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Title: Placental infection and maternal immunity in the Baby Bio Bank
Author: Leon, L. J.
ISNI:       0000 0004 8499 4267
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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The Baby Bio Bank (BBB) is a UK based pregnancy complications cohort, with clinical data and biological samples from over 2500 mother, father, and infant trios. Within this large cohort, a significant number of infants were born preterm (< 37 weeks gestation). The experimental work outlined in this thesis focused on these participants, alongside a selection of full term pregnancies for comparison. All investigations were based on the hypothesis that many preterm births, particularly those precipitated by spontaneous events, have an underlying infectious aetiology. Total bacterial load in samples of placental DNA from 225 term and 141 preterm pregnancies was quantified, using quantitative PCR. An increase in total bacterial load was observed in placenta from spontaneous preterm births, compared to all other outcome groups. A subsection of these samples were then taken forward for next generation sequencing of the 16S gene. We hypothesised that bacterial DNA found in the placenta would differ qualitatively, as well as quantitatively, between preterm and term pregnancies. An enrichment of genera previously associated with adverse outcomes, such as Mycoplasma spp., was observed in spontaneous preterm placenta. Other, less established oral species were also associated with this outcome, such as Capnocytophaga spp. Evidence for the existence of a normal, healthy placental microbiome was less clear, and these analyses were complicated by a significant impact of delivery contaminants on sequencing results. The concentrations of 27 cytokines were also quantified in 149 maternal sera samples. These samples were from pregnancies that resulted in either term or spontaneous preterm births, and were taken within six weeks of delivery. Associations between cytokine concentrations and outcomes of interest were investigated. An upregulation of CC-type chemokines, as well as a number of other cytokines, was observed in spontaneous preterm pregnancies, implicating inflammatory events in the aetiology of spontaneous preterm birth.
Supervisor: Moore, G. E. ; Stanier, P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available