An investigation of antenatal infection and inflammation and their contribution to preterm delivery and lung disease of prematurity

Despite the evidence linking intrauterine infection (IUI) to preterm labour and chronic lung disease, antibiotics have failed to have much impact on these clinical problems.;Polymerase chain reaction (PCR)-based techniques of microbial detection have a greater sensitivity than culture methods without sacrificing specificity. Discrepancies in the diagnosis of IUI may have affected the accuracy of previous studies. In this thesis a methodology for the molecular detection of IUI and inflammation was successfully developed without the need for amniocentesis.;PCR-based microbial detection was applied to a range of samples harvested from preterm deliveries. Inflammation was detected by histological examination and by measuring fluid and tissue cytokines. Clinical effects on the cohort of infants were also assessed.;The majority of spontaneous singleton preterm deliveries were associated with the detection of microbial genes by PCR. These genes were still detectable even after maternal antibiotic treatment. The findings of this work support the contention that high levels of intrauterine inflammation usually result from IUI, a matter which has been the subject of debate. Gastric fluid appeared to be a potentially useful sample for the microbial detection in future studies.;A univariate analysis of the clinical data demonstrated a reduction in radiological respiratory disease syndrome following fetal exposure to IUI, as well as increase in intraventricular haemorrhage. Both fetal inflammation and pulmonary inflammation were associated with fetal exposure to IUI. A strong fetal cortisol response correlated with fetal inflammation. Mechanisms by which neonatal lung disease may be modified by IUI may include a direct effect of pro-inflammatory cytokines or an increase in fetal cortisol