Clinical trial NCT06131749: Genital Tract Infections, the Vaginal Microbiome and Gestational Age at Birth Among Pregnant Women in South Africa
Official title: Genital Tract Infections, the Vaginal Microbiome and Gestational Age at Birth Among Pregnant Women in South Africa
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
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
Keywords: Sexually transmitted infections
Preterm birth
Gestational age at birth
Vaginal microbiome
Genital mycoplasmas
Organism load
Vaginal yeast
Antenatal care
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: Foundation for Professional Development
name: Utrecht University
name: University of Pretoria
name: University of Cape Town
name: University of Southern California
name: University of Alabama at Birmingham
name: Louisiana State University Health Sciences Center in New Orleans
First posted: 2023-11-14
Enrollment: 603
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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).

Primary outcomes:
measure: Gestational age at birth
timeFrame: Recorded within 2 weeks of delivery
Secondary outcomes:
measure: Preterm birth
timeFrame: Recorded within 2 weeks of birth
measure: Low birth weight
timeFrame: Measured within 72 hours of birth
measure: Miscarriage
timeFrame: Collected throughout pregnancy until delivery
measure: Stillbirth
timeFrame: Collected throughout pregnancy until delivery
Other outcomes:
measure: Prevalence of microorganisms
timeFrame: Measured at enrolment visit and at 30-34 week visit
measure: Incidence of microorganisms
timeFrame: Measured at 30-34 week visit
Locations:
city: East London
country: South Africa
facility: Empilweni Gompo Community Health Centre
state: Eastern Cape
Study officials:
affiliation: University of Bern
name: Nicola Low, MD
role: PRINCIPAL_INVESTIGATOR
References: