Practices for respecting the newborn's sleep-wake cycle: Interventional study in the neonatal intensive care unit.

Objectives: Premature newborns are exposed to a great deal of over-stimulation, which can affect their cerebral development. For better sleep, certain practices should be recommended. The aim of this study was to evaluate the effect of a professional training program on the improvement of practices promoting respect for the newborn's sleep-wake cycle. Materials and Methods: This was an interventional study with a longitudinal, single-group, and before-and-after design. The experimental design followed a three-stage time series: Eight months before, three months after, then eight months after intervention. It targeted a comprehensive sample of 66 professionals. It took place between October 2020 and March 2022 at the Neonatal Intensive Care Unit of the Hassan II University Hospital in Fez, Morocco. It was based on an observation grid and a self-administered questionnaire, validated and tested with a Cronbach's alpha reliability of 0.91. Results: The light environment showed significant differences between the 1st and 3rd step (3.3% vs. 45.0%; P = 0.02; confidence interval [CI] = 13.644-10.456) for knowledge and (13.3% vs. 78.3%; P = 0.01; CI = 14.412-10.888) for practices; the noise environment showed a positive improvement between the 2nd and 3rd intervention (31.7% vs. 41.7%; P < 0.001; CI = 5.954-2.913) for knowledge and (65.0% vs. 73.3%; P < 0.001; CI = 3.597-1.236) for practices, with an average of (8.98 ± 0.30-28.15 ± 0.48; CI = 3.806-1.094) between the 1st and 3rd step. Practices surrounding sleep and wakefulness reported significant improvement between the three periods (14.35 ± 0.22 vs. 18.10 ± 0.35 vs. 19.90 ± 0.35; P P < 0.001; CI = 4.647-2.853) for sleep and (13.25 ± 0.48 vs. 22.27 ± 0.59; P < 0.001; CI = 10.563-7.471) for wakefulness with statistically significant correlations between knowledge and practices (0.426**) for sleep and (0.606**) for wakefulness. Conclusion: The study demonstrated the positive impact of this sleep management and assessment program on the development of professional skills. Its implementation requires rigorous application of developmental support strategies for individualized care in neonatology.

Developmentally supportive care in neonatology: Correlational study of the knowledge and declared practices of professionals.

•Developmental Care contributes to improving the quality of neonatal life.•Professionals must develop multidisciplinary approaches to clinical practice.•This research identified a low level of knowledge and practice in Developmental Care.•Significant correlations were detected between clinical practice and knowledge.•The implementation of Developmental Care seems to be a priority.

Rare variants in KDR, encoding VEGF Receptor 2, are associated with tetralogy of Fallot.

PURPOSE: Rare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear. METHODS: We conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. We studied gene-targeted mice and conducted cell-based assays to explore the role of KDR genetic variation in the etiology of TOF. RESULTS: Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11). CONCLUSION: Rare KDR variants, in particular PTVs, strongly associate with TOF, likely in the setting of different inheritance patterns. Supported by genetic and in vivo and in vitro functional analysis, we propose loss-of-function of VEGFR2 as one of the mechanisms involved in the pathogenesis of TOF.

Percutaneous coarctation dilatation under transthoracic echocardiography guidance solely without fluoroscopy in neonate intensive care.

INTRODUCTION: Neonatal coarctation has to be diagnosed and treated urgently. Actually, the surgical treatment is the main option. The coarctation dilatation is usually achieved under fluoroscopy guidance whenever indicated. Balloon angioplasty could be an alternative approach or transient measure in difficult cases with cardiogenic shock or severe cardiac insufficiency.In the reported case, we prove and discuss the major role of transthoracic echocardiography, which is used solely to guide the coarctation dilatation in neonate environment. OBJECTIVE: The reported case aims to assess the safety and the efficiency of two-dimensional TEE to guide the dilatation of aortic coarctation in neonate. CASE PRESENTATION: We describe successful dilatation of neonatal coarctation done exclusively using echocardiography in neonatal ICU at the bed. The procedure duration was 40 minutes (from the puncture to sheath removal). The coarctation was diagnosed easily and well described using TTE with good image quality obtained from supra-sternal plane and upper and left lateral view. TayShak balloon measuring 6 and 8 mm were used with a 0.018 French guided exchange wire.Complete relief of the coarctation was checked by TTE without recording any complication. The follow-up in the third month (the submission time of this manuscript) showed very good results without requiring any surgical intervention or additional restenosis. CONCLUSION: Our initial experience confirmed the safety and efficiency of coarctation dilatation using TTE as the only guidance tool at the bed in neonatal stage, especially in a case presenting severe metabolic and cardiac failure. This report suggests and encourages other potential applications in neonatology intensive care.

Absence of GATA4 Mutations in Moroccan Patients with Atrial Septal Defect (ASD) Provides Further Evidence of Limited Involvement of GATA4 in Major Congenital Heart Defects.

OBJECTIVE: Atrial septal defect (ASD) is one of the most common types of congenital heart disease (CHD). It is mainly caused by mutations of NK2 homeobox 5, GATA binding protein 4 (GATA4), and myosin heavy chain 6 in non-syndromic cases. This study aims to carry out, for the first time, the GATA4 mutation screening in a Moroccan population affected by ASD and compare the obtained mutation rate across populations. MATERIALS AND METHODS: A total of 33 patients were enrolled in this study. DNAs were extracted from peripheral blood samples, and we performed PCR-sequencing for GATA4 coding regions. Sequences were analyzed by sequence alignment and functional impact prediction tools. Mutation rate comparisons were performed by R software using the appropriate statistical tests. RESULTS: We detected 7 variants, but no pathogenic mutation was revealed, except for Asn352= that was assessed by human splicing finder algorithms to have a potential impairing effect on the splicing mechanism. Until proven by in vitro functional studies, the current pathogenic mutation rate in our cohort seems to be 0%. Statistical comparison with previous studies from all over the world shows no significant difference. Seemingly, comparison of previous GATA4 mutation rates among tetralogy of Fallot (TOF) populations shows no significant difference. CONCLUSION: The low rates of GATA4 mutations observed throughout ASD and TOF international populations may suggest a limited causality of GATA4 mutations in the main CHDs, which further confirms the co-involvement of additional genetic and/or environmental factors in the manifestation of these phenotypes.

Anomalous origin of left pulmonary artery from the ascending aorta: echocardiography assessment.

Anomalous origin of one pulmonary artery from the ascending aorta is a rare cardiac anomaly in which the pulmonary artery abnormally arises from the ascending aorta. Physiologically, most patients develop signs of cardiac failure due to high flow to both lungs. The purpose of this study is to demonstrate, with this rare anomaly, the accurate place of the echocardiography to establish diagnosis especially in the systemic or supra-systemic pulmonary hypertension.

GATA4 molecular screening and assessment of environmental risk factors in a Moroccan cohort with tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD) with an incidence of 1/3600 live births. This disorder was associated with mutations in the transcription factors involved in cardiogenesis, like Nk2 homeobox5 (NKX2-5), GATA binding protein4 (GATA4) and T-BOX1 (TBX1). GATA4 contributes particularly to heart looping and differentiation of the second heart field. OBJECTIVES: The aim of this study was to screen a Moroccan cohort with tetralogy of Fallot for GATA4 mutations, and to assess environmental risk factors that could be involved in the occurrence of this disorder. METHODS: Thirty-one non-syndromic TOF patients, enrolled between 5th April 2014 and 18th June 2015, were screened for GATA4 mutations using direct sequencing of GATA4 coding exons. Statistical assessment of different risk factors, which is a retrospective study, was carried out using Chi-square and Fisher's exact tests. RESULTS: We identified seven exonic variants in nine patients (two missense and five synonymous variants); in addition of eight intronic variants. Assessment of environmental risk factors shows significant association of maternal passive smoking with TOF in the Moroccan population. CONCLUSION: The present study allowed, for the first time, the molecular and environmental characterisation of Moroccan TOF population. Our findings emphasise particularly the strong association of passive smoking with the emergence of tetralogy of Fallot.

Novel NKX2-5 germline mutation in a Moroccan child with transitional atrio-ventricular septal defect (tAVSD).

Atrioventricular septal defect is a complex congenital heart defects (CHD) with a prevalence of approximately 4% of all CHDs. Transitional form of atrio-ventricular septal defect (tAVSD) associates ostium primum atrial septal defect, common atrioventricular annulus with distinct atrioventricular valvar orifices in addition of restrictive ventricular septal defect. We describe in this report clinical and molecular features of a Moroccan boy that carries a novel NK2 homeobox 5 (NKX2-5) germline mutation (Pro141Ala), and exhibits a transitional atrio-ventricular septal defect. This phenotype has never been reported in association with NKX2-5 germline mutations. Pro141Ala is a non-reported pathogenic mutation that alters the nuclear localization signal sequence, leading to disruption of NKX2-5 nuclear translocation mechanism. Such alteration would decrease nuclear transcriptional activity of NKX2-5 and impair cardiogenesis process. The present report comes to widen the phenotypic spectrum of congenital heart disease caused by NKX2-5 germline mutations, and highlights as well the importance of the nuclear localization system in NKX2-5 activity.

NKX2-5 molecular screening and assessment of variant rate and risk factors of secundum atrial septal defect in a Moroccan population.

OBJECTIVE: Secundum atrial septal defect (ASDII) has multifactorial etiology that is combination of environmental (e.g., mother's exposure to toxicity, ethnicity) and genetic causes. Aim of the present study was to screen a Moroccan population with ASDII for NKX2-5 variants and to assess risk factors that may contribute to emergence of the disorder. METHODS: Thirty-two non-syndromic ASDII patients were screened for NKX2-5 variants using direct sequencing of polymerase chain reactionamplified coding regions. Risk factor rates were compared to general population and assessed using Fisher's exact and chi-square tests. In this retrospective study, criteria of exclusion were suggestive or confirmed syndrome association. RESULTS: Three heterozygous variants were detected in 4 patients. NKX2-5 variant rate in present cohort is estimated to be about 9.4%. Two prominent risk factors in the Moroccan population were highlighted: consanguinity, rate of which was significantly high at 30.8%, and previous maternal miscarriage or sibling sudden death, observed in 34.6% of cohort. CONCLUSION: Impact of identified variants was discussed and possible disease-predisposing effect is suggested. Findings indicate that ASD may be favored by consanguineous marriage and that NKX2-5 variant rate in ASD patients may be affected by ethnicity. High level of maternal miscarriage and sibling sudden death suggests potential non-sporadic nature as result of putative genetic defect.

What prognosis for Ebstein's anomaly without surgery? Hassan II teaching hospital experience.

Background From the first description in 1886, significant progress was made on the treatment of Ebstein disease by mono and bi-ventricular surgery. Aim To highlight the prognosis of Ebstein's anomaly in the pediatric department of Hassan II hospital in Fez. Methods This is a descriptive and retrospective study of 4 years. Results We collected nine patients (seven boys and two girls) with a mean age of 5.3 years. Cyanosis was the main mode of revelation of the disease. In three patients Ebstein's anomaly was part of a malformative syndrome. All patients had only symptomatic medical treatment. Five patients are still alive at a follow up of one to six years. Conclusion Symptomatic medical treatment of Ebstein malformation may improve the prognosis of the disease.

Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases).

Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified.

Noonan syndrome-causing genes: Molecular update and an assessment of the mutation rate.

Noonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was PTPN11, followed by SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, and RIT1, and recently SOS2, LZTR1, and A2ML1, among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate laying the groundwork for future molecular diagnosis research, and the development of novel treatment strategies.

The first PTPN1 1 mutations in hotspot exons reported in Moroccan children with Noonan syndrome and comparison of mutation rate to previous studies.

BACKGROUND/AIM: Noonan syndrome is an autosomal dominant disorder with an incidence of 1/1000-2500. It results from protein-tyrosine phosphatase, nonreceptor type 11 (PTPN11) mutations in roughly 50% of cases. Mutational screening of PTPN11 has been carried out in different populations. Thus, the aim of this study was to screen, for the first time, PTPN11 mutations in a series of Moroccan Noonan syndrome patients. MATERIALS AND METHODS: We used bidirectional sequencing of exons 3 and 8, considered as PTPN11 mutation hot spots, and then compared the rate of mutational events of these exons between different populations using chi-square and Fisher's exact tests. RESULTS: We detected 3 heterozygous mutations (Asp6lGly, Tyr63Cys, and Asn308Ser) in 4 individuals of 16 sporadic patients (25%). The rate of mutation in our cohort did not differ from that of other populations. However, we found significant differences in the mutation rate of exon 8 between one Japanese cohort and some populations, which requires more investigations to be explained. CONCLUSION: The present study allowed identification of mutations clustered in exons 3 and 8 of the PTPN11 gene in a Moroccan Noonan syndrome cohort and enabled us to give appropriate genetic counseling to the mutation-positive patients.

Cutis Laxa syndrome: a case report.

Cutis laxa (CL) is a heterogeneous group of inherited and acquired connective tissue disorders characterized by a loose skin and variable systemic involvement (inguinal hernia, cardiopulmonary disease, and emphysema). Autosomal dominant, autosomal recessive and x-linked recessive patterns have been described in the inherited forms. Acquired forms of this disease have been associated with a previous inflammatory skin disorder (urticaria…). The characteristic symptomatological pattern is resulting from paucity of elastic fibers. We report an 18 months old baby boy with a congenital cutis laxa. He was admitted in pediatric unit for respiratory disorders. The diagnosis of CL syndrome is based on clinical assessment of typical skin features and the associated extracutaneous finding.

Multicentric Castleman's Disease in a Child Revealed by Chronic Diarrhea.

Multicentric Castleman's disease is a rare benign and unexplained lymphoproliferative disorder that is extremely uncommon in children. It presents with fever, systemic symptoms, generalized lymphadenopathy, and laboratory markers of inflammation. Its treatment is not standardized and its prognosis is poor. We report a novel case of multicentric Castleman's disease in a 13-year-old girl who had presented with chronic diarrhea as the only initial presenting symptom. The diagnosis of celiac or inflammatory bowel diseases was suspected, but two and a half years later, the diagnosis of multicentric Castleman's disease was brought following the appearance of abdominal mass whose biopsy revealed Castleman's disease in the plasma cell form. The outcome was favorable after treatment by corticosteroid, chemotherapy, and surgery. The occurrence of diarrhea as the initial symptom of multicentric Castleman's disease without lymph node involvement is very rare. This case report underlines the diagnostic difficulties and the long interval between onset and diagnosis when diarrhea occurs first.

Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review.

Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug.