Cervical stiffness measurements as a predictive test for spontaneous preterm birth

Presented by Hannah Rosen O’Sullivan

Objective
– To determine if cervical stiffness measurements differ between those delivering
term and preterm
– To determine if cervical stiffness measurements correlate with cervical length,
fetal fibronectin (fFN) and other biomarkers
– To determine if cervical stiffness measurements can predict risk of spontaneous
preterm birth in an asymptomatic high risk population

Study Designs
– Observational study – serial cervical stiffness measurements at 5 gestational
timepoints taken from asymptomatic women at high risk of spontaneous preterm birth
– Cervical stiffness measurements taken using an aspiration device (Pregnolia system)
– Device consists of a control unit, tubing and a small cup, which is placed on the
anterior lip of the cervix during speculum examination, a weak vacuum is created
which aspirates the cervical tissue to a depth of 4mm and records the amount of pressure
required to do this (mbar)
– Paired cervical length, quantitative fFN and high vaginal swabs taken

Results
– Cervical stiffness is significantly lower in women delivering preterm compared
to those delivering at term (mean cervical stiffness term 71.9 mbar, mean cervical stiffness preterm 40.0, p=0.04)
– There is correlation between cervical stiffness and gestation at delivery, cervical
length and fetal fibronectin
– Area under the curve for cervical stiffness as a predictive test for spontaneous preterm
birth <37 weeks in this cohort = 0.8, compared with the AUC for cervical length = 0.7 and
fetal fibronectin = 0.67.

Conclusion 
– Cervical stiffness measurements appear to be a good predictive test for risk of
spontaneous preterm birth <37 weeks in a high-risk asymptomatic population
and warrants ongoing investigation
– Further groups to be added including a threatened preterm labour cohort

Author(s)
Hannah Rosen O’Sullivan, Natalie Suff, Nicole Moriarty, Andrew Shennan

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Non-invasive prediction models of intraamniotic infection in women with preterm labor

Presented by Teresa Cobo

Objective
Among women with preterm labor, those with intra-amniotic infection present the highest risk of early delivery and the most adverse outcomes. Identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Non-invasive methods for identifying intra-amniotic infection and/or early delivery are critical to focus early efforts on high-risk while avoiding unnecessary interventions in low-risk preterm labor women. We modeled the best performing models integrating biochemical data with clinical and ultrasound information to predict a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days.

Study designs
From 2015-2020, we used data from a cohort of women admitted with diagnosis of preterm labor below 34 weeks at Hospital Clinic and Hospital Sant Joan de Déu, Barcelona, who had undergone amniocentesis to rule in/out intra-amniotic infection or inflammation. Transvaginal ultrasound, maternal blood and vaginal samples were prospectively performed at admission. Using high-dimensional biology, we explored vaginal proteins (by multiplex immunoassay), amino acids (by high-performance liquid chromatography) and bacteria (by 16S rRNA gene amplicon sequencing) to predict the composite outcome. We selected ultrasound, maternal blood and vaginal predictors that could be tested with rapid diagnostic techniques and developed prediction models employing Machine Learning that were applied in a validation cohort.

Results
We studied a cohort of 288 women with PTL below 34 weeks, of which 103 (35%) had a composite outcome of IAI and/or spontaneous delivery within 7 days. The sample was divided into derivation (n=116) and validation cohorts (n=172). Four prediction models were proposed, including ultrasound transvaginal cervical length, maternal C-reactive protein, vaginal IL-6 (using automated immunoanalyzer), vaginal pH (using pH meter), vaginal lactic acid (using reflectometer) and vaginal Lactobacillus genus (using quantitative-PCR), with areas under the curve ranging from 82.2% (+-3.1% 95% confidence interval) to 85.2%(+-3.1% 95% confidence interval), sensitivities ranging from 76.1 to 85.9% and specificities of 75.2 to 85.1%.

Conclusion
These results provide proof-of-principle of how non-invasive methods suitable for point-of-care systems can select high-risk cases among women with preterm labor and might substantially aid in clinical management and outcomes, while improving use of resources and patient experience.

Authors
Teresa Cobo, Xavier P Burgos-Artizzu, MC Collado, V Andreu, AB Sánchez-Garcia, X Filella, S Marín, M Cascante, J Bosch, S Ferrero, D Boada, C Murillo, C Rueda, J Ponce, M Palacio, E Gratacós

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Vaginal microbiota composition as a potential indicator of adverse pregnancy outcomes : a prospective observational study, France

Presented by Laura Lesimple

Objective
Identify vaginal microbiota signatures predictive of preterm birth (PTB) and premature rupture of membranes (P-PROM).

Study designs
A prospective observational cohort study was initiated in 3 academic obstetrical centres in the Paris area, France, in 2018. Pregnant women were recruited in 4 groups, by increasing risk of PTB, P-PROM.

– Low-risk controls, receiving routine antenatal screening for group B Streptococcus colonization 34-37 weeks of gestation (WG)
– T-PROM controls, term premature rupture of membranes (>37 WG)
– PTL, preterm labor or threatened preterm labor with intact membranes
– P-PROM, preterm premature rupture of membranes (<37 WG)

Vaginal swabs were sampled at inclusion/delivery for analysis by conventional culture methods.
Sociodemographic information were also collected.

Results
A total of 2,411 patients were included (control, n=1,099 ; T-PROM, n=493 ; PTL, n=489 ; P-PROM, n=330).

Significant differences in the microbiological characteristics of the vaginal samples at inclusion were found between groups. Intermediate and high Nugent score (≥4) indicative of a subnormal microbiota and vaginosis were more frequent in P-PROM (p<0.0001). Accordingly, lactobacilli were more frequently absent from bacterial cultures in PTL and P-PROM (p<0.0001) and anaerobes indicative of bacterial vaginosis (including Gardnerella vaginalis and Streptococcus anginosus) were overrepresented in T-PROM, PTL and P-PROM (p=0.0012). Last, particular species including Escherichia coli and Klebsiella pneumoniae were more frequent in T-PROM , PTL and P-PROM (<0.0001).

Conclusion
Differences in vaginal microbiota composition were found among low and high risks groups. Analysis of species abundance and correlation with metagenomics and pregnancy outcomes are ongoing.

Authors
Laura Lesimple, Jessica Rousseau, Céline Plainvert, Luce Landraud, Nathalie Grall, Signara Gueye, François Goffinet, Pierre-Yves Ancel, Christophe Pannetier, Claire Poyart, Laurent Mandelbrot, Asmaa Tazi

Real-time ultrasound demonstration of uterine isthmus contractions during pregnancy

Presented by Alba Ferràs

Objective
Isthmic contractions are a common occurrence during pregnancy, particularly triggered by bladder voiding. They can disrupt accurate cervical length assessment and potentially lead to incorrect placenta previa diagnosis. Research on the prevalence and characteristics of these contractions is scarce.

The aim of this study was to investigate the frequency and characteristics of isthmic contractions, and their impact on cervical length assessment. Additionally, the study aimed to showcase novel fast-motion videos of these contractions, providing real-time visualization of this physiological phenomenon.

Study designs
This prospective observational study involved 30 singleton pregnancies in their second trimester. We recorded extended videos of the uterine cervix, measured isthmic and cervico-isthmic lengths, and observed their changes over time. Participants were categorized based on the presence or absence of contractions. Fast-motion videos were created for enhanced visualization.

Results
43% of participants showed isthmic contractions post-bladder voiding. These contractions lengthened the isthmus and had a median duration of 18 minutes. In half of the cases, the isthmus exhibited an undulating relaxation pattern. A 18mm isthmic length cutoff differentiated women with contractions from those without. Fast-motion videos highlighted these contractions’ dynamic nature.

Conclusion
Isthmic contractions, common in the second trimester, can distort cervical length assessment and potentially create inaccurate placenta previa images. We advise cervical assessment 20 minutes post-bladder voiding to minimize bias. Fast-motion videos revealed new insights into isthmic contractions, enhancing the understanding of their role in pregnancy physiology. More research is necessary to understand these contractions’ impact on pregnancy and birth outcomes.

Authors
Alba Farràs, Sara Catalán, Alba Casellas, Teresa Higueras, Inés Calero, Maria Goya, Nerea Maiz, Maia Brik, Elena Carreras.

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