Parents lived experience and multi-omic exploration of Placenta Accreta Spectrum

Placenta Accreta Spectrum (PAS) is a rare and poorly understood obstetric condition. It is an important cause of global maternal morbidity and mortality. Although rare, the incidence has increased due to the rise in women giving birth by Caesarean delivery. Several aspects of PAS are investigated in this thesis. These are broadly divided into an in-depth exploration of the lived experience of women with a history of PAS and their partners, and a multi-omic approach to investigate the pathophysiology and prognostic prenatal imaging of severe histopathological subtypes. The lived experience of those impacted by PAS was explored through in depth interviews taking an interpretive phenomenological analysis approach, with both women and their partners included. Themes developed from interviews related to three distinct timepoints, namely “living with PAS” which included the pregnancy and birth, and “living beyond PAS”, which describes the postnatal and long term experience. Interviews highlighted the significant emotional toll of a pregnancy complicated by PAS, which lasted many months and years after the birth. Furthermore, we explored the experience of anaesthesia of both women and healthcare providers involved in PAS care through two descriptive survey studies. Based on participants responses, we present recommendations for providing family centred care. The qualitative lived experience research highlighted the significant and prolonged psychological sequalae of a pregnancy complicated by PAS. Therefore, we identified a need for improved risk stratification models for PAS to facilitate patient counselling and appropriate care pathways, which aim to reduce the maternal morbidity and associated psychological burden we reported. Through several multi-omic experiments including radiomics of T2-weighted magnetic resonance imaging, and spatial transcriptomics and proteomics of the maternal-fetal interface, we explore prenatal risk stratification and PAS pathophysiology. These experiments were performed using data obtained prospectively as part of a PAS database and biobank, which runs in parallel with an established multi-disciplinary PAS service between two large tertiary referral hospitals. We found particular radiomic features are associated with severe clinical and histopathological subtypes of PAS. Using spatial transcriptomics and proteomics, we identified differentially expressed genes and proteins in these severe histopathological subtypes were involved in biological processes including extracellular matrix degradation, immune changes and regulation of trophoblast invasion. These data suggest these cases have a particular biological phenotype, and contribute new findings to our understanding of the pathophysiology of these severe cases. In summary, this thesis provides an in-depth exploration of the lived experience of women and their partners of a pregnancy complicated by PAS, an area which previously received little attention. The multi-omic experiments provide new insights into imaging biomarkers and biological changes characteristic of severe histopathological PAS subtypes, which may form the building blocks of a future risk stratification model aiming to reduce the maternal morbidity and psychological trauma of a pregnancy complicated by PAS.