postpartum infection. Because the lifetime harm from the neonatal grave and the sequelae of infection in the mother are usually mild, we recommend that antenatal corticosteroids be administered to patients with PPROM between the gestational ages of 24-33 weeks in the absence of frank maternal or fetal infection or fetal compromise. With the increasing acceptance of antenatal corticosteroid therapy, it is unlikely that any further prospective randomized trials will be possible because withholding corticosteroids may expose patients to unacceptable potential harm. Therefore, clinical judgments may have to made based solely on the limited data presently available. Hopefully, future clinical investigations will provide useful information about the relation between antenatal corticosteroids and perinatal infections of the mother and infant in the setting of prophylactic antibiotic exposure. Additionally, there is also a need for information establishing a clinical profile for the patient with PPROM that accurately predicts when she is likely to enter spontaneous labor, thus allowing clinicians to increase the likelihood of appropriately administering corticosteroids within 1 week of delivery to maximize potential neonatal benefit.     

Antibiotic therapy for preterm premature rupture of membranes

Antibiotic treatment of the patient with preterm premature rupture of membranes remote from term significantly prolongs pregnancy and reduces amnionitis without increasing the risk of cesarean delivery. Antibiotic treatment reduces perinatal infectious morbidity including neonatal sepsis, GBS sepsis, and pneumonia. Stratified analysis of the currently available prospective trials also demonstrates a significant reduction in gestational-dependent morbidity, specifically respiratory distress and intraventricular hemorrhage with treatment. This is supported by a reduction in composite infant morbidity and other gestational age-dependent morbidities in the NICHD-MFMU trial. Although the optimal treatment regimen has not been determined, limited duration broad spectrum antibiotic treatment is justified in the setting of conservative management of pPROM remote from term. The patient with pPROM and documented pulmonary maturity near term may benefit more from expeditious delivery than from expectant management with antibiotics.     

Intra-amniotic infection and premature rupture of the membranes

Antiphospholid antibodies (APL) have a notable association with recurrent miscarriages, arterial and venous thrombosis and thrombocytopenia. Analysis of the potential pathogenic effects of such human antibodies has been hampered by the considerable difficulty in producing IgG as opposed to IgM monoclonal immunoglobulins. We have developed four human monoclonal IgG APL (LJ1, AH2, DA3 and UK4) by fusing the peripheral blood lymphocytes of three patients with SLE with a mouse human heteromyeloma cell line, CB-F7. These antibodies bind to a variety of anionic phospholipids, two (LJ1 and AH2) bind total histones but none binds to ssDNA or dsDNA. Binding to beta 2 GPI is non-specific. UK4 alone demonstrates lupus anticoagulant activity. All four have lambda light chains, two are IgG1 (AH2 and UK4) and two are IgG3 (LJ1 and DA3). These APL utilize VH genes present in the fetally restricted repertoire and multiple somatic mutations in the CDR suggest an antigen-driven process. In contrast, there is no restriction in V lambda gene usage and only one lambda chain is extensively mutated. Two clonally related hybridomas were isolated from a single patients. This supports the theory that clonal expansion is the mechanism whereby antigen selects high affinity mutations.     

An increase in fetal plasma cortisol but not dehydroepiandrosterone sulfate is followed by the onset of preterm labor in patients with preterm premature rupture of the membranes

OBJECTIVE: The role of steroid hormones in the control of human parturition has been a subject of debate. Activation of the fetal hypothalamic-pituitary-adrenal axis leading to an increase in plasma cortisol is followed by the onset of parturition in sheep. In contrast, androgens, specifically, dehydroepiandrosterone sulfate, have been implicated in the control of parturition in nonhuman primates. The purpose of this study was to determine the relationship between human fetal plasma cortisol and dehydroepiandrosterone sulfate and the onset of preterm labor in patients with preterm premature rupture of the membranes. STUDY DESIGN: Fetal blood sampling was performed in 51 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. Corticosteroids had not been administered before fetal blood sampling. Cortisol and dehydroepiandrosterone sulfate were measured with sensitive and specific immunoassays. Analysis was conducted with nonparametric statistics and survival analysis. RESULTS: (1) Patients who went into spontaneous labor and delivered within 7 days of cordocentesis had a significantly higher median level of fetal plasma cortisol but not of dehydroepiandrosterone sulfate than those delivered after 7 days (for fetal plasma cortisol: median 8.35 [4.7 to 12.4] micrograms/dL vs median 4.75 [3.0 to 10.4] micrograms/dL, P <.0001; for fetal plasma dehydroepiandrosterone sulfate: median 154.4 [8.6 to 333.8] micrograms/dL vs median 194.6 [96.7 to 402.5] micrograms/dL, P =.09). (2) The cordocentesis-to-delivery interval was significantly shorter in patients with a fetal plasma cortisol value of >/=7 micrograms/dL (derived by receiver-operating characteristic curve analysis) than in those with fetal cortisol <7 micrograms/dL (median 49 [4 to 1849] hours vs median 325 [11 to 2590] hours, P <.001). (3) Fetal plasma cortisol, but not maternal cortisol, was an independent predictor of the duration of pregnancy after we adjusted for gestational age and the results of amniotic fluid culture (hazards ratio 2.9, P <.05). (4) There was a significant correlation between fetal plasma cortisol and fetal plasma interleukin-6 (r = 0.3, P <.05). (5) A strong relationship was found between the fetal plasma cortisol/dehydroepiandrosterone sulfate ratio and the interval to delivery (P <.005). CONCLUSION: An elevation in fetal plasma cortisol but not dehydroepiandrosterone sulfate was followed by the onset of spontaneous preterm labor in patients with preterm premature rupture of the membranes.     

Antenatal corticosteroids in pregnancies complicated by preterm premature rupture of membranes

In 1994, the National Institutes of Health Consensus Development Conference on Antenatal Steroids recommended corticosteroids between 24 and 30-32 weeks' gestation in pregnancies complicated by preterm premature rupture of membranes (PROM). Since the Consensus Conference, the use of antenatal corticosteroids has increased to approximately 60% of potential treatment candidates. Some of the remaining 40% of pregnant candidates may go untreated because of concern that corticosteroids could increase the risk of neonatal infection. Using decision-analysis techniques, we compared the potential benefit of antenatal corticosteroids in reducing the incidence of severe intraventricular hemorrhage with the potential risk of increasing the rate of neonatal sepsis. Our analysis indicates that the benefit of a small decrease in severe intraventricular hemorrhage outweighs the potential harm of a large increase in the rate of neonatal sepsis. Therefore, we support the Consensus Conference panel's recommendation that antenatal corticosteroids be used in pregnancies complicated by preterm PROM.     

The clinical outcome of preterm premature rupture of membranes in twin versus singleton pregnancies

Initial findings of panic disorder as an independent risk factor for suicidal ideation and behavior could not be replicated in studies with psychiatric patients. Instead, it was concluded that panic and anxiety disorders are risk factors when they co-occur with a primary mood disorder. In the present study, the effect of diagnostic comorbidity on rates of suicidality is analyzed on depressive inpatients treated at special depression wards. In a prospective follow-up study, suicidality and anxiety were assessed by means of a modified German version of the Diagnostic Interview Schedule (DIS). Patients with the symptom of panic attacks showed significantly elevated lifetime prevalence rates of suicidality in comparison with patients who did not report this additional symptom. For the follow-up period, however, there were no significant differences between these two groups. According to these results, the group of depressives with additional panic attacks is not more at risk for suicidal behavior, after being treated in an adequate manner.     

The etiology of premature rupture of the membranes

The etiology of PROM is multifactorial. It is clear that maternal enzymes, maturational and mechanical forces, chorionicamniotic membrane phospholipid content, collagen disruption, amniotic cell cytokines induced by fetal signals, and bacterial phospholipases and collagenases all play major and interrelated roles. It is also clear that the production of oxytocic prostaglandins is a major, if not exclusive, common pathway leading to PROM and preterm delivery. The increasing awareness of the fetal role, i.e., fetal interleukins, fetal polymorphonuclear leukocytes and type V collagenase, make this area of research ripe for further investigation. The complex host defense mechanisms and biologic variability make any universal treatment impossible. Even with a specific etiology determined, the reduced availability of pharmacologic interventions for the fetal compartment portend suboptimal success. Therefore, it appears that continued research and aggressive measures to optimize the quality and availability of prenatal care are the best foci of our efforts.     

Perinatal and neonatal outcome and late pulmonary sequelae in infants born after preterm premature rupture of membranes

The regulation of the lytic and lysogenic development in the life cycle of bacteriophage Mu is regulated in part by its repressor, c, which binds to three operator sites, O1, O2 and O3, overlapping two divergent promoters. The oligomeric structure of this repressor protein was investigated by hydrodynamic and biochemical methods. Size-exclusion chromatography, analytical ultracentrifugation, dynamic light scattering, crosslinking and direct electron microscopy observations suggest that c exists primarily as a hexamer with a molecular mass of 120-140 kDa at low concentrations, i.e. in the 10-microM range. This molecule undergoes a self-assembly process leading to dodecamers and higher order species as the concentration is further increased in a manner depending on the nature of the solvent. Our results also suggest that these species have an elongated structure, and a possible arrangement of the subunits within the hexamer is proposed. The implication of this unusual quaternary structure for a repressor in its interaction with the operator sites O1 and O2 remains to be elucidated.     

Neonatal sepsis after prolonged premature rupture of membranes

The objective of this study was to prospectively evaluate the incidence of neonatal sepsis after prolonged premature rupture of membranes (PROM), to correlate sepsis with gestational age and with the duration of PROM, and to evaluate the necessity for prophylactic antibiotic therapy in neonates born after PROM. Of 12,182 infants, 135 (1.1%) were delivered after PROM with a latency period of > 24 hours. Neonatal sepsis occurred in 11 infants (8.1%), 10 of whom were premature. The only term, septic newborn was a small-for-gestational-age infant. A latency period > 72 hours was not associated with an increased incidence of sepsis. Maternal fever, neonatal signs of infection including leukopenia, leukocytosis, thrombocytopenia, and positive gastric aspirate cultures, were not good predictors of sepsis. Of premature infants with PROM, 15% had sepsis, and thus the administration of prophylactic antibiotic therapy in these cases may be warranted. However, it may be unnecessary to administer prophylactic antibiotics to term, appropriate-for-gestational-age infants born after PROM.     

Premature rupture of fetal membranes and chorioamnionitis

The article presents a survey of preterm rupture of the amniotic membranes at term (more than 1 hour prior to uterine contractions) and preterm (< 37 weeks). The diagnosis of rupture can be suspected from the history alone in 90% of the cases, and confirmed by inspection. In doubtful cases the pH in fluid from the posterior fornix of the vagina is determined and microscopy is performed. Amniotic fluid is alkaline. Microscopy of a dried specimen shows "ferning" when amniotic fluid is present (crystallization test). Staining with Nil blue will reveal orange foetal cells in fresh specimens, usually only late in pregnancy (after the 38 week). The crystallization test is useful, however, in all three trimesters. The cause of membrane rupture and of chorioamnionitis may be infection. Chorioamnionitis is a serious clinical condition, but can be subclinical and may occur with intact membranes. It can lead to preterm delivery. It is important that chorioamnionitis be diagnosed (maternal fever, tachycardia, uterine contractions, abdominal pain, foul smelling vaginal discharge and elevated C-reactive protein). The condition is treated with antibiotics and labour must be induced.     

Effects of barometric pressure and lunar phases on premature rupture of the membranes

Meteorologic events have often been blamed for premature rupture of the fetal membranes. This study analyzed the relationship of barometric pressure and lunar phase to membrane rupture and found no evidence that membrane rupture is influenced by those phenomena.     

The relationship between umbilical artery Doppler findings, fetal biophysical score and placental inflammation in cases of premature rupture of membranes

BACKGROUND: To assess the relationship between placental inflammation, umbilical artery Doppler waveforms and fetal biophysical profile score, umbilical artery Doppler studies and fetal biophysical evaluations were performed in 24 preterm pregnants with premature rupture of membranes (PPROM). SUBJECTS: After delivery, the placentas were microscopically examined and two subgroups were formed including noninflamed or inflamed placentas. RESULTS: In the first group, which includes 14 cases with no histological signs of placental inflammation, we found increased systolic/diastolic ratio only in one patient, whereas in the second group including ten cases with microscopically proven inflammation, nine were found to have increased systolic/diastolic ratios (p < 0.05). Mean systolic/diastolic ratio in the first and the second groups were 2.74 +/- 0.18 and 4.64 +/- 0.93 respectively (p < 0.001). Mean biophysical profile score was 9 +/- 1.04 in the first group and 7 +/- 1.05 in the second group (p < 0.001). CONCLUSION: Abnormal biophysical profile scores along with increased arterial systolic/diastolic ratios have been shown to be the markers of impending clinical infection.     

欣普贝生用于足月胎膜早破引产临床效果观察与护理

足月胎膜早破,是指发生在妊娠37周之后未临产发生的胎膜破裂.足月胎膜早破的处理是产科临床中较为常见的问题,但若处理不当,可能并发羊膜腔感染、胎盘早剥、羊水过少、胎儿窘迫利新生儿呼吸窘迫综合征等,从而导致同产期和新生儿期并发症增加.     

Preterm premature rupture of membranes and the associated risk for placental abruption. Inverse correlation to gestational length

18Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 microg/kg; administered intravenously) resulted in 30% mortality. Neither 0.5 microg/kg or 0.25 microg/kg NFEP resulted in any significant changes in cardiorespiratory parameters, but plasma catecholamines increased (2- to 3-fold). Further studies are needed to determine the safety of NFEP that are specifically designed to assess the catecholamine response. Our results suggest that it is not advisable to initiate human PET studies with [18F]-NFEP without further evidence supporting its safety.     

Management of premature rupture of membranes in a monofetal pregnancy before 28 weeks gestation

To establish appropriate management of premature rupture of the membranes before 28 weeks, we examined maternal and fetal risks in pregnancies complicated by this rare problem (1-7/1000). Three main factors were identified in such circumstances: prematurity, infection and oligohydramnios. Prematurity is inevitable and depends on three factors: gestational age at rupture of the membranes which is an independent predictor of poor prognosis before 22 weeks; gestational age at delivery as neonates born before 26 weeks gestation have an overall perinatal survival < 50%, and latency period between preterm rupture of the membranes and delivery which ranged from 1 to 161 days with a mean 7.8 days. Infection is the second factor with a high incidence (> 30%) of chorioamnionitis. The third factor is skeletal deformations and pulmonary hypoplasia predicted by severe and prolonged (> 14 days) oligohydramnios. Only about 40% of such women will take home a live baby. Successful outcome can be achieved in about 60% of these survivors. Termination of pregnancy is warranted at 22 weeks gestation or less and may be proposed. Beyond 22 weeks gestation, management is based on a wait-and-see attitude with ultrasonographic and bacteriological surveillance. After 25 weeks gestation, management becomes more active with use of antibiotics, tocolytics and steroids which can help prolong the latency period and improve fetal outcome. Ongoing counselling and psychological support are essential in the management of this morbid complication of pregnancy.