Twin-twin transfusion syndrome – investigation of the effect of fetoscopic laser ablation and reviews of diagnosis and treatment

Fox, Caroline Elizabeth (2014). Twin-twin transfusion syndrome – investigation of the effect of fetoscopic laser ablation and reviews of diagnosis and treatment. University of Birmingham. M.D.

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The first aim of this thesis was to systematically review the literature to determine the diagnostic accuracy of ultrasound in the first trimester to screen for twin-twin transfusion syndrome (TTTS) and predict its outcome after diagnosis, as well as the effectiveness of its two main treatments. Quantitative analysis revealed that a crown rump discordance or abnormal nuchal translucency in the first trimester was useful to screen for TTTS, but after diagnosis no single test could reliably predict outcome. In both situations a negative test was not reliable for excluding TTTS or a poor outcome. Fetoscopic laser ablation (FLA) is likely to confer a benefit both in terms of survival and morbidity in survivors.
The second aim was to determine what happened to biological markers in TTTS and how FLA affected them. It appeared that TTTS may be associated with abnormal placentation as maternal serum α-fetoprotein (MSAFP) approximately doubled and free β-human chorionic gonadotrophin (f- β hCG) tripled. The balance of angiogenic factors i.e. 2-3 fold increased angiogenin 2 and 1.5 fold increased soluble vascular endothelial growth factor receptor 1 appeared to favour angiogenesis in response to hypoxia or ischaemia in TTTS. Maternal cell-free messenger RNA was reliably detected and showed similar alteration in angiogenic markers. Interestingly, TTTS was associated with minimal changes in cytokine levels. In response to FLA there was an increase in transplacental haemorrhage (MSAFP increased 445%) rather than trophoblast destruction (f-hCG unchanged) as well as a transient increase in some anti-angiogenic markers. Although, in general angiogenic factors and cytokines are altered little by this therapy. If the biomarker changes detected precede the onset of clinically apparent disease, they may be useful to improve the performance of first trimester ultrasound screening. Composite tests may be more useful to predict outcome and FLA should continue to be utilised to reduce morbidity.

Type of Work: Thesis (Higher Doctorates > M.D.)
Award Type: Higher Doctorates > M.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: None/not applicable
Subjects: R Medicine > R Medicine (General)


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