Preterm labour is a major reproductive health problem. In this thesis, I started with an epidemiological investigation of preterm birth risk factors in the local hospital population. Smoking, social problems, premature rupture of the membranes, vaginal bleeding, previous history of preterm birth and threatened preterm-Iabour were significantly associated with preterm delivery. However, women who stopped smoking in early pregnancy had no increased risk of preterm birth compared to non- smokers. Medically indicated preterm deliveries were associated with hypertension and fetal growth restriction. The second part of this thesis is a proteomics study of placental blood with the aim to understand the basic mechanisms of human parturition. By comparing five different types of delivery, 33 genes were found to have significantly alte4red expression profiles. The major pathways changed in labour correspond to "immune and defence responses". Although the signal transduction and regulation of these pathways varied among modes of delivery, hepatocyte nuclear factor 1 homeobox A (HNF1A) emerged as a shared protein in the mechanism of labour. Moreover, several apolipoproteins such as APOA4 and APOE were found to change with labour and these changes were also confirmed in maternal plasma. APOA 1 and APOB were negatively and positively correlated, respectively, with gestational age. Changes in alpha-fetoprotein (AFP) in placental blood levels were also replicated in maternal peripheral plasma, whereas the change in alpha 1 B-glycoprotein (A 1 BG) was limited to placental plasma. The last part of the thesis is a systematic review of the literature and meta- analysis AFP and apolipoproteins in order to obtain observational evidence to assess their possible roles in human parturition. The meta-analysis has demonstrated that AP01 and APOB levels are significantly associated with increasing gestational age, and could potentially be used as labour onset biomarkers. The meta-analysis also found a strong association between elevated maternal circulating AFP levels and preterm birth, but the association may be confounded by abnormalities in other biomarkers and pregnancy complications.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:559724 |
| Date | January 2011 |
| Creators | Yuan, Wei |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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