Dissertations / Theses on the topic 'Prenatal stage'

La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative fatale de l’adulte caractérisée par la dégénérescence des motoneurones (MNs) et ayant une étiologie multifactorielle. La plupart des études sur la SLA se sont focalisées aux stades symptomatiques selon l’hypothèse que la pathogénicité apparaît lorsque la maladie devient symptomatique. Cependant, un nombre grandissant d’évidences indique que la pathogénicité se développerait bien avant les symptômes. Mon travail de thèse de Doctorat a été basé sur l’hypothèse selon laquelle la SLA – familiale et sporadique – découlerait de déficits présents dès le développement précoce. La première partie de ma thèse a consisté à analyser les courants post-synaptiques GABA/glycine (IPSCs) au niveau des MNs embryonnaire (E) E17,5, localisés dans la colonne motrice ventro-laterale, chez la souris SOD1G93A (SOD) modèle de la SLA, en parallèle à l’analyse de l’homéostasie chlorure. Nos résultats ont montré que les IPSCs sont moins fréquents chez les animaux SOD en accord avec une réduction des terminaisons synaptiques VIAAT autour des MNs. Les MNs SODs avaient un ECI 10 mV plus positif que les MNs sauvages (WT) de la même portée. Ce déficit était lié à une réduction du co-transporteur chlorure KCC2. Les IPSCs évoqués et spontanés présentaient une relaxation plus longue chez les MNs SOD, en corrélation à une [Cl-]i plus élevée. La modélisation a montré que cet excès de relaxation permettait de compenser la moindre efficacité de l’inhibition GABA/glycine liée au ECI dépolarisé. De manière intéressante, les simulations ont révélé la nature excitatrice des potentiels dépolarisants post-synaptiques GABA/glycine (dGPSPs) survenant à basse fréquence (<50Hz) sur les MNs SOD mais pas sur les MNs WT. A plus haute fréquence, les dGPSPs basculaient vers une inhibition du MN liée à une sommation de composantes « shuntantes ». La seconde partie de ma thèse a donc focalisé sur les effets de dGPSPs évoqués électriquement at différentes fréquences (7,5 - 100 Hz) sur de vrais MNs E17,5 au niveau desquels un ECl dépolarisant (sous le seuil du PA) était imposé. Le but était d’examiner si l’effet excitateur pouvait être lié aux changements morphologiques des MNs E17,5 décrits précédemment. Les résultats ont montré que certains MNs étaient bien excités par les dGPSPs basse fréquence et inhibés à plus forte fréquence (MNs bi-effet) alors que d’autres MNs étaient inhibés quelles que soient les fréquences (MNs inhibés). L’effet double était plus souvent détecté au niveau des MNs SOD. Les MNs WT ont été classés en deux groupes en fonction de leur résistance d’entrée (Rin), les MNs bi-effet ayant une Rin élevée et les MNs inhibés une Rin basse. Les données morphométriques ont mis en avant un arbre dendritique réduit pour les MNs WT bi-effet (Rin élevée) et un arbre dendritique étendu pour les MNs inhibés (Rin basse). Ce n’était pas le cas des MNs SOD excités ou inhibés indépendamment de leur morphologie. En accord avec les simulations montrant qu’une baisse de la densité des courants inhibiteurs sur le soma du MN favorise l’excitation des dGPSPs, nous avons trouvé moins de terminaisons synaptiques VIAAT sur le soma et dendrites proximales des MNs SOD, et une fréquence réduite des dGPSPs spontanés. Dans leur ensemble, les données de ma thèse soulignent une altération précoce de l’homéostasie chlorure et de l’innervation GABA/glycine des MNs SOD1G93A. Avant la naissance, une population dominante de MNs avec Rin basse émerge chez les animaux WT. Ces MNs qui sont inhibés par les dGPSPs pourraient correspondre aux futures MNs vulnérables (rapides, FF). Ces MNs ne sont pas inhibés chez les animaux SOD. Le dysfonctionnement de l’inhibition pourrait être attribué à deux facteurs distincts : la morphologie et la densité des synapses inhibitrices péri-somatiques. Parmi ces facteurs, le deuxième joue un rôle majeur en contrôlant la capacité des neurones GABA/glycine à façonner la sortie motrice spinale
Amyotrophic lateral sclerosis (ALS) is a fatal and adult-onset neurodegenerative disease characterized by a progressive degeneration of motoneurons (MNs) with complex multifactorial aetiology. Most ALS studies have focused on symptomatic stages based on the hypothesis that ALS pathogenesis occurs when the disease becomes symptomatic. However, growing evidence indicates that ALS pathogenesis might start long before symptom onset. My PhD thesis work was based on the hypothesis that ALS - familial and sporadic - stems from deficits taking place during early development. With the aim of identifying early changes underpinning ALS neurodegeneration, the first part of my thesis analysed the GABAergic/glycinergic inhibitory postsynaptic currents (IPSCs) to embryonic (E) E17.5 MNs located in the ventro-lateral motor column from SOD1G93A (SOD) mice, in parallel with the analyse of chloride homeostasis. Our results showed that IPSCs are less frequent in SOD animals in accordance with a reduction of synaptic VIAAT-positive terminals in the close proximity of MN somata. SOD MNs exhibited an ECI 10 mV more depolarized than wild type (WT) MNs. This deficit in GABA/glycine inhibition was due to a reduction of the neuronal chloride transporter KCC2. SOD spontaneous IPSCs and evoked GABAAR-currents exhibited a slower decay correlated to elevated [Cl-]i. Using computer modelling approach, we revealed that the slower relaxation of synaptic inhibitory events acts as a compensatory mechanism to strengthen or increase the efficacy of GABA/glycine inhibition when ECI is more depolarized. Interestingly, simulations revealed an excitatory effect of low frequency (<50Hz) depolarizing GABA/glycine post-synaptic potentials (dGPSPs) in SOD-like MNs but not in WT-like littermates. At high frequency, dGPSPs switched to inhibitory effect resulting from the summation of the shunting components. The second part of my PhD thesis focussed on the effect of electrically evoked-dGPSPs, at different frequencies (7.5 to 100 Hz), on real lumbar E17.5 MNs in which a depolarized ECI (below spike threshold) was imposed. The aim was to examine whether the excitatory effect could be linked to morphological changes previously described in E17.5 SOD MNs. Results showed that some MNs were excited by low frequency dGPSPs and inhibited by high frequency dGPSPs (Dual MNs) and others were inhibited at all frequencies (Inhibited MNs). Dual effect was more often detected in SOD MNs. WT MNs were classified into two clusters according to their input resistance (Rin), Dual MNs being specific to high Rin and Inhibited MNs to low Rin. Morphometric data pointed out a reduced dendritic tree in high Rin WT Dual MNs and a large dendritic tree in low Rin Inhibited MNs. This was not the case in SOD MNs that were excited or inhibited whatever their morphology and Rin. In agreement with simulation showing that a less density of inhibitory current on MNs soma favours excitatory dGPSPs, we found less synaptic VIAAT terminals on the soma and proximal dendrites of SOD MNs, compared to littermate WT MNs, as well as a lower frequency of spontaneous dGPSPs. Altogether, my thesis data emphasize a prenatal defect in the CI- homeostasis and GABA/glycine innervation in the SOD1G93A ALS MNs. Before birth, a dominant population of MNs with low Rin emerges in WT animals. These MNs that are inhibited by dGPSPs could represent future ALS vulnerable fast MNs (putative FF). Interestingly, those MNs are not inhibited in SOD animals. The inhibitory dysfunction could be attributed to two distinct factors: morphology and perisomatic inhibitory synapse density. Of these two factors, the latter plays a major role by controlling capability of GABAergic/glycinergic neurons for shaping spinal motor output

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
Considerando-se que o acesso das gestantes ao atendimento digno, humanizado e de qualidade à alÃm de um direito, uma necessidade da mulher, o MinistÃrio da SaÃde expressa e oficializa por meio de portarias, a intenÃÃo de investir na atenÃÃo à gravidez, ao parto e ao puerpÃrio, instituindo o Programa de HumanizaÃÃo no PrÃ-natal e Nascimento (PHPN). à um Programa inÃdito, pois consulta ampla na literatura nÃo identificou nenhum outro no formato do PHPN. Ademais, à uma proposta de intervenÃÃo para um paÃs em desenvolvimento; oferece diretrizes para as diferentes instÃncias da assistÃncia; descreve as condiÃÃes mÃnimas para a atenÃÃo com incentivo financeiro atrelado ao cumprimento de tais condiÃÃes; e propÃe um sistema de informaÃÃo (SISPRENATAL), que oferece ao gestor local, monitorar avanÃos e desafios e corrigir falhas. Neste contexto, decidiu-se pela realizaÃÃo do presente estudo que teve como objetivo geral avaliar a qualidade da assistÃncia prÃ-natal no Cearà a partir da implementaÃÃo do PHPN, tendo como objetivos especÃficos avaliar indicadores de processo do PHPN geradores no SISPRENATAL no Estado; analisar aspectos especÃficos da atuaÃÃo do enfermeiro na atenÃÃo prÃ-natal, informados no sistema; e identificar a receita financeira gerado pelo PHPN para o CearÃ. O estudo caracterizou-se como sendo do tipo exploratÃrio e descritivo e teve como universo o Sistema de SaÃde do CearÃ. Parte dos dados foi coletada na CÃlula de InformaÃÃo da Secretaria Estadual da SaÃde por meio de busca no Sistema de InformaÃÃo do PrÃ-Natal e outra parte na Coordenadoria de Controle e AvaliaÃÃo da mesma Secretaria. Os indicadores de processo serviram de subsÃdios para analisar a qualidade da assistÃncia prÃ-natal no CearÃ, no perÃodo de junho de 2001 a agosto de 2006. Ao longo desses seis anos foram notificados 691.001 nascidos vivos (NV) no SISPRENATAL. Contudo, foram detectados apenas 312.507 cadastros de gestantes, ou seja, 44,4% do nÃmero de NV, incluindo gestantes com idade gestacional atà 120 dias entre 2001 a 2003 e a partir de entÃo as gestantes de todas as idades gestacionais. Observou-se aumento crescente nos indicadores de cadastramento precoce das gestantes (<120 dias) no programa, saindo de 88,3%, em 2001, para 96,4%, em 2006. A avaliaÃÃo de todas as condiÃÃes determinadas no Componente I do PHPN, juntas, que define uma melhor qualidade da assistÃncia prÃ-natal prestada, o percentual atingiu 15,67% das gestantes cadastradas. Este resultado foi superior em aproximadamente 50% o resultado encontrado no PaÃs, tendo em vista que a conclusÃo do referido indicador em nÃvel nacional foi de cerca de 10,12% para o mesmo perÃodo. Ficou demonstrado que os Enfermeiros atuam amplamente na assistÃncia prÃ-natal nas unidades bÃsicas de saÃde do Estado, pois 95% dos cadastros de adesÃo de gestantes e 88% das consultas de puerpÃrio foram realizadas por esse profissional. Quanto ao aspecto financeiro ao verificar-se a diferenÃa dos valores de procedimentos que foram realizados e informados no BPA dos municÃpios mas, nÃo tiveram aprovaÃÃo temos um valor total Estadual de R$ 323.040,00. O que se percebe, pelo valor à a possÃvel falta interesse ou atà mesmo o desconhecimento por parte dos gestores, em resolver problemas que geram a desaprovaÃÃo das informaÃÃes e obstruem a arrecadaÃÃo de recursos, diminuÃdo, desta forma, a possibilidade de maiores avanÃos nesta Ãrea. Enfim, com este estudo pÃde-se perceber que se faz necessÃrio uma intensificaÃÃo nas discussÃes entre profissionais, gestores e comunidade, levantando os avanÃos e desafios em cada municÃpio, em cada Ãrea adstrita de PSF, a fim de promover uma visualizaÃÃo das diversas necessidades no campo da assistÃncia prÃ-natal, buscando soluÃÃes viÃveis e eficazes. à inaceitÃvel que uma Ãrea do cuidado tÃo necessÃria e tantas vezes priorizada nas polÃticas pÃblicas de saÃde deste PaÃs ainda padeÃa de negligÃncia pela ausÃncia de garantias tÃo bÃsicas como a realizaÃÃo de exames laboratoriais essenciais, imunizaÃÃo anti-tetÃnica e o seguimento puerperal, realidade detectada no Cearà e tambÃm descrita no cenÃrio nacional. Hà de reconhecer o papel ativo do enfermeiro nessa Ãrea do cuidado e de ser inadiÃvel que gestores municipais se apropriem do processo de financiamento do PHPN e possam minimizar oportunidades perdidas de aquisiÃÃo de recursos.
Pregnant womenâs access to a decent, humanized and qualified service is not only a right, but a womenâs necessity. The Health Department expresses and makes official through regulations, the intention of investing in attention to pregnancy, childbirth and post-delivery, establishing the Program of Humanization in Prenatal and Birth (PHPN). It is an unprecedented program, as a deep search in literature did not identify any other program like PHPN. Besides, it is a proposal of intervention for a country that is in process of development; it offers directives for the different instances of assistance; it describes the minimum conditions for the attention with financial incentive connected to the execution of such conditions; and it suggests an information system (SISPRENATAL), with offers the local administrator to monitor progress and challenges and to correct imperfections. In this context, it was decided to carry out the present study which had as a general objective to evaluate the quality of prenatal assistance in Cearà from the implementation of PHPN on. The specific objectives were to evaluate process indicators of PHPN generator in the SISPRENATAL in the State; to analyze specific aspects of the nurseâs performance in the prenatal attention, informed in the SISPRENATAL; and to identify the financial income produced by PHPN to the state of CearÃ. The study was characterized as exploratory and descriptive and its universe was the Health System of CearÃ. Part of the data was collected in the Information Department of the Health State Secretariat through a search in the Prenatal Information System (SISPRENATAL). The other part was collected in the Coordination of Control and Evaluation of the same Secretariat. The process indicators served as supplementary information to analyze the quality of prenatal assistance in CearÃ, between June, 2001 and August, 2006. Throughout these six years 691.001 live born infants (NV) were notified in the SISPRENATAL. However, only 312.507 registrations of pregnant women were notified, that is, 44,4% of NV, including pregnant women with pregnancy age until 120 days from 2001 to 2003, and from then on women with all pregnancy ages. It was observed a continuous increase in the indicators of pregnant womenâs early registration (<120 days) in the program, from 88,3%, in 2001, to 96,4%, in 2006. In the evaluation of all conditions determined in Component I of PHPN, together, which defines a better quality of prenatal assistance, the percentage reached 15,67% of registered pregnant women. This result was about 50% superior to the result found in the Country, considering that the conclusion of this indicator in national level was about 10,12% in the same period. It was demonstrated that nurses act extensively in prenatal assistance of basic health units of the State, because 95% of pregnant womenâs registration and 88% of post-delivery service were carried out by this professional. Concerning the financial aspect, when we verify the difference of the value of the actions which were carried out and informed at the BPA of the municipalities but were not approved, we have a State total value of R$ 323.040,00. It is noticeable by this value the possible lack of interest or even the lack of Knowledge that governors have when solving problems that produce the disapproval of information and block the collection of resources, what decreases the possibility of greater progress in this area. In conclusion, it was possible to notice through this study that it is necessary to intensify the discussions among professionals, governors and community about progress and challenges in each municipality, in each area of PSF, in other to promote a visualization of several necessities in prenatal assistance and look for possible and effective solutions. It is unacceptable that the area of care which is so necessary and considered many times a priority by public policies suffer because of negligence and absence of basic guarantees like the realization of essential lab exams, anti-tetanus immunization and post-delivery service. This is a reality detected in Cearà and also described in the national scenery. We have to recognize the active role of the nurse in this area of care and that it is urgent that governors of the municipality appropriate the financing process of PHPN and minimize missed opportunities to obtain financial resources for the Health Local System.

Prenatal alcohol exposure results in alterations in numerous physiological systems, including neuroendocrine and neuroimmune systems. The purpose of this study was to determine whether prenatal ethanol exposure results in long-term alteration of neural gene expression, particularly in genes related to neuroendocrine and neuroimmune function. Utilizing a well-established animal model of prenatal ethanol exposure, ethanol was administered to pregnant Sprague-Dawley dams throughout gestation in a liquid diet fed ad libitum (36% calories derived from ethanol). Maltose-dextrin was isocalorically substituted for ethanol in a liquid control diet for a pair-fed group, and a control group received a pelleted control diet ad libitum. In young adulthood, an adjuvant-induced arthritis paradigm was utilized, where female offspring were injected with either saline or complete Freund’s adjuvant, to induce an inflammatory response and elucidate dysregulated neuroimmune pathways. Gene expression was analyzed in the prefrontal cortex and hippocampus at both the peak and resolution of arthritis using whole genome gene expression microarrays. Within saline-injected animals, prenatal alcohol exposure alone resulted in significant changes in gene expression in both the prefrontal cortex and hippocampus. Included were multiple genes related to, cell death, transcriptional regulation, neuronal signaling and neurodevelopment. Among the genes involved in neurodevelopment, Acs13 has also been shown to be variably methylated in humans according to in utero exposure to environmental factors. Prenatal alcohol exposure also altered the gene expression response to adjuvant-induced arthritis. Many genes showed a significantly different pattern of expression in ethanol-exposed animals compared to both pair-fed and control, in both prefrontal cortex and hippocampus. These genes were either differentially up- or downregulated in ethanol-exposed compared to control animals or failed to show the adjuvant-induced change in regulation shown by controls. As well, several of these genes were mediators of the response to immune or stress challenge, such as Lcn2 and Bhlhe40. Genes found to be differentially expressed in this study are potential mediators contributing to the long-term alterations in neuroendocrine and neuroimmune function observed in prenatal alcohol exposure.

Background: Antenatal Psychosocial Assessment (APA) has recently been introduced into routine antenatal care, but the ways in which maternity service providers assess and respond to maternal stress are subject of debate. There is a lack of consensus on the instrument(s) of choice and lack of evidence regarding appropriate interventions. Further, national guidelines have not kept apace with the conceptual shift from ‘postnatal depression’ to ‘perinatal anxiety and depression’. Adopting the Medical Research Council Complex Interventions Framework, the ARMS research aimed to inform the development of interventions that support women who are experiencing, or at risk of, mild-moderate mental health disorder in pregnancy. Methods: A mixed methods approach was adopted. In the quantitative element (Study Part 1) participants (n=191) completed a questionnaire when attending for their first formal antenatal appointment, using a procedure and materials that had been previously tested in a pilot study. Details including mental health assessment and referrals were obtained from their health records, following delivery. In the qualitative element (Study Part 2) a sub-sample of women (n=22) experiencing high levels of maternal stress took part in up to three serial in-depth interviews during pregnancy and the early postnatal period.Findings: Maternal stress was found to be common. Using the Edinburgh Postnatal Depression Scale (EPDS) threshold of ≥10, approximately 1 in 4 women were classed as high depression (halving to 1 in 8 at the more conservative threshold of ≥13). Almost 1 in 3 women were classed as high anxiety, using the state scale of the State-Trait Anxiety Inventory (STAI-S, threshold ≥41), compared with 1 in 5 using the two-item GAD (threshold ≥3). Fewer than half of the women identified as high anxiety were identified by both measures. Factor analyses of the symptom measures were consistent with wider literature suggesting a three-item anxiety component of the EPDS; however, concurrent validation using regression analyses did not indicate that the EPDS could be used as an anxiety case finding instrument. Women reported that maternal stress had significant impact on their lives that may not be captured with existing clinical approaches. Women commonly found it difficult to self-assess severity of maternal stress and the assessment process could itself act as an intervention. The research provided the first validation of the depression case finding questions in UK clinical practice. The Whooley items completed in clinical practice identified only half of the possible cases identified by the EPDS, at both commonly adopted EPDS thresholds. Inclusion of the Arroll 'help' question as a criterion improved specificity of the assessment completed in clinical practice but substantially compromised sensitivity, missing 9 in 10 possible cases. Women’s mental health history and treatment history were similarly under-reported, particularly concerning anxiety. APA was introduced into routine clinical practice without attention to topics of relevance to women, context of disclosure or to provision of adequate resources for consistently responding to identified need. Women experiencing, or at risk of, mild-moderate disorder were thus usually ineligible for further support. Implications: Care pathways are needed that encompass both assessing and responding to maternal stress, where communication with health professionals, subsequent referral and management are addressed. The development, implementation and evaluation of low-cost resources embedded in such pathways are a priority and the research presented in the thesis offers a foundation on which to build.

博士
國立中山大學
生物醫學研究所
100
Prevalence of childhood asthma in Taiwan has increased 9 times from 1.3% to 10-14% in the past 4 decades. Many studies worldwide have demonstrated that many genes in different chromosomes are implicated in childhood asthma in different ethnic populations. A growing body of evidence suggests that allergic sensitization could occur in perinatal stage and correlate to the development of childhood asthma. Epidemiological studies, however, indicate that prevalence of childhood asthma is much higher in developed countries than that in developing countries; and prevalence of childhood asthma in metropolitan area is higher than that in country sites. This suggests that certain genes can interact with the environmental factors in developed countries to promote the development of childhood atopic disorders. Interests are now increasing on what is (are) the real pathogenic gene-gene interaction(s) for childhood atopic disorders under influence of age, gender and environmental factors? In a large perinatal cohort study with 1,211 pregnant women and their offspring from the obstetrics and pediatrics of Kaohsiung Chang Gung Memorial Hospital, we analyzed 159 allergy candidate genes with 384 single nucleotide polymorphisms and showed that 14 genes over 22 somatic and X chromosomes risk to or protective from cord blood immunoglobulin E (CBIgE) elevation are different from those genes associated with IgE elevation in children under 1.5, 3 and 6 years of age (12, 15 and 12 genes, respectively). CX3CL1, IL13, PDGFRA and FGF1 polymorphisms were associated with elevated IgE at earlier ages (newborn, 1.5 and 3 years); HLA-DPA1, HLA-DQA1, CCR5 and IL5RA polymorphisms were associated with IgE production at 6 years of age. Further analysis by multifactor dimensionality reduction (MDR) developed from data reduction strategy, we found that there are interactions among innate immunity, adaptive immunity, and response and remodeling genes on IgE production begin in prenatal stage. For example, The gene-gene interaction among IL13, rs1800925, CYFIP2, rs767007 and PDE2A, rs755933 was significantly associated with IgE production at 3 years of age. This suggests that different genotypes of genes interact one another on the IgE production contributing to the development of allergic diseases. Since the concentration of IgE is an important indicator of atopic disorders and allergic sensitization, we believe after clarifying the natural course of the genomic profiles on IgE elevation, certain early predictor(s) and preventive regimens for allergic sensitization or atopic disorders may be made possible.

O diagnóstico pré-natal engloba uma vasta gama de técnicas genéticas e obstétricas que visam avaliar o estado de saúde de um embrião ou feto. Grande parte dos distúrbios genéticos estão associados a uma elevada taxa de morbilidade, mortalidade e défice intelectual, causando sofrimento e ansiedade aos futuros pais. A história do diagnóstico pré-natal foi marcada pelo desenvolvimento de técnicas invasivas, pelo progresso da análise cromossómica e ainda pelo surgimento de um programa de rastreio pré-natal. Apesar de ser uma história com mais de 40 anos, as técnicas invasivas atualmente utilizadas nos serviços de saúde ainda estão associadas a um risco de aborto e os exames de rastreio disponíveis continuam pouco sensíveis no diagnóstico da maioria dos distúrbios genéticos. Deste modo, a deteção de ADN fetal livre na circulação materna durante a gravidez suscitou um grande interesse por parte dos investigadores, proporcionando o desenvolvimento do chamado diagnóstico pré-natal não invasivo. Além disso, como os novos avanços na investigação têm proporcionado um maior conhecimento sobre os distúrbios genéticos, também a análise genética tem experienciado um desenvolvimento notável. Os procedimentos citogenéticos têm permitido a deteção de um número de anomalias cromossómicas cada vez maior com um tempo de resposta bastante inferior. A análise genética molecular tem contribuído significativamente para o aumento da capacidade diagnóstica e a aplicação do array chromosome genomic hybridization (aCGH) ao diagnóstico pré-natal tem permitido a deteção de desequilíbrios genómicos associados a malformações congénitas e/ou atrasos cognitivos até então não identificados. Apesar da introdução destas novas metodologias na prática clínica trazer claros benefícios, levanta também questões éticas importantes que devem ser cuidadosamente discutidas. Este artigo de revisão pretende abordar as técnicas vulgarmente utilizadas no diagnóstico pré-natal, invasivo e não-invasivo, assim como os métodos de análise cromossómica desde a sua origem até aos dias de hoje.
Prenatal Diagnosis comprises a variety of obstetric and genetic techniques to determine the health and condition of an embryo or fetus. A high proportion of genetic disorders are associated with significant morbidity, mortality and intellectual disabilities, causing suffering and anxiety to expectant parents. Milestones in its history include the development of invasive techniques, the progress of chromosome analysis and the emergence of a screening program. Although prenatal diagnosis has more than 40 years, the invasive techniques currently used in health programmes are still associated with a miscarriage risk and the screening methods available have poor accuracy to detect the majority of genetic disorders. Thereby, when cell-free fetal DNA (cffDNA) was detected in the maternal circulation during pregnancy, a desire to avoid contact with the fetus grew out and a lot of techniques were developed in order to create the so-called non-invasive prenatal diagnosis (NIPD). Moreover, as researchers are gaining knowledge about the genetic disorders, also genetic analysis has experienced an extraordinary evolution. Cytogenetic methodologies have improved its resolution of detecting chromosome abnormalities and have decreased the turnaround time. Molecular genetic analysis have highly contributed to the diagnostic capacities and the application of array chromosome genomic hybridization (aCGH) to prenatal diagnosis allowed the detection of genomic imbalances associated with congenital malformations and/or intellectual disabilities which were not identified by previous techniques. The introduction of these new approaches into clinical practice brings clear benefits but also poses several ethical and social challenges. The purpose of this review is to present some of the techniques currently available to diagnose genetical conditions in utero, invasive and non-invasive, and to evaluate the evolution of chromosomal analysis over the years.

A research report submitted to Faculty of Health Sciences in partial fulfilment of the requirements for the degree of Master of Science in Epidemiology in the field of Implementation Science, School of Public Health University of The Witwatersrand. Johannesburg June 2018.
Background Intermittent Preventive Therapy using sulfadoxine pyrimethamine (IPTp-SP) is a malaria control strategy to reduce cases of malaria in malaria endemic countries. However, the administration of the recommended three doses of IPTp throughout the stages of pregnancy still remains low in Nigeria even though, Nigeria is a malaria endemic country. Quality improvement approach has been demonstrated to improve practice among healthcare providers. This study therefore used a quality improvement approach to train and coach healthcare providers in order to improve the administration of the recommended doses of IPTp to pregnant women receiving antenatal care (ANC) services. Methods A quasi-experimental study design was carried out to evaluate the effect of quality improvement approach consisting of training and coaching of healthcare providers to improve the administration of IPTp during ANC service. Primary Healthcare Centre (PHC) Samaru was purposively selected and twelve healthcare providers participated in the study. ANC daily register was reviewed pre-intervention, intervention and post-intervention period of the study. Data were analysed using line graphs and run charts. Results A total of 36 ANC visit weeks were observed between 21st November 2016 and 27th July 2017. The mean level for IPTp1 administration pre-intervention was 105.85% (SD: 29.28) and 75.20% (SD: 16.89) for IPTp2+. The levels of IPTp1 administration were relatively stable from Week 1 to Week 10 although, there was overestimation of IPTp1 as 8 of the 16 Weeks in the pre-intervention period i.e. Weeks 3, 5, 7, 8, 11, 13, 15 and 16 all had more than 100% of eligible women administered IPTp1. The patterns of IPTp2+ administrations shows the levels of IPTp2+ administration were erratic. There was evidence indicating the process of IPTp1 was relatively stable post-intervention as the data crosses the median line only six times i.e. 7 runs. This indicates that the process of IPTp1 was within normal variation over the post-intervention period. There was an upward shift showing immediate improvement of the administration of IPTp2+ post-intervention although, there was a non-random variation in the administration of IPTp2+. The iv improvements of IPTp were not sustainable due to stock-outs. The quality of the ANC daily register was poor. Conclusion The integrated training and coaching intervention approach improved the administration of the recommended three doses of IPTp within the context of a PHC. These findings should be interpreted with caution as the impact of the intervention may not have reached its full impact due to the short post-intervention assessment. Stock-outs remains a huge barrier to the administration of IPTp under DOT during ANC services. The data quality of the ANC daily register improved post-intervention however, there were still slight errors thus, indicating that healthcare providers need constant coaching. It is important to integrate training and coaching of healthcare providers in order to have desired and sustained outcomes. Keywords: Malaria in pregnancy, IPTp, IPTp-SP, SP, ANC, Pregnant women, Healthcare providers, administration, QI, integrated training and coaching.
LG2018

abstract: Intake of alcohol, tobacco, and illicit substances such as marijuana and methamphetamine during pregnancy can have significant deleterious effects on a developing fetus and the resulting infant. The existence of substance-exposed newborns also has negative impacts on society as a whole; these include financial burdens placed on taxpayers and the additional time and resources required by health care professionals, social workers, and law enforcement authorities to properly care for such infants. Existing literature show a strong correlation between prenatal care and improved birth outcomes, including abstinence from or reduction of prenatal substance abuse. The Health Start Program in the state of Arizona attempts to mitigate the incidence of substance-exposed newborns, among other goals, by employing community health workers who identify high-risk pregnant and postpartum women, inform these women about how to receive prenatal care services, educate them on appropriate prenatal and neonatal care, and provide program and referral services to both pregnant and postpartum women. Community health workers interact directly with women most at-risk for prenatal substance abuse and should be well-versed in the understanding of the complex issues related to substance-exposed newborns. In an attempt to discover, analyze, and compile those complex issues with which community health workers should be knowledgeable, this project explores existing federal regulations regarding substance-exposed newborns, compares Arizona’s regulations to Minnesota’s, Virginia’s, and Washington’s, and analyzes prevailing literature in the field about the various implications associated with screening and reporting substance-exposed newborns to law enforcement authorities. After an intensive literature review, this project concludes that the Health Start Program needs a comprehensive resource document which enumerates federal and select state policies, landmark cases involving substance-abusing pregnant women and the precedence set by each, and recommendations from medical and public health experts. The document should also provide clear guidelines by which each stakeholder should abide and why, and recommend potential best practices the state of Arizona could adopt into law based on other state policies which have proven to be effective.
Dissertation/Thesis
Masters Thesis Biology 2015