Despite the scientific, technological and surgical improvements of the past 50 years organ dysfunction following elective paediatric cardiac surgery utilising cardiopulmonary bypass continues to account for increased complications, often leading to a protracted course in hospital with a longer stay in intensive care and the potential for irreversible organ damage long term. Furthermore, paediatric cardiac surgeons are routinely undertaking more complex operations with a shift from palliation to early correction. This has resulted in younger children being subjected to longer periods on the bypass machine with increased effects on vital organs. This thesis describes two clinical studies designed to further assess and characterise peri-operative cardiac, renal and pulmonary function in children undergoing elective cardiac repair at a tertiary referral centre in Scotland, UK. In the first instance a prospective, observational study was undertaken in forty-five children to examine the use of tissue Doppler imaging in the assessment of peri-operative cardiac function, its relationship to myocardial injury and clinical outcome. Tissue Doppler parameters were obtained using a Vivid 7 ultrasound scanner with a 7-MHz probe pre-operatively, on admission to paediatric intensive care and on day one. Myocardial injury was assessed using Troponin-I on the first post-operative day by a commercially available chemiluminescent immunoassay. In twenty children within this group peri-operative renal function was also investigated using standard estimates of glomerular filtration rate, namely creatinine clearance measured by the kinetic Jaffe method during the first and second twelve hour post-operative periods, in comparison to serum creatinine and the novel biomarker cystatin C. Routine plasma retained pre-operatively and on days 0, 1, 2 and 3 post-operatively was used to measure serum cystatin C and creatinine using a particle-enhanced nephelometric immunoassay and the Roche Creatinine Plus enzymatic assay respectively. The association between cystatin C and recorded perfusion parameters including bypass duration, pump flow, haematocrit, oxygen delivery and Troponin-I was investigated. Peri-operative pulmonary function was evaluated through a phase IV, randomised, double-blind, placebo controlled trial. In total, twenty four children were randomised to receive oral sildenafil or equivalent volume placebo four times the day before surgery. Blood samples were collected peri-operatively to measure serum cyclic guanosine monophosphate with a commercially available competitive enzyme immunoassay. Haemodynamic data and echocardiography were acquired at two and twenty four hours post-operatively including pulmonary vascular resistance index and bi-ventricular contractility. Post-operative oxygenation was also determined at the same time by oxygen delivery and oxygenation index. In Chapter 2, peri-operative cardiac function as assessed by tissue Doppler imaging was examined. The results of this study demonstrated that pre-operatively, bi-ventricular systolic function in the study group was reduced compared with normal controls, displaying a significant step-wise decrease with increasing complexity of lesion. This picture persisted post-operatively predominantly in the right ventricle and was significantly associated with the extent of myocardial injury. Impaired peri-operative left ventricular function correlated with clinical outcomes. In Chapter 3, peri-operative renal function as assessed by cystatin C and its association with parameters of perfusion was examined. The results of this study demonstrated that in comparison to serum creatinine, cystatin C had a superior correlation with glomerular filtration rate in the early post-operative period. An elevated level of this biomarker was significantly associated with bypass duration, minimum pump flow and post-operative myocardial injury. Haematocrit was not directly linked to renal dysfunction in this study although evidence of a critical dysoxic threshold within the kidney was suggested indirectly through oxygen delivery calculations. In Chapter 4, peri-operative pulmonary function and vascular reactivity in association with the pre-operative administration of oral sildenafil (0.5mg/kg, six hourly) was examined. The results of this trial demonstrated that compared to placebo, pre-operative sildenafil resulted in modest elevations of serum cyclic guanosine monophosphate, limited effects on pulmonary vascular resistance index, significant reductions in peri-operative bi-ventricular contractility, significant reductions in post-operative oxygen delivery and a trend for increasing ventilatory support. In summary, the current thesis has demonstrated that in children undergoing corrective cardiac surgery peri-operative bi-ventricular function can be accurately assessed by tissue Doppler imaging which to date has had limited use in this patient group. With regards to renal function, cystatin C was shown to be a better estimate of glomerular filtration rate and a more sensitive marker of early renal dysfunction in children after surgery. Furthermore, cystatin C identified a transient post-operative renal impairment, the magnitude of which was associated with duration of bypass, pump flow and myocardial injury. In relation to pulmonary function, this research identified that pre-operative administration of oral sildenafil to children undergoing cardiac surgery produced limited effects on pulmonary vascular resistance but was associated with reduced ventricular contractility and post-operative oxygenation raising significant concerns over its routine clinical use.

‘FRIENDS for Life’ is a manualised, 10 week, Cognitive Behavioural Therapy (CBT) based programme designed to be run in school and community settings (Barrett, 2010b). The programme has been introduced to schools within the local authority where the researcher is based via the local Targeted Mental Health in Schools (TAMHS) project. The programme is well reviewed and is recommended by the World Health Organisation for the treatment of anxiety disorders in children (World Health Organisation, 2004). Previous research has evaluated the programme when delivered in closely monitored situations with optimal implementation. The aim of this study is to evaluate the impact of FRIENDS for Life as implemented in a mainstream secondary school by school staff trained as part of the TAMHS initiative. This study makes an original contribution to the existing research base by evaluating the programme in a naturalistic, real world setting using an alternative methodology to the majority of published evaluations. Data regarding implementation of the programme was collected and analysed using activity theory. A single case experimental design was used to monitor the impact of the intervention on the emotional distress, anxiety levels and coping strategies of 5 secondary school participants (aged 11-13) who had been identified by school staff as appearing anxious. The findings suggest that participation in FRIENDS did not result in the hypothesised reductions in emotional distress, anxiety and negative coping skills or the hypothesised improvement in active coping skills. These results are discussed with regard to the finding that some aspects of the programme were not delivered. Analysis of the context using activity theory suggested that factors such as lack of time, space for delivery and experience and training impacted upon implementation. Methodological issues contributing to these findings are considered and implications for the local TAMHS project and for Educational Psychologists are discussed.

Background: Epilepsy is a serious chronic neurological disorder that has a higher incidence in children and young people (CYP) than in adults. Epilepsy negatively impacts physical and psychosocial quality of life of CYP. Good outcomes of epilepsy are associated with optimal choice of drug treatment and adequate adherence to the prescribed medicines. Research on the patterns of medication use and adherence to prescribed medicines in CYP remains limited. The long-term clinical outcomes and costs of treating epilepsy have not been extensively studied in CYP in the UK. Aim of the study: This thesis aimed to investigate the pattern of antiepileptic drug (AED) prescribing and the dynamic of medication adherence in CYP with epilepsy. The long-term clinical outcomes and direct costs of treating epilepsy in CYP were estimated at population level. Methods: This study is an observational cohort study of CYP, age 0-17 years, identified from The Health Improvement Network (THIN) primary care database from the UK between January 1988 and December 2004. Four different analyses were carried out on this cohort. First, a cross-sectional design repeated annually was employed to estimate the incidence and prevalence of epilepsy and the pattern of AED prescribing in this population. Secondly, the long-term adherence to prescribed AEDs was calculated using the medication possession ratio (MPR) method. Applying panel data analysis and the Generalised Estimating Equation (GEE) multivariate regression, factors that may have been associated with adherence to the prescribed AEDs were examined. Thirdly, seizure outcomes in terms of seizure frequency and remission of seizures and potential associated factors were assessed using the method of multiple failure survival analysis. Finally, the direct costs of treating epilepsy in CYP in primary care were estimated and stratified by the number of years after the first recording of epilepsy in THIN data. Results: Of total 528,760 CYP born on or after 1st January 1988 and registered in general practices contributed to THIN until 31st December 2004, 2020 CYP were identified who had a diagnosis of epilepsy, from under 1 up to 16.3 years of age (mean=5.6; SD=4.1). The annual incidence of epilepsy in CYP stratified by calendar years ranged from 44.4 (95% CI=31.9-61.8) to 61.2 (95% CI=50.6 -74.1) per 100,000 person-years. Incidence of epilepsy was significantly higher in children with greater socioeconomic deprivation than those with lower deprivation. Around 60% of CYP with epilepsy were prescribed monotherapy each year. Old AEDs such as carbamazepine and sodium valproate were the most frequently prescribed drugs and often prescribed as monotherapy to control epilepsy throughout 1990-2003. Prescribing of lamotrigine, a new AED, increased from 0.07 per person-years in 1992 to 2 per person-years in 2003. The calculated annual adherence to AEDs showed that around 50% of CYP adhered to at least 80% of the prescribed medications each year. Demographic characteristics of CYP were of little significance to affect adherence levels. The incidence of seizures was 0.73 (95% CI=0.71-0.75) per person-years. Incidence of seizures was higher in younger children up to 2 years and decreased with increasing age. A proportion of 94% (95% CI=93%, 96%) of CYP achieved 1 year remission of seizures, 80% (95% CI= 78%, 83%) achieved 2 years and 47% (95% CI=43%, 50%) achieved 5 years remission of seizures. The mean total direct cost associated with treating epilepsy in CYP, according to information in the general practice records that also indicated specialist and hospital care, was estimated at £ 1,153 (SD=1,808) per child in the first year following epilepsy diagnosis and at £459 (SD=1,633) per child for subsequent years. The costs of hospital care and AEDs represented the highest contribution to the total direct costs of epilepsy. The annual direct cost was significantly higher in younger children up to 2 years old. No significant difference in the annual costs was observed between CYP who adhered to at least 80% of medications and those who adhered to less than 80%. Conclusions: The incidence of epilepsy was highest in young children and CYP of higher socioeconomic deprivation. Old AEDs were most often prescribed as first-line drugs and as monotherapy to control epilepsy. Of newer AEDs, there was an increasing trend of prescribing lamotrigine and topiramate as add-on therapy. Long-term adherence to prescribed AEDs was suboptimal in one-half of CYP and positively associated with higher seizure frequency. Inpatient hospital care and drugs were the major contributors to the direct costs of treating epilepsy in CYP. Non-adherence to prescribed medicines was associated with higher hospital care costs but not with total direct costs as the medicines themselves made large contribution to the direct costs

This study presents an evaluation of the FRIENDS for Life program (Barrett, 2010) with an autism spectrum (AS) population. FRIENDS for Life is an intervention program underpinned by the principles of cognitive behavioural therapy (CBT) with a primary aim of reducing participant anxiety levels (Barrett, 2010). Existing research suggests it is an effective intervention in reducing participant anxiety levels (Briesch, Hagermoser Sanetti and Briesch, 2010) and it has been recognised by the World Health Organisation (2004) as the only evidence based program effective in reducing anxiety as a universal and targeted intervention. In recent years an evidence base for the application of CBT with children with AS has emerged, though primarily this research has been conducted in a clinical setting. Therefore this study aims to contribute to both evidence bases through implementing the FRIENDS for Life program within a new population as well as contributing to the broader evidence base evaluating the effectiveness of CBT with children with AS. The study adopted a post positivist epistemology and used a single case experimental design (SCED) to evaluate the effectiveness of the intervention in reducing the anxiety of four participants, aged nine to eleven, accessing special school provision. Anxiety was measured during a baseline, intervention and follow up phase using two weekly measures: the Paediatric Index of Emotional Distress (PI-ED;O'Connor et al, 2010); a short pupil questionnaire, and a weekly observation of participant behaviour. These measures were also triangulated with pre and post measures of anxiety using the Spence Child Anxiety Scale, child (Spence, 1997) and parent (Spence, 1999) version, and the School Anxiety Scale- Teacher Form (Lyneham, Street, Abbott and Rapee, 2008). Outcomes from the SCED showed that for all four pupils there was a significant decrease in anxiety from baseline to follow up on at least one weekly measure of anxiety, indicating a delayed effect on anxiety. The parent, child and teacher report triangulation measures suggested there was no significant change in anxiety post intervention. When considering outcomes, several key limitations to the study's design and implementation were taken into account including threats to construct validity and missing data in the intervention phase for two participants. The study concludes with support for the positive impact on participant anxiety as a result of the FRIENDS for Life intervention and recommendations are made for further investigation of the use of CBT interventions in schools with an AS population.

Bakgrund: Årligen insjuknar runt 250-300 barn och unga i Sverige i cancer. Att som ung drabbas av en svår sjukdom är en ny och omvälvande situation som påverkar hela livet för både den drabbade och alla andra i dennes närhet. Sjuksköterskans kunskaper om erfarenheter av att leva med cancer kan förhoppningsvis leda till omvårdnad som främjar barns och ungdomars hälsa och välbefinnande. Syfte: Beskriva barns och ungdomars erfarenheter av att leva med cancer Metod: En litteraturstudie baserad på 8 kvalitativa studier. Resultat: Resultatet presenterades i 2 kategorier vilka var: “barns och ungdomars behov” och “barns och ungdomars känslor” med tillhörande 7 underkategorier. Resultatet visade att barn och ungdomar som på grund av cancer förlorat sitt vanliga liv kände sig annorlunda, oroliga och ensamma samtidigt som de också erhöll känslan av tillfredsställelse. Barn och ungdomar med cancer har ett uttalat behov av stöd, aktivitet och lek och information för att skapa kontroll. Konklusion: För att främja behov av aktivitet, stöd samt kontroll, respekt och information antas lek- och gruppterapi vara värdefullt, liksom för att stärka barnens och ungdomarnas känsla av sammanhang. Lekterapi ger yngre barn verktyg till att hantera sin situation meningsfullt medan gruppterapi kan stärka samhörigheten hos ungdomar. Avslutningsvis behövs mer forskning kring barns och ungdomars erfarenheter av cancer.

Bakgrund Barn som kommer till sjukvården kan komma i kontakt med procedurrelaterad smärta genom olika typer av provtagningar eller behandlingar. Barn har inte samma coping-förmåga som vuxna vilket kan påverka deras eventuella rädsla och smärtupplevelse inför smärtsamma procedurer. Avledning kan vara en effektiv metod att använda sig av för att minska barnets lidande. Avledning utgår ifrån antagandet att genom att flytta barnets fokus till något engagerande och attraktivt, hindras hens förmåga att ta in smärtsamma stimuli vilket minskar smärta. Syfte Syftet med litteraturstudien var att undersöka olika avdelningsmetoders effekt på procedurrelaterad smärta hos barn. Metod En litteraturstudie där 12 originalartiklar kvalitetsgranskades och resultatet sammanställdes och analyserades. Resultat Avledningsmetoderna skiljde sig markant mellan de olika studierna. Överlag visade resultatet på att avledning vid smärtsamma procedurer minskade smärtan. Två avledningsmetoder minskad inte smärtan. Slutsats Avledning är ett effektivt sätt att minska procedurrelaterad smärta hos barn.  Avledning kan förbättra eventuella framtida erfarenheter med vården på grund av att negativa upplevelser minskas. Fler studier behövs för att se vilka avledningsmetoder som passar till vilka barn, eftersom alla barn är olika kan vissa avledningsmetoder vara mer effektiva hos vissa barn än andra. / Background Children who come in contact with healthcare can experience procedure related pain through different types of tests or treatments. Children do not have the same coping ability as adults, which can affect how much fear and pain they experience during painful procedures. Distraction may be an effective method to lessen a child's suffering. The idea behind distraction is that by moving a child's focus to something interesting and pleasant the ability to take in painful stimuli is hampered, thus pain is reduced. Aim The purpose of this literature study was to investigate the effect distraction has on procedure related pain in children. Method A literature study based on 12 original articles. The quality of the articles was examined and results were compiled and analyzed. Results Distraction methods differed significantly between the different articles. Overall, the results showed that the use of distraction during painful procedures reduced pain. Two distraction methods did not decrease pain. Conclusion Distraction is an effective way of reducing procedure related pain in children. Distraction can improve potential future experiences with health care because negative experiences are reduced. Further research is needed to see what distraction methods are suitable to each child, because all children are different certain distraction methods can be more effective in some children than in others.

The general aims of the thesis were to study GH responsiveness by estimation of pharmacokinetics and bioavailability of injected recombinant human GH (rhGH), of growth response as gain in heightSDS during childhood and puberty, and IGF-I response as change in circulating IGF-ISDS and IGFBP3SDS. Methods Short children were recruited during 1988–1999 into two national randomized multicentre clinical trials on growth until adult height. A group of 117 GHD patients who had been treated from prepuberty with a single GH dose of 33μg/kg/day for at least 1 year were randomized at onset of puberty either to remain on this dose regimen or to an increased dose, GH67μg/kg/day, administered once daily or divided into two doses, GH33x2μg/kg/day. Data on IGF-ISDS and IGF binding protein 3 (IGFBP3)SDS were available from 111 patients and analysed as stated below. The 151 short prepubertal non-GHD patients were randomized into three groups: untreated controls, GH33 or GH67μg/kg/day. A subpopulation from both trials, 128 patients examined annually in Gothenburg, formed the study sample on GH uptake. They received sc GH injections to obtain 16–24 hour GH curves and the GH pharmacokinetics and bioavailability was calculated. Results: A dose-dependent effect on Cmax was found with great intra- and inter-individual variability. Of the Cmax variability, 43% was explained by the rhGH dose and proxies for injection depth. Median bioavailability of the injected dose was 71%, with great variation, mainly dependent on injection depth. In the IGHD group a dose-dependent difference in pubertal gain in heightSDS was found, with mean of 0.8 for the GH67 group and 0.4 for GH33, p<0.01. The mean total gain in heightSDS during treatment was 1.9 for GH67 and 1.4 for GH33, p<0.01. A dose-dependent pubertal ΔIGF-ISDS was 0.5 vs −0.1, p=0.007, correlating to pubertal gain in heightSDS, p=0.003; and was the most important variable to explain the variation in pubertal gain in heightSDS. In the non-GHD group the ΔIGF-ISDS from baseline to mean study level was dose-dependent 2.07 vs 1.20, p=0.001; and correlated negatively with baseline values of IGF-ISDS, rho= -0.56 for GH67, p=0.001, vs rho= -0.82 for GH33, p=0.0001, and correlated positively with gain in heightSDS in both GH-treated groups, rho= 0.42, p<0.001. In multivariable regression analyses, ΔIGF-ISDS was always an important explanatory variable for long-term growth response from the prepubertal period until adult height, while the IGF-ISDS study level per se was not. Conclusion: Growth response to GH treatment was dose dependent with great variability between patients. More pubertal growth was attained by an increased rhGH dose, mimicking the physiology of healthy children, in whom GH secretion rate increases during puberty. This resulted in a gain in IGF-ISDS closely correlating to pubertal gain in heightSDS in both IGHD and non-GHD patients. A broad range in GH responsiveness was found for both growth and IGF response in both diagnostic groups, but lower in the non-GHD group. Higher uptake of a given GH dose was observed after a deep injection and a higher GH concentration. These results are clinically applicable for individuals who remain short close to onset of puberty; by identifying and deeply injecting a rhGH dose that accounts for individual responsiveness, we can stimulate an increment in IGF-ISDS that correlates to gain in heightSDS during puberty.

The work presented in this thesis is the result of 2 years of investigation into pathogenic mechanisms resulting in the development of osteonecrosis in children and young people treated for acute lymphoblastic leukaemia (ALL). This was a study using in vitro methods to investigate the effects of corticosteroids (namely dexamethasone which is used in the treatment of ALL) on osteocyte angiogenesis with particular focus on vascular endothelial growth factor (VEGF) and markers of bone remodelling. Interactions between dexamethasone and vitamin D were investigated in order to identify potential preventative or therapeutic strategies for osteonecrosis that could be studied in vivo. The actions of sex steroids on osteocyte biology and their interactions with dexamethasone were also studied in order to begin to explain the increased susceptibility to osteonecrosis that is exists in both adolescent and female patients. Results demonstrate a number of novel findings including; i) significant interactions between dexamethasone and vitamin D on osteocyte VEGF gene expression and protein secretion as well as the RANKL: OPG ratio which is crucial to bone remodelling, ii) dexamethasone treatment leading to significant alterations in expression levels of an array of genes expressed by osteocytes that are involved in angiogenesis pathways and iii) significant effects of sex steroids on osteocyte VEGF production and modulation of the effects of dexamethasone by oestradiol. Osteonecrosis is an extremely disabling side effect of the treatment for ALL which in the vast majority of cases is now a curable disease. The results of this thesis contribute to the current understanding of the pathogenesis and have identified a number of potential therapeutic pathways to target.

Adverse drug reactions (ADRs) are common in children. They contribute significantly to patient morbidity, mortality and hospitalisation costs. There is limited data on the avoidability of ADRs in children and wide variation in avoidability rates has been reported. There is currently no standardised method for determining avoidability and many of the established tools are not suitable or designed for use in paediatrics. The aim of this thesis was to develop and test a new avoidability assessment tool that is suitable for use in paediatrics. The stimulus for this work was difficulty using other tools including the one developed by Hallas et al. (1990). Ideally the new tool should also be applicable and generalisable to a variety of other settings. A secondary objective was to identify potential strategies for clinical practice that might reduce the incidence of ADRs. Three key themes for avoidability have been established through a review of existing literature these are: inappropriate or suboptimal prescribing, inadequate monitoring and inadequate patient or parent education. The development of the LAAT was a multistep process which involved a multidisciplinary team (MDT). Individual and group assessments were conducted and qualitative and quantitative analyses of the assessments were carried out. The LAAT has undergone validity and reliability testing for groups and individuals. The newly validated LAAT was used to assess 249 ADR case reports from a prospective paediatric admissions study by one individual and compared to existing avoidability assessments conducted using the Hallas scale. Assessment of these ADR case reports using the LAAT found that 19.3% were either possibly or definitely avoidable. This was similar to results using the Hallas scale where 22% of the reactions were either possibly or definitely avoidable. Overall percentage exact agreement (%EA) between LAAT and the Hallas scale was 90%; when subcategorised into oncology and non-oncology cases the %EA was found to be 94.2 and 86% respectively. The kappa score between LAAT and Hallas scale assessments was 0.71 (95% CI 0.60 - 0.82) for all cases, 0.54 (95% CI 0.40 - 0.68) for the oncology cases and 0.73 (95% CI 0.58 - 0.88) for the non-oncology cases. The most common avoidability theme detected in this study was inappropriate or suboptimal prescribing. Assessing the avoidability of ADRs is a complex process which requires taking into account a number of factors. Strategies to avoid ADRs can be applied at different levels including: patient, ward, departmental institutional, professional, and national. A common theme that emerged from this work was the lack of available guidelines that could be used to assess whether ADRs were avoidable. Where guidelines were available few contained information about ADRs or their prevention. The majority of clinicians relied on their experience and tacit knowledge rather than on guidelines. Some of the ADRs categorised as either possibly or definitely avoidable may have been avoidable with improved prescribing, more frequent monitoring or improved education of patients and/or parents. Other possible prevention strategies include creating an awareness of ADRs in general and their prevention throughout a clinician’s training. Improved communication and documentation in patient records is a simple but effective method of ADR reduction. In summary, we have designed a novel avoidability assessment tool, developed by a multidisciplinary team, and have shown that the new tool is comparable to an existing avoidability tool, can be used by individuals and most importantly is suitable for use in paediatrics or other areas where clinical conditions extend beyond the expertise of individuals. The LAAT refers to guidelines and patient history rather than to abstract concepts such as ‘present-day knowledge of good medical practice’ and ‘effort exceeding the obligatory demands’ as per Hallas. Further work to identify potentially avoidable ADRs and strategies to prevent them is needed.

In Malawi there has been significant progress in reducing post-neonatal and under-5 deaths over the past decade but very little progress in reducing neonatal deaths. The major causes of neonatal deaths in Malawi are prematurity, infections and birth asphyxia. Neonatal sepsis has been shown to have long term complications ranging from motor deficits to cognitive impairment, epilepsy and behavioural disorders in preterm very low birth weight infants in the developed setting. Contrary to the epidemiology in the developed setting where neonatal sepsis is predominantly seen in preterm low birth weight infants, in the developing setting neonatal sepsis is also common among term babies. However, very little is known on the long term outcome of neonatal sepsis in the resource restrained setting. In this thesis the aetiology and outcome of neonatal sepsis and meningitis is investigated. METHODOLOGY This was study had 2 components; a cross sectional arm and a prospective cohort arm. The cross sectional study was looking at the aetiology, resistance pattern and in hospital outcome of severe neonatal infection cases presenting at QECH in Blantyre. The prospective cohort arm involved participants who were recruited in the cross sectional arm at QECH and were residing within Blantyre urban and infants that never had an episode of severe neonatal infection were recruited from Zingwangwa health Centre. The infants from Zingwangwa acted as controls. The participants in the prospective cohort arm were followed up to the age of 1 year where neurodevelopmental outcomes were assessed using the Bayley’s assessment tool. These participants also had detailed neurologic examination during the follow up visits at 6 and 12 months of age. A comparison between the cases and controls was made to ascertain the impact of neonatal infection outcome. RESULTS During the study a total of 412 cases were enrolled in the cross sectional arm. 75% of the cases had late onset disease. GBS was the commonest organism grown in blood culture 17/42(40%) and CSF culture 16/33(48%). 44% had abnormal serum sodium levels on admission and hypernatraemia was independently associated with an increased risk of dying in hospital (8.34[95% CI 1.95-35.7]). 51% of the gram negative organisms were multidrug resistant. In the long term outcome neonatal sepsis without overt meningitis was associated with an up to 6.6 –fold {95% CI (2.38-18.4) increased risk of developmental delay at 1 year of age. Meningitis was associated with a 17-fold {95% CI 4.89- 61.7} increased risk of developmental delay at 1 year of age. Positive blood or CSF culture and being HIV exposed were independent predictors of delay at I year of age. CONCLUSION GBS is a significant cause of neonatal infections in Malawi. The magnitude of developmental delay observed in infants who had neonatal sepsis without meningitis is worrying up to 35% of these infants were delayed. It is therefore important to employ measures that can prevent neonatal infections. Follow up is recommended in infants who had an episode of severe neonatal infection.