A research report Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Masters of Science in Epidemiology and Biostatistics 15 June 2017, Johannesburg, South Africa / Introduction: Worldwide, cardiovascular diseases are the number one cause of death with a three-quarter of cardiovascular disease deaths occurring in low-middle income countries. Childhood social adversity as a proxy of psychosocial stress has been found to be associated with later adult risk of cardiovascular diseases, with studies investigating the mechanisms linking early exposure to social adversity and later risk of cardiovascular diseases. CRP has been a biomarker that is found to be associated with the risk of cardiovascular diseases in adults, however, the association between CRP levels in adolescence and social adversity in children (prenatal and postnatal periods) is not well documented. Assessing the association between childhood social adversity and CRP levels in late adolescent period will encourage further studies to explore whether high levels of CRP tracks from adolescence to adulthood and ultimately increase the risk of cardiovascular diseases in the South African context. Aim: This study aims to determine the association between social adversity from the prenatal period to two years of age and the level of CRP in the same cohort at the age of 18 (from 1990 to 2008) Methods: The study was a secondary data analysis of the Birth to Twenty longitudinal study which recruited 3273 singleton children. Four measures (prenatal and postnatal (0-2 years)) of social adversity in children (which are maternal prenatal stress, maternal prenatal general feeling, maternal postnatal depression and household socioeconomic status) were used. The high-sensitivity C-reactive protein was grouped into tertiles (1st tertile: hs-CRP<0.48 mg/l, 2nd tertile: 0.48<hs-CRP<1.16, 3rd tertile: hs-CRP>1.16) and multinomial logistic regressions were therefore used to assess the association between childhood social adversities and tertiles of high sensitivity C-reactive protein. Results: The primary Birth to Twenty longitudinal study had more than 35% loss to follow-up at 18 years. No statistically significant difference (p>0.05) was found on demographic variables of those included in the analysis compared to those not included (due to current study criteria and loss to follow-up). A unit increase in maternal marital stress score during pregnancy was associated with an increase by 2.23 (p=0.03) in the relative risk of the youth being in the 2nd high sensitivity C-reactive protein tertile in comparison to being in the 1st high sensitivity C-reactive protein tertile. For a unit increase in maternal family stress score, the relative risk of the youth being in the 3rd high sensitivity C-reactive protein is 1.61 (p=0.04) times greater in comparison to being in the 1st high sensitivity C-reactive protein tertile. No statistically significant associations were observed among the other categories of social adversity (p>0.05) and high sensitivity C-reactive proteins. Low social support to mothers during pregnancy was associated with elevated high-sensitivity C-reactive protein in adolescents. Conclusion: A positive association was observed between a prenatal measure of social adversity and elevated high-sensitivity C-reactive protein; In particular, increased levels of family and relationship-related prenatal stress during pregnancy is a predictor of elevated high-sensitivity C-reactive protein in children. This study contributes to the empirical evidence from studies done in animals suggesting that early development of adult health complication starts during the intrauterine period. The findings of this study will further guide intervention research to target conditions during intrauterine period in preventing adult health complications. / MT2017

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Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 208-220).

Thesis (MMedVet (Med) (Veterinary Science))--University of Pretoria, 2009. / Includes bibliographical references. Also available in print format.

It has recently been shown that elevated C-reactive protein (CRP) levels are associated with a blunted systemic endothelial vasodilator function, indicative of a systemic inflammatory response. It has also been recognized that inflammation may contribute to all stages of the atherosclerotic process. Several prospective studies have shown that the level of CRP is a strong predictor of future myocardial dysfunction, stroke, peripheral arterial disease, and vascular death among individuals without known cardiovascular disease. CRP is also found in association with the senile plaques and neurofibrillary tangles of Alzheimer disease. Hence, determination of the blood serum levels of CRP is of a great clinical importance. / This thesis discusses the results on the development of two electrochemical immunosensors: (i) the avidin (model) immunosensor, and (ii) the CRP immunosensor. The suitability of using a range of electrochemical techniques in probing antibody-antigen interactions was also investigated. / It was shown that a gold working electrode surface could be successfully modified by covalent binding of NHS-biotin to a self-assembled-monolayer of cystamine dihydrochloride, resulting in the construction of the avidin immunosensor. Avidin could then bind to this immunosensor (biotinated electrode) and detected using the electrochemical techniques of cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV) and chronoamperometry (CA). It was also shown that polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) can be used to qualitatively and quantitatively characterize avidin bound to the immunosensor. The results demonstrated that all experimental techniques used were suitable in characterizing with high sensitivity the avidin-biotin interaction, and the amount of avidin in solution. The avidin calibration curves showed high linearity in concentrations ranging from 10-10 to 5 x 10-7 M. AFM imaging confirmed that avidin forms clusters upon binding to the immunosensor, with the cluster size ranging between 28 and 33 nm. The avidin-biotin binding constant was determined to be 3.09 x 1012 M-1 . It was also determined that the avidin-biotin equilibrium is reached in ca. 20 minutes. / The CRP immunosensor was then designed on the basis of the avidin immunosensor architecture. Using a range of electrochemical techniques and PM-IRRAS, it was demonstrated that a gold electrode surface could be functionalized by CRP antibodies, covalently attached to the surface through a duplex cystamine/glutaraldehyde layer. This architecture represents the CRP immunosensor. It was then shown that CRP antigen specifically binds to the CRP immunosensor (i.e. the immobilized CRP antibody). This interaction could be characterized with high sensitivity using the electrochemical techniques of CV, EIS, DPV and CA. The CRP concentration range investigated was 10-14 to 10-8 M. A linear calibration plot was obtained. The CRP antibody-antigen binding constant was determined to be 3+/-1 x 108 M-1. The corresponding binding equilibrium is reached in ca. 10 minutes. The results show that the developed CRP immunosensor is a good candidate for further research towards developing a commercial CRP immunosensor.

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Call number: LD2668 .T4 1964 D57 / Master of Science

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