Genital tract infections, the vaginal microbiome and gestational age at birth among pregnant women in South Africa: a cohort study protocol

<bold>Introduction: </bold>Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.<bold>Methods and analysis: </bold>This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are >= 18 years and at <27 weeks of gestation, confirmed by ultrasound. At enrolment and 30-34 weeks of pregnancy, participants receive on-site tests for Chlamydia trachomatis and Neisseria gonorrhoeae, with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification of Trichomonas vaginalis, Candida spp., Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.<bold>Ethics and dissemination: </bold>This protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences.