Mixed Bacterial Growth in Prenatal Urine Cultures; An Investigation into Prevalence, Contributory Factors and the Impact of education-based Interventions

PURPOSE: Undiagnosed urinary tract infections (UTIs) in pregnancy are associated with adverse perinatal outcome. Urine microbiology cultures reported as 'mixed bacterial growth' (MBG) frequently present a diagnostic dilemma for healthcare providers. We investigated external factors contributing to elevated rates of (MBG) within a large tertiary maternity centre in London, UK, and assessed the efficacy of health service interventions to mitigate these. DESCRIPTION: This prospective, observational study of asymptomatic pregnant women attending their first prenatal clinic appointment aimed to establish (i) the prevalence of MBG in routine prenatal urine microbiology cultures, (ii) the association between urine cultures and the duration to laboratory processing and (iii) ways in which MBG may be reduced in pregnancy. Specifically we assessed the impact of patient-clinician interaction and that of an education package on optimal urine sampling technique. ASSESSMENT: Among 212 women observed over 6 weeks, the negative, positive and MBG urine culture rates were 66%, 10% and 2% respectively. Shorter duration from urine sample collection to laboratory arrival correlated with higher rates of negative cultures. Urine samples arriving in the laboratory within 3 hours of collection were most likely to be reported as culture negative (74%), and were least likely to be reported as MBG (21%) or culture positive (6%), compared to samples arriving > 6 hours (71%, 14% and 14% respectively; P < 0.001). A midwifery education package effectively reduced rates of MBG (37% pre-intervention vs 19% post-intervention, RR 0.70, 95% CI 0.55 to 0.89). Women who did not receive verbal instructions prior to providing their sample had 5-fold higher rates of MBG (P < 0.001). CONCLUSION: As many as 24% of prenatal urine screening cultures are reported as MBG. Patient-midwife interaction before urine sample collection and rapid transfer of urine samples to the laboratory within 3 hours reduces the rate of MBG in prenatal urine cultures. Reinforcing this message through education may improve accuracy of test results

Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin

© 2018 The Author(s). Background: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P=0.026) and persisted following membrane rupture (31%, P=0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P=0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Conclusions: Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined

Data from: Preterm birth prevention post-conization: a model of cervical length screening with targeted cerclage

Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth 37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of preterm birth

First trimester circulating MicroRNA biomarkers predictive of subsequent preterm delivery and cervical shortening

Preterm birth (PTB) is the leading cause of infant death and disability worldwide. The onset of preterm uterine contractions is preceded by asymptomatic cervical remodelling and ripening, which can be seen on trans-vaginal ultrasound as cervical shortening. This study aimed to identify plasma miRNA biomarkers that predict preterm birth and/or cervical shortening. We collected serial plasma samples from pregnant women prospectively from 12 to 22 weeks gestation. The nCounter miRNA assay was used to identify differentially expressed miRNAs associated with spontaneous PTB and/or cervical shortening (n = 16 term no short, n = 13 preterm, n = 24 short). Predictive values of the miRNA biomarkers were confirmed in an independent validation cohort consisting of 96 women who delivered at term, 14 preterm and 21 early cervical shortening at <20 weeks gestation. Nine miRNAs (hsa-let-7a-5p, hsa-miR-374a-5p, hsa-miR-15b-5p, hsa-miR-19b-3p, hsa-miR-23a-3p, hsa-miR-93-5p, hsa-miR-150-5p, hsa-miR-185-5p and hsa-miR-191-5p) were differentially expressed (P < 0.001) in women subsequently experiencing PTB or cervical shortening. Hsa-miR-150-5p had the strongest ability to predict PTB (AUC = 0.8725) and cervical shortening (AUC = 0.8514). Plasma miRNAs in the first trimester can predict PTB and cervical shortening in women at risk of preterm delivery. This is a key period in pregnancy when early identification of PTB risk allows time to deliver outcome-modifying interventions

Sensitivity, specificity, likelihood ratios, and positive and negative predictive values for cerclage intervention and/or preterm birth <37 weeks, for screening time-points A, B and C, and percentage difference in CL between screening time-points A, B and C.

<p>Sensitivity, specificity, likelihood ratios, and positive and negative predictive values for cerclage intervention and/or preterm birth <37 weeks, for screening time-points A, B and C, and percentage difference in CL between screening time-points A, B and C.</p

Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage - Fig 2

<p><b>Mean difference in CL (mean % Δ CL) between time-points A: 13+0–15+6 weeks, B: 16+0–18+6 weeks, C: 20+0–22+6 weeks (A-B, B-C, and A-C) according to delivery outcome and cerclage insertion.</b> In women receiving a cerclage, mean CL started above 25mm at timepoint A, and went on to shorten, most significantly at timepoint C. The greatest difference in CL is observed between timepoints B-C and A-C in those that received a cerclage and went on to deliver preterm <37weeks, followed by term delivery with a cerclage. (<i>% ΔCL = percentage change in CL (mm) between screening time points; PTB = preterm birth <37 weeks; Screening time points = A</i>: <i>13+0–15+6 weeks</i>, <i>B</i>: <i>16+0–18+6 weeks</i>, <i>C</i>: <i>20+0–22+6 weeks; SD = standard deviation; Term = birth >37 weeks; W = weeks)</i>.</p

Preterm birth rates: A in the UK; B in the local population (three study units); C estimated in women post-cervical treatment based on UK rates; D in this study cohort.

<p>Preterm birth rates: A in the UK; B in the local population (three study units); C estimated in women post-cervical treatment based on UK rates; D in this study cohort.</p

Patient characteristics for women that delivered at term without cerclage (Group 1) and women that had cerclage or delivered prematurely (Group 2).

<p>Patient characteristics for women that delivered at term without cerclage (Group 1) and women that had cerclage or delivered prematurely (Group 2).</p

Mean CL (mm)(SD) at screening time-points A, B, C and mean percentage ΔCL (SD) between screening time-points A-B, B-C, and A-C for Group 1 and 2.

<p>Mean CL (mm)(SD) at screening time-points A, B, C and mean percentage ΔCL (SD) between screening time-points A-B, B-C, and A-C for Group 1 and 2.</p