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Title: Universal antenatal screening for group B streptococcus colonisation in the UK
Author: Seedat, Farah
ISNI:       0000 0004 7425 5460
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2017
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Background: Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis. Currently, the UK recommends against universal antenatal screening to prevent early-onset GBS disease (EOGBS, < 7 days). Key gaps around GBS natural history, harms from screening and a lack of high-quality data to prove screening effectiveness make it difficult to ensure the benefits of GBS screening outweigh the harms. There is also a wider gap on policy-making processes for screening. The overall aim of this thesis is to address these gaps and examine whether the UK should introduce universal GBS screening as a result. Methods: In addition to a literature review, I used two approaches: systematic review/metaanalysis and ecological trend analysis. The systematic reviews synthesised evidence on the screening policy-making processes, mechanisms of EOGBS and adverse events from intrapartum antibiotic prophylaxis (IAP) to prevent EOGBS. In the absence of RCTs, I combined ecological data on the benefits and harms of GBS screening, then analysed their trends across time compared with other prevention strategies in regression analyses adjusting for context differences. Results: Evidence from 17 countries showed that most GBS screening recommendations were not developed by screening organisations and it is not known whether screening principles and the likely unseen harms of GBS screening were considered. Seventeen studies revealed that we do not fully understand the natural history of why some mothers, but not others, transmit GBS to their neonates, or which neonates will develop EOGBS. There was consistent evidence that heavy bacterial load was associated with transmission and progression to EOGBS. Neonates colonised with serotype III were also twice as likely to develop EOGBS compared with serotype Ia and II. However, the evidence was old and at high risk of bias. The selective culture test at 35 to 37 weeks gestation is not an accurate predictor of EOGBS and at least 99% of screen-positive and treated mothers (and their neonates) would be over-treated. Seventeen observational studies and 13 RCTs showed a wide range of potential harms from IAP, including cerebral palsy, functional impairment and antibiotic resistance. However, there was little high-quality and applicable evidence to quantify the frequency of adverse events. The three ecological trend analyses combining data from 59 geographical areas showed that EOGBS incidence decreased by approximately 0.02 per 1,000 livebirths per year in areas that most recently reported GBS screening, whereas it increased by approximately 0.01 to 0.02 per 1,000 livebirths in areas most recently reporting risk-based prevention. Areas that recently did not have GBS prevention displayed conflicting EOGBS trends. By contrast, there was no evidence that screening impacted annual early-onset sepsis trends compared with other, or no prevention strategies; however, this study did not have a sufficient sample size. The was no harmful impact of GBS screening on LOGBS trends compared with other, or no prevention. There was also no evidence that screening increased early-onset E. coli incidence and the percentage of GBS cases resistant to clindamycin and erythromycin, compared with risk-based or no prevention; again, these analyses did not have a sufficient sample size. The findings of these studies must be treated with caution as some results may be due to low statistical power and others were unstable across analyses. The findings also contain numerous limitations as covariates were poorly collected in most countries. Therefore, the evidence on the benefits and harms of universal GBS screening remains inconclusive. Conclusion: GBS infection is an important health condition and its persistence, poor screening tests and the IAP harms stress the need for a better understanding of the natural history of GBS and more effective prevention. Evidence on the harms and benefits of GBS screening is limited, therefore, screening should not be introduced in the UK. Ecological trend analysis was not an adequate method to inform GBS screening decisions, however, it may be useful for screening decisions on other conditions.
Supervisor: Not available Sponsor: Economic and Social Research Council ; UK National Screening Committee
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RA0421 Public health. Hygiene. Preventive Medicine ; RG Gynecology and obstetrics