Investigation Into the Microorganisms in Pregnant Women

• ClinicalTrials.gov Identifier: NCT04688866
• Recruitment Status: Recruiting
• First Posted: December 30, 2020
• Last Update Posted: March 10, 2022
• Sponsor: Chinese University of Hong Kong
• Collaborators: Hallym University; Health and Medical Research Fund
• Information provided by (Responsible Party): Stephen Chim, Chinese University of Hong Kong

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Cervical Insufficiency; Preterm Birth	Other: Sequencing

Detailed Description:

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: Investigation Into the Fungal Microbiome (Mycobiome) in the Cervices of Cervical Insufficiency Patients Receiving Cerclage Treatment and Resulting in Term or Preterm Birth
• Actual Study Start Date: June 5, 2012
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
Pregnant women with cervical insufficiency (Cases); Pregnant women with a shortened (<25 mm) or dilated cervix in the second trimester (or late first trimester)	Other: Sequencing; 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.
Pregnant women without cervical insufficiency (Controls); Pregnant women with a normal-length (>= 25 mm) and closed cervix in the second trimester (or late first trimester)	Other: Sequencing; 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.

Outcome Measures

Primary Outcome Measures :

1. Abundances of microorganisms in the cervix [ Time Frame: 1 year ]
   Abundances of microorganisms including bacteria and fungi in the cervix are measured by normalized sequencing read counts

Secondary Outcome Measures :

1. Gestational age at delivery [ Time Frame: 1 year ]
2. Mode of delivery [ Time Frame: 1 year ]
3. Number of participants who received cerclage or ring pessary in the current pregnancy [ Time Frame: 1 year ]

Biospecimen Retention:   Samples With DNA

Cervical swab samples obtained comprise ample amount of DNA for PCR amplification or sequencing.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women who attend preterm clinics or receive antenatal care at the participating hospitals.

Criteria

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

Contacts and Locations

Contacts

Contact: Stephen S Chim, PhD; (852)35051324; sschim@cuhk.edu.hk

Contact: Karen K Wong, MPhil; (852); wkwkaren@cuhk.edu.hk

Locations

Hong Kong

Research Laboratory, Dept of Obstetrics & Gynaecology, The Chinese University of Hong Kong; Recruiting

Hong Kong, Hong Kong, 852

Contact: Stephen S Chim, PhD 852-35051324 sschim@cuhk.edu.hk

Contact: Wong K Karen, MPhil 852-23521798 wkwkaren@cuhk.edu.hk

Sponsors and Collaborators

Chinese University of Hong Kong

Hallym University

Health and Medical Research Fund

Investigators

• Principal Investigator: Stephen S Chim, PhD; Chinese University of Hong Kong

More Information

• Responsible Party: Stephen Chim, Associate Professor, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT04688866
• Other Study ID Numbers: 2012.243
• First Posted: December 30, 2020
• Last Update Posted: March 10, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stephen Chim, Chinese University of Hong Kong:

preterm birth; cervical insufficiency; cerclage; pessary

Additional relevant MeSH terms:

Premature Birth; Uterine Cervical Incompetence; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Uterine Cervical Diseases; Uterine Diseases; Abortion, Habitual; Abortion, Spontaneous