BACKGROUND. There are various methods of health care follow-up of children born very preterm (VP, ≤31 week gestation) from a neonatal intensive care unit (NICU). Whilst the gold standard is the systematic NICU based follow-up program, which provides highly specialised neurodevelopmental and medical assessment, it is not feasible at all the appropriate times for all infants because of cost and geographical constraints. In Queensland, and elsewhere, 50% of children born VP rely on primary care-general practice for their screening and health needs once discharged from hospital. Recently, randomised and interrater agreement studies have shown the feasibility of the use of a questionnaire-based collection of late health status in children born VP. A preterm-targeted childhood primary health screening and surveillance program which draws from these methods may be effective in collecting long-term disability data and meeting the screening needs of children born VP. AIM. To (1) develop and (2) assess a Preterm-Targeted Screening and Surveillance Program against the routine National Health Medical Research Council (NHMRC) program for the early detection of sensorineural based disability in children born VP by general practitioners in the primary health setting for (1) prevalence estimation and (2) as a screening tool. METHODS. A two-part approach was chosen. Part 1 was a reconstructed cross-sectional cohort of 388 of 523 (74.2%) located and consented 2, 4 and 7 year ca (corrected age) children with a birthweight ≤ 1250 grams (g) born in Queensland. Epidemiological information was collected on child health outcomes and factors relating to the feasibility of providing a standardised targeted screening and surveillance program to be used by general practitioners to detect sensorineural based disability in children born VP. The Preterm- Targeted Screening and Surveillance Program was developed using World Health Organisation (WHO) screening program criteria and NHMRC evidence based health practice criteria. Part 2 was a multicentred randomised controlled trial to test the efficacy of the newly developed program in 202 VP infants who were randomised to receive the NHMRC or Preterm-Targeted Screening and Surveillance Program. The primary outcome was correct identification of sensorineural disability (developmental quotient >-1 standard deviation (SD), cerebral palsy, bilateral blindness or deafness requiring aids) at 12-months ca by general practitioners assessed against gold standard paediatric assessments. The odds ratios (OR) calculated the disability status (agreed vs. disagreed/unsure). Kappa statistics (k) and screening test characteristics calculated interrater agreement and screening accuracy (agreed vs. disagreed). Logistic regression investigated factors that might affect agreement between general practitioners and paediatric assessment for disability. Secondary outcomes were designed to be descriptive and included post-natal depression, parental stress, health service utilisation and satisfaction. RESULTS. Part 1 demonstrated that in Queensland there is no state-based information on 25.8% of children born VP. Children assessed suffer from sensorineural impairment and a range of other health and developmental problems. In addition, there is limited specialist child health resources located outside the major metropolitan areas and families rely heavily on general practitioners for child health care. Parents and general practitioners clearly demonstrated that they would use an evidence-based targeted childhood screening and surveillance program for children born VP. The Preterm-Targeted Screening and Surveillance Program provide parents and health practitioners with an evidence based-high accuracy standardised screening for sensorineural and non-sensorineural domains. In Part 2, 195 of 202 infants randomised were assessed for the primary outcome. There was no difference in the correct identification of sensorineural disability between general practitioners in either group shown by an OR of 0.91 (95%CI 0.50, 1.65) (preterm-targeted 65.6% vs. NHMRC 67.6%). No prognostic factors independently affected this outcome. Interrater agreement was fair (preterm-targeted k =0.30, p for Ho=0.001 vs. NHMRC k =0.29, p for Ho=0.002). The preterm-targeted group had more disability identified (73% vs. 33%) with less under-referrals (27% vs. 67%) but poorer specificity (70% vs. 92%) with more over-referrals (30% vs. 8%) compared to the NHMRC group. Secondary outcomes showed that children born VP experience high rates of health services use but their families experience similar rates of depression and parental stress compared to the general paediatric population. Satisfaction results suggest that the program was well received. CONCLUSION. A comprehensive epidemiological approach to collecting a broad range of VP child health outcomes and health service data was successfully used to develop an evidence-based Preterm-Targeted Screening and Surveillance Program which proved to have excellent uptake by parents and general practitioners. Assessing the program using a randomised methodology has allowed demonstration of its efficacy as a screening tool when used by general practitioners in the primary health setting. The Preterm-Targeted Screening and Surveillance Program is superior in identifying disability at 12-month ca compared to the standard NHMRC program. Whilst the results are promising, the program will not provide totally accurate prevalence of disability data because of the overestimation of disability.

No description available.

BACKGROUND. There are various methods of health care follow-up of children born very preterm (VP, ≤31 week gestation) from a neonatal intensive care unit (NICU). Whilst the gold standard is the systematic NICU based follow-up program, which provides highly specialised neurodevelopmental and medical assessment, it is not feasible at all the appropriate times for all infants because of cost and geographical constraints. In Queensland, and elsewhere, 50% of children born VP rely on primary care-general practice for their screening and health needs once discharged from hospital. Recently, randomised and interrater agreement studies have shown the feasibility of the use of a questionnaire-based collection of late health status in children born VP. A preterm-targeted childhood primary health screening and surveillance program which draws from these methods may be effective in collecting long-term disability data and meeting the screening needs of children born VP. AIM. To (1) develop and (2) assess a Preterm-Targeted Screening and Surveillance Program against the routine National Health Medical Research Council (NHMRC) program for the early detection of sensorineural based disability in children born VP by general practitioners in the primary health setting for (1) prevalence estimation and (2) as a screening tool. METHODS. A two-part approach was chosen. Part 1 was a reconstructed cross-sectional cohort of 388 of 523 (74.2%) located and consented 2, 4 and 7 year ca (corrected age) children with a birthweight ≤ 1250 grams (g) born in Queensland. Epidemiological information was collected on child health outcomes and factors relating to the feasibility of providing a standardised targeted screening and surveillance program to be used by general practitioners to detect sensorineural based disability in children born VP. The Preterm- Targeted Screening and Surveillance Program was developed using World Health Organisation (WHO) screening program criteria and NHMRC evidence based health practice criteria. Part 2 was a multicentred randomised controlled trial to test the efficacy of the newly developed program in 202 VP infants who were randomised to receive the NHMRC or Preterm-Targeted Screening and Surveillance Program. The primary outcome was correct identification of sensorineural disability (developmental quotient >-1 standard deviation (SD), cerebral palsy, bilateral blindness or deafness requiring aids) at 12-months ca by general practitioners assessed against gold standard paediatric assessments. The odds ratios (OR) calculated the disability status (agreed vs. disagreed/unsure). Kappa statistics (k) and screening test characteristics calculated interrater agreement and screening accuracy (agreed vs. disagreed). Logistic regression investigated factors that might affect agreement between general practitioners and paediatric assessment for disability. Secondary outcomes were designed to be descriptive and included post-natal depression, parental stress, health service utilisation and satisfaction. RESULTS. Part 1 demonstrated that in Queensland there is no state-based information on 25.8% of children born VP. Children assessed suffer from sensorineural impairment and a range of other health and developmental problems. In addition, there is limited specialist child health resources located outside the major metropolitan areas and families rely heavily on general practitioners for child health care. Parents and general practitioners clearly demonstrated that they would use an evidence-based targeted childhood screening and surveillance program for children born VP. The Preterm-Targeted Screening and Surveillance Program provide parents and health practitioners with an evidence based-high accuracy standardised screening for sensorineural and non-sensorineural domains. In Part 2, 195 of 202 infants randomised were assessed for the primary outcome. There was no difference in the correct identification of sensorineural disability between general practitioners in either group shown by an OR of 0.91 (95%CI 0.50, 1.65) (preterm-targeted 65.6% vs. NHMRC 67.6%). No prognostic factors independently affected this outcome. Interrater agreement was fair (preterm-targeted k =0.30, p for Ho=0.001 vs. NHMRC k =0.29, p for Ho=0.002). The preterm-targeted group had more disability identified (73% vs. 33%) with less under-referrals (27% vs. 67%) but poorer specificity (70% vs. 92%) with more over-referrals (30% vs. 8%) compared to the NHMRC group. Secondary outcomes showed that children born VP experience high rates of health services use but their families experience similar rates of depression and parental stress compared to the general paediatric population. Satisfaction results suggest that the program was well received. CONCLUSION. A comprehensive epidemiological approach to collecting a broad range of VP child health outcomes and health service data was successfully used to develop an evidence-based Preterm-Targeted Screening and Surveillance Program which proved to have excellent uptake by parents and general practitioners. Assessing the program using a randomised methodology has allowed demonstration of its efficacy as a screening tool when used by general practitioners in the primary health setting. The Preterm-Targeted Screening and Surveillance Program is superior in identifying disability at 12-month ca compared to the standard NHMRC program. Whilst the results are promising, the program will not provide totally accurate prevalence of disability data because of the overestimation of disability.

BACKGROUND: Pre-term delivery is known to cause developmental problems due to the fragile nature of the premature brain. In particular, ventriculomegaly is a commonly observed phenomenon due to the hemorrhaging of the germinal matrix, and may cause alterations in the volumes of gray matter, white matter and cerebrospinal fluid in growing pre-term children. METHODS: The volume and symmetry of a sample population of ELGAN (Extremely Low Gestational Age Newborns) and normal-term population obtained from the NIH Study of Normal Brain Development was evaluated. The ELGAN group consisted of 88 subjects from age group 9 to 11 and the normal-term group consisted of 68 subjects from age group 7 to 11. Magnetic resonance images were taken from both samples and the intracranial matter was measured and segmented. RESULTS: Histograms of the obtained volumes showed a normal distribution and statistical analysis for each sample group and gender. The ELGAN group had higher intracranial volumes and showed statistically significant asymmetry that was not present in the normal term population with a larger right brain than left brain. Discussion: Results indicate that preterm delivery may alter processes that allow for symmetrical brain development and heavily favor the relative higher expansion of the right side of the brain. CONCLUSION: Further analysis of the concentration and location of the white matter and gray matter in both preterm and normal term children is necessary in order to understand the adaptive mechanisms that may be activated in order to offset the damage done to the premature brain.

The objective of this study was to explore a possible association between infant mortality rate (IMR) and Medicaid dental benefit payouts per state, as well as propose an expansion of the dental benefits provided through Medicaid. Data was obtained from the Vital Statistics report 2012 and the Center for Medicare & Medicaid Services (CMS) Medicaid coverage database for fiscal year 2011. Population and demographic data was also collected for further comparison. The states observed were Alabama, Georgia, Kentucky, Louisiana, North Carolina, South Carolina, and Tennessee. The IMR data was ranked in ascending order and then the dental payments were compared between the seven southern states. There did not appear to be an association between the two variables. It was hypothesized that the state with the highest IMR would have the least amount of Medicaid dental payments; possibly indicating limited benefits and a need for expansion. The data did not support the hypothesis. Although Mississippi had the highest IMR at 9.9 per 1,000 live births, the amount dental benefits paid through Medicaid was not the lowest. Kentucky had the lowest IMR at 6.9 per 1,000 live births, and North Carolina had the highest amount of dental payments with $352,602 being paid by the state. However, the comparing variable in each state did not reflect an association. Limitations of the study were addressed and suggested improvements were made for future studies that would possibly yield significant findings. In conclusion, the data collected and observed did not provide evidence that the expansion of Medicaid dental benefits would combat infant mortality rates across the country.

The implementation of developmental care in South Africa seems problematic. As an effective care approach, developmental care (DC) reduces short- and long-term sequelae for pre-term and sick infants. This study therefore investigates and documents how DC can be implemented successfully in a South African context. The research design chosen, intervention design and development, has six phases: problem analysis and project planning, information gathering and synthesis, design, implementation, evaluation and advanced development, and dissemination. The sixth phase fell outside this study’s scope. Phase One, problem analysis and project planning, involved analysing and describing the level of DC practiced at the research site before implementation, and planning the implementation of DC in a South African public NICU. Planning involved consulting relevant literature and the multidisciplinary team of the NICU. Phase Two, information gathering and synthesis, consisted of identifying the factors involved in DC implementation from national and international examples of such implementation in neonatal intensive care. These factors were derived from available literature and other resources, including institutions where DC and kangaroo-mother care have been implemented, to provide a contextual framework for the intervention plan. The intervention plan for DC implementation at the research site was designed in Phase Three, based on the information gathered in Phase Two. The plan consisted of descriptive representations of the realities of clinical practice combined with applicable theoretical perspectives on the practice of DC. Guidelines for implementing DC were established as part of the plan. Phase Four involved the execution of the intervention plan in a South African public NICU, with participation from members of the multidisciplinary team. The intervention plan was refined and developed further in Phase Five, through monitoring and evaluating DC principles in the NICU. The guidelines were validated by an expert group. The study used Lincoln and Guba’s model (1985: 305) to ensure trustworthiness. No experimental and control groups were used as DC was implemented uniformly in the NICU, with all infants receiving this care. Harm or damage to research participants were not expected, as DC implementation benefits them and improves their working environment. Confidentiality was ensured for all participants and institutions involved. Informed consent for participation was obtained from individual members of the multidisciplinary team. Clearance was obtained from the ethics committee of the University of Pretoria, and institutional consent was obtained from the necessary organisations. This intervention study targeted the multidisciplinary team where medical, nursing, allied health profession and non-medical support personnel were involved in implementing DC. Phase One’s targets and goals included improving the quality of care rendered at the research setting, reducing developmental delays for preterm and sick infants and improved the working environment for the multidisciplinary team. Personnel targets were increasing the staffs’ knowledge and skills, and improving staff morale and job satisfaction. These targets and goals were achieved. / Thesis (PhD (Nursing Science))--University of Pretoria, 2006. / Nursing Science / unrestricted

No description available.

A vital factor for foetal development is the nutrient transport at placental level. This is because any disturbances in the maternal compartments, for example due to maternal stress or nutritional status, which will affect foetal development, will involve the foetal-placental barrier. Moreover, numerous studies have linked other factors such as preterm labour as the leading cause of perinatal morbidity and mortality in the developed world. To this date, despite a numerous epidemiological and clinical studies that identify potential risk factors for the mother as well as the foetus, there is no comprehensive analysis at all these levels taken from the same cohort of patients. Our working hypothesis is that for a successful pregnancy certain events at nutritional, biochemical, genetic and molecular level could be tightly linked. Therefore, in this study we followed a “holistic” approach investigating how maternal stress, nutrition, placental mTOR and glucocorticoid receptor (GR) signalling can influence pregnancy outcome. We have decided to map in detail the components of these two signalling pathways as they appear to cross-talk as well as been implicated in stress responses. The largest part of the questionnaire was focused on the nutritional status with questions targeting the maternal dietary habits before, as well as during, pregnancy. The collection of data took place at the Department of Obstetrics and Gynecology, University of Crete Medical School. With regards to this profile, key findings included the significant reduction in the intake of alcohol, caffeine-containing and sugar-containing refreshments, whereas passive smoking during pregnancy stayed the same. Another major finding of this part of the study was the effects of maternal stress on foetal weight and how pregnancy planning was implicated in this complex relation. In our cohort, women with negative attitudes during pregnancy gave birth to infants with significantly lower birth weights (2.5Kg) than those women showing positive or neutral attitudes towards their pregnancy (2.9Kg). We then assessed how maternal stress might affect this signalling cascade using two placental models (BeWo and JEG-3 cell lines) mimicking a stress milieu in vitro. Treatment of these cell lines with cortisol (100nM and 1000nM) significantly downregulated Deptor and upregulated GAS5 at mRNA level. In an attempt to dissect further a potential gene-environment interaction, we have assessed how 4 well-characterised polymorphisms (ThtIII 1, Bcl I, ER22/23EK, N363S) of the GR gene might affect foetal and placental weight. We have demonstrated that only the maternal ThtIII 1 polymorphism was suggestive of a nature-nurture interaction since only in ThtIII 1 II (CC), maternal stress attitude predicts foetal weight-reduction, but not in ThtIII 1 (GC) independent of confounders such as BMI, pregnancy planning or fast food eating during pregnancy. This is the first time that a gene-environment interaction between a common GR polymorphism and foetal weight was noted. Finally, one of the most important findings of our study came from the preclinical studies using placental tissues. Quantitative PCR revealed that the major transcripts in the human placenta are GRα, GAS5 (decoy for GR DNA binding) and Deptor. We have shown for first time that there are marked differences in the relative mRNA abundance of these components between term and preterm labour as well as colocalisation of GRα with GAS5. With regards to placental regulation these data conclusively demonstrate that: a) there is evidence of gene-environment interaction between maternal stress, pregnancy planning, glucocorticoid receptor polymorphisms and foetal weight and b) potential cross-talk of mTOR and glucocorticoid signalling. We propose that measuring maternal stress levels in addition to circulating cortisol and mapping for known GR polymorphisms could become a useful non-invasive tool of diagnostic and prognostic value, with implications for preterm labour.

The serum fraction of blood is an ideal material in which to search for novel biomarkers for disease. It is easily obtained through relatively non-invasive means, routinely collected, and a rich treasure-trove of information about the health of an individual. Cells react to signal molecules, take up nutrients, and release waste products, fragments that are the result of proteolysis, and other molecules out into the bloodstream. If these components are unique to the cells in question, that part of the complex mixture that is the blood stream can potentially characterize the health of the tissue or organ those cells are a part of. Serum is dense with proteins that span over ten orders of magnitude in size and abundance. The top 22 most abundant proteins in serum account for 99% of the total protein. These abundant proteins are well-characterized and not useful in a search for novel biomarkers for disease. Removal of these large proteins is accomplished using an organic-solvent precipitation step. Analyzing the resultant mixture of low-molecular-weight serum peptides using cLC-MS produces large, data-rich, and very complex data files. We have developed a manual analysis method we have developed that is capable of performing all of the processing steps necessary to identify novel biomarkers for disease as well as a method for the sequencing of low-abundance, highly charged peptide species without additional sample preparation. These methods are applied to two serum sample sets collected to investigate two pregnancy-related diseases: preterm birth, and preeclampsia. Three novel biomarkers of preterm birth have been identified and a combination of these with 5 previously studied markers can predict women who will have preterm birth with a sensitivity of 89.9% and a specificity of 81.0%. Nineteen different molecular species have been identified that predict women at risk for preeclampsia with a p-value of <0.05. Weighted combinations of various groups of the 19 biomarkers can increase the sensitivity up to 96% and the specificity up to 100%. The use of cLC-MS in the search for novel serum biomarkers of pregnancy-related disease allows for seamless integration from potential biomarker selection to polypeptide sequence identification.

This work presents the development of 3D printed microfluidic devices and their application to microchip analysis. Initial work was focused on the development of the printer resin as well as the development of the general rules for resolution that can be achieved with stereolithographic 3D printing. The next stage of this work involved the characterization of the printer with a variety of interior and exterior resolution features. I found that the minimum positive and negative feature sizes were about 20 μm in either case. Additionally, micropillar arrays were printed with pillar diameters as small as 16 μm. To demonstrate one possible application of these small resolution features I created microfluidic bead traps capable of capturing 25 μm polystyrene particles as a step toward capturing cells. A second application which I pioneered was the creation of devices for microchip electrophoresis. I separated 3 preterm birth biomarkers with good resolution (2.1) and efficiency (3600 plates), comparable to what has been achieved in conventionally fabricated devices. Lastly, I have applied some of the unique capabilities of our 3D printer to a variety of other device applications through collaborative projects. I have created microchips with a natural masking monolith polymerization window, spiral electrodes for capacitively coupled contactless conductivity detection, and a removable electrode insert chip. This work demonstrates the ability to 3D print microfluidic structures and their application to a variety of analyses.