Gregory J. Locksmith

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 crossreferencing 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 individuals 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.

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

OBJECTIVEnTo determine the accuracy of amniotic fluid (AF) matrix metalloproteinase-9 measurements for diagnosing intra-amniotic infection in women with preterm labor.nnnMETHODSnWe 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.nnnRESULTSnAll 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.nnnCONCLUSIONnMeasuring 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

OBJECTIVESnWe compared maternal and neonatal infection rates under 3 different group B streptococcal prevention strategies and also evaluated reasons for each protocols failures in preventing neonatal disease.nnnSTUDY DESIGNnWomen 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 protocols failures in preventing neonatal infection.nnnRESULTSnClinical 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.nnnCONCLUSIONSnThe 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.

Performance Characteristics of Putative Tests for Subclinical Chorioamnionitis

Objective: To evaluate amniotic fluid glucose, matrix metalloproteinase (MMP)-9, interleukin (IL)-6, and IL-12 for diagnosing subclinical chorioamnionitis in women with preterm labor. Methods: Forty-four women in preterm labor at 22–35 weeks gestation with suspected subclinical chorioamnionitis underwentamniocentesis.Amniotic fluid analysis included Gram stain, culture, and determination of glucose, MMP-9, IL-6, and IL-12 concentrations. Median values of these analytes were compared using the Mann-Whitney U test. Sensitivity, specificity, and positive and negative predictive values were calculated for tests using a positive amniotic fluid culture or delivery within 24 hours as the key outcome variables Results: Amniotic fluid concentrations of glucose, MMP-9, and IL-6 correlated closely with positive culture or delivery within 24 hours. IL-12 concentrations did not correlate with either a positive culture or delivery within 24 hours. Conclusions: Amniotic fluid glucose, MMP-9, and IL-6 reliably predict microbial invasion of the amniotic cavity or imminent delivery. IL-12 values did not correlate with amniotic fluid culture results or imminent delivery.

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 χ2 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.

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

New diagnostic tests for gonorrhea and chlamydia

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.

Infection, antibiotics, and preterm delivery.

Abstract Genitourinary infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis pose significant public health problems in this country. Our ability to effectively screen for, and prevent the spread of, these organisms depends on the availability of accurate and efficient detection methods. Culture has been the traditional reference standard for both organisms and has the advantage of 100% specificity. Gonorrhea culture is very inexpensive, whereas chlamydia culture is moderately expensive. The disadvantages of culture include variable sensitivity, complex logistics, and slow turnaround times. Antigen detection methods, such as direct fluorescent antibody testing and enzyme immunoassay, have fast turnaround times and simplified logistics but lower sensitivity than culture. Recently developed tests using nucleic acid technology offer the potential for improved sensitivity, ease of handling, and rapid processing at costs comparable to, or less than, antigen detection methods. Hybridization techniques utilize fluorescent DNA probes that bind directly to species-specific ribosomal RNA. The polymerase chain reaction (PCR) and ligase chain reaction (LCR) amplify species-specific DNA sequences prior to detection. The hybridization techniques are the least expensive and appear to have similar accuracy to PCR and LCR. Polymerase chain reaction and LCR may be performed on first-catch urine samples, which offer the advantages of ease of collection and greater yield of organisms. Urine samples typically contain organisms inhabiting both the urethra and endocervix, whereas endocervical specimens do not contain organisms in women who are colonized solely in the urethra. Endogenous inhibitors limit the sensitivity of the amplification techniques. If their effect could be eliminated, PCR and LCR would provide clear clinical advantages over any of the other methods in use.