Cardiopulmonary bypass down-regulates NOD signaling and inflammatory response in children with congenital heart disease

In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pediatric CHD patients at five different time points: before CPB, immediately after CPB, and 1, 3, and 7 days after CPB. Real-time PCR, Western blot, and ELISA were performed to measure the expression of NOD1 and NOD2, their downstream signaling pathways, and inflammatory cytokines at various time points. Proinflammatorycytokine IL-6 and TNF-α levels in response to stimulation with either the NOD1 agonist Tri-DAP or the NOD2 agonist MDP were significantly reduced after CPB compared with those before CPB, which is consistent with a suppressed inflammatory response postoperatively. The expression of phosphorylated RIP2 and activation of the downstream signaling pathways NF-κB p65 and MAPK p38 upon Tri-DAP or MDP stimulation in PBMCs were substantially inhibited after CPB. The mRNA level of NOD1 and protein levels of NOD1 and NOD2 were also markedly decreased after CPB. Our results demonstrated that NOD-mediated signaling pathways were substantially inhibited after CPB, which correlates with the suppressed inflammatory response and may account, at least in part, for the increased risk of postoperative infection in pediatric CHD patients.

Adult congenital heart disease : long-term survival, arrhytmias, and emerging therapy

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A Québec mystery unveiled : the quest to understand hereditary sensory and autonomic neuropathy type 2

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors.

Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil

RAMOS, Ana Maria de Oliveira et al. Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil. Pediatric and Developmental Pathology, v.3, n.1, p.29-35, 2000

Chief Medical Officer's Report - Evidential Base and Clinical Practice Aspects of Congenital Cardiac Services (August 2013) (PDF 77KB)

Report on Evidential Base and Clinical Practice Aspects of Congenital Cardiac Services The principle drivers that should determine the optimal arrangements for the provision of congenital cardiac services, including  paediatric and adult cardiac surgery, for the population of Northern Ireland is how best those services can be configured to ensure the safest possible care that is of the highest quality possible in order to optimise outcomes and experience for patients and carers. Of necessity, this requires consideration of all requisite supporting services and arrangements to ensure access across the continuum of care. Such a configuration should support safe, high quality service provision on an on-going basis i.e. ensure sustainability as far as can be determined. In addressing this issue, consideration to the changing profile of population need and the evolving nature specialist services is required.  

Comparison of In-Person Versus Telephone Interviews for Early Syphilis and HIV Partner Services in King County, Washington (2010-2014)

Thesis (Master's)--University of Washington, 2016-08

Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil

RAMOS, Ana Maria de Oliveira et al. Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil. Pediatric and Developmental Pathology, v.3, n.1, p.29-35, 2000

Resting energy expenditure, macronutrient utilization, and body composition in term infants after corrective surgery of major congenital anomalies: a case-study

Introduction - Knowledge on the metabolic changes and nutritional needs during the postsurgical anabolic phase in infants is scarce. This analysis explores the associations of resting energy expenditure (REE) and macronutrient utilization with body composition of full-term infants, during catch-up growth after corrective surgery of major congenital anomalies. Methods - A cohort of full-term appropriate for-gestational-age neonates subjected to corrective surgery of major congenital anomalies were recruited after gaining weight for at least one week. REE and macronutrient utilization, measured by respiratory quotient (RQ), were assessed by indirect calorimetry using the Deltatrac II Metabolic Monitor ®. Body composition, expressed as fat-free mass (FFM), fat mass (FM) and adiposity defined as percentage of FM (% FM), was measured by air displacement plethysmography using the Pea Pod ®. Results - Four infants were included at 3 to 5 postnatal weeks. Recommended energy and macronutrient intakes for healthy term infants were provided. Through the study, the median (min-max) REE (Kcal/Kg FFM/d) was 70.8 (60.6-96.1) and RQ was 0.99 (0.72-1.20). Steady increases in both body weight and FFM were associated with initial decrease in FM and adiposity followed by their increase. Low RQ preceded decrease in adiposity. Conclusion - The marked adiposity depletion, not expected during steady weight gain in the postsurgical period, prompts us to report this finding. The subsequent adiposity catch-up was associated with relatively high REE and RQ, suggesting preferential oxidation of carbohydrates and preservation of lipids for fat storage.

Is there a relation between environmental exposure to teratogenic substances during pregnancy and congenital anomalies in the newborn? A pilot study in Portugal

Background: Maternal occupation as a proxy of environmental exposure has been consistently associated with specific congenital anomalies (CA) in the foetus and newborn. On the other hand, geographical location of the mother such as place of residence and place of work have not been used as proxy for environmental exposures during pregnancy. We designed a pilot study aiming to investigate the association between maternal place of residence and workplace during pregnancy and CA in Portugal. Methods: Cases and controls are identified in the maternity unit. Cases are all live births with at least one CA delivered in the Barreiro hospital located in a heavy industrial area near Lisboa. Controls are the two normal births following each case. Residents outside the study area, stillbirths and women who decline to participate or are incapable of giving consent are excluded. A health professional interviews the mothers using a questionnaire adapted from the registry form of the Portuguese national registry of CA and includes information on places during pregnancy (residence, workplace, leisure), and demographic characterization as place of birth, infant sex, weight, description of CA, age of mother, ethnicity, maternal birth place. Maternal health and obstetric history, education, smoking, alcohol, drugs and medication use is also collected as potential confounders. Results: The pilot study started in January 2016 and at the moment two cases and four controls have been recruited without refusals. The study will continue to be implemented and it is proposed to start in other hospital units during 2016.

A systematic review of trends and patterns of congenital heart disease in children in Nigeria from 1964-2015.

Background: Congenital heart diseases cause significant childhood morbidity and mortality. Several restricted studies have been conducted on the epidemiology in Nigeria. No truly nationwide data on patterns of congenital heart disease exists. Objectives: To determine the patterns of congenital heart disease in children in Nigeria and examine trends in the occurrence of individual defects across 5 decades. Method: We searched PubMed database, Google scholar, TRIP database, World Health Organisation libraries and reference lists of selected articles for studies on patterns of congenital heart disease among children in Nigeria between 1964 and 2015. Two researchers reviewed the papers independently and extracted the data. Seventeen studies were selected that included 2,953 children with congenital heart disease. Results: The commonest congenital heart diseases in Nigeria are ventricular septal defect (40.6%), patent ductus arteriosus (18.4%), atrial septal defect (11.3%) and tetralogy of Fallot (11.8%). There has been a 6% increase in the burden of VSD in every decade for the 5 decades studied and a decline in the occurrence of pulmonary stenosis. Studies conducted in Northern Nigeria demonstrated higher proportions of atrial septal defects than patent ductus arteriosus. Conclusions: Ventricular septal defects are the commonest congenital heart diseases in Nigeria with a rising burden.

Attention Deficit Hyperactivity Disorder in a Patient With Congenital Mirror Movement Disorder and Colpocephaly

Introduction: Congenital mirror movement disorder designates involuntary movements on one side of the body that occur as mirror of the intentional movements on the contralateral side. Colpocephaly is described as persistence of fetal configuration of lateral ventricles. Case Presentation: A two-month old male infant was brought to the hospital due to bilateral identical movements of the hands. Except for bilateral involuntary synkinetic imitative movements in hands, neurological and physical examination was normal. Cranial MRI showed corpus callosum dysgenesis, hypogenesis and dilation of bilateral lateral ventricular posterior horns (colpocephaly). At the age of 7 years, he was started to use metylphenydate to mitigate attention deficit and hyperactivity disorder. The mirror movements were decreasing in amplitude by years and were not so serious to affect normal life activities. Conclusions: Mirror movements, diagnosed usually during childhood, may be congenital or secondary to neurological diseases. Although they generally do not affect normal life activities, in some cases severity of mirror movements causes a real debilitating disease. In our case the patient was diagnosed at the age of 2 months and on follow-up no debilitating problems were observed. This is the first case to describe the association of colpocephaly and mirror movements. The exact mechanism of this association is not known. Although it is known that mirror movements may be in relation with some pychiatric pathologies, this is the first report of attention deficit and hyperactivity disorder in conjunction with mirror movements and/or colpocephaly. Managing comorbidities, either physical or psyhchological, will help the patient to live in good health without trying to cope with other pathological diseases.

Evaluation of Neurodevelopment and Factors Affecting it in Children With Acyanotic Congenital Cardiac Disease

Background: The rate of congenital heart disease is 0.8% in all live births. The majority of this, however, is acyanotic congenital heart disease. The survival rate of children with cardiac disease has increased with the developments provided in recent years and their lifetime is extended. Objectives: This study aims to evaluate neurodevelopment of children with uncomplicated acyanotic congenital heart disease in preschool period and determine the factors affecting their neurodevelopmental process. Patients and Methods: 132 children with acyanotic congenital heart disease aged 6 - 72 months were involved in the study. Mental development and intelligence levels of patients under 2 years old were assessed by using Bayley Development Scale-III, and Stanford Binet Intelligence test was employed for patients over 2 years old. Denver Developmental Screening Test II was applied to all patients for their personal-social, fine motor, gross motor and language development. Results: The average age of patients (67 girls, 65 boys) included in the study was 35.2 ± 19.6 months. It was determined that there were subnormal mental level in 13 (10%) patients and at least one specific developmental disorder in 33 (25%) patients. Bayley Mental Development Scale score of patients who had received incubator care in perinatal period was found significantly low (88 ± 4.2) compared to those with no incubator care (93.17 ± 8.5) (P = 0.028). Low educational level of father was established to be linked with low mental development scores at the age of 2 and following that age (P < 0.05). Iron deficiency anemia was discovered to be related to low psychometric test scores at every age (P < 0.05). Conclusions: Neurodevelopmental problems in children with acyanotic congenital heart disease were found higher compared to those in society. Mental development and intelligence levels of patients were determined to be closely associated with receiving incubator care, father’s educational level and iron deficiency anemia.

Congenital thoracic vertebral malformations in brachycephalic “screw-tailed” dog breeds: Validation of a human classification scheme and a method of Cobb angle measurement in the assessment of vertebral column deformity

Congenital vertebral malformations are common in brachycephalic “screw-tailed” dog breeds such as French bulldogs, English bulldogs, Boston terriers, and Pugs. Those vertebral malformations disrupt the normal vertebral column anatomy and biomechanics, potentially leading to deformity of the vertebral column and subsequent neurological dysfunction. The initial aim of this work was to study and determine whether the congenital vertebral malformations identified in those breeds could be translated in a radiographic classification scheme used in humans to give an improved classification, with clear and well-defined terminology, with the expectation that this would facilitate future study and clinical management in the veterinary field. Therefore, two observers who were blinded to the neurologic status of the dogs classified each vertebral malformation based on the human classification scheme of McMaster and were able to translate them successfully into a new classification scheme for veterinary use. The following aim was to assess the nature and the impact of vertebral column deformity engendered by those congenital vertebral malformations in the target breeds. As no gold standard exists in veterinary medicine for the calculation of the degree of deformity, it was elected to adapt the human equivalent, termed the Cobb angle, as a potential standard reference tool for use in veterinary practice. For the validation of the Cobb angle measurement method, a computerised semi-automatic technique was used and assessed by multiple independent observers. They observed not only that Kyphosis was the most common vertebral column deformity but also that patients with such deformity were found to be more likely to suffer from neurological deficits, more especially if their Cobb angle was above 35 degrees.