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Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder diagnosed in childhood. It is largely accepted that ADHD is a product of gene-environment interactions and method of infant feeding has been proposed as a factor influencing the expression and/or severity of ADHD. The objectives of this study were to determine the relationship between infant feeding (i.e. formula feeding or breast feeding) and subsequent hyperactive/inattentive (H/I) behaviours and ADHD diagnosis and if the relationship between infant feeding and academic performance is moderated by H/I scale score. This study used data from the 2000/1, 2002/3, 2006/7 and 2008/9 cycles of the National Longitudinal Survey of Children and Youth (NLSCY) (n= 3,895) to follow children longitudinally from the age of 0 to 1 years old to 6 to 7 years old. Infant feeding at 0 to 1 years old, and child H/I score, ADHD diagnosis and academic performance scores at 6 to 7 years old were reported by the biological mother. Multivariable logistic and linear regression were used to determine the relationship between infant feeding and H/I score, ADHD and academic performance adjusting for a range of sociodemographic, birth and home environment factors. Breastfeeding for more than 12 months was found to be significantly associated with decreased H/I scale scores in the most adjusted model (OR=0.3; 95% CI 0.2-0.8, p<0.01). Infant feeding was not associated with ADHD diagnosis and there was no moderating effect of the H/I score on the relationship between breastfeeding and academic performance. A small proportion of mothers breastfeed beyond one year in Canada and this study shows that there might be important child benefits incurred by breastfeeding for longer than 12 months. / May 2016

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The aims were to critically assess methodologies relevant to PK studies tailored to the needs of children. In view of the significant challenges associated with pain control in children paracetamol and ketorolac were selected for the study. Methods: Two bioanalytical methods were developed to measure paracetamol and enantiomers of ketorolac in paediatric samples, to support PK studies of IV paracetamol and ketorolac in children less than 16 years old. All studies had ethical approval and clinical trial authorisation. Results: The developed bioanalytical methods were reliable, requiring only 30 μl of blood for paracetamol, and 50 μl of plasma for ketorolac. Paracetamol concentrations from finger-prick samples in the first hour post dose were greater than from venous samples (349% at 15, 72% at 30, and 9.3% at 60minutes). There were no differences in median CL (0.41, 0.31 and 0.37 1h^-1kg^-1), V_d (0.90, 0.95 and 0.90 1/kg) and t_1/2 (1.7, 2.2 and 1.6 h) among the respective age groups 2-5, 6-10 and 11-15 years. All PK parameters were different for R- and S- ketorolac, with V_d and CL of R- being lower than those of S- (0.12 vs. 0.17 1/kg; 0.017 vs. 0.049 1/h/kg). The median half-life of R- was longer than that of S- (5.0 vs. 3.1 h, <i>P =</i> 0.043). Conclusions: Bioanalytical method did not limit PK trials in children. Sampling method affected PK parameter estimation, and prolonging cannula patency was the most challenging procedure during blood sampling. The PK of IV paracetamol was similar in children 2-15 years old, and the enantiomers of ketorolac were found to have different PKs in children.

The unprecedented scale of health sector reform in the course of radical political transformation in post-apartheid South Africa is well-documented. This thesis examines child health policy reform as a crucial part of this process. The goals of broader health sector reform were to improve the overall health status of citizens, in particular those most vulnerable, and eliminate inequities in health service provision and health status outcomes. Although children were accorded explicit prioritisation during this time, child health indicators remain poor and some have worsened. Amidst the documented explanations for the poor progress with child health indicators, the specific role and contribution of child health policies had not been interrogated. The thesis examines the development, design and implementation of national child health policies, with particular focus on equity. The National School Health Policy serves as a case-study for the analysis. Three complementary policy analysis frameworks guide the enquiry. Findings are based on a documentary analysis of key policies and 81 qualitative interviews with national policy makers and managers, provincial and district managers, and service providers in three socioeconomically different provinces of South Africa. The common assertion by South African health system analysts, that "policies are good, but implementation is poor", is refuted by this research. The findings show that child health policies have many deficiencies in their design and development. These "poor policies" contribute to inadequate child health service provision, which in turn have a bearing on poor child health outcomes. In particular the failure in clearly defining and conceptualising equity in policy development and design contributed to the absence of equity considerations in the implementation phase. The explanations for these policy failures include: lack of strategic direction for child health services; poor policy making capacity; a lack of clear policy translation; and the diverse politics, power and passion of policy actors. Broader health system factors, such as an immature and poorly functioning district health system, compound these policy failures. The thesis deepens the understanding of child health policy reform through a retrospective policy analysis and so contributes to the body of knowledge on policy reform in South Africa and in low- and middle-income countries more generally.

South Africa experienced a major measles outbreak from 2009 to 2011. This study was done to describe the patient profile of children admitted with measles for a period during the outbreak. It includes patient demographics, clinical presentation, management and outcomes. An audit of the notification system was also performed.

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Background and Aim: Preterm infants frequently receive blood transfusion (BT) during their stay in the neonatal unit. The aim of this study was to measure the effect of BT on cerebral and gut blood flow and oxygenation in preterm infants in relation to postnatal age. Another aim of the study was also to investigate the influence of measured pre-transfusion RCV on gut perfusion in preterm infants receiving first blood transfusion for clinical indication using NIRS and Doppler ultrasound scan. Methods: Preterm infants admitted to neonatal unit were recruited to three postnatal age groups: 1 to 7 days (group 1; n=20), 8 to 28 days (group 2; n=21) & ≥29 days of life (group 3; n=18). Pre and post-BT Anterior Cerebral artery (ACA) Time Averaged Mean Velocity (TAMV) and Superior Vena Cava (SVC) flow were measured to assess cerebral blood flow. Pre and post-BT Superior mesenteric artery (SMA) peak systolic velocity was measured to assess gut or splanchnic blood flow. Cerebral and gut Tissue Haemoglobin Index (THI), Oxygenation Index (TOI) were measured from 15-20 minutes before to 15-20 minutes post-BT using NIRS. Cerebral and gut fractional tissue oxygen extraction (FTOE) was calculated from the TOI and saturation of oxygen (SaO2). Vital parameters and blood pressure (BP) were also measured continuously from overhead monitors. Pretransfusion red cell volume (RCV) was measured by fetal haemoglobin (HbF) dilution method and compared with the cerebral and gut perfusion and oxygenation changes following blood transfusion. The cerebral and gut perfusion and oxygenation were also measured over a three hour period in 12 control infants not receiving blood transfusion. Results: There were 71 infants included in the study; of them 59 were study infants receiving blood transfusion and 12 were control infants. Amongst the vital parameters, mean BP increased significantly, and there was no significant change in heart rate (HR), respiratory rate (RR) or SaO2 following BT. Pre-transfusion ACA TAMV was higher in Group 2 and 3 compared to Group 1 (p < 0.001) which remained significant after multivariate analysis (p < 0.05). Pretransfusion ACA TAMV decreased significantly (p≤0.04) in all 3 postnatal age groups; pre-transfusion SVC flow decreased significantly in Group 1 (p=0.03) and Group 3 (p < 0.001) following transfusion. Pre-transfusion cTOI was significantly lower in Group 3 compared to Group 1 (p=0.02) which remained significant after multivariate analysis (p < 0.011). The cTHI (p < 0.001) and cTOI (p < 0.05) increased significantly post-transfusion in all three postnatal age groups. PDA had no effect on these measurements. Pre-transfusion SMA PSV increased with postnatal age (group 3 vs. group 1: p < 0.01; CI 0.6 to 0.1), proportion of feeds (> 50% feeds: 0.91±0.4 vs. < 50% feeds: 0.71±0.4 m/sec, p < 0.01); and decreased with presence of PDA (closed PDA: 0.94±0.4 vs. open PDA: 0.68±0.3 m/sec, p=0.006, CI 0.07 to 0.45); but remained unaltered following transfusion. The pre-transfusion sTOI varied with postnatal age (Group 2:44.6 vs. Group1: 36.7%; p=0.03, CI -0.6 to -15.2) on univariate analysis but was not significantly different on multivariate analysis; pre-transfusion sTOI was not influenced by feeds or presence of PDA. The sTHI and sTOI increased (p < 0.01) and sFTOE decreased (p < 0.01) significantly following transfusion in all postnatal age groups.