Leslie A. Meyn

Maternal Morbidity Associated With Vaginal Versus Cesarean Delivery

OBJECTIVE: To describe postpartum maternal morbidity associated with mode of delivery in term, singleton pregnancies. METHODS: The Magee Obstetric Medical and Infant database was examined for the years 1995 to 2000. Patients were grouped into 6 types of delivery mode: spontaneous vaginal delivery, operative vaginal delivery, primary cesarean delivery without trial of labor, primary cesarean delivery with trial of labor, repeat cesarean delivery without trial of labor, and repeat cesarean delivery with trial of labor. Multivariable logistic regression provided odds ratios and 95% confidence intervals (CI) for morbidity by delivery mode adjusted for demographic characteristics and comorbidities. Spontaneous vaginal delivery was used as the referent group (odds ratio = 1). RESULTS: Of 32,834 subjects, 27,178 had vaginal delivery (operative = 4,908; spontaneous = 22,270) and 5,656 had cesarean delivery. Third- or fourth-degree lacerations occurred in 1,733 (7.8%) women who had spontaneous vaginal delivery compared with 1,098 (22.3%) who had operative vaginal delivery. Overall, 523 women (1.6%) had endometritis. Compared with spontaneous vaginal delivery, primary cesarean delivery with trial of labor conferred a 21.2-fold increased risk of endometritis (95% CI 15.4, 29.1). Even without trial of labor, women after primary cesarean delivery were 10.3 times more likely to develop endometritis (95% CI 5.9, 17.9) than after spontaneous vaginal delivery. The risk of transfusion was highest in women delivered by primary cesarean after labor, 4.2 times higher (95% CI 1.8, 10.1) than spontaneous vaginal delivery. The risk of pneumonia was 9.3 times higher (95% CI 3.4, 25.6) after repeat cesarean delivery with labor. Deep venous thromboses occurred in 15 (0.1%) after spontaneous vaginal delivery, 2 (0.04%) after operative vaginal delivery, and 12 (0.2%) after cesarean delivery. CONCLUSION: Compared with spontaneous vaginal delivery, cesarean delivery is associated with increased risks of endometritis, the need for transfusion, and pneumonia; however, these rates are lower than reported previously. LEVEL OF EVIDENCE: II-2

Remodeling of vaginal connective tissue in patients with prolapse.

OBJECTIVE: As pelvic organ prolapse progresses, the morphology of the vagina dramatically changes. The objective of this study was to determine whether these changes observed clinically correlate with histologic and biochemical evidence of tissue remodeling METHODS: After informed consent, full-thickness biopsies of the vaginal apex were obtained at the time of surgery from 77 women. The tissue of 15 premenopausal women with less than stage II prolapse (controls) was compared with that of 62 women with prolapse divided according to their menopausal status. All specimens were examined histologically. Scanning confocal microscopic analysis of fluorescent micrographs was used to quantitate collagen subtypes I, III, and V. Collagen fiber orientation was analyzed by scanning electron microscopy. Gelatin zymography was used to quantitate the expression of the proenzyme and active forms of matrix metalloproteinases (MMP) –2 and –9. Median values were compared using Mann-Whitney U or Kruskal-Wallis tests, where appropriate RESULTS: Vaginal collagen fibers are arranged in a whorled pattern, with collagen III as the predominant fibrillar collagen. The amount of total collagen in the vagina was increased in women with prolapse relative to women without prolapse (P = .054) primarily due to increased expression of collagen III (P = .031). There was no difference in the expression of proMMP-2, active MMP-2, or proMMP-9; however, active MMP-9 was increased in patients with prolapse (P = .030) CONCLUSION: The increase in collagen III and active MMP-9 expression in the vaginal tissues of patients with prolapse suggests that this tissue is actively remodeling under the biomechanical stresses associated with prolapse. Level of Evidence: II-2

Pelvic symptoms in women with pelvic organ prolapse.

OBJECTIVE: To assess symptoms of bladder, bowel, and sexual function in women with pelvic organ prolapse and to compare symptoms by different degrees of prolapse. METHODS: This retrospective study used data from 352 women with prolapse or urinary incontinence. The pelvic organ prolapse quantification measurements, as well as responses to 3 self-administered questionnaires assessing urinary, bowel, and sexual function were used. For each individual, pelvic organ prolapse quantification measures of prolapse were obtained in centimeters in relation to the hymen for 3 compartments: anterior vagina, vaginal apex or cervix, and posterior vagina. Data were analyzed by comparing the frequency of symptoms to centimeter measures of the most advanced prolapse (regardless of site) and the other compartments of prolapse. RESULTS: Of the 330 patients available for analysis, 2.4% had stage I, 46.1% had stage II, 48.2% had stage III, and 3.3% had stage IV prolapse. The average age was 58.8 years (± 12.1), with a median parity of 3. Forty-eight percent were postmenopausal and taking estrogen, 27% were postmenopausal and not taking estrogen, and 25% were premenopausal. Patients who had stress incontinence symptoms had less advanced prolapse (median 5 cm less prolapse in the apical compartment) than patients without stress incontinence. Women who required manual assistance to urinate had more advanced prolapse (median 3.5 cm more prolapse in the most advanced compartment) than those who did not. Patients with urinary urgency and urge incontinence also had less advanced prolapse, although the differences were smaller than for stress incontinence (median 3 cm difference or less). There were no clinically significant differences in any compartment for symptoms related to sexual or bowel function. CONCLUSION: Women with more advanced prolapse were less likely to have stress incontinence and more likely to manually reduce prolapse to void; however, prolapse severity was not associated with sexual or bowel symptoms. LEVEL OF EVIDENCE: II-2

A Delicate Balance : Risk Factors for Acquisition of Bacterial Vaginosis Include Sexual Activity, Absence of Hydrogen Peroxide-Producing Lactobacilli, Black Race, and Positive Herpes Simplex Virus Type 2 Serology

Background: The etiology of bacterial vaginosis (BV) is poorly understood, but better definition of the risk factors associated with its acquisition should improve our understanding of this complex disease entity. Methods: A longitudinal cohort study of young sexually active women was conducted to identify variables associated with BV acquisition. Seven hundred seventy-three women without BV at enrollment were followed at 4-month intervals for 1 year. At each visit, demographic and behavioral interview data, a vaginal smear for the Gram stain diagnosis of BV, and a serum sample for detection of herpes simplex virus type 1 (HSV-1) and HSV-2 type-specific antibodies were collected. Results: The overall incidence of BV acquisition was 36 cases/100 woman-years (223 acquisitions of BV during 619 woman-years of follow-up). Acquisition of BV was independently associated with black race, cigarette smoking, vaginal intercourse, receptive anal sex before vaginal intercourse, sex with an uncircumcised male partner, lack of vaginal H2O2-producing lactobacilli, and the detection of HSV-2 serum antibodies at the visit before BV acquisition. Longitudinal analyses revealed that HSV-2 serum antibodies were independently associated with loss of H2O2-producing lactobacilli. Conclusions: Our findings suggest that multiple and diverse risk factors can contribute to BV acquisition. They also illustrate why a more complete understanding of BV pathogenesis and the formulation of effective BV prevention strategies have been elusive. Further work will be needed to determine the specific effects of HSV-2 infection on vaginal flora composition and the acquisition of BV.

Risk factors for infection with Herpes simplex virus type 2: Role of smoking, douching, uncircumcised males, and vaginal flora

Background Herpes simplex virus type 2 (HSV-2), the primary cause of genital herpes, is one of the most prevalent sexually transmitted diseases worldwide. Epidemiologic serosurveys suggest that infections occur more frequently in women than in men. Goal The goal of the study was to identify unique correlates of HSV-2 infection in women that might contribute to their increased susceptibility of infection or suggest opportunities for decreasing the incidence of disease. Study Design We enrolled 1207 women aged 18 to 30 years from three Pittsburgh health clinics in a cross-sectional study. Each woman provided demographic and behavioral information, vaginal swab specimens for bacterial culture, a vaginal smear for Gram stain diagnosis of bacterial vaginosis, and blood for HSV-1 and HSV-2 serology. Results Black race, older age, cigarette smoking, douching, a greater number of lifetime sex partners, a history of intercourse with an uncircumcised partner, the presence of vaginal group B Streptococcus, and abnormal vaginal flora were among the independent predictors of HSV-2 infection. Conclusion HSV-2 infection may be occur more often in women who douche, smoke, have sex with uncircumcised partners, or have bacterial vaginosis; these represent alterable risk factors.

The Associations Between Pelvic Inflammatory Disease, Trichomonas vaginalis Infection, and Positive Herpes Simplex Virus Type 2 Serology

Objective: Roles for Chlamydia trachomatis and Neisseria gonorrhoeae infections in pelvic inflammatory disease pathogenesis are well delineated; however, the etiologic contributions of herpes simplex virus type 2 (HSV-2) and Trichomonas vaginalis have been underexplored. Goal: The goal of this study was to investigate the association between acute and plasma cell endometritis, fallopian tube obstruction, HSV-2 serology, and T. vaginalis infection. Study Design: The authors conducted a cross-sectional secondary analysis of 736 women at risk for bacterial sexually transmitted diseases that used endometrial biopsy data obtained at enrollment as well as hysterosalpingography results obtained 12 weeks after enrollment. Results: Women diagnosed with T. vaginalis at enrollment were more likely to have histologic evidence of acute endometritis. Both plasma cell and acute endometritis were significantly more common among women with positive serology HSV-2; furthermore, women coinfected with HSV-2 and C. trachomatis, N. gonorrhoeae, T. vaginalis, or bacterial vaginosis were much more likely to be diagnosed with acute endometritis than were women infected with HSV-2 or one of these pathogens alone. Among women with available HSV-2 serology and hysterosalpingogram results, HSV-2 was the only genital tract pathogen infection associated with fallopian tube obstruction. Conclusions: Our analyses demonstrate that T. vaginalis infection and positive HSV-2 serology are associated with endometritis. Further work will be needed to determine the specific roles these pathogens may play in pelvic inflammatory disease pathogenesis.

Vaginal yeast colonization in nonpregnant women: a longitudinal study.

OBJECTIVE: We sought to investigate the prevalence and risk factors for vaginal yeast colonization over a 1-year period. METHODS: We conducted a longitudinal cohort study of 1,248 asymptomatic young women by collecting demographic and behavioral data at baseline, 4, 8, and 12 months. RESULTS: Seventy percent of women were colonized by vaginal yeast at one or more visits, but only 4% were colonized at all 4 visits. Using an adjusted generalized estimating equation model, factors associated with vaginal yeast colonization were marijuana use in the previous 4 months, depomedroxyprogesterone acetate use in the past 4 months, sexual intercourse in the previous 5 days, and concurrent colonization with lactobacilli and group B streptococcus. Symptoms of pruritus and vulvovaginal burning were associated with yeast colonization, but antifungal use was not. CONCLUSION: Recent sexual intercourse and use of injection contraceptives are risk factors for yeast colonization. Rates of antifungal use did not show an association with yeast colonization. The reporting of antifungal use by women lacking yeast colonization suggests that self-diagnosis is inaccurate. LEVEL OF EVIDENCE: II-2

Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis.

Background It is known that glycosidases and proteases are produced by the anaerobic gram-negative bacteria associated with bacterial vaginosis (BV). We hypothesized that these enzymes enzymatically degrade mucins, thereby destroying the mucus gel that otherwise helps protect against sexually transmitted pathogens, including HIV. Goal The goal was to determine glycosidase and protease production by vaginal bacteria associated with BV and to compare these with symptoms and signs of abnormal discharge and to test vaginal fluid viscosity. Study Design The anaerobic gram-negative rods recovered from the vaginas of 153 women with normal flora, intermediate flora, or BV were tested for production of sialidase, fucosidase, galactosidase, glucosaminidase, and glycine and arginine aminopeptidases. Results Women with BV had higher frequencies and concentrations of bacteria producing mucin-degrading enzymes than did women with intermediate and normal flora (P < 0.001). Women with higher concentrations of bacteria producing mucin-degrading enzymes were more likely to have a thin discharge associated with BV (P < 0.001). The viscosity of diluted vaginal fluid samples from women with BV was significantly lower than those from women with normal flora (P = 0.001). Conclusion These data support the hypothesis that BV organisms degrade the protective mucus gel.

Subclinical pelvic inflammatory disease and infertility.

OBJECTIVE: The reported incidence of acute pelvic inflammatory disease (PID) has decreased but rates of tubal infertility have not, suggesting that a large proportion of PID leading to infertility may be undetected. Subclinical PID is common in women with uncomplicated chlamydial or gonococcal cervicitis or with bacterial vaginosis. We assessed whether women with subclinical PID are at an increased risk for infertility. METHODS: A prospective observational cohort of 418 women with or at risk for gonorrhea or chlamydia or with bacterial vaginosis was recruited. Women with acute PID were excluded. An endometrial biopsy was performed to identify endometritis (subclinical PID). After provision of therapy for gonorrhea, chlamydia and bacterial vaginosis participants were followed-up for fertility outcomes. RESULTS: There were 146 incident pregnancies during follow-up, 50 pregnancies in 120 (42%) women with subclinical PID and 96 in 187 (51%) women without subclinical PID. Women with subclinical PID diagnosed at enrollment had a 40% reduced incidence of pregnancy compared with women without subclinical PID (hazard ratio 0.6, 95% confidence interval 0.4–0.8). Women with Neisseria gonorrhoeae or Chlamydia trachomatis, in the absence of subclinical PID, were not at increased risk for infertility. CONCLUSION: Subclinical PID decreases subsequent fertility despite provision of treatment for sexually transmitted diseases. These findings suggest that a proportion of female infertility is attributable to subclinical PID and indicate that current therapies for sexually transmitted diseases are inadequate for prevention of infertility. LEVEL OF EVIDENCE: II

Antimicrobial Prophylaxis for Cesarean Delivery Before Skin Incision

OBJECTIVE: To estimate the effect of a hospital-wide change in the timing of antimicrobial prophylaxis in cesarean deliveries on maternal and neonatal infections. METHODS: In November 2004, our institution instituted guidelines recommending that the administration of antimicrobial prophylaxis for cesarean delivery be administered before skin incision rather than after umbilical-cord clamping. We reviewed all cesarean deliveries from two time periods. Group 1 received antibiotics after umbilical-cord clamping (July 2002 to November 2004). Group 2 received antibiotics before skin incision (June 2005 to August 2007). Rates of maternal and neonatal infectious complications were compared between groups. RESULTS: There were 4,229 cesarean deliveries in group 1 and 4,781 cesarean deliveries in group 2. Compared with women receiving antimicrobial prophylaxis after umbilical-cord clamping, those administered antimicrobial prophylaxis before skin incision had lower rates of postpartum endometritis (2.2% compared with 3.9%) and wound infection (2.5% compared with 3.6%). After multivariable logistic regression, antimicrobial prophylaxis before skin incision remained associated with lower rates of endometritis (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.47–0.79) and wound infection (OR 0.70, 95% CI 0.55–0.90). Antimicrobial prophylaxis before skin incision had no adverse effect on neonatal infection rates or on the evaluation of the neonate. CONCLUSION: Antimicrobial prophylaxis before skin incision, compared with after cord clamping, resulted in lower rates of maternal infections and had no effect on neonatal infections. Antimicrobial prophylaxis for cesarean delivery should occur before skin incision, consistent with basic tenets of surgical antimicrobial prophylaxis. LEVEL OF EVIDENCE: II