Use of antioxidants supplementation on developmental outcomes in children with Down syndrome-A systematic review and meta-analyses.

BACKGROUND: The background of this study is to evaluate the published literature on the use of antioxidants in improving developmental outcomes in children with DS. METHODS: The systematic review included interventional studies (randomized controlled trials [RCTs] and quasi-RCTs [q-RCTs]) of children aged 0 to 18 years diagnosed with DS who received antioxidants to improve developmental outcomes. Studies were excluded if they were interventional studies with non-random allocation or lack of control group or non-interventional studies including observational studies, systematic and narrative review articles, editorials and commentaries. Studies were also excluded if data from participants with DS were included as part of a larger group of participants (e.g., children with intellectual disability) and the data could not be separated for subgroup analysis, or if outcomes did not assess developmental domains (e.g., reported biochemical markers only). The review included children with other conditions associated with developmental disability, only when data for children with DS were separately reported. RESULTS: Eleven RCTs and q-RCTs fulfilled the eligibility criteria with 683 participants with Down syndrome ranging in age from newborns to 17 years. Nine studies did not show any statistically significant clinical benefit of using antioxidants. Three studies were included in a meta-analysis comparing changes in the effect sizes (post and pre-intervention) in Global Developmental Quotient (GDQ) between the intervention and control groups. CONCLUSION: This review concludes that it is likely that the results are valid and suggest that the use of Antioxidant has no improvement in GDQ for children with DS. It is also unclear if any benefit exists for other developmental domains.

Infantile Spasms: Clinical profile and treatment outcomes.

BACKGROUND AND OBJECTIVE: Infantile spasm (IS) is one of the severe epileptic encephalopathies which affect children in early two years of life. Our objective was to determine the clinical profile, etiology and outcome of treatment in children with infantile spasms attending tertiary care hospital at Karachi, Pakistan. METHODS: This is retrospective study of 36 patients out of 94 registered as IS, aged three months to two years, managed and followed up at Aga Khan University Hospital, Karachi, from 2010 to 2015. Data of all children with IS was collected from case record. Details including clinical observations, lab investigations, anti-epileptic medications and treatment outcome was collected and analyzed. Patients who received treatment for six weeks to document response were included. The treatment response was categorized as complete response, partial response (>50% improvement) and no response. Data was analyzed on SPSS using descriptive statistics. RESULTS: Thirty- six patients (38.29%) with IS fulfilled eligibility criteria. The mean ± SD age at presentation was 4.6±2.1 months. Male to female ratio was 2:1. Consanguinity and developmental motor delay was observed in 66.6% and 89% respectively. Symptomatic etiology was predominant (61%) and hypoxic ischemic insult (32%) was the commonest underlying cause. EEG and MRI were diagnostic tools whereas metabolic studies were not helpful. Multiple antiepileptic drugs were used for seizure control and vigabatrin was the most frequently used (88%) drug. Short term treatment response was not different in idiopathic or symptomatic infantile spasms. CONCLUSION: Majority of patients had symptomatic infantile spasms and generalized tonic clonic along with myoclonic jerks were predominant seizure types. EEG and MRI were diagnostic in most of cases. Multiple AEDs were required to control seizures and VGB was most common drug (88%) used. Treatment outcome was not different in idiopathic and symptomatic groups.

Menkes disease: A rare disorder.

Menkes disease (MD) (OMIM: 309400) is also known as kinky hair disease, trichopoliodystrophy, and steely hair. A 7-months-old, male infant presented to our outpatient department in June 2016 with history of developmental delay and seizures. Seizures started at 3 months of age and worsened progressively to clusters of extensor spasms. Physical examination showed sparse and kinky hair. Neurological examination revealed a central hypotonia with marked decrease in muscle power with normal deep tendon reflexes. The serum ceruloplasmin level and serum copper level were decreased. Ultrasound KUB showed Hutch diverticulum along left ureteric orifice. Magnetic resonance imaging (MRI) carried out at five months of age showed frontal cortical atrophy. His EEG was consistent with hypsarrythmia pattern. Patients with classic MD usually exhibit a severe neurodegenerative course, with poor long term outcome and death before the third year of life.

Knowledge Of Maintenance Intravenous Fluid Therapy In Acutely Ill Hospitalized Children Among Residents.

BACKGROUND: Isotonic saline is recommended as maintenance intravenous fluid therapy (MIVFT) for most of the acutely ill hospitalized children. The aim of this study is to assess the current knowledge of paediatric residents regarding the selection of MIVFT in hospitalized children. METHODS: We conducted a paper-based questionnaire survey to paediatric residents from ten centres asking selection of MIVFT in four common clinical scenarios in 6-month and 10-year old patients as well as monitoring of fluid balance and electrolyte. RESULTS: 445 responses were collected (>90% response rate). Majority [78.3% (n=348)] of them were FCPS-trainees. The 0.9%, 0.45% and 0.2% solution were selected by 45.8%, 43.98% and 10.92% respectively. The isotonic and hypotonic solution was prescribed in 6- mo (35.22% vs. 64.76% [p<0.001]) and 10-year (54.49% vs. 44.98%) in four different clinical scenarios respectively. 0.45% solution was most commonly prescribed MIVFT in pneumonia (50.22%) and meningitis (45.39%) and 0.9% solution was most commonly selected in acute gastroenteritis (55.05%) and post-operative patients (51.23%). Fluid balance and electrolyte monitoring were selected by 96.9% and 55.7% respondents respectively. CONCLUSIONS: Our survey reports that more than fifty percent of paediatric residents have inadequate knowledge about maintenance intravenous fluid therapy in acutely ill hospitalized children.

Referral Profile of Developmental Disabilities at a Tertiary Care Hospital in a Resource-limited Country.

The burden and the spectrum of neuro-developmental disabilities are well-established in the developed countries, however, they continue to be a challenge in the Low Middle-Income Countries. The aim of this study was to present the referral profile and trends of developmental disabilities in the child development centre of The Agha khan University, from 2012 to 2021. All children (1 month to 18 years), who had undergone diagnostic evaluations for suspected neurodevelopmental disabilities were included. A total of 1340 children were evaluated at the centre. The mean age of the children at the presentation was 5.4 ± 3.0 years. Male to female ratio was 3:1. Autism Spectrum Disorder (ASD) was the most common diagnosis (n=446, 33.3%). This study highlights a considerable burden and an increasing trend of children being referred for suspected developmental disabilities in Pakistan. Key Words: Developmental disabilities, Referral, Pakistan, Autism spectrum disorder.

Maternal and environmental Impact assessment on Neurodevelopment in Early childhood years (MINE): a prospective cohort study protocol from a low, middle-income country.

INTRODUCTION: Environmental and psychosocial adversities negatively impact children's developmental outcomes. When these factors are experienced in early childhood-a sensitive period of development-the developing brain can be altered. While these associations have been drawn in high-income countries, it is necessary to understand child growth, neurodevelopment, and the role of environmental factors in developmental trajectories in low-income settings. The objective of this study is to longitudinally assess how demographic factors, maternal health, maternal development, and child health, are related to child development on a behavioural, cognitive, and neuroimaging level in low-socioeconomic communities. METHODS AND ANALYSIS: Mother-child dyads will be identified in the peri-urban field sites of Rehri Goth and Ibrahim Hyderi, Karachi, Pakistan. Dyads will undergo yearly assessments for 4 years beginning when the child is 1 month, 3 months or 6 months of age (+≤30 days of age) (depending on group assignment). Maternal assessments include anthropometry, behavioural, cognitive, and developmental assessments (Edinburgh Postnatal Depression Scale; Parenting Stress Index; Maternal Autonomy Index; Hurt, Insult, Threaten, Scream Tool; Reynolds Intellectual Assessment Scales (RIAS)), and biological samples collection (breast milk, blood, stool, hair). Children's assessments include anthropometry, developmental assessments (Global Scales for Early Development (GSED); RIAS), MRI brain assessments, and biological sample collection (blood, stool, hair). Using cross-sectional and longitudinal data with statistical analysis tools, associations will be quantified between brain structure (MRI) and connectivity (resting state connectivity and diffusion tensor imaging), general cognitive skills (RIAS, GSED) and environmental influences (nutrition via biological samples, maternal mental health via questionnaires) through repeated measures analysis of variance tests and χ2 tests. Quantile regression and cortical analyses will be conducted to understand how demographic factors are related to the associations found. ETHICS AND DISSEMINATION: The study has received ethical approval from the Aga Khan University Ethics Review Committee. The study's findings will be disseminated through scientific publications and project summaries for the participants.

Neurocognitive abilities in individuals with Down syndrome-a narrative review.

Down syndrome (DS), or trisomy 21, is the most common genetic syndrome associated with intellectual disability. Despite the variability in expression, there is a distinct developmental phenotype characterized by deficits in learning/memory, executive functions, and language skills accompanying the psychomotor delay. The severity of intellectual impairment has the dominant effect on functioning, other influences such as parental and societal attitudes, supports available and social opportunities also play a role in the attainment of skills.

Brown-Vialetto-Van Laere syndrome: a novel diagnosis to a common presentation.

Brown-Vialetto-Van Laere syndrome (BVVLS) or riboflavin transporter deficiency (OMIM 211530) is a rare treatable autosomal recessive neurodegenerative disorder. This condition is associated with progressive pontobulbar palsy. We describe the clinical course of a 16-month-old boy with BVVLS and a novel homozygous mutation from Pakistan. Our patient presented with stridor and respiratory insufficiency. Hearing loss which is the most common sign of this condition was absent, making it an unusual presentation of BVVLS. His examination revealed ptosis and tongue fasciculation. His riboflavin receptor mutational analysis showed the homozygous mutation in the SLC52A3 gene. Per oral riboflavin was administered, and subsequently, he was able to be weaned off the ventilator. Now the child is improving and attaining developmental milestones.

Acute Necrotizing Encephalopathy of Childhood Secondary to Dengue Infection: A Case Report from Pakistan.

Acute necrotizing encephalopathy of childhood (ANEC) is a rare condition mainly affecting children with a distinct clinico-radiologic pattern. Initially thought to be secondary to respiratory viral infections, there have been more insights to the pathogenesis of ANEC including genetics. We present a case of a girl who developed this condition with classical clinico-radiologic findings of ANEC secondary to severe dengue infection and could not survive. We report this case with the aim to raise awareness about this fatal complication of dengue infection as dengue has become a global health-care problem.

Frequency and Outcome of Acute Neurologic Complications after Congenital Heart Disease Surgery.

OBJECTIVES: To determine the frequency and immediate outcome of acute neurologic complications (ANCs) in children undergoing congenital heart surgery (CHS). MATERIALS AND METHODS: In this retrospective study, all patients undergoing CHS at our hospital from January 2007 to June 2016 were included. Patients were followed up for the development of seizures, altered level of consciousness (ALOC), abnormal movements, and stroke. Results are presented as mean with standard deviation and frequency with percentages. RESULTS: Of 2000 patients who underwent CHS at our center during the study, 35 patients (1.75%) developed ANC. Seizures occurred in 28 (80%), ALOC in 5 (14%), clinical stroke in 2, brain death in 6 patients. Antiepileptic drugs (AEDs) were started in 32 patients, of which 13 patients required more than one AED. Mean length of stay was 10 ± 7.36 days. Of 35 patients who developed ANC, 7 expired during the study. CONCLUSION: Neurological complications are scarce but significant morbidity after CHS at our center.

Clinical profiles and outcomes of children admitted to the pediatric intensive care unit from the emergency department.

The aim of this study was to describe clinical profiles and outcomes of children admitted directly from the Emergency Room (ER) to the Pediatric Intensive Care Unit (PICU) of academic hospital. The medical records of all children (1 month to 16 years) admitted in PICU from ER, from January 2011 to December 2012 were reviewed. Of the 26,774 patients seen in the ER during the study period, 468 (1.7%) were admitted to the PICU which constituted about 41.5% (468/1127) of all the total PICU admissions. Sixty three percent (n=294) were under-five; males were 60.9% (285), 82.3% (385) were in medical category. Neurological and respiratory illnesses were the most common groups (> 50% of all ER admissions). Multi-organ dysfunction syndrome and co-morbidity were present in 25.2% (n=118) and 23.5% (n=110) respectively. The mean length of stay was 5 ± 3.7 hours. The case-fatality rate was 20.3% (n=95) as compared to the overall PICU mortality rate of 11.9% (n=135).