O pé torto congênito (PTC) é a deformidade congênita de maior prevalência na ortopedia. No Brasil, cerca de 2:1000 nascidos vivos são acometidos por essa malformação. As deformidades fundamentais são adução, e supinação do antepé, varo do calcâneo, equinismo na articulação subtalar. O tratamento pode ser cirúrgico ou conservador e deve ser iniciado o mais cedo possível. Os métodos biomecânicos descrevem o movimento das estruturas do aparelho locomotor durante as atividades funcionais. O objetivo geral desta pesquisa de mestrado foi realizar a análise cinemática dos movimentos entre o antepé e o retropé de crianças com pé torto congênito, tratadas pelo método Funcional Francês Adaptado. Para isto foram avaliadas 7 crianças com idades entre dois e 8 anos por meio de quatro câmeras filmadoras digitais que gravaram os deslocamentos de marcadores colocados em pontos anatômicos dos membros inferiores durante a fase de apoio e balanço da marcha em velocidade auto selecionada. Posteriormente os pontos foram digitalizados, a reconstrução tridimensional e o calculado dos ângulos de Euler foram feitos por meio do programa Matlab. Os movimentos de pronação/supinação, dorsiflexão/flexão plantar e abdução/adução destes dois segmentos do pé destas crianças foram comparados com crianças com desenvolvimento típico. Apenas o movimento de pronação/supinação do retropé foi igual entre as crianças com desenvolvimento típico e crianças com pé torto congênito. Este é o primeiro estudo que mostra como se comportam os movimentos do antepé e retropé de crianças com pé torto congênito, durante a marcha em esteira. Estes resultados são importantes, pois auxiliam a compreender compõem um estudo pioneiro na identificação da mobilidade do pé durante a marcha em crianças com pé torto congênito / Congenital clubfoot (PTC) is the most prevalent congenital deformity in orthopedics. In Brazil, about 2: 1000 live births are affected by this malformation. The fundamental deformities are adduction, and supination of the forefoot, varus of the calcaneus, equinism in the subtalar joint. Treatment may be surgical or conservative and should be started as soon as possible. Biomechanical methods describe the movement of structures of the locomotor apparatus during functional activities. The general objective of this master\'s research was to perform the kinematic analysis of walking of children with congenital crooked feet. Seven children aged between two and eight years were evaluated through four digital camcorders recording the displacements of markers placed in anatomical points of the lower limbs during the support phase and self-selected speed gait. After the points were digitalized, the three-dimensional reconstruction and the Euler angles calculation were done through programming routines written in Matlab. The pronation / supination movements, dorsiflexion / plantar flexion and abduction / adduction of these two foot segments were compared with children with typical development. Only the pronation / supination movement of the hindfoot was the same among children with typical development and children with congenital crooked feet. This is the first study that shows how the movements of the forefoot and hindfoot of children with congenital clubfoot behave during treadmill walking. These results are important because they help to understand the joint mobility of the feet of children during gait and to contribute to the treatment of patients with congenital clubfoot

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / INTRODUÃÃO: O misoprostol (CytotecÂ) à um anÃlogo de prostaglandina E1, inicialmente comercializado com finalidades terapÃuticas do trato gastrintestinal, de uso proscrito em gestantes pelo risco de abortamento. A realidade do aborto e o ineficiente controle de medicamentos em nosso paÃs tornaram generalizado seu uso como mÃtodo abortivo. Estudos demonstram que o potencial abortivo do misoprostol à variÃvel e seu uso sem acompanhamento mÃdico pode levar a uma gestaÃÃo que nÃo se perde, gerando risco para o embriÃo/feto. VÃrios relatos de casos e estudos epidemiolÃgicos associam o uso de misoprostol durante a gestaÃÃo com crianÃas malformadas, especialmente seqÃÃncia de MÃebius, defeitos de reduÃÃo de membros e diversas anomalias do sistema nervoso central. O risco do surgimento destes defeitos nÃo pÃde ainda ser determinado com os dados atualmente disponÃveis, fazendo-se necessÃrio a continuidade de pesquisas. OBJETIVOS: Identificar em recÃm nascidos (RNs) malformados nas principais maternidades de Fortaleza e em controles normais a freqÃÃncia de exposiÃÃo ao misoprostol e apresentar o espectro de MFs dos neonatos expostos. MÃTODOS: Estudo de caso controle, com busca ativa diÃria de RNs malformados e controles pareados em quatro maternidades pÃblicas de Fortaleza â CE, no perÃodo de julho a novembro de 2005, para entrevista com a parturiente utilizando questionÃrio estruturado, na busca por exposiÃÃes diversas durante a gestaÃÃo, inclusive ao misoprostol. RESULTADOS: Os grupos eram homogÃneos quanto ao perfil sÃcio-demogrÃfico e principais caracterÃsticas, apresentando diferenÃas somente em desfechos desfavorÃveis mais esperados em RNs MFs, como menor peso (p=0,0001), menor adequaÃÃo peso x idade gestacional (p=0,006), maior natimortalidade (p=0,024) e maior mortalidade perinatal (p=0,0001). Ambos os grupos tiveram Ãndice de assistÃncia prÃ-natal no mÃnimo adequada (69%), diferindo somente na quantidade de ultra-sonografias (US) realizadas a mais pelos casos (p=0,003). Quanto aos fatores de risco, a Ãnica diferenÃa consistiu no grupo caso ter apresentado maior freqÃÃncia em apresentaÃÃo pÃlvica (19,8%, p=0,037). Aproximadamente 84% das mÃes relataram exposiÃÃo a pelo menos um medicamento durante a gestaÃÃo, e a mÃdia de medicamentos consumidos por gestante foi de 3,72. O uso de fumo, Ãlcool e drogas ilÃcitas foi pouco reportado, e somente o fumo apresentou-se mais freqÃente no grupo controle (p=0,0171). A maior parte das gestaÃÃes foi declarada como planejada ou desejada (70% do total). O relato de tentativa de aborto foi de 6,8% do total da amostra, havendo maior citaÃÃo de uso de misoprostol no grupo caso, embora nÃo tenha sido estatisticamente significativo. CONCLUSÃO: Os achados deste estudo sugerem que ocorre uma maior exposiÃÃo de misoprostol durante a gestaÃÃo em RNs malformados comparados a RNs saudÃveis, Odds Ratio (OR) = 3,65 [IC95%: 0,74;17,91]. O espectro de MFs encontradas, associadas ao misoprostol foi: hidrocefalia, mielomeningocele, agenesia de quadril, pà equinovaro, luxaÃÃo de joelho, luxaÃÃo de quadril, agenesia de falanges distais, sindactilia, polidactilia, imperfuraÃÃo anal, ausÃncia de testÃculos no bolso escrotal e higroma cÃstico. / INTRODUCTION: Misoprostol (CytotecÂ) is a prostaglandin E1 analog, previously commercialized with therapeutic purposes, with proscribed use in the gravid due to the risk of miscarriage. The common practice of abortion and the inefficient control on access to drugs in our country has lead to the generalized use of this drug as an abortive method. Studies have shown that the abortive potency of misoprostol is variable and its use without medical assistance may lead to thriving gestation, and a consequent risk of malformation to the fetus. Various case reports and epidemiological studies associate the use of misoprostol during gestation with offspring bearing malformations, especially with the MÃebius sequence, terminal transverse-limb defects and diverse other anomalies of the central nervous system. The risk of acquiring these malformations cannot however be determined with available data, thus, there is a need for continuous research. OBJECTIVE: Identifying newborns bearing malformations in the leading maternities in Fortaleza and selecting their respective study controls, determining the frequency of exposition to misoprostol and identifying the spectrum of anomalies in the exposed group. METHODS: A case control-study, with a daily active search within the four largest maternities in Fortaleza, Ceara for newborn with congenital defects and a paired control, from July to November 2005. Every mother was interviewed with a questionnaire in the search for diverse expositions during pregnancy, including misoprostol. RESULTS: The groups were homogenous in respect to their socioeconomic profile and other main characteristics. Differences were found in respect to unfavorable outcomes among newborn with congenital defects like low weight (p=0,0001), low weight in relation to gestational age (p=0,006), increased natimortality (p=0,024) and increased perinatal mortality (p=0,0001). Both groups had adequate pre-natal assistance (69%), deferring only in the amount of ultrasonographic exams carried out in the case group (p=0,003). In regards to risk factors, the only deference encountered was the case group having more breech presentation (19,8%, p=0,037). Approximately 84% of mothers had been exposed to at least one medication during gestation, and the average number of drugs consumed was 3, 72. The use of tobacco, alcohol and illicit drugs was rarely informed, and only tobacco smoking was more frequent in the control group (p=0,0171). Most gestation were reported as planed or desired (70% of the total). Attempted abortion was reported in 6,8% of whole sample, with the use of misoprostol in the case group, although without statistic significance. CONCLUSION: The findings of these study suggest that exposition to misoprostol during gestation occurs more frequently in newborn with congenital defects compared with healthy ones, Odds Ratio (OR) = 3,65 [IC95%: 0,74;17,91]. The spectrum of malformations found and associated with misoprostol was hydrocephalus, meningomyelocele, agenesis of hip, equinovarus, luxation of the knee, hip congenital dislocation, absence of distal phalanges, syndactyly, polidactyly, anal imperforation, criptorchidism and cystic higroma.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A assistÃncia de enfermagem à crianÃa portadora de cardiopatia congÃnita com Ãnfase na investigaÃÃo de dados antropomÃtricos à recomendada precocemente, pois significantes atrasos no peso e comprimento devido ao comprometimento hemodinÃmico relacionam-se intimamente aos problemas nutricionais. Buscou-se avaliar o estado nutricional de crianÃas menores de 2 anos de idade, portadoras de cardiopatias congÃnitas, mediante estudo antropomÃtrico, caracterizar os dados sociodemogrÃficos, histÃria alimentar e antecedentes perinatais, analisar os percentis e escore Z de peso/comprimento, peso/idade, comprimento/idade, circunferÃncia braquial, Ãndice de massa corporal/idade e verificar os preditores de alteraÃÃo dos parÃmetros antropomÃtricos, dos percentis e escore Z nessas crianÃas. Estudo transversal e observacional desenvolvido em duas instituiÃÃes de saÃde ambulatorial e hospitalar, referÃncias em doenÃas cardÃacas. A coleta de dados ocorreu de janeiro a junho de 2009, utilizando formulÃrio estruturado em dados: identificaÃÃo da crianÃa, sociodemogrÃficos, antecedentes perinatais, diagnÃstico patolÃgico, registro alimentar atual e medidas antropomÃtricas. Respeitaram-se todos os aspectos Ãticos e avaliaram-se 132 crianÃas predominantemente de Fortaleza-CE, do sexo masculino, com mediana de idade atà 8,5 meses e portadoras de cardiopatias congÃnitas acianÃticas, tipo comunicaÃÃo interatrial, em acompanhamento ambulatorial, no perÃodo prÃ-operatÃrio. Conforme os achados, a maioria de crianÃas era desprovida financeiramente; as mÃes haviam cursado atà nove anos de estudo, restritas Ãs atividades do lar, e dividiam com os companheiros os cuidados do filho. A maior parte das crianÃas consumia fÃrmulas lÃcteas infantis acrescentadas de complementos alimentares. Segundo os antecedentes perinatais, evidenciaram-se mÃes com atà dois filhos e aproximadamente 27 anos de idade no nascimento do filho cardiopata, alimentaÃÃo adequada durante o perÃodo gestacional, assinalado por intercorrÃncias: infecÃÃes do trato urinÃrio, sangramentos transvaginais, dores, ameaÃa de aborto, hiperÃmese gravÃdica, hipertensÃo arterial, rubÃola, anemia ferropriva, diabetes gestacional, anorexia e edema. Metade das mÃes realizou atà seis consultas de prÃ-natal. Grande parcela das crianÃas nasceu de parto cesÃreo e foi classificada como RN a termo, com elevados escores de Apgar. Com referÃncia à antropometria, tiveram valores de peso e comprimento adequados ao nascer e outras medidas obtidas no momento do estudo consideradas dentro do padrÃo de normalidade. Os percentis e escores Z predominantes no estudo concentraram-se dentro da faixa de normalidade nutricional. No entanto, os valores de escores Z apresentaram variaÃÃes negativas com desvio para a esquerda, portanto, mesmo incluÃdas na faixa nutricional adequada, as crianÃas estÃo em risco iminente de desenvolver alteraÃÃes nutricionais e seus valores de escores Z ainda sÃo discrepantes em relaÃÃo Ãs crianÃas sadias. Na anÃlise de fatores preditores, a ocorrÃncia de desnutriÃÃo imediata e desnutriÃÃo aguda està relacionada à diminuiÃÃo do valor da prega cutÃnea subescapular e a ocorrÃncia de desnutriÃÃo imediata refere-se ao elevado escore de Apgar no primeiro minuto. AlÃm disso, a desnutriÃÃo crÃnica relacionou-se Ãs crianÃas do sexo feminino com idades maiores. Por fim, em face da magnitude do defeito cardÃaco e sua profunda repercussÃo no estado nutricional da crianÃa, estudos podem aperfeiÃoar o conhecimento do enfermeiro e subsidiar o acompanhamento do crescimento que possibilite melhor prognÃstico dessas crianÃas em diferentes contextos da saÃde.

O hipotireoidismo congênito (HC) é um distúrbio do metabolismo, caracterizado pela produção deficiente dos hormônios tireoidianos. A literatura ressalta que crianças podem apresentar alterações cognitivas, linguísticas e problemas comportamentais, mesmo quando o diagnóstico e o tratamento iniciaram precocemente. O estudo teve como objetivo verificar desempenho em habilidades motoras, comunicativas e cognitivas de indivíduos com hipotireoidismo congênito, tratados desde o período neonatal e comparar esses achados com seus pares sem alterações da tireoide. Participaram deste estudo 15 indivíduos com o diagnóstico de hipotireoidismo congênito do gênero feminino, com idade cronológica variando entre 36 a 71 meses, com Quociente de Inteligência superior a 70, denominado Grupo Experimental (GE); e 15 indivíduos típicos, sem alterações da tireoide, denominado Grupo Comparativo (GC). Os participantes dos dois grupos foram pareados quanto à idade cronológica e nível socioeconômico. Os instrumentos de avaliação utilizados foram: Entrevista com pais; Observação do Comportamento Comunicativo; Teste de Vocabulário por Imagem Peabody TVIP; Teste de Screening de Desenvolvimento DenverII. Foi realizada avaliação psicológica, quanto ao nível intelectual, com a aplicação da Escala de Inteligência StanfordBinet. Os resultados mostraram que o desempenho das crianças do GE quanto às habilidades comunicativas, de linguagem, cognitiva e de linguagem receptiva apresentaram diferença estatística significante quando comparado com o GC. Os achados desse trabalho confirmam a interferência do HC no desenvolvimento infantil, ressaltando que indivíduos com HC, mesmo diagnosticados e tratados precocemente, podem apresentar alterações motoras, comunicativas e cognitivas e esses prejuízos poderão afetálos no decorrer da vida, inclusive nas habilidades escolares. Reiterase que estudos longitudinais são importantes para acompanhar e prevenir essas alterações. / Congenital hypothyroidism (CH) is a metabolic disorder characterized by deficient production of thyroid hormones. The literature points out that children may have cognitive, language and behavioral problems changes even when the diagnosis and treatment started early. The study aimed to verify performance in motor, communication and cognitive abilities of individuals with congenital hypothyroidism treated from the neonatal period and to compare these findings with their peers without thyroid changes. The study included 15 subjects with a diagnosis of congenital hypothyroidism females with chronological age ranging from 36 to 71 months, with Intelligence Quotient greater than 70, called Experimental Group (GE); and 15 typical individuals without thyroid changes, called Comparative Group (GC). Participants in both groups were matched for chronological age and socioeconomic status. The assessment instruments used were: Interview with parents; Observation of Communicative Behavior; Vocabulary Test Peabody Picture TVIP; Screening Test Development DenverII. Psychological assessment was conducted, on the intellectual level, with the application of the StanfordBinet Intelligence Scale. The results showed that children\'s performance of GE regarding communication skills, language, cognitive and receptive language showed statistically significant differences when compared to the GC. The findings of this study confirm the interference of HC in child development, noting that individuals with HC, even if diagnosed and treated early, may have driven, communicative and cognitive changes and these losses may affect them throughout their lives, including in school skills. It is reiterated that longitudinal studies are important to monitor and prevent these changes.

A opacificação do cristalino presente ao nascimento ou nos primeiros meses de vida é denominada de Catarata Congênita (CC). As primeiras semanas de vida são importantes no desenvolvimento visual, já que há diferença significativa no desempenho visual de crianças que passaram pela cirurgia até seis semanas de vida (com melhor desempenho visual) em relação às crianças que realizaram a cirurgia após seis semanas de vida. Crianças que tiveram privação visual durante a primeira infância por catarata bilateral apresentam redução da visão espacial. O objetivo deste trabalho foi verificar o impacto na Função de Sensibilidade ao Contraste (FSC) em crianças de tratamento cirúrgico de Catarata Congênita, durante a fase de desenvolvimento visual. Foram avaliados três grupos: 11 crianças do grupo controle (média idade =6,83; DP=1,38), 9 crianças do grupo CC (média idade =6,87; DP=2,03) e 15 indivíduos adultos (média idade =27,63; DP=4,16). Foi utilizado o software Metropsis para avaliação da sensibilidade ao contraste de luminância de grade senoidal nas frequências espaciais de 0,2 cpg; 0,5 cpg; 1,0 cpg; 2,0 cpg; 4,2 cpg e 8,9 cpg e luminância média de 34,4 cd/m². Houve redução em toda a curva de sensibilidade ao contraste (SC) do grupo CC quando comparado ao grupo controle e não houve relação entre o tempo de privação e a redução da SC / The opacification of the lens present at birth is called Congenital Cataract (CC). The first weeks of life are important in visual development since there is not any significant difference in visual performance of children who had surgery within six weeks of life (with better visual performance) compared with children who underwent surgery after this period. Children who have visual deprivation during infancy due to bilateral cataracts have reduced spatial vision. The aim of this study was to assess the impact on Contrast Sensitivity Function (CSF) in children with Congenital Cataract surgery during the visual development age range. We evaluated three groups: 11 control children (mean age = 6.83, SD = 1.38), 9 children in the CC group (mean age = 6.87, SD = 2.03) and 15 adults (mean age = 27.63, SD = 4.16). Metropsis software was used to evaluate sensitivity to luminance contrast of the sinusoidal grating spatial frequencies of 0.2 cpd, 0.5 cpd, 1.0 cpd, 2.0 cpd, 4.2 cpd and 8.9 cpd with an average luminance of 34.4 cd / m². There was a reduction in the contrast sensitivity function (CSF) of the CC group compared to the control group and there was no correlation between the duration of deprivation and the impairment in the SC

Background: Children with congenital heart disease (CHD) often face barriers unique to their diagnoses, making participation in community physical activity programs difficult. This pilot, feasibility study evaluated the appropriateness (i.e. feasibility and enjoyment ) of the Sportball program among a group of children with CHD. This study also sought to observe any changes in physical literacy outcomes and to explore physical activity perceptions of participants, in order to better inform the future use of community-based interventions for this population. Methods: This study employed a mixed-methods evaluation of a 10-week community-based intervention. Data from two focus groups (baseline and post-intervention) and field notes after each intervention session were collected. Physical literacy outcomes were determined using the Canadian Assessment of Physical Literacy. Results: Participants with CHD (n=9) successfully participated in Sportball, as demonstrated by the ability of all participants to complete program activities, participants’ overall enjoyment of the program and fair attendance (approximately 80% of intervention sessions). Improvements in motor skill and torso strength were observed, with a statistically significant difference (p < 0.01) in motor skill classification. Participation in Sportball facilitated positive social interactions during sport and was influenced by personal, social and environmental factors. Conclusion: Overall, participation in Sportball is appropriate for children with CHD who may have motor development delays and/or activity restrictions.

Congenital microcephaly (conMiC) is a manifestation of severely disrupted prenatal brain development, caused by genetic defects, toxins, severe maternal malnutrition, or infection. The Zika virus outbreak and the devastating impact of Zika infection on the fetal brain have focused much attention on the cellular and molecular pathophysiology of conMiC. Mendelian conMiC disorders offer a unique opportunity for understanding gene and protein networks that direct cellular processes essential for prenatal brain development. Using OMIM and literature searches, I analyzed 68 conMiC disorders and their 65 corresponding genes. ConMiC-disorder phenotypes were characterized by analyzing the co-occurrence of ID, retinal abnormalities, seizures, and short stature. Short stature co-occurred with 70% of conMiC disorders, while seizures and retinopathy co-occurred with 68% and 37%, respectively. In 53% of conMiC disorders, seizures and short stature overlapped, while all features overlapped in 22% of conMiC disorders; only 7% of conMiC disorders lacked one of these co-occurring features. This shows conMiC genes are rarely specialized for brain growth, with generalized functions in overall body growth, retinal development, and/or regulation of neural activity. ConMiC-gene transcript accumulation in the brain is typically greatest during the prenatal period, and then declines postnatally, suggesting active transcriptional repression. Nonetheless, in neurons and glia of the adult brain, 44 conMiC genes had confirmed persistent protein accumulation. Experimental evidence indicates transcription in neural progenitor cells (NPCs) for at least 82% of conMiC genes. The spatiotemporal expression patterns of conMiC genes tend to align well with their biological functions and corresponding mutant phenotypes. Nearly 60% of conMiC gene products have functions in the cell cycle and/or DNA repair. Most conMiC disorders are caused by recessive, loss-of-function mutations. There are direct binding and regulatory interactions amongst many conMiC genes, which interact in larger networks and shared pathways. Depletion of single conMiC gene products can affect the transcript and/or protein levels of other conMiC gene products, which could have a “domino effect”, and disrupt entire networks important for brain development. Further evidence for this model is that 22 conMiC genes are consistently dysregulated in Zika-infected developing human brain tissue. Due to the complexity of conMiC genes and their interactions, there are many unique challenges to developing treatments for conMiC, particularly conMiC caused by maternal Zika-virus infection. However, insights to treatment strategies could be gained by using human genetics to find potential modifiers, screening for drugs that can normalize disrupted cell cycle and DNA-repair processes, or can stabilize protein complexes that are disrupted due to a conMiC gene mutation.

>Magister Scientiae - MSc / Despite widespread rubella virus (RV) vaccination programs, annually RV still causes severe congenital defects in an estimated 100,000 children globally. A concerted attempt to eradicate RV is currently underway and analytical tools to monitor the global decline of the last remaining RV lineages will be useful for assessing the effectiveness of this endeavour. Importantly, RV evolves rapidly enough that much of its epidemiological information might be inferable from RV genomic sequence data. Using BEASTv1.8.0, I analysed publically available RV sequence data to estimate genome-wide and gene-specific nucleotide substitution rates, to test whether the current estimates of RV substitution rates are representative of the entire RV genome. During these investigations, I specifically accounted for possible confounders of nucleotide substitution rate estimates, such as temporally biased sampling, sporadic recombination, and natural selection favouring either increased or decreased genetic diversity (estimated by the PARRIS and FUBAR methods) at nucleotide sites within RV nucleic acid secondary structures (predicted by the NASP method). I determined that RV nucleotide substitution rates range from 1.19×10-3 substitutions/site/year (in the E1 region) to 7.52×10-4 substitutions/site/year (in the P150 region). I found that these differences between nucleotide substitution rate estimates in various RV gene regions are largely attributable to temporal sampling biases, such that datasets containing a higher proportion of recently sampled sequences will tend to have inflated estimates of mean substitution rates. Although there exists little evidence of positive selection or natural genetic recombination in RV, I revealed that RV genomes possess extensive biologically functional nucleic acid secondary structures and that purifying selection acting to maintain these structures contributes substantially to variations in estimated nucleotide substitution rates across RV genomes. Although both temporal sampling biases and purifying selection favouring the conservation of RV nucleic acid secondary structures have an appreciable impact on substitution rate estimates, I find that these biases do not preclude the use of RV sequence data to date ancestral sequences and evaluate the associated RV phylodynamics. The combination of uniformly high substitution rates across the RV genome and strong temporal signal within the available sequence data enabled me to analyse the epidemiological and demographical dynamics of this virus during these attempts to eradicate it. By implementing a generalized linear model (GLM) and symmetrical model of discretized phylogeographic spread, I was able to identify several predictive variables of geographical RV spread and detect transmission linkages between distinct geographical regions. These results suggest that, in addition to strengthened vaccination strategies, there also needs to be an increased effort to educate people about the effects of vaccination and risks of RV infection.

No description available.

Pulmonary vascular disease (PVD) and lung hypoplasia (LH) are the two main causes of mortality and morbidity in patients with congenital diaphragmatic hernia (CDH). Previous studies have shown that remodeling of the extracellular matrix (ECM) by elastase and matrix metalloproteinase (MMP) enzymes, concomitant with smooth muscle cell (SMC) proliferation and deposition of ECM proteins and growth factors, leads to primary pulmonary hypertension (PH) and that blockade of this pathway results in disease reversal. The aim of our study is to determine whether a similar pathway is induced in the PVD associated with CDH and to verify whether its inhibition will lead to reversal of PVD. Firstly, we confirmed various aspects of PVD in the nitrofen induced CDH rat model. These included: left lung hypoplasia, right ventricular hypertrophy, and increased arterial smooth muscle wall thickness alongside decreases in arterial lumen area and total number of distal pulmonary vessels. We also showed increases in elastase and matrix metalloproteinase (MMP) enzyme activities within distal pulmonary arteries (PAs), which, we were able to inhibit using serine elastase (sivelestat, elafin, and serpina1) and MMP (GM6001) inhibitors. Furthermore, we confirmed increased SMC proliferation and deposition of osteopontin (OPN) and epidermal growth factor (EGF) within the diseased vasculatures. We are now working on using sivelestat and GM6001 pharmaceuticals as well as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) modified to express elafin and serpina1 to determine their abilities to reverse the PVD associated with CDH. This project is part of our translational research program with the ultimate goal of developing a novel strategy of targeting PVD in infants with CDH to improve patient survival and long-term outcome.