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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Premature Birth; Microbial Colonization; Pregnancy; Infection; Bacterial Vaginosis; Trichomonas Vaginitis; Neisseria Gonorrheae Infection; Chlamydia Trachomatis Infection; Mycoplasma Genitalium Infection; Genital Mycoplasma Infection; Vaginal Candida; Sexually Transmitted Infections (Not HIV or Hepatitis); Ureaplasma Urealyticum Infection
• Intervention / Treatment: Other: No intervention

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.

• Study Type: Observational
• Enrollment (Actual): 603

Contacts and Locations

Study Locations

• South Africa
  • Eastern Cape
    • East London, Eastern Cape, South Africa, 5209
      • Empilweni Gompo Community Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women receiving antenatal care at one primary health care facility in Buffalo City Metropolitan Municipality, Eastern Cape Province, South Africa.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women; No intervention. Followed during pregnancy at baseline and 30-34 weeks. Followed after delivery at 3-6 days.	Other: No intervention; No intervention, observational cohort study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age at birth	Gestational age in days, estimated using data from obstetric ultrasound at enrolment visit	Recorded within 2 weeks of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Low birth weight	Number of babies with birth weight <2500g	Measured within 72 hours of birth
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of microorganisms	Number of women with a specific microorganism / number of women tested	Measured at enrolment visit and at 30-34 week visit
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

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: University of Alabama at Birmingham; University of Southern California; Louisiana State University Health Sciences Center in New Orleans; University of Cape Town; Utrecht University; University of Pretoria; Foundation for Professional Development
• Investigators: Principal Investigator: Nicola Low, MD, University of Bern

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 14, 2023

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Preterm birth; Antenatal care; Sexually transmitted infections; Vaginal microbiome; Gestational age at birth; Genital mycoplasmas; Organism load; Vaginal yeast
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Immune System Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Genital Diseases, Female; Liver Diseases; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Protozoan Infections; Parasitic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Vulvar Diseases; Vulvitis; Vaginitis; Sexually Transmitted Diseases, Bacterial; Neisseriaceae Infections; Mycoses; Vaginal Diseases; Vulvovaginitis; Candidiasis; Trichomonas Infections; Pathological Conditions, Signs and Symptoms; Premature Birth; Hepatitis; HIV Infections; Communicable Diseases; Sexually Transmitted Diseases; Pregnancy Complications, Infectious; Vaginosis, Bacterial; Gonorrhea; Candidiasis, Vulvovaginal; Trichomonas Vaginitis
• Other Study ID Numbers: SNSF197831

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