Investigation Into the Microorganisms in Pregnant Women

Study Overview
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Brief Summary
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Pregnant women with short cervical length (<25 mm) in second-trimester ultrasonographic assessment are at high risk for preterm birth, a major cause of perinatal mortality and morbidity worldwide. Some of these short-cervix women proceed to a more advanced stage manifested as a painless prematurely dilated cervix in the second trimester. It is not fully understood why some women have short cervical length or prematurely dilated cervix (cervical insufficiency), although evidence is mounting that there is an association between short cervical length and infection by microorganisms. The investigators hypothesize that the cervical microorganisms in pregnant women with a shortened or dilated cervix are different, compared with those in women with normal cervical length and a closed cervix.

Detailed Description
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Previously, culture-dependent methods were used to detect bacterial or fungal infection, but the sensitivity was low, since not all species grew well in culture. Recently, molecular methods based on PCR amplification of the bacterial 16S ribosomal RNA (rRNA) gene or the fungal internal transcribed spacer (ITS) followed by capillary sequencing has been used to identify bacteria and fungi. However, the resolution of such capillary sequencing-based method (<100 sequencing reads/sample) is too low to capture the major collection of microorganisms in a sample. Less abundant but possibly pathogenic microorganisms associated with short cervical length remain undetectable. To address the current gap in this field, we propose to more comprehensively survey microbial communities in the cervix of pregnant women by PCR amplification of the 16S rRNA region, ITS or other genomic regions with taxonomic classification potential. This will be followed by next-generation sequencing (>40,000 sequencing reads/sample), which has been proven to capture the majority of microorganisms in a sample.

Official Title
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Investigation Into the Fungal Microbiome (Mycobiome) in the Cervices of Cervical Insufficiency Patients Receiving Cerclage Treatment and Resulting in Term or Preterm Birth

Conditions
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Cervical Insufficiency, Preterm Birth

Intervention / Treatment
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* Other: Sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with or without cervical insufficiency (cervical length <25 mm or dilated cervix in the second trimester or the late first trimester) Exclusion Criteria: multiple pregnancies and pregnancies associated with fetal chromosomal abnormality

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant women with cervical insufficiency (Cases)<br>Pregnant women with a shortened (<25 mm) or dilated cervix in the second trimester (or late first trimester) | Other: Sequencing<br>* This is an observational study, since the assignment of the medical intervention (e.g. cerclage or pessary) is not at the discretion of the investigator. However, cervical samples collected from both groups are subjected to amplicon sequencing for taxonomic classification of microorganisms.<br>|
| Pregnant women without cervical insufficiency (Controls)<br>Pregnant women with a normal-length (>= 25 mm) and closed cervix in the second trimester (or late first trimester) | Other: Sequencing<br>* This is an observational study, since the assignment of the medical intervention (e.g. cerclage or pessary) is not at the discretion of the investigator. However, cervical samples collected from both groups are subjected to amplicon sequencing for taxonomic classification of microorganisms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abundances of microorganisms in the cervix | Abundances of microorganisms including bacteria and fungi in the cervix are measured by normalized sequencing read counts | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational age at delivery |  | 1 year | 
| Mode of delivery |  | 1 year | 
| Number of participants who received cerclage or ring pessary in the current pregnancy |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm birth, cervical insufficiency, cerclage, pessary