Investigation Into the Microorganisms in Pregnant Women

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

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.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Cervical Insufficiency
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Stephen S Chim, PhD; Phone Number: (852)35051324; Email: sschim@cuhk.edu.hk
• Study Contact Backup: Name: Karen K Wong, MPhil; Phone Number: (852); Email: wkwkaren@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong, 852
    • Recruiting
    • Research Laboratory, Dept of Obstetrics & Gynaecology, The Chinese University of Hong Kong
    • Contact: Stephen S Chim, PhD; Phone Number: 852-35051324; Email: sschim@cuhk.edu.hk
    • Contact: Wong K Karen, MPhil; Phone Number: 852-23521798; Email: wkwkaren@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Health and Medical Research Fund; Hallym University
• Investigators: Principal Investigator: Stephen S Chim, PhD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2012
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 28, 2020
• First Posted (Actual): December 30, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: preterm birth; cerclage; pessary; cervical insufficiency
• Additional Relevant MeSH Terms: Uterine Cervical Diseases; Uterine Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Abortion, Habitual; Abortion, Spontaneous; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Premature Birth; Uterine Cervical Incompetence
• Other Study ID Numbers: 2012.243

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No