786 resultados para PRETERM
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O objectivo deste estudo foi estudar o comportamento do tronco inferior antes e após um período de 4 meses de intervenção. Para isso avaliaram-se os ajustes posturais antecipatórios durante um movimento voluntário, realizado na posição de pé, recorreu-se à electromiografia para avaliar a actividade muscular da musculatura focal e postural e plataforma de forças para estimar a migração do CP. A amostra foi constituída por duas crianças de 6 e 8 anos, com o mesmo quadro motor, diplegia. Ambas são pré termo de 31 e 32 semanas de gestação e com lesão por LPV. Verificou-se que ambos activaram os paravertebrais, antes do deltóide anterior, no período antecipatório, mas não os abdominais. O CP deslocou-se posteriormente. Após intervenção os tempos de activação dos abdominais e o deslocamento do CP eram mais curtos. Foi demonstrado que melhorou a capacidade de activação da musculatura ventral após o período de intervenção.
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OBJECTIVE: To compare estimates of low birth weight (LBW), preterm birth, small for gestational age (SGA), and infant mortality in two birth cohorts in Brazil. METHODS: The two cohorts were performed during the 1990s, in São Luís, located in a less developed area in Northeastern Brazil, and Ribeirão Preto, situated in a more developed region in Southeastern Brazil. Data from one-third of all live births in Ribeirão Preto in 1994 were collected (2,839 single deliveries). In São Luís, systematic sampling of deliveries stratified by maternity hospital was performed from 1997 to 1998 (2,439 single deliveries). The chi-squared (for categories and trends) and Student t tests were used in the statistical analyses. RESULTS: The LBW rate was lower in São Luís, thus presenting an epidemiological paradox. The preterm birth rates were similar, although expected to be higher in Ribeirão Preto because of the direct relationship between preterm birth and LBW. Dissociation between LBW and infant mortality was observed, since São Luís showed a lower LBW rate and higher infant mortality, while the opposite occurred in Ribeirão Preto. CONCLUSIONS: Higher prevalence of maternal smoking and better access to and quality of perinatal care, thereby leading to earlier medical interventions (cesarean section and induced preterm births) that resulted in more low weight live births than stillbirths in Ribeirão Preto, may explain these paradoxes. The ecological dissociation observed between LBW and infant mortality indicates that the LBW rate should no longer be systematically considered as an indicator of social development.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Objectivo: Estabelecer valores de referência da robustez óssea nos primeiros dias de vida, em recém-nascidos de termo e pré-termo adequados para a idade de gestação nascidos em Portugal. Métodos: Foi medida a velocidade do som (VdS) (m/s) por ultrassonografia quantitativa, numa amostra sistemática de recém-nascidos adequados para a idade de gestação, de termo e pré-termo, respectivamente nos primeiros dois e cinco dias após o nascimento. Foi avaliada a homogeneidade de valores entre géneros e entre grupos de idade de gestação. Resultados: A amostra constou de 158 recém-nascidos, 34 de termo e 124 pré-termo (idade de gestação entre 26 a 41 semanas), com peso de nascimento de 595 g a 4195 g, 84 do sexo masculino (53,2%) e 20 gémeos (10,8%). A média da VdS aumenta significativamente com a idade de gestação. São providenciados valores de referência da VdS para os percentis 10, 25, 50, 75 e 90, para grupos de idade de gestação, sem distinção para o género. Conclusão: São disponibilizados valores de referência de VdS nos primeiros dias de vida, de recém-nascidos adequados para a idade de gestação, de termo e pré-termo, nascidos em Portugal. Estes valores reflectem a robustez óssea intrauterina e servem de referência basal para estudos evolutivos realizados em Portugal.
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The didactic update on requirements, types of feeding and dosages of nutrients by Su is a useful guide for clinicians on optimization of nutrition in preterm infants. We take this opportunity to focus on postdischarge nutrition in very preterm infants, which has not yet reached consensus, because of concerns regarding the potentially negative consequences of rapid catch-up growth on obesity and metabolic programming. Some formula feeding approaches have been proposed when mother’s milk is not available.
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OBJECTIVE: To investigate the relationship between physical activity during the second trimester pregnancy and low birth weight, preterm birth, and intrauterine growth restriction. METHODS: Case-control study including 273 low birth weight newborns and 546 controls carried out in the city of São Paulo, Southeastern Brazil, in 2005. Low birth weight cases were grouped into two subsamples: preterm birth (n=117) and intrauterine growth restriction (n=134), with their related controls. Information was collected by means of interviews with mothers shortly after birth and transcription of medical records. Data were analyzed using conditional multiple and hierarchical logistic regression. RESULTS: Light physical activity for over 7 hours per day was shown to be protective against low birth weight (adjusted OR=0.61; 95% CI 0.39-0.94) with a dose-response relationship (p-value for trend=0.026). A similar trend was found for intrauterine growth restriction (adjusted OR=0.51; 95% CI 0.26-0.97). Homemaking activities were associated as a protective factor for both low birth weight and preterm birth (p-value for trend=0.013 and 0.035, respectively). Leisure-time walking was found to be protective against preterm birth. CONCLUSIONS: Mild physical activity during the second trimester of pregnancy such as walking has an independent protective effect on low birth weight, preterm birth, and intrauterine growth restriction.
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OBJECTIVE To identify independent risk factors for non-breastfeeding within the first hour of life.METHODS A systematic review of Medline, LILACS, Scopus, and Web of Science electronic databases, till August 30, 2013, was performed without restrictions on language or date of publishing. Studies that used regression models and provided adjusted measures of association were included. Studies in which the regression model was not specified or those based on specific populations regarding age or the presence of morbidities were excluded.RESULTS The search resulted in 155 articles, from which 18 met the inclusion criteria. These were conducted in Asia (9), Africa (5), and South America (4), between 1999 and 2013. The prevalence of breastfeeding within the first hour of life ranged from 11.4%, in a province of Saudi Arabia, to 83.3% in Sri Lanka. Cesarean delivery was the most consistent risk factor for non-breastfeeding within the first hour of life. “Low family income”, “maternal age less than 25 years”, “low maternal education”, “no prenatal visit”, “home delivery”, “no prenatal guidance on breastfeeding” and “preterm birth” were reported as risk factors in at least two studies.CONCLUSIONS Besides the hospital routines, indicators for low socioeconomic status and poor access to health services were also identified as independent risk factors for non-breastfeeding within the first hour of life. Policies to promote breastfeeding, appropriate to each context, should aim to reduce inequalities in health.
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Introdução: Os recém-nascidos pré-termo estão em risco acrescido de desenvolver osteopénia, pela dificuldade no suprimento parentérico de aporte mineral suficiente. Existe uma grande amplitude de doses de cálcio e fósforo recomendadas para estes recém-nascidos por via parentérica, havendo também um elevado risco de precipitação mineral nestas soluções. A ultrassonografia quantitativa é um método recentemente utilizado para avaliação da mineralização óssea em recém-nascidos pré-termo. Objectivo: Medir a mineralização óssea a recém-nascidos pré-termo submetidos a nutrição parentérica com duas doses diferentes doses de cálcio e fósforo. Métodos: Foram incluídos recém-nascidos pré-termo (IGd<33semanas) consecutivos, com necessidade de aporte nutricional parentérico, que foram aleatorizados para receber um aporte parentérico diário de cálcio de 40-50mg.kg-1 (1,00-1,25 mmol.kg-1) (grupo Convencional) ou 70-80mg.kg-1 (1,75-2,00mmol.dl-1) (grupo Alta). Foi mantida a razão mássica Ca:P de 1,7:1 nos dois grupos. Foram efectuadas medições semanais por ultrassonografia quantitativa no ponto médio da tíbia, até serem atingidas as 40 semanas de idade de gestação corrigida. Estabeleceu-se um outro grupo (Controlo) referente apenas à mineralização óssea na primeira semana de vida de recém-nascidos (IGd<40 semanas), para reflectir a mineralização intrauterina. Resultados: Foram incluídos 19 recém-nascidos (grupo Convencional=7, grupo Alta=12), com (média±DP) IG 30,4±1.9 semanas e peso à nascença 1360±400g. Os recém-nascidos inclídos no grupo convencional apresentaram uma mineralização óssea significativamente inferior à dos controlos, o que não ocorreu quando comparados os grupos alta e controlo (para as 32 semanas de idade de gestação corrigida). Os recém-nascidos do grupo Convencional apresentaram ainda mineralização óssea significativamente mais baixa na terceira semana pós-natal, comparativamente com o grupo Alta (p=0,030). Conclusões: A manter-se a tendência, talvez haja um efeito benéfico de uma dose parentérica mais elevada de cálcio e fósforo na mineralização óssea de RNs pré-termo sem o risco de nefrocalcinose. A mineralização óssea intrauterina parece ser superior à do recém-nascido submetido a nutrição parentérica sem manipulação do seu aporte mineral; no entanto, a utilização de soluções parentéricas enriquecidas em minerais ósseos parece provocar uma mineralização óssea semelhante à adquirida no útero.
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RESUMO: Contexto: Indicadores fidedignos da composição corporal são importantes na orientação das estratégias nutricionais de recém-nascidos e pequenos lactentes submetidos a cuidados intensivos. O braço é uma região acessível para avaliar a composição corporal regional, pela medida dos seus compartimentos. A antropometria e a ultrassonografia (US) são métodos não invasivos, relativamente económicos, que podem ser usados à cabeceira do paciente na medição desses compartimentos, embora esses métodos não tenham ainda sido validados neste subgrupo etário. A ressonância magnética (RM) pode ser usada como método de referência na validação da medição dos compartimentos do braço. Objectivo: Validar em lactentes pré-termo, as medidas do braço por antropometria e por US. Métodos: Foi estudada uma coorte de recém-nascidos admitidos consecutivamente na unidade de cuidados intensivos neonatais, com 33 semanas de idade de gestação e peso adequado para a mesma, sem anomalias congénitas major e não submetidas a diuréticos ou oxigenoterapia no momento da avaliação. Nas vésperas da alta, foram efectuadas medições do braço, com ocultação, pelos métodos antropométrico, ultrassonográfico e RM. As medidas antropométricas directas foram: peso (P), comprimento (C), perímetro cefálico (PC), perímetro braquial (PB) e prega cutânea tricipital (PT). As área braquial total, área muscular (AM) e área adiposa foram calculadas pelos métodos de Jeliffee & Jeliffee e de Rolland-Cachera. Utilizando uma sonda PSH-7DLT de 7 Hz no ecógrafo Toshiba SSH 140A foram medidos os perímetros braquial e muscular e calculadas automaticamente as áreas braquial e muscular, sendo a área adiposa obtida por subtracção. Como método de referência foi utilizada a RM – Philips Gyroscan ACS-NT, Power-Track 1000 ®, 1.5 Tesla com uma antena de quadratura do joelho. Na análise estatística foram utilizados os métodos paramétricos e não paramétricos, conforme adequado. Resultados: Foram incluídas 30 crianças, nascidas com ( ±DP) 30.7 ±1.9 semanas de gestação, pesando 1380 ±325g, as quais foram avaliadas às 35.4 ±1.1 semanas de idade corrigida, quando pesavam 1786 ±93g. Nenhuma das medidas antropométricas, individualmente, constitui um indicador aceitável (r2 <0.5) das medições por RM. A melhor e mais simples equação alternativa encontrada é a que estima a AM (r2 = 0.56), derivada dos resultados da análise de regressão múltipla: AMRM = (P x 0.17) + (PB x 5.2) – (C x 6) – 150, sendo o P expresso em g, o C e o PB em cm. Nenhuma das medidas ultrassonográficas constitui um indicador aceitável (r2 <0.4) das medições por RM. Conclusões: A antropometria e as medidas ultrassonográficas do braço não são indicadores fidedignos da composição corporal regional em lactentes pré-termo, adequados para a idade de gestação.----------ABSTRACT: Background: Accurate predictors for body composition are valuable tools guiding nutritional strategies in infants needing intensive care. The upper-arm is a part of the body that is easily accessible and convenient for assessing the regional body composition, throughout the assessment of their compartments. Anthropometry and by ultrasonography (US) are noninvasive and relatively nonexpensive methods for bedside assessment of the upper-arm compartments. However, these methods have not yet been validated in infants. Magnetic resonance imaging (MRI) may be used as gold standard to validate the measurements of the upper-arm compartments. Objective: To validate the upper-arm measurements by anthropometry and by US in preterm infants. Methods: A cohort of neonates consecutively admitted at the neonatal intensive care unit, appropriate for gestational age, with 33 weeks, without major congenital abnormalities and not subjected to diuretics or oxygen therapy, was assessed. Before the discharge, the upper-arm was blindly measured by anthropometry, US and MRI. The direct anthropometric parameters measured were: weight (W), length (L), head circumference (HC), mid-arm circumference (MAC), and tricipital skinfold thickness. The arm area (AA), arm muscle area (AMA) and arm fat area were calculated applying the methods proposed by Jeliffee & Jeliffee and by Rolland-Cachera. Using the sonolayer Toshiba SSH 140A and the probe PSH-7DLT 7Hz, the arm and muscle perimeters were measured by US, the arm and muscle areas included were automatically calculated, and the fat area was calculated by subtraction. The MR images were acquired on a 1.5-T Philips Gyroscan ACS-NT, Power-Track 1000 scanner, and a knee coil was chosen for the upper-arm measurements. For statistical analysis parametric and nonparametric methods were used as appropriate. Results: Thirty infants born with ( ±SD) 30.7 ±1.9 weeks of gestational age and weighing 1380 ±325g were included in the study; they were assessed at 35.4 ±1.1 weeks of corrected age, weighing 1786 ±93g. None of the anthropometric measurements are individually acceptable (r2 <0.5) for prediction of the measurements obtained by MRI. The best and simple alternative equation found is the equation for prediction of the AMA (r2 = 0.56), derived from the results of multiple regression analysis: AMARM = (W x 0.17) + (MAC x 5.2) – (L x 6) – 150, being the W expressed in g, and L and MAC in cm. None of the ultrasonographic measurements are acceptable (r2 <0.5) predictors for the measurements obtained by MRI. Conclusions: The measurements of the upper-arm by anthropometry and by US are not accurate predictors for the regional body composition in preterm appropriate for gestational age infants.
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RESUMO - A Paralisia Cerebral (PC) deve ser olhada como uma patologia do neurodesenvolvimento: a infância é um período de actividade exploratória por essência, a restrição motora condiciona as várias áreas do desenvolvimento. Contextos, apoios, oportunidades e experiências de vida serão determinantes no desenvolvimento de todo o seu potencial. Objectivos/finalidade: Identificar, descrever, comparar e analisar factores de risco associados à PC, sua caracterização multidimensional e integração escolar aos 5 e 10 anos. Procurou‐se contribuir para a sua prevenção primária e secundária, e obter dados para planeamento e implementação dos programas de apoio. Métodos: Adoptou‐se a abordagem do Programa Nacional de Vigilância da Paralisia Cerebral (PNVPC) e da Surveillance of Cerebral Palsy in Europe (SCPE). Analisaram‐se factores de risco, competências funcionais, défices associados, severidade e integração escolar de duas populações de Lisboa e Vale do Tejo, (nascimento 1996/1997‐2001/2002 e prevalência aos 5 e 10 anos). Descreveram‐se os dados, efectuaram‐se correlações, aplicaram‐se testes de independência e compararam‐se com dados dos nadovivos, dados nacionais e europeus. Analisaram‐se os factores que influenciaram a integração escolar através de métodos de regressão logística. Resultados/Conclusões/Recomendações: 1,65‰ e 1,57‰ dos nadovivos desenvolveram PC; a prevalência aos 5 anos foi de 1,7‰ e de 1,48‰; 5,9% e 7,9% faleceram antes dos 5 anos. Em 2001/2002 verificou‐se aumento de: PC espástica bilateral‐2/3membros, prematuridade, causa pos‐neonatal, níveis funcionais ligeiros e graves; percentil estaturo‐ponderal <3 (5‐anos). Diminuição de: disquinésia, anóxia e alguns défices associados. Destacaram‐se as associação: prematuridade e PC espástica bilateral‐ 2/3membros; nascer de termo e anóxia, disquinésia, primíparas, défices associados e severidade; infecção pré‐natal e QI<50, epilepsia e severidade; causa pos‐neonatal e PC espástica bilateral‐4membros e múltiplos défices. Aos 5 anos, as variáveis explicativas para a não inclusão escolar foram: QI<50 e epilepsia; uma elevada percentagem de crianças com PC moderada/grave encontrava‐se integrada; 75% das que se encontravam desintegradas mantiveram‐se nesta situação aos 10. Nesta idade, as variáveis explicativas para a não inclusão escolar foram: QI<50 e motricidade fina; 35,1% encontrava‐se fora do ensino regular; 4,5%, embora em idade de escolaridade obrigatória, não frequentavam qualquer estabelecimento escolar. Informação sistematizada, abrangente, objectiva, simples e acessível, sobre novos casos de PC, factores de risco, prevalência em idades‐chave e caracterização multidimensional constitui uma ferramenta clínica e epidemiológica, que deve sustentar as políticas de saúde, educacionais e sociais, contribuindo para a permanência destas crianças no ensino regular, trazendo às crianças e famílias o suporte que as encorajem e sustentem nestes processos. ABSTRACT ------- Cerebral Palsy (CP) must be recognized as a neurodevelopmental disorder: childhood is, on its nature, a period for exploring the environment and therefore motor deficit interferes with all developmental areas. The context, support, opportunities and life experiences are determinants for the development of his full potential. Objective/Aim: To identify, describe, compare and analyze CP risk factors the multidimensional characterization and school integration levels at the age of 5 and 10 years. We aim to contribute to CP primary and secondary prevention and provide information for service planning and implementation of support programs. Methods: The approach of National Cerebral Palsy Surveillance Programme (NCPSP) and Surveillance of Cerebral Palsy in Europe (SCPE) were used. For two groups of children from Lisboa e Vale do Tejo region, birth data 1996/1997‐2001/2002 and prevalence at 5 and 10 years, were analyzed: CP risk factors, functional ability, associated impairments, severity and school integration settings. Data collected was described, analyzed using correlations, applied tests of independence and compared with new born data, national data and european data. To analyze the factors related to school inclusive settings, logistic regression was appealed. Results/Conclusions/Recommendations: 1,65% and 1,57‰ of the new‐born alive developed CP. The prevalence at 5 years was 1,7‰ and 1,48‰ 5,9% and 7,9% died before their 5th birthday. Bilateral spastic CP 2/3limb, preterm birth, cases of post‐neonatal origin, mild and sever functional impairment; weight and height percentile <3 at 5 years old Increased in 2001. Decreased dyskinetic CP, anoxia and some additional imparments. Were identified among other the association between prematurity and spastic bilateral CP‐2/3 members; born at term and anoxia, dyskinetic CP, first child, associated impairments and severity; prenatal infection and IQ<50, epilepsy and severity; post‐neonatal cause and spastic bilateral CP‐4 members and associated impairments. At 5‐years‐old the more explanatory variables for not be in a school inclusive settings were IQ<50 and epilepsy, a high percentage of children with moderate/severe CP was attending regular school, but most children who were out of inclusive settings at 5 years continue on this situations at 10‐years‐old. At this age the more explanatory variables for not be in a school inclusive settings were: IQ<50 and upper limb function; 35,1% were out of regular school; 4,5%, even in compulsory school age, are out of school. Standardized comprehensive, objective, simple and accessible information about CP new cases, risk factors, prevalence in the key‐age and children multidimensional characterization constitutes a clinical and epidemiological tool that should sustain health, educational and social policy. This would support the continuity of these children in regular schools, encouraging g them and their families in these processes.
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Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
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OBJECTIVE: To report a full-term newborn infant that developed a sepsis associated to meningitis caused by Neisseria meningitidis serogroup C on the 14th day of life. CASE DESCRIPTION: The patient was a term female infant, born to a mother with Systemic Lupus Erythematosus, with birth weight of 2,610g, Apgar Score 1, 4 and 8, who needed mechanical ventilation for 24 hours. On the 7th day of life, the neonate was discharged from the hospital with good overall condition. On the 15th day of life, the newborn infant presented fever and respiratory failure. The cerebrospinal fluid showed 1042 cells/mm³, with neutrophilic predominance, protein of 435 mg/dL, and glucose < 10 mg/dL. The blood and the cerebrospinal fluid cultures were positive for Neisseria meningitidis serogroup C. The neonate was hospitalized, needing mechanical ventilation and vasoactive drugs, and received 21 days of crystalline penicillin. After hospital discharge, there were no signs of neurological sequels and the infant was able to be breastfed. The case report presents a unique situation: an uncommon etiology of neonatal meningitis and favorable evolution, despite neurological sequels reported in the literature. This report emphasizes the need to prevent the premature exposure of newborn infants to pathological agents, especially if they presented birth injuries and/or are preterm, due to their lack of immunological capacity.
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Introduction: Uncontrolled studies suggest that twins conceived by in vitro fertilization have increased rates of preterm birth and low birth weight and would warrant increased antenatal monitoring. The objective of this study was to compare the obstetric outcome of twin pregnancies conceived by in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) and ovulation induction with those conceived spontaneously. Methods: All twin deliveries achieved by IVF/ICSI (n=235) and ovulation induction (n=68) from September 1994 through December 2010 were evaluated. Both groups and an additional control group who conceived spontaneously (n=997) and was delivered during the same time period were compared with each other. Results: In univariate analysis, patients who conceived with the assistance of IVF/ICSI had a significantly higher risk of being older (p=0.01), nulliparous (p=0.01), having hypertensive disorders (p=0.012), gestational diabetes mellitus (p=0.031), cesarean section (p=0.008) and lower gestational age at birth, compared with the control group. Newborns had similar birthweights in all groups (2229±544g; 2102±619g; 2251±553g). Spontaneous pregnancies had a higher risk of being monochorionic 38.4% versus 16.2% and 10.2% (p=0.01). Multivariate analysis however showed that patients who conceived with the assistance of IVF/ICSI only had a higher risk of gestational diabetes (OR=1.91,95%CI 1.168-3.120; p=0.01). Conclusions: Our study shows that twin pregnancies conceived with the assistance of IVF/ICSI had a higher risk of gestacional diabetes and a lower gestacional age at birth. Birthweights were similar, as was the incidence of perinatal death, low birth weight infants, and congenital malformations.
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This retrospective study was designed to evaluate the outcome of pregnancies in women diagnosed with systemic lupus erythematosus (SLE) followed in a tertiary fetal–maternal center. Data were collected from clinical charts between January 1993 and December 2007, with a total of 136 pregnancies (107 patients). Mean maternal age was 29 years, with the vast majority of patients being Caucasian. Most patients were in remission 6 months prior to pregnancy (93%) and the most frequently affected organs were the skin and joints. Renal lupus accounted for 14% of all cases. Twenty-nine percent of patients were positive for at least one antiphospholid antibody (aPL) and nearly 50% had positive SSa/SSb antibodies. All patients with positive aPL received low-dosage aspirin and low molecular- weight heparin (LMWH). There were no pregnancy complications in more than 50% of cases and hypertensive disease and intrauterine growth restriction were the most common adverse events. There were 125 live births, one neonatal death, eight miscarriages, and three medical terminations of pregnancy. Preterm delivery occurred in 25% of pregnancies. Our results are probably the conjoined result of a multidisciplinary approach together with a systematic management of SLE pregnancies, with most patients keeping their prior SLE medication combined with low-dosage aspirin and LMWH in the presence of aPL.
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Background: Although epilepsy is common in children with cerebral palsy (CP), no data exists on prevalence rates of CP and epilepsy. Aims: To describe epilepsy in children with CP, and to examine the association between epilepsy and neonatal characteristics, associated impairments and CP subtypes. Methods: Data on 9654 children with CP born between 1976 and 1998 and registered in 17 European registers belonging to the SCPE network (Surveillance of Cerebral Palsy in Europe)were analyzed. Results: A total of 3424 (35%) children had a history of epilepsy. Among them, seventy-two percent were on medication at time of registration. Epilepsy was more frequent in children with a dyskinetic or bilateral spastic type and with other associated impairments. The prevalence of CP with epilepsy was 0.69 (99% CI, 0.66e0.72) per 1000 live births and followed a quadratic trend with an increase from 1976 to 1983 and a decrease afterwards. Neonatal characteristics independently associated with epilepsy were the presence of a brain malformation or a syndrome, a term or moderately preterm birth compared with a very premature birth, and signs of perinatal distress including neonatal seizures, neonatal ventilation and admission to a neonatal care unit. Conclusions: The prevalence of CP with epilepsy followed a quadratic trend in 1976e1998 and mirrored that of the prevalence of CP during this period. The observed relationship between epilepsy and associated impairments was expected; however it requires longitudinal studies to be better understood.