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Title: The use of antibiotics and probiotics to prevent preterm birth
Author: Othman, Mohammad Salahuddin
ISNI:       0000 0004 2702 0837
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2009
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Pretenn birth is the most important cause of neonatal death and morbidity, with immense costs to families and health care systems. In spite of advances in obstetric care, approximately thirteen million pretenn birth occur annually world wide. Preterm birth is multifactorial in origin, but in the last 20 years, infection has emerged as an important and frequent cause of pretenn labour and birth. The most common pathway of infection into the uterus is the ascending route from the vagina. Since infection is associated with pretenn birth and there are adverse effects from antibiotic use, it is logical to ask whether antibiotics can prevent prematurity. Do antibiotics given systemically (for example: for urinary infection or dental caries) which have the potential to alter vaginal flora, decrease the incidence of pretenn birth? To assess the effectiveness of antibiotics given for any reason to prevent pretenn labour an umbrella review was carried out to assess systematically clinical trials of antibiotics and other relevant systematic reviews. Forty five clinical trials were included in the meta-analysis. The results indicated that the use of antibiotics during pregnancy for any reason had no effect in preventing pretenn labour before 34 weeks and this is accompanied by an increase in the maternal adverse effects. Another important finding was that metronidazole may increase the risk of pretenn labour. Antibiotics were also shown to be not effective in preventing neonatal morbidity associated with prematurity. A historical review was carried out as piece of methodological work to assess the numbers and quality of randomised clinical trials. The results confirmed our hypothesis that the number and quality of randomised clinical trials of antibiotics during pregnancy improved since the sixties. Probiotics may be a potential preventitive treatment for preterm labour. Normal vaginal flora is dominated by Lactobacilli which is associated with reduced risk of bacterial vaginosis and urinary tract infection. Probiotics consist of live Lactobacilli that are freeze dried with or with out sugar. Probiotic Lactobacilli displace bacteria, block pathogen attachment to vaginal epithelium and produce bacteriocins which inhibit pathogen multiplication. More importantly, lactobacilli produce hydrogen peroxide which maintains vaginal acidity - an unfavourable environment for pathogens. Probiotics have been shown to modulate the immune response by interfering with the inflammatory cascade that leads to preterm labour and birth. The administration of probiotics has been shown to be safe and effective in reducing and treating urogenital infections in non-pregnant populations. It is logical to ask whether probiotic therapy can restore the normal flora and may decrease the incidence of preterm birth? To assess probiotic's effectiveness and safety for preventing preterm labour and birth a Cochrane review was conducted. Four trials were assessed for inclusion in the review. One trial started in February 2005 and is still ongoing. One trial was excluded because there were no data to be extracted from the article. Of the two trials included in the review, one enrolled women after 34 weeks of pregnancy using oral fermented milk as probiotic, while the other study utilised commercially available yogurt to be used vaginally by women diagnosed with bacterial vaginosis in early pregnancy. Reduction in genital infection was the only prespecified clinical outcome for which the data were available. Results of this review showed that although the use of probiotics appears to treat vaginal infections in pregnancy, there are currently insufficient data from trials to assess impact on preterm birth and its complications. Given the lack of evidence highlighted in the Cochrane review, there was a compelling case to conduct a randomised controlled trial to test whether probiotics are effective in preventing preterm labour and birth or not. An exploratory trial was to be an important part of this thesis. A trial protocol was prepared but it was not approved by the MHRA. MHRA authorisation was refused because probiotics are licensed as food supplements and only medicinal products can be used in clinical trials. Given the failure to get MHRA approval, a decision was taken to perform an exploratory study to investigate if cervical immunology and morphology would better refme high risk status for future clinical trials. The hypothesis behind this cervix study is that a defective cervical barrier is a major cause of preterm labour. This hypothesis was assessed immunologically by using flow cytometry to quantity leucocytes subpopulation in the cervix, morphologically by cervical length and volume as assessed by 3D ultrasound, and the cervical blood circulation was assessed by 3D ultrasound with power Doppler in patients at high risk of preterm labour. Immunologically, the most prevalent cervical leukocyte was the macrophage. Macrophages and the rest of leukocyte types in general were fewer in high risk patients than in normal pregnant controls, but this difference did not reach statistical significance. This could be due to the sample size. Or this could be due to the collection of the cervical samples very early in pregnancy. The influx of leukocytes is expected later in pregnancy or at the time of cervical ripening prior to labour. Morphologically, this study showed a significant association between cervical length and preterm labour, but not cervical volume. This could be due to the sample size or due to the difficulty of estimating cervical volume. Also, there is increase in the vascularisation of the cervix in preterm labour patients and this could be due to the small sample size, difficulty of defining the cervix landmarks or premature remodelling of cervical architecture since all these women had previous histories of preterm labour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available