- Title
- Relationships between in utero exposures, cord blood immune cell populations and early life lung function
- Creator
- Martins Costa Gomes, Gabriela
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2022
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- This thesis contributed to and was crucial for understanding the effect of maternal environmental, cellular and genetic factors on cord blood cells from babies born to asthmatic mothers and how changes in cell populations are linked with the early development of the infant lung and its function. In this research, I had the unique opportunity to quantify blood biomarkers and investigate the immunity of the newborn prior to respiratory disease onset in a high-risk population with comprehensive clinical follow-up of the mother through pregnancy and the child in early life. The first research chapter (chapter 3) shows that maternal inhaled air pollutants during pregnancy are associated with changes in the cord blood cell profile. Early exposure to air pollution may affect the newborn immune system, leading to long-term effects on lung function and potentially affecting respiratory health throughout life. The second research chapter (chapter 4) investigated whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines sites in cord blood, which themselves predicted birthweight. This is the first study to report potential mediation of cord blood deoxyribonucleic acid methylation linking eCO measurements during early pregnancy with birthweight. The third research chapter (chapter 5) presents a study where higher chemoattractant receptor-homologous molecule (CRTh2high) within innate lymphoid cells type 2 (ILC2) numbers, and reduced lung function at six weeks may be surrogate markers for the strong predisposition conferred by maternal asthma on the development of asthma and wheeze in childhood. This is the first study to identify that CRTh2high ILC2 cells in cord blood are associated with infant lung function. Fetal CRTh2high ILC2 cells were characterised by two distinct analysis methodologies and were associated with poorer infant lung function at six weeks of age, measured by an integrated output of the entire respiratory system (tPTEF/tE%) and by lung ventilation inhomogeneities. The fourth research chapter (chapter 6) presents a study where maternal asthma is associated with lower lung function in male babies, which may have life-long implications on their lung function trajectories and future risk for wheeze and asthma. In this research, I had the unique opportunity to analyse the combined data from two large prospective multicentre birth cohorts to investigate the effect of a history of maternal asthma on lung function in early life assessed using tidal breathing flow-volume loop analysis. Together, these studies have investigated the influence that environmental and molecular factors have on cord blood composition and its further influence on lung development and function. Prenatal factors are associated with changes in cord blood cells and influence fetal development. Further, cord blood cells that were previously influenced by maternal smoking and/or environmental factors are themselves associated with decreased lung function and may influence the development of infant respiratory disease. By studying cord blood in this thesis and on the basis of previous research, I suggest that in utero programming of airway responses has a role in childhood asthma risk.
- Subject
- asthma; maternal exposure; in utero exposures; cord blood; prenatal risk factors; infant lung function; CRTh2 ILC2; air pollutants; tobacco use; immune cells
- Identifier
- http://hdl.handle.net/1959.13/1468402
- Identifier
- uon:48046
- Rights
- Copyright 2022 Gabriela Martins Costa Gomes
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 4 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 629 KB | Adobe Acrobat PDF | View Details Download |