Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection.

OBJECTIVE: This study was undertaken to determine whether matrix metalloproteinase-8, which is produced by neutrophils, is a useful marker for the detection of intra-amniotic infection. STUDY DESIGN: We performed a case-control study using enzyme-linked immunosorbent assays to detect matrix metalloproteinase-8 in 77 amniotic fluid specimens that were obtained by amniocentesis from women with preterm contractions or preterm labor and intact fetal membranes (n = 66) and from women with preterm premature rupture of membranes (n = 11). RESULTS: Thirty women had culture-proven intra-amniotic infection (cases), 21 of whom had intact membranes. After constructing receiver operating characteristic curves to establish the optimal threshold concentration of matrix metalloproteinase-8 for a positive test result, we detected matrix metalloproteinase-8 in 27 of 30 women with intra-amniotic infection; only 10 of 47 control specimens contained matrix metalloproteinase-8 (P <.001; odds ratio, 33.3; 95% CI, 8.4, 132.7). Matrix metalloproteinase-8 was present in 20 of 21 women with intact membranes and intra-amniotic infection and in only 10 of 45 control subjects (P <.001; odds ratio, 70.0; 95% CI, 8.3, 587.6). Among women with intact membranes, the sensitivity of the assay was 0.95 and the specificity was 0.78. CONCLUSION: Our results indicate that matrix metalloproteinase-8 is highly correlated with intra-amniotic infection and that enzyme-linked immunosorbent assay for matrix metalloproteinase-8 may be a clinically useful test for the diagnosis of intra-amniotic infection in women with preterm contractions and preterm labor.

Teaching the Laufe-Piper forceps technique at cesarean delivery.

OBJECTIVE: To present a method of teaching forceps technique during cesarean delivery of breech-presenting infants using Laufe-Piper forceps and to evaluate its usefulness. STUDY DESIGN: For several years, residents at the University of Texas Medical Branch, Galveston, have learned and practiced Piper forceps technique during cesarean delivery. To assess their experience with this method, we mailed questionnaires to third- and fourth-year residents and recent graduates of the Galveston program. The same surveys were mailed to a control group of residents and recent graduates of two other programs where this teaching exercise is not practiced routinely. RESULTS: Responses were received from 32 (74%) study subjects and 63 (71%) controls. Demographic characteristics and experience with vaginal breech delivery were similar between the two groups. Respondents from the Galveston program noted greater annual use of forceps for vaginal delivery of cephalic-presenting infants (P = .012). They also rated themselves as more comfortable (P = .023) and more skilled (P = .006) with Piper forceps than controls. Of 53 respondents who had had previous experience with this teaching method, 47 noted that it provided a great or moderate educational benefit, and 36 strongly or moderately believed it gave them more confidence in using Piper forceps during vaginal breech delivery. Using multiple regression analysis, sex, overall level of experience, Piper forceps experience during vaginal delivery and overall forceps use were stronger determinants of self-rated comfort and skill than was experience with Laufe-Piper forceps during cesarean. CONCLUSION: Laufe-Piper forceps can be used for cesarean delivery of breech-presenting infants. This practice promotes confidence and skill for their use at vaginal delivery.

Amniotic fluid concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 during pregnancy and labor.

OBJECTIVE: This study was undertaken to determine whether obstetric factors affect the concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the amniotic fluid. STUDY DESIGN: We prospectively collected amniotic fluid samples from 109 women at various stages of pregnancy and labor and determined matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 concentrations by means of enzyme-linked immunosorbent sandwich assay systems. With multiple regression analysis we evaluated relationships between amniotic fluid matrix metalloproteinase 9 concentration and tissue inhibitor of metalloproteinase 1 concentration and the following factors: gestational age, presence of labor, cervical dilatation, membrane status, presence of clinical chorioamnionitis, and microbial colonization of the amniotic fluid. RESULTS: The detectable presence of amniotic fluid matrix metalloproteinase 9 was independently associated with intra-amniotic infection, labor, cervical dilatation, and spontaneous rupture of membranes. Chorioamnionitis and amniotic fluid matrix metalloproteinase 9 concentrations were correlated with tissue inhibitor of metalloproteinase 1 levels. CONCLUSIONS: Intra-amniotic infection, advanced labor, and rupture of membranes before the onset of labor were independently associated with the presence of matrix metalloproteinase 9 in the amniotic fluid. Both pathologic and physiologic processes appear to produce shifts in the balance between degradation and synthesis of the extracellular matrix.

Expanded-spectrum antibiotics with preterm premature rupture of membranes.

OBJECTIVE: To compare maternal infection rates, neonatal sepsis rates, and bacterial resistance patterns in cases of neonatal sepsis for three antibiotic protocols for women with preterm premature rupture of membranes (PROM). METHODS: From January 1, 1988 to February 28, 1998, women with preterm PROM not requiring immediate delivery were treated according to one of three antibiotic protocols. During three distinct periods, patients received no antibiotics, intravenous ampicillin for 48 hours followed by oral amoxicillin, or intravenous ticarcillin-clavulanic acid for 48 hours followed by oral amoxicillin-clavulanic acid. Rates of chorioamnionitis, endometritis, and neonatal sepsis were compared, as were antimicrobial resistance patterns. Statistical analysis was done using chi(2) analysis, Fisher exact test, and the log-likelihood ratio test. The Bonferroni correction was used for multiple comparisons. RESULTS: During the three periods, preterm PROM was diagnosed in 1695 women. The incidence of endometritis was lower during the third (5.3%) compared with the first (15.1%, P <.001) and second (11.6%, P <.001) protocols. Chorioamnionitis rates were 13.6%, 12.7%, and 15.6% (P =.34) for the first, second, and third periods, respectively, and neonatal sepsis rates were 2.2%, 0.6%, and 1.1% (P =.08), respectively. Neonatal sepsis with gram-negative (P =.02) and ampicillin-resistant (P =.04) organisms was more likely when mothers received antepartum ampicillin or ticarcillin-clavulanic acid. CONCLUSION: Antibiotic therapy for patients with preterm PROM was associated with a decrease in the rate of endometritis and a trend toward less neonatal sepsis but an increase in the proportion of gram-negative and ampicillin-resistant organisms causing neonatal sepsis.

Amniotic fluid embolism.

Amniotic fluid embolism occurs rarely but is one of the leading causes of maternal mortality in the United States. The risk of death associated with this syndrome is 60% to 80% with half of survivors suffering long-term neurologic disability. The pathophysiology of amniotic fluid embolism is poorly understood. A review of the largest case series to date concluded that the physiologic and hematologic manifestations bear a greater resemblance to septic and anaphylactic shock than to any embolic phenomenon. Care of the patient who suffers amniotic fluid embolism is supportive. To date, no therapeutic interventions have been found to improve survival.

Amniotic fluid matrix metalloproteinase-9 levels in women with preterm labor and suspected intra-amniotic infection.

OBJECTIVE: To determine the accuracy of amniotic fluid (AF) matrix metalloproteinase-9 measurements for diagnosing intra-amniotic infection in women with preterm labor. METHODS: We performed amniocenteses in 44 women between 22 and 35 weeks' gestation who presented to our center with preterm labor and clinical suspicion of intra-amniotic infection. Each sample was analyzed by glucose measurement, Gram stain, and culture for aerobes, anaerobes, and mycoplasmas. We tested the AF for matrix metalloproteinase-9 using gelatin zymography and a commercial enzyme-linked immunosorbent assay (ELISA) system. We calculated accuracy and confidence intervals (CIs) for AF matrix metalloproteinase-9, glucose, and Gram stain for diagnosing intra-amniotic infection, using culture as the criterion standard. RESULTS: All patients who had matrix metalloproteinase-9 detectable by ELISA also demonstrated matrix metalloproteinase-9 by zymography. Six cases of intra-amniotic infection were confirmed by culture (prevalence 14%). The performance statistics of AF matrix metalloproteinase-9 for diagnosing intra-amniotic infection were: sensitivity 83% (95% CI 53, 99), specificity 95% (95% CI 88, 99), positive predictive value 71% (95% CI 37, 99), and negative predictive value 97% (95% CI 92, 99). Two women had false-positive results; one had gram-negative rods on the AF Gram stain and developed clinical signs and symptoms of chorioamnionitis several hours after amniocentesis and the other had a purulent vaginal discharge and an AF glucose level less than 15 mg/dL. Both delivered within 24 hours of amniocentesis. CONCLUSION: Measuring matrix metalloproteinase-9 in the AF appeared to be reliable for diagnosing intra-amniotic infection. An elevated matrix metalloproteinase-9 concentration in the AF at a preterm gestational age may portend imminent delivery regardless of microbiologic confirmation of intra-amniotic infection.

Maternal and neonatal infection rates with three different protocols for prevention of group B streptococcal disease.

OBJECTIVES: We compared maternal and neonatal infection rates under 3 different group B streptococcal prevention strategies and also evaluated reasons for each protocol's failures in preventing neonatal disease. STUDY DESIGN: Women who were delivered at our center from August 1, 1991, through April 30, 1998, were managed by 1 of 3 protocols for prevention of early-onset neonatal group B streptococcal infection: a selective screening protocol, The American College of Obstetricians and Gynecologists protocol, and the Centers for Disease Control and Prevention-recommended universal screening strategy. We compared maternal infection rates and neonatal group B streptococcal infection rates under each protocol. We also compared reasons for each protocol's failures in preventing neonatal infection. RESULTS: Clinical chorioamnionitis rates were 7.4% with selective screening, 7.7% under The American College of Obstetricians and Gynecologists' protocol, and 5.2% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8). Endometritis rates were 4.0% with selective screening, 4.6% with The American College of Obstetricians and Gynecologists protocol, and 2. 8% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8). Overall neonatal group B streptococcal infection rates were lower under the 2 more recent strategies, but not significantly so. Despite the ability of universal screening to find more women at risk for group B streptococcal transmission, half of the neonatal infections under this protocol occurred when the mothers were not considered candidates for prophylaxis. CONCLUSIONS: The Centers for Disease Control and Prevention-endorsed universal screening strategy for group B streptococcal infection prevention was associated with significantly lower rates of clinical chorioamnionitis and endometritis than were the other strategies. We were unable to document statistically significant improvement in neonatal outcome under the universal screening protocol.

Preventing neural tube defects: the importance of periconceptional folic acid supplements.

OBJECTIVE: To inform the obstetrician-gynecologist of recent scientific evidence regarding the use of supplemental folic acid for prevention of neural tube defects (NTDs). DATA SOURCES: We selected English language articles via MEDLINE published from January 1990 through February 1997, using the search terms "folic acid" and "neural tube defect." Additional sources were identified through cross-referencing and through searching selected journals published from March through October 1997. METHODS OF STUDY SELECTION: Articles were selected on the basis of their relevance to the relationship between folate intake and NTD incidence, mechanisms of folate responsive NTD formation, and folate provision strategy. We referenced 55 papers in total. TABULATION, INTEGRATION, AND RESULTS: The majority of evidence demonstrates a decreased incidence of NTDs with increased folic acid consumption. The most convincing trials were performed in Europe among women who were planning pregnancy by using multivitamin or folic acid supplements. Some studies suggest that the protective effect of folate is explained, in many cases, not through correction of dietary deficiencies, but through correction of metabolic defects. Other evidence implies that it reduces NTDs by causing abortion of affected conceptuses. Supplemental folic acid tablets are the most proven means of improving an individual's folate status, but ensuring compliance with a strategy using vitamin tablets is problematic. CONCLUSION: Women of reproductive age should be advised to take multivitamin supplements containing 0.4 mg folic acid daily. Women with previously affected offspring who intend to become pregnant should take daily supplementation containing 4 mg of folic acid in the periconceptional period to reduce the risk of recurrence.

Antibiotic therapy in preterm premature rupture of membranes.

Good quality evidence supports the use of antibiotic therapy in women with preterm PROM for whom expectant management is planned. The best evidence supports the choice of an extended-spectrum agent or combination administered intravenously for 2 days followed by an extended spectrum or combination of oral agents for several more days. Despite the effectiveness of antimicrobial therapy in this setting, the potential risks of systemic antibiotic administration, such as allergic reactions, overgrowth of commensal organisms, and emergence of resistant pathogens, much always be kept in mind. Nevertheless, in the majority of cases, assuming the patient is a good candidate for expectant management, the benefits of antibiotic therapy outweigh the risks.

Modification of an intrauterine shunt catheter to reduce the incidence of spontaneous displacement.

OBJECTIVE: To determine which of four types of catheters would be the least likely to become displaced spontaneously when employed as a fetoamniotic shunt, by testing the force required to remove the catheters from a lamb's bladder. METHODS: The catheter designs tested were unfeathered straight, unfeathered pig-tailed, superficially feathered, and deeply feathered. The catheters were placed percutaneously into the urinary bladders of recently euthanized newborn lambs. The force required to withdraw the catheters was determined, employing nine measurements for each catheter design. RESULTS: The mean force required to remove the straight catheter was 12 g (95% confidence interval [CI] 2-21 g), the pig-tailed catheter 22 g (95% CI 13-32 g), and the superficially feathered catheter 149 g (95% CI 139-160 g). Extracting the deeply feathered catheter consistently required a force greater than 300 g, which was the upper limit of detection for our instruments. CONCLUSION: Feathering the catheter increases the force required to extract it from a fetal viscus. We believe that use of feathered catheters will significantly reduce the incidence of unwanted spontaneous displacement.

Assessment of the value of routine blood cultures in the evaluation and treatment of patients with chorioamnionitis.

OBJECTIVE: The objective of this investigation was to determine the usefulness of blood cultures in evaluating patients with chorioamnionitis who were treated in accordance with a specific antibiotic protocol. METHODS: We reviewed the records of 539 patients with chorioamnionitis who delivered at our facility over a 3 year period (July 1, 1989-June 30, 1992). Patients had one set of aerobic and anaerobic blood cultures at the time of their initial assessment. They were treated initially with ampicillin or vancomycin plus gentamicin. Those who required cesarean delivery also received clindamycin postoperatively. Patients who had a poor initial response to therapy were treated empirically with selected antibiotics targeted against likely resistant organisms until the results of bacteriologic cultures were available. Bacteremic patients had repeat blood cultures while on therapy. We analyzed the medical records to determine the frequency with which blood culture results led to meaningful changes in patient management. We also compared the duration of febrile morbidity in bacteremic vs. nonbacteremic patients. RESULTS: Thirty-nine of 538 patients (7.2%, 95% confidence interval [CI] 5.2-9.2%) had positive blood cultures. In only one patient did the result of the blood culture definitively alter therapy. This patient had a fever of unknown origin, and the finding of a positive blood culture ultimately led to the diagnosis of chorioamnionitis. The mean duration of febrile morbidity was not significantly different in bacteremic vs. nonbacteremic patients (2.03 vs. 1.74 days). None of the repeat blood cultures was positive. The cost of blood cultures in the study population was $72,759.00. CONCLUSIONS: The routine use of blood Cultures in the assessment of patients with chorioamnionitis rarely provides information that justifies a change in clinical management when patients are treated in accordance with the specific antibiotic protocol outlined in this investigation.