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Background: Spontaneous preterm birth is a leading cause of neonatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could reduce the spontaneous preterm birth rate, but conventional methods such as obstetrical history and maternal cervical length screening identify only a minority of spontaneous preterm birth cases. Cervicovaginal fluid might prove to be a useful, readily available biological fluid for identifying spontaneous preterm birth biomarkers., Objective: The objective of the study was to identify cervicovaginal fluid biomarkers of early spontaneous preterm birth in a high-risk cohort of pregnant women with a history of spontaneous preterm birth using targeted and shotgun proteomic analyses., Study Design: A nested case control study (cases were spontaneous preterm birth <34 weeks in the current pregnancy; controls were spontaneous labor and delivery at 39-41 weeks) was performed using cervicovaginal fluid samples collected at 3 study visits (10 0/7 to 18 6/7 weeks, 19 0/7 to 23 6/7 weeks, and 28 0/7 to 31 6/7 weeks). All participants had a history of at least 1 prior spontaneous preterm birth. Targeted proteomic analysis was performed using a stable isotope-labeled proteome derived from endocervical and vaginal mucosal cells. This served as a standard to quantitate candidate protein levels in individual cervicovaginal fluid samples from the second and third study visits using liquid chromatography-multiple reaction monitoring mass spectrometry. The ratio of endogenous peptide area/stable isotope-labeled proteome-derived peptide area was used to measure levels of 42 peptides in 22 proteins. To maximize biomarker discovery in the cervicovaginal fluid samples, shotgun proteomic analysis also was performed utilizing liquid chromatography and ion trap mass spectrometry. A validation study was performed in second-trimester cervicovaginal fluid samples from an independent study group (12 spontaneous preterm birth cases, 19 term delivery controls) using enzyme-linked immunosorbent assay for 5 proteins expressed at higher levels in spontaneous preterm birth cases compared with controls in targeted or shotgun proteomic analyses., Results: For targeted proteomics, cervicovaginal fluid samples from 33 cases and 32 controls at 19 0/7 to 23 6/7 weeks and 16 cases and 14 controls at 28 0/7 to 31 6/7 weeks from the same pregnancies were analyzed. When samples were compared between cases and controls, the relative abundance of 5 proteins was greater (P = .02-.05) in cases at both visits, while the relative abundance of 1 protein was lower (P = .03) in cases at both visits. For shotgun proteomics analyses, cervicovaginal fluid samples were pooled for 9 spontaneous preterm birth cases and 9 term delivery controls at each study visit. Shotgun proteomics yielded 28 proteins that were detected at levels >2 times higher and 1 protein that was detected at a level <0.5 times lower in spontaneous preterm birth cases compared with controls at all 3 study visits. Validation enzyme-linked immunosorbent assay for 5 proteins that were detected at higher levels in cervicovaginal fluid samples from spontaneous preterm birth cases compared with term delivery controls in proteomics analyses did not demonstrate statistically significant differences between spontaneous preterm birth cases and controls., Conclusions: Potential biomarkers of spontaneous preterm birth were identified by targeted and shotgun proteomics analyses in cervicovaginal fluid samples from high-risk, asymptomatic women. Many of the proteins detected at higher levels in cervicovaginal fluid samples from spontaneous preterm birth cases are extracellular matrix proteins and/or regulate cell membrane physiology. These proteins have substantial biological interest, but validation enzyme-linked immunosorbent assay for 5 of these proteins did not yield clinically useful biomarkers for spontaneous preterm birth., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of institutional protocols for vaginal preparation with antiseptic solution and the surgical site infection rate in women undergoing cesarean delivery during labor., Methods: This is a secondary analysis of a multicenter randomized controlled trial of adjunctive azithromycin prophylaxis for cesarean delivery performed in laboring patients with viable pregnancies. The primary outcome for this analysis was the rate of superficial or deep surgical site infection within 6 weeks postpartum, as per Centers for Disease Control and Prevention criteria. Maternal secondary outcomes included a composite of endometritis, wound infection or other infections, postoperative maternal fever, length of hospital stay, and the rates of hospital readmission, unexpected office visits, and emergency department visits., Results: A total of 523 women delivered in institutions with vaginal antisepsis policies before cesarean delivery and 1,490 delivered in institutions without such policies. There was no difference in superficial and deep surgical site infection rates between women with and without vaginal preparation (5.5% vs 4.1%; odds ratio [OR] 1.38, 95% CI 0.87-2.17), even after adjusting for possible confounders (adjusted OR 0.86, 95% CI 0.43-1.73). The lack of significant benefit was noted in all other maternal secondary outcomes., Conclusion: Institutional policies for vaginal preparation before cesarean delivery were not associated with lower rates of surgical site infection in women undergoing cesarean delivery during labor.

Objective: To evaluate whether vaginal flora is altered by antibiotic exposure and associated with a risk of preterm birth, particularly among women with initially normal vaginal flora., Methods: This was a secondary analysis of a randomized trial of metronidazole and erythromycin for the prevention of preterm birth among women with a positive fetal fibronectin test. Vaginal swabs for Nugent Gram stain score were collected for classification of bacterial vaginosis before and after antibiotic exposure and read at a central laboratory. Change in Nugent score was assessed for women with (score 7 or higher) or without (score lower than 7) bacterial vaginosis. Linear regression analysis evaluated whether change in Nugent score was associated with preterm birth., Results: Two hundred women without and 69 women with bacterial vaginosis had Gram stain performed before and after antibiotic therapy. Median Nugent score for all women declined from 4.0 to 2.0 after antibiotic therapy (P<.001). Nugent score declined both for those without (from 2.0 to 1.5, P=.11) and, more dramatically, those with bacterial vaginosis (from 8.0 to 3.0, P<.01). The components of the Nugent score that were affected by antibiotic exposure were similar among women with and without bacterial vaginosis. Antibiotic exposure and the change in Nugent score were unrelated to preterm birth among bacterial vaginosis-negative women., Conclusion: Antibiotic exposure is not associated with preterm birth and does not worsen Nugent score among women with normal vaginal flora and positive fetal fibronectin., Level of Evidence: II.

Background: Vaginal douching is consistently associated with bacterial vaginosis (BV), but whether it is a cause or result of BV remains unknown. The association between BV and other feminine hygienic behaviors is less studied; if BV symptoms caused behavior change then all hygiene behaviors might be more common among women with BV. Lack of association between nondouching hygiene behavior and BV would argue against reverse causation., Methods: In the Longitudinal Study of Vaginal Flora 3620 women had 13,517 visits where BV (Nugent score) was assessed. Associations between hygienic behavior and BV were assessed by Poisson regression., Results: After adjusting for demographic and sexual behavior factors, neither type of underwear (nylon vs. cotton prevalence ratio (PR) 1.05, 95% CI: 0.97-1.13), menstrual protection (tampons vs. pads; PR: 1.04, 95% CI: 0.95-1.12; pads and tampons vs. pads 1.00, 95% CI: 0.92-1.07), use of pads or panty liners when not menstruating (PR: 0.99, 95% CI: 0.95-1.05), nor weekly or greater use of hygiene spray (PR: 1.01, 95% CI: 0.94-1.09), powder (PR: 1.02, 95% CI: 0.96-1.07) or towlettes (PR: 1.03, 95% CI: 0.94-1.13) were strongly associated with BV. PR for daily versus less than daily bathing and showering were 1.06 (95% CI: 1.02-1.12) and 1.04 (95% CI: 1.00-1.09). Douching remained associated with BV (PR for weekly or greater vs. never 1.17, 95% CI: 1.09-1.26) and was not substantially impacted by adjustment for other hygienic behavior., Conclusions: Douching, but not other feminine hygiene behaviors, is significantly associated with BV, providing additional evidence that douching may be causally associated with BV and is not simply a response to BV symptoms.

Objective: To estimate the frequency of genital tract colonization by methicillin-resistant Staphylococcus aureus (MRSA) among pregnant women and evaluate the association of such colonization with infant outcome., Methods: Between July 2003 and July 2006, anovaginal screening cultures for group B Streptococcus (GBS) were prospectively obtained in the third trimester (35 to less than 37 weeks of gestation) and were also processed for identification of Staphylococcus aureus including methicillin-resistant strains. Maternal colonization by MRSA was linked to a computerized database of invasive neonatal infections that occurred at our center during the study period., Results: Among 5,732 mothers (who delivered 5,804 infants) with GBS screening cultures and infant infection data available, 22.9% were GBS-positive and 14.5% were positive for Staphylococcus aureus. A total of 24.3% of the Staphylococcus aureus isolates were MRSA. The overall MRSA colonization rate was 3.5%. Colonization by any Staphylococcus aureus (relative risk 1.6, 95% confidence interval 1.4-1.9) as well as MRSA (relative risk 2.2, 95% confidence interval 1.6-2.8) was significantly more common among GBS-positive than among GBS-negative women. No cases of early-onset invasive neonatal infection by MRSA occurred among infants in the study., Conclusion: Genital tract colonization with MRSA affected 3.5% of pregnant women. Such MRSA colonization is associated with colonization by GBS but does not predispose to a high risk of early-onset neonatal MRSA infection., Level of Evidence: III.

Objectives: The objectives of this study were to determine whether women who douche regularly would enter a randomized trial of douching cessation or continuation, whether they would adhere to the assigned behavior, and whether there was a dramatic impact on vaginal flora., Goal: The goal of this study was to determine the feasibility of a large, definitive trial of douching cessation., Study Design: Women who douched at least weekly and who had either bacterial vaginosis or normal flora by Gram stain were assigned at random either to continue douching or to stop for 8 weeks. Vaginal Gram stains were obtained every 7 days from each woman., Results: Forty-eight women were randomized. Those assigned to continue reported douching during 77% of study weeks; those assigned to stop denied douching in 94% of weeks. No dramatic differences in flora were observed between women in the continue versus stop groups., Conclusion: A large randomized trial of douching cessation is feasible.

Objective: To compare the use of midtrimester vaginal polymorphonuclear cell (PMN) counts on Gram-stain preparations with PMN to epithelial cell (EPI) ratios for the prediction of subsequent spontaneous preterm birth., Methods: From a prospective cohort study, 83 women with a spontaneous preterm birth at less than 35 weeks of gestation (cases) were compared with a control group of 108 women who delivered at term. Vaginal Gram-stain preparations were obtained at the initial study visit (20-25 weeks). Vaginal PMN and epithelial EPI cell counts were assessed on 5 nonadjacent oil immersion fields under x 1,000 magnification. Vaginal PMN/EPI ratios for each evaluated slide field were calculated to control for intraslide variation in cellular density., Results: Mean delivery gestational age was 31.5 +/- 3.5 weeks for the cases and 39.8 +/- 1.2 weeks for the controls. Mean PMN counts were similar in the cases (13 +/- 20 cells per oil immersion field) and the controls (10 +/- 14 cells per oil immersion field) (P = .17). The mean PMN/EPI ratio, however, was significantly higher among the cases (3.4 +/- 6.0) than among the controls (1.8 +/- 2.4, P = .01). When PMN counts and PMN/EPI ratios were dichotomized by the 95th percentile cutoff (based on control values), the PMN/EPI ratio was significantly associated with subsequent development of spontaneous preterm birth at less than 35 weeks of gestation (odds ratio 3.8, 95% confidence interval 1.3-11.2), whereas PMN counts were not (odds ratio 2.1, 95% confidence interval 0.7-6.1)., Conclusion: Midtrimester vaginal PMN counts on Gram-stain preparations were not significantly associated with subsequent spontaneous preterm birth in this population. However, the ratio of PMN to EPI counts, which provides internal standardization of variation in slide cellular density, was significantly higher in women with subsequent spontaneous preterm birth at less than 35 weeks.

Objective  To evaluate if fundal (F) dominance of the electrohysterogram is associated with vaginal delivery and lack of F dominance is associated with cesarean for labor dystocia. Study Design  We conducted a prospective cohort study of nulliparous women in spontaneous labor at ≥36 weeks. Clinicians were blinded to electrohysterography data which were in addition to standard cardiotocography. All contractions in the hour preceding diagnosis of complete cervical dilation (for women delivering vaginally) or the hour preceding the decision for cesarean were analyzed. Results  Of 224 patients, 167 had evaluable data. The proportion of F dominant contractions was not different for women undergoing cesarean for labor dystocia (n  = 11) compared with all others (n  = 156)—88.7 ± 10.2 versus 86.0 ± 11.4%; p  = 0.44. Results were similar when comparing the cesarean for labor dystocia group to those undergoing cesarean for other indications (n  = 10) and vaginal deliveries (n  = 146)—88.7 ± 10.2 versus 86.5 ± 10.0 versus 85.9 ± 11.5%; p  = 0.74. Conclusion  We were unable to confirm our earlier finding that F dominance of the electrohysterogram is associated with vaginal delivery and lack of F dominance is associated with cesarean for dystocia. [ABSTRACT FROM AUTHOR]

Objective Chorioamnionitis, an important cause of maternal and neonatal morbidity, is influenced by epidural use and the occurrence of epidural fever. We evaluated the association between chorioamnionitis, histologic placental findings, and intrapartum factors focusing on epidural use. Materials and Methods We conducted a secondary analysis of a randomized controlled trial of different doses of oxytocin to prevent postpartum hemorrhage among women who delivered vaginally. The primary outcome was clinical diagnosis of chorioamnionitis leading to antibiotic therapy. Intrapartum factors examined included epidural use, parity, labor induction, gestational age, maternal age, ethnicity, body mass index, cervical dilatation at admission, preeclampsia/eclampsia, preterm labor, and duration of labor. Results Of the 1,798 women randomized, we excluded 13 multifetal births leaving 1,785 for analysis: 1,491 had an epidural and 294 did not. Of those with epidural, 8.0% had clinically diagnosed chorioamnionitis compared with only 1.0% without epidural: unadjusted odds ratio (OR) = 8.3 (95% confidence interval [CI]: 2.63-26.40); p < 0.0001. After multivariable logistic regression, epidural use (adjusted OR: 5.80; 95% CI: 1.77-19.11), increasing parity (0.42; 0.32-0.55), and preeclampsia (0.31; 0.14-0.66) were significantly associated with chorioamnionitis. Conclusion Epidural use is statistically associated with an increase in clinical diagnosis of chorioamnionitis. A cause and effect relationship cannot be confirmed from this study. Independently of labor duration and increasing parity, preeclampsia appeared protective. [ABSTRACT FROM AUTHOR]

: ObjectiveTo estimate whether antibiotic treatment of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in the second trimester would reduce the risk of spontaneous preterm delivery.: MethodsWomen were screened between 21 weeks 0 days and 25 weeks 6 days of gestation with cervical or vaginal swabs for fetal fibronectin. Women with a positive test (50 ng/mL or more) were randomized to receive metronidazole (250 mg orally three times per day) and erythromycin (250 mg orally four times per day) or identical placebo pills for 10 days. The primary outcome was spontaneous delivery before 37 weeks’ gestation after preterm labor or premature membrane rupture.: ResultsA total of 16,317 women were screened for fetal fibronectin, and 6.6% had a positive test; 715 fetal fibronectin test–positive women consented to randomization. Outcome data were available for 703 women: 347 in the antibiotic group and 356 in the placebo group. The antibiotic and placebo groups were not significantly different for maternal age (P = .051), ethnicity (P = .849), marital status (P = .127), education (P = .244), and bacterial vaginosis (P = .236). No difference was observed in spontaneous preterm birth before 37 weeks’ (odds ratio [OR] 1.17, 95% confidence interval [CI] 0.80, 1.70), less than 35 weeks’ (OR 0.92, 95% CI 0.54, 1.56), or less than 32 weeks’ (OR 1.94, 95% CI 0.83, 4.52) gestation in antibiotic- compared with placebo-treated women. Among women with a prior spontaneous preterm delivery, the rate of repeat spontaneous preterm delivery at less than 37 weeks’ gestation was significantly higher in the active drug compared with the placebo group (46.7% versus 23.9%, P = .039).: ConclusionTreatment with metronidazole plus erythromycin of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in the late second trimester does not decrease the incidence of spontaneous preterm delivery. [Copyright &y& Elsevier]

Objective: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth.Study Design: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation.Results: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001).Conclusions: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine the midtrimester prevalence of Mycoplasma genitalium in women who had subsequent spontaneous preterm birth.Study Design: In a prospective study of lower genital tract infections, we identified 127 women who subsequently had spontaneous preterm birth. Vaginal samples were obtained between 21 and 25 weeks' gestation for pH, for bacterial vaginosis Gram stain, and cultures that yielded Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. M genitalium was identified by using validated polymerase chain reaction (PCR) primers, and the results were compared to pregnancy outcomes.Results: Of 124 women with spontaneous preterm births, only five (3.9%) had PCR assays positive forM genitalium. The mean +/- SD delivery gestational age was similar for women with a positive PCR (34.6 +/- 2.2 weeks) and a negative PCR (34.0 +/- 2.7 weeks) (P =.62). None of the women with positive PCR results tested positive for any other sexually transmitted disease, whereas 36 (30%) women with negative PCR results tested positive.Conclusions: The occurrence of M genitalium in the vagina at midtrimester is infrequent in women with subsequent spontaneous preterm birth. [ABSTRACT FROM AUTHOR]

Discusses the relationship of intrauterine infections and preterm delivery. Specific forms of intrauterine infection; Epidemiology of preterm delivery; Bacteria identified in women with spontaneous preterm labor; Timing of infection; Bacterial vaginosis; Mechanisms of preterm delivery due to infection; Markers of infection; Treatment of infection to prevent preterm delivery; Conclusions.