Genital Tract Infections, the Vaginal Microbiome and Gestational Age at Birth Among Pregnant Women in South Africa

HIV Infections Clinical Trial

Official title:

Genital Tract Infections, the Vaginal Microbiome and Gestational Age at Birth Among Pregnant Women in South Africa

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06131749
• Other study ID #: SNSF197831
• Status: Active, not recruiting
• Start date: March 1, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: November 2023
• Source: University of Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This cohort study plans to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.

The study enrols pregnant women at one public health care facility in East London, South Africa. At enrolment and 30-34 weeks of pregnancy, participants provide swabs for testing for sexually transmitted infections, vaginal yeasts and genital mycoplasmas; for microscopy and Nugent scoring; and for 16S ribosomal ribonucleic acid gene sequencing and quantification. The primary outcome is gestational age at birth.

Statistical analyses include: regression modelling to explore associations between specific microorganisms (including microbiota) and gestational age at birth; construction of an index of vaginal inflammation, using data about microorganism load and inflammatory potential; classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.

Description:

Background: Preterm birth complications are the most common cause of death in children under 5 years. In South Africa, the prevalence of both genital tract infections and adverse pregnancy outcomes are high. This study takes a holistic approach, investigating both the presence and quantity of multiple lower genital tract microorganisms, including vaginal microbiota, in pregnancy and their associations with gestational age at birth. Specific objectives are to explore: (1) the association between the presence of specific lower genital tract microorganisms and gestational age at birth (primary outcome), as well as secondary adverse pregnancy outcomes; (2) the association between quantified load of vaginal and sexually transmitted microorganisms and gestational age at birth (primary outcome) as well as secondary adverse pregnancy outcomes; and (3) the combinations of microorganisms that are most strongly associated with earlier gestational age at birth.

Methods: This prospective closed cohort study follows women enrolled during pregnancy until after they give birth. This cohort study is part of a larger project, called Philani Ndiphile (meaning 'be healthy and I will be healthy' in isiXhosa).

A trained study field worker checks for eligibility and obtains written informed consent. A study nurse performs an abdominal ultrasound to estimate the gestational age and confirm eligibility.

At the enrolment visit and a follow-up visit at 30-34 weeks, a study nurse collects vaginal specimens for: on-site testing for Chlamydia trachomatis and Neisseria gonorrhoeae (with antibiotic treatment if positive); and offsite testing for: Nugent scoring; detection and quantification of Mycoplasma genitalium, M. hominis, Ureaplasma. parvum, U. Urealyticum, Trichomonas vaginalis, Candida spp. and 16S rRNA amplicon sequencing for vaginal microbiota analyses.

At a post-natal visit, 3-6 days after giving birth, a study nurse collects information about the birth outcome.

Statistical analyses include:

Objective 1. a) univariable and multivariable regression analyses for associations between specific microorganisms and gestational age at birth. b) compositional multivariable analysis methods to analyse individual taxon relative abundances and mixed effects models to assess associations between pregnancy outcome and vaginal microbiota diversity, vaginal microbiota types and absolute abundances of predefined bacterial groups.

Objective 2. Development of a 'vaginal inflammation index', based on quantification of the vaginal microbiota and their inflammatory potential. This vaginal inflammation index will be analysed as a fixed effect in mixed effects models with pregnancy outcomes.

Objective 3. Classification and regression tree analyses to examine the combination of microorganisms that best predicts earlier gestational age at birth.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 603
• Est. completion date: September 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Living in Buffalo City Metropolitan Municipality

• Intend to deliver in the same municipality

• <27 weeks of gestation at enrolment, confirmed by ultrasound

• Provide written informed consent

Exclusion Criteria:

• Participation in any other research study

• Inability to understand and speak a local language (English, Afrikaans, or isiXhosa).

Related Conditions & MeSH terms

• Bacterial Vaginosis
• Chlamydia Trachomatis Infection
• Communicable Diseases
• Genital Mycoplasma Infection
• Gonorrhea
• HIV Infections
• Infections
• Microbial Colonization
• Mycoplasma Genitalium Infection
• Mycoplasma Infections
• Neisseria Gonorrheae Infection
• Pleuropneumonia
• Pregnancy Complications, Infectious
• Premature Birth
• Reproductive Tract Infections
• Sexually Transmitted Diseases
• Sexually Transmitted Infections (Not HIV or Hepatitis)
• Trichomonas Vaginitis
• Vaginal Candida
• Vaginitis
• Vaginosis, Bacterial

Intervention

Other:
• No intervention
No intervention, observational cohort study

Locations

Country	Name	City	State
South Africa	Empilweni Gompo Community Health Centre	East London	Eastern Cape

Sponsors (8)

Lead Sponsor	Collaborator
University of Bern	Foundation for Professional Development, Louisiana State University Health Sciences Center in New Orleans, University of Alabama at Birmingham, University of Cape Town, University of Pretoria, University of Southern California, Utrecht University

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Prevalence of microorganisms	Number of women with a specific microorganism / number of women tested	Measured at enrolment visit and at 30-34 week visit
Other	Incidence of microorganisms	Number of women with new detection of a specific microorganism per 1000 woman years of follow-up	Measured at 30-34 week visit
Primary	Gestational age at birth	Gestational age in days, estimated using data from obstetric ultrasound at enrolment visit	Recorded within 2 weeks of delivery
Secondary	Preterm birth	Number of babies liveborn before 37 completed weeks of pregnancy, estimated using data from obstetric ultrasound at enrolment visit	Recorded within 2 weeks of birth
Secondary	Low birth weight	Number of babies with birth weight <2500g	Measured within 72 hours of birth
Secondary	Miscarriage	Number of foetuses delivered dead before 28 completed weeks of pregnancy or with birth weight below 1000g. Gestational age estimated using data from obstetric ultrasound at enrolment visit	Collected throughout pregnancy until delivery
Secondary	Stillbirth	Number of foetuses delivered dead at or after 28 completed weeks of pregnancy or with birth weight above 1000g at delivery. Gestational age estimated using data from obstetric ultrasound at enrolment visit	Collected throughout pregnancy until delivery