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https://hdl.handle.net/2440/112815
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Type: | Theses |
Title: | Diet and DNA damage in infants: the DADHI study |
Author: | Dass Singh, Mansi |
Issue Date: | 2017 |
School/Discipline: | Adelaide Medical School |
Abstract: | Accumulation of DNA damage during infancy may increase risk of accelerated ageing and degenerative diseases such as cancers. Pregnancy is understood to be a state of high expression of inflammatory genes. It may be possible that infants, born to women at high risk of preeclampsia (PE): a condition associated with increased oxidative stress, inflammation and altered gene expression, may have increased DNA damage compared with infants born to women at low risk of developing PE. However, currently there are no baseline DNA damage data for infants born to mothers in relation to their low/high risk of developing PE in Australia. This PhD project had four phases: *A systematic literature search was conducted with the aim to explore the literature and identify knowledge gaps in the role of folate in the etiology and prevention of PE. The review found (i) deficiency of folate and other B vitamins, with higher concentrations of oxidative stress biomarkers in maternal tissues and body fluids of women with PE when compared with women at low risk of PE, and (ii) some of this dysregulation may be balanced epigenetically with oral intake of methyl donors including folate and vitamins B2. *A prospective cohort study was conducted; ‘Diet and DNA damage in Infants’ (The DADHI study), with the aim to study: (i) DNA damage, cytostasis, and cytotoxicity utilizing a comprehensive Cytokinesis block micronucleus cytome (CBMN-Cyt) assay in lymphocyte of Australian born infants [at birth (cord blood, n=82), 3 (n=64) and 6 months (n=53) (heel prick blood)] of mothers at low risk of PE (ii) association of maternal factors and infant birth outcomes with CBMN-Cyt biomarkers (iii) whether mode of feeding influences CBMN-Cyt biomarkers in infants at 3 and 6 months after birth This study found significant positive associations of infant birth outcomes (gestation age, birth weight, head circumference, birth length and APGAR score) and maternal anthropometric variables with CBMN-Cyt biomarkers, suggesting possible genotoxic effects on infant’s DNA by metabolic processes that promote excessive growth and higher body mass index. * The next aim was to determine (i) association of blood micronutrient status with CBMN-Cyt biomarkers in cord blood at birth and infant’s blood at 3 and 6 months (ii) whether mode of feeding influences blood micronutrient status at 3 and 6 months after birth The study observed significant associations of DNA damage biomarkers with infant birth outcomes and micronutrient status suggesting that both under and oversufficiency of some nutrients may be detrimental for cell growth and repair. *A pilot project [in ‘Investigations in the Folic acid clinical trial’ (INFACT study)] with the aim to collect DNA damage data in the cord blood collected from infants of women at increased risk of developing PE. The study found that (i) maternal anthropometric variables may influence infant birth outcomes, mainly birth size, and (ii) INFACT cases (n=10) had higher frequency of CBMN-Cyt biomarkers compared with gender and birth weight matched DADHI controls (n=15). These preliminary data could be used to form the design of larger studies required to confirm the association of maternal factors and PE with DNA damage in the infants at birth and later in life in the first 1000 days. |
Advisor: | Hague, William Fenech, Michael Felix Thomas, Philip |
Dissertation Note: | Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2017. |
Keywords: | micronuclei DNA damage infant birth outcomes cord blood lymphocytes cytotoxicity |
Provenance: | This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals |
DOI: | 10.4225/55/5b209f8198bb1 |
Appears in Collections: | Research Theses |
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01front.pdf | 736.29 kB | Adobe PDF | View/Open | |
02whole.pdf | 6.32 MB | Adobe PDF | View/Open | |
Permissions Restricted Access | Library staff access only | 360.16 kB | Adobe PDF | View/Open |
Restricted Restricted Access | Library staff access only | 6.42 MB | Adobe PDF | View/Open |
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