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

NCT ID: NCT06131749

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 603 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2024-07-31

Brief 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.

Detailed 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.

Conditions

Sexually Transmitted Infections (Not HIV or Hepatitis); Premature Birth; Pregnancy; Infection; Microbial Colonization; Chlamydia Trachomatis Infection; Neisseria Gonorrheae Infection; Trichomonas Vaginitis; Mycoplasma Genitalium Infection; Bacterial Vaginosis; Vaginal Candida; Ureaplasma Urealyticum Infection; Genital Mycoplasma Infection; HIV Infections

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pregnant women

No intervention. Followed during pregnancy at baseline and 30-34 weeks. Followed after delivery at 3-6 days.

No intervention

Intervention Type: OTHER

No intervention, observational cohort study

Interventions

No intervention

No intervention, observational cohort study

Intervention Type: OTHER

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Professional Development

UNKNOWN

Sponsor Role: collaborator

Utrecht University

OTHER

Sponsor Role: collaborator

University of Pretoria

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Louisiana State University Health Sciences Center in New Orleans

OTHER

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicola Low, MD

Role: PRINCIPAL_INVESTIGATOR

University of Bern

Locations

Empilweni Gompo Community Health Centre

East London, Eastern Cape, South Africa

Countries

South Africa

References

Gigi RMS, Mdingi MM, Jung H, Claassen-Weitz S, Butikofer L, Klausner JD, Muzny CA, Taylor CM, van de Wijgert JHHM, Peters RPH, Low N. Genital tract infections, the vaginal microbiome and gestational age at birth among pregnant women in South Africa: a cohort study protocol. BMJ Open. 2023 Dec 28;13(12):e081562. doi: 10.1136/bmjopen-2023-081562.

Reference Type: DERIVED

PMID: 38154893 (View on PubMed)

Other Identifiers

SNSF197831

Identifier Type: -

Identifier Source: org_study_id