Pediatric craniopharyngioma: a 20-year study on epidemiological features, clinical presentation, and survival outcomes in a tertiary care center from LMIC.

INTRODUCTION: Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. METHODS: We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up. RESULTS: Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5 years (SD ± 4.5 years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5 years (± 2.1 SD, range: 2-10 years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed. CONCLUSIONS: Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life.

Process evaluation of paediatric fellowship training programs at a University Hospital in Pakistan.

BACKGROUND: Fellowship programs offer training in a subspecialty focusing on distinct and advanced clinical/academic skills. This advanced postgraduate training allows physicians, who desire a more specialized practice, to further develop clinical, academic, research, and leadership/administrative skills. The Aga Khan University (AKU) is one of the few institutes offering paediatric sub-specialty training in Pakistan. We aimed to evaluate the current Paediatric fellowship programs at AKU. METHODS: Process evaluation of six paediatric fellowship programs (cardiology, neurology, endocrinology, critical care medicine, neonatology, and infectious disease) was conducted from September 2020 to April 2021 by senior clinicians and medical educationists. Evidence was collected through document review (using existing postgraduate medical education program information form), observation of teaching and learning support, and focused group discussions/interviews with program faculty and fellows were conducted. A review of the evaluation report was done as part of this study. This study received an exemption from the ethical review committee. The quantitative data were analyzed using SPSS (22.0) while the reports of discussion with fellows and friends underwent content analysis. RESULTS: All fellowship programs met the criteria for having a robust competency-based fellowship curriculum as per the institutional and national guidelines. Formative assessment in the form of continuous evaluation was found to be integrated into all the fellowship programs, however, most of the programs were found to lack a summative assessment plan. Fellows in training and program faculty were satisfied with the opportunities for mentorship, teaching, and learning. Thematic analysis of the discussion reports with faculty and fellows revealed three key themes including, program aspects translating into strengthening the training, gaps in the training program in delivering the expectations, and making ways to reach par excellence. CONCLUSIONS: The process evaluation of paediatric fellowship programs provided an opportunity to holistically review the current strengths and quality of the training in individual programs along with the unmet needs of the trainees. This will help the program stakeholders to prioritize, align and allocate the resources to further enhance the quality of training and outcome of individual fellowship programs to ensure wider impacts at a regional, national, and international health system level.

Complementary Feeding Pattern and Nutritional Status of Children.

OBJECTIVE: To determine the complementary feeding patterns and their association with malnutrition. STUDY DESIGN: Prospective observational study. Place and Duration of the Study: Outpatient clinics of Aga Khan University Hospital, Pakistan, from June to November 2019. METHODOLOGY: A total of 207 children from age six to twenty-four months, who presented in the outdoor clinics of the study place, were enrolled. Data were recorded in a predesigned data sheet adopted from the infant and young child feeding module. Chi-square test was applied post-stratification and a p-value of <0.05 was taken as significant. RESULTS: Among a total of 207 children, 115 (55.6%) were males and 92 (44.4%) were females, with a mean age of 14.15 ± 5.6 months. Complementary feeding was started at an appropriate age in 124 (60%) children. Normal weight was seen in 133 (64.3%) children, while 73 (35.3%) were underweight. Stunting was presented in 44 (21.3%) children, whereas 163 (78.7%) children were of normal length. The most common reason for early initiation of complementary feeding was difficulty in continuing to breastfeed (n=50, 24.2%); the most common reason behind late complementary feeding was bottle feeding (n=45, 21.7%). CONCLUSION: Only sixty percent of mothers living in an urban setting started complementary feeding at an appropriate age. Various myths are counteracting complementary feeding practices. KEY WORDS: Complementary feeding, Infant's nutrition, Stunting, Wasting, Z-score.

Neonatal outcomes and congenital anomalies in pregnancies affected by hypothyroidism.

BACKGROUND: Maternal hypothyroidism has been reported to have concerns over neonatal outcomes, not only in the context of neurocognitive development but also in the short term as birth weight and neonatal jaundice. PATIENTS AND METHODS: We conducted a cross-sectional retrospective study on 638 cases who delivered live births in the Aga Khan University Hospital after ethical approval. Data were collected on hypothyroid pregnant females who were diagnosed before conception or during their antenatal visits during the year 2008-2016. Neonatal outcomes were noted for birth weight, maturity, and neonatal jaundice, neonatal hypothyroidism, neonatal respiratory distress syndrome, sepsis, hypocalcaemia, congenital anomalies, need for intensive care admission, and neonatal death. Subgroup analysis was performed on the timing of diagnosis of maternal hypothyroidism. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Neonatal jaundice was the most common neonatal outcome (37.6%) in our cohort of 662 live births. Nearly 15% required intensive care unit admission, however, neonatal death was very rare. The most common clinically significant congenital anomalies were cardiovascular defects, whereas Mongolian spots were the commonest congenital condition to report. There is a statistically significant association between low birth weight (OR 1.86, 95% CI 1.0-3.2, p ≤ 0.05) and congenital anomalies (OR 2.39, 95% CI 1.4-4.0, p ≤ 0.05) with women diagnosed with hypothyroidism before pregnancy. CONCLUSION: We report the neonatal outcomes and spectrum of congenital anomalies of hypothyroid pregnancies diagnosed before and during conception for the first time from the region of Pakistan.KEY MESSAGEOverall, none of the neonates of hypothyroid pregnancies developed congenital hypothyroidism.Cardiovascular defects in these neonates imply extensive screening and monitoring during pregnancy.Low birth weight and congenital anomalies are associated with the timings of diagnosis of hypothyroidism in pregnancy.

Establishing reference interval for thyroid-stimulating hormone in children below two-year ages in Pakistani population.

INTRODUCTION: Reference intervals (RIs) of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are age, assay and population specific. Currently, the age and assay-specific RIs for TSH are not available for children under two years of age. This study aimed to establish reference intervals for serum concentrations of TSH and FT4 in healthy children aged 1-24 months as per CLSI C28-A3 guidelines. METHODS: This prospective cross-sectional study was conducted in children from 1 to 24 months visiting the clinical laboratory for serum vitamin D testing but without any recent illness, hospitalization, medication and history of maternal thyroid diseases from August 2018 to March 2019 were invited to participate in the study.Serum TSH and FT4 were measured on ADVIA Centaur (Siemens Diagnostics, US), using chemiluminescence immunoassay. Kolmogorov-Smirnov test assessed normality of the data and RIs based on central 95% of the population were established using the non-parametric approach. RESULTS: After excluding one subject with confirmed congenital hypothyroidism, a total of 131 children were included in the study. The median (IQR) age of the study subjects was 12 months (11), and majority 78 (59.5%) were boys. The RIs were established using non-parametric approach as the data was not normally distributed. Reference interval for TSH was 0.73-4.94 µIU/mL and for FT4 was 0.81-1.51 ng/dl. CONCLUSION: We established assay-specific RIs for serum TSH and FT4 in children aged 1-24 months in our population. The RIs were slightly lower from RIs developed on other platforms in different population.

Needs assessment for curricular reform of a post graduate paediatric training programme at a private university hospital in Karachi, Pakistan.

In order to make and sustain changes in the curriculum, needs assessment is the key. We conducted a need assessment survey using a questionnaire based on a 7 point Likert Scale by residents and alumni. Over all response rate in the study was 77.5%. Fifty eight percent participants were females. Highest level of agreement (mean score 5.7) was found between the alumni and residents regarding the need to revise the content, teaching and assessment strategies in the programme. Twenty seven alumni (n= 38, 71%) had cleared their FCPS exams. The alumni thought that the existing teaching and assessment strategies do not facilitate in passing professional certificate exams (mean score 3.6). The mean attempts required by the alumni for clearing this exam was 3.3, and 84.2% considered their weak clinical skills as the reason for their recurrent failure.

Mabry Syndrome in a Child of South Asian Descent.

Mabry syndrome is the triad of seizures, hyperphosphatasia, and mental disability. It usually manifests in first year of life and has an autosomal recessive mode of inheritance. Besides the usual triad, other manifestations of Mabry syndrome include hypoplasia of distal phalanges, brachytelencepahly, gastrointestinal malformations and constipation, hypertelorism, short nose with a broad nasal bridge and dip, and thin upper lip with down turned corners of the mouth. More than 20 cases of Mabry syndrome have been reported in medical literature. Herein, we report the case of a six-month child with Mabry syndrome that presented with decreased neck holding, hypotonia and delayed motor milestones. The child also had a high-arched palate and hyperplastic malar eminences. Constipation was present but had a delayed onset, starting at 19 months of age. This is the first case of Mabry syndrome occurring in a child of South Asian descent.

Non O1, non O139 Vibrio cholerae bacteraemia in an infant; case report and literature review.

Non 01, Non O139 Vibrio cholerae bacteraemia is a rare but potentially fatal occurrence. There have been very few incidents of this infection from around the world. The treatment regimen of antibiotics also varies in literature. We present a case of bacteraemia caused by Non O1, Non O139 Vibrio cholerae along with associated risk factors, disease manifestations, laboratory diagnosis and treatment regimen. This serves to add additional information regarding symptoms and signs of this infection along with management of patient. Knowledge regarding this topic shall be highly useful to professionals if further cases are detected. In the discussion section, a review of literature of previous cases is also presented.

Spectrum of complications of severe DKA in children in pediatric Intensive Care Unit.

OBJECTIVES: To describe the spectrum of complications of Diabetic Ketoacidosis (DKA) observed in children admitted with severe DKA. METHODS: Retrospective review of the medical records of all children admitted with the diagnosis of severe DKA in Pediatric Intensive Care Unit (PICU) of the Aga Khan University Hospital, from January 2010 to December 2015 was done. Data was collected on a structured proforma and descriptive statistics were applied. RESULTS: Total 37 children were admitted with complicated DKA (1.9% of total PICU admission with 1.8% in 2010 and 3.4% in 2015). Mean age of study population was 8.1±4.6 years and 70% were females (26/37). Mean Prism III score was 9.4±6, mean GCS on presentation was 11±3.8 and mean lowest pH was 7.00±0.15. Complications observed included hyperchloremia (35.94%), hypokalemia (30.81%), hyponatremia (26.70%), cerebral edema (16.43%), shock (13.35%), acute kidney injury (10.27%), arrhythmias (3.8%), and thrombotic thrombocytopenic purpura (5.4%), while one patient had myocarditis and ARDS each. 13/37 children (35%) needed inotropic support, 11/37 (30%) required mechanical ventilation while only one patient required renal replacement therapy. Two patients (5.4%) died during their PICU stay. CONCLUSION: Hyperchloremia and other electrolyte abnormalities, cerebral edema and AKI are the most common complications of severe DKA.

Longitudinal changes in body mass index in children with craniopharyngioma.

OBJECTIVE: We investigated the relationship of body mass index at presentation and pituitary status with long-term changes in BMI over a period of 5 years. STUDY DESIGN: Craniopharyngioma patients (n = 25) attending a tertiary pediatric endocrine center were divided into three groups based on their BMI at presentation [BMI ≥ 2 standard deviation scores (SDS), 0-1.99 SDS, and <0 SDS) and then analyzed for trends of BMI over a period of up to 5 years. RESULTS: Median (interquartile range) BMI SDS and hypopituitarism at presentation versus at the 5-year follow-up were as follows: BMI SDS ≥ 2 group (n = 10): 3.55 (0.68), 6/10 versus 3.76 (1.13), 8/10; BMI SDS 0-1.99 group (n = 11): 1.68 (1.05), 3/11 versus 1.64 (2.04), 7/11, and BMI SDS <0 group (n = 4): -0.23 (0.93), 2/4 versus 0.61, 4/4. At the 5-year follow-up, 10/10, 7/11, and 1/4 subjects when divided in groups according to BMI at presentation were obese. CONCLUSIONS: Our data indicate that obesity at presentation, rather than panhypopituitarism either at or after presentation, predicts obesity 5 years after diagnosis. However, obesity at presentation is not always associated with the subsequent development of panhypopituitarism. Pediatric craniopharyngioma subjects who have BMI SDS ≥ 2 at presentation require early and aggressive intervention to help prevent the complications of obesity.

The upsurge of SSPE--a reflection of national measles immunization status in Pakistan.

Subacute sclerosing panencephalitis (SSPE) is a rare disorder in the developed world. However, an upsurge has been seen lately in our part of the world owing to inadequate measles immunization coverage. At the midst of our struggle against polio, we are struggling with the war against other vaccine-preventable childhood illnesses like measles. The increasing numbers of SSPE that we reported over the past half decade suggest an underlying periodic measles epidemic in Pakistan. In addition, children are now presenting with SSPE in early childhood, warranting a relook, reinforcement and strengthening of primary immunization and mandatory two-dose measles vaccination for all children nationwide. Previously undertaken Measles Supplementary Immunization Activity were a failure in terms of providing the expected cover against measles in young children. Intensive surveillance and establishment of SSPE registers at the district level is essential for eradication of this easily preventable disorder. Unless timely efforts are made to achieve global immunization, SSPE is bound to add to the national disability burden.

Adrenal insufficiency in a child with MELAS syndrome.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) are established subgroups of mitochondrial encephalomyopathy. m.3243A>G a common point mutation is detected in tRNA in majority of patients with MELAS phenotype whereas m.8344A>G point mutation in tRNA is observed, in MERRF phenotype. Adrenal insufficiency has not been reported in mitochondrial disease, except in Kearns-Sayre Syndrome (KSS), which is a mitochondrial deletion syndrome. We report an unusual presentation in a five year old boy who presented with clinical phenotype of MELAS and was found to have m.8344A>G mutation in tRNA. Addison disease was identified due to hyperpigmentation of lips and gums present from early childhood. This is the first report describing adrenal insufficiency in a child with MELAS phenotype.

Clinical profile and outcomes of paediatric patients with diabetic ketoacidosis at a tertiary care hospital in Pakistan.

OBJECTIVES: This study aims to present an experience in the management and clinical features of 88 children presenting with diabetic ketoacidosis (DKA) from Pakistan. METHODS: A retrospective medical chart review of all patients, < or = 15 years of age, who presented to the Aga Khan University Hospital, Karachi, Pakistan in the last ten years with a diagnosis of diabetic ketoacidosis was carried out. Severity of DKA was defined as mild (venous pH < 7.30 or bicarbonate=15mEq/l), moderate (venous pH < 7.2 or bicarbonate = 10 mEq/l) and severe (venous pH < 7 or bicarbonate < 5 mEq/l). These classes correspond to 1st, 2nd and 3rd degrees of diabetic ketoacidosis severity respectively. Cases in which diabetic ketoacidosis had occurred at onset of diabetic diagnosis were not included in the study. RESULTS: Mean age was 7.5 +/- 3.6 years; 58 (66%) patients were male. Twenty six patients had mild diabetic ketoacidosis, 44 had moderate while 18 had severe diabetic ketoacidosis at the time of presentation. Severity of diabetic ketoacidosis was significantly associated with the presence of infection, history of omission of insulin, poor compliance, presence of shock at time of presentation, length of stay in the hospital, final outcome (p < 0.01 for each of these associations) and Glasgow Coma Scale score (p = 0.02). Mortality in this series was 3.4%. CONCLUSION: Poor compliance was associated with the severity of diabetic ketoacidosis. Paediatric endocrinologists' should ensure that patients and their parents understand the importance of the need for regular insulin injections and regular monitoring of blood glucose.

Use of miltefosine in the treatment of visceral leishmaniasis in children at a tertiary care hospital of Karachi.

Existing standard treatment options for visceral leishmaniasis are less than optimal. We report here the use of oral miltefosine in the treatment of two paediatric cases of visceral leishmaniasis at a tertiary care hospital in Karachi, Pakistan. One patient came from Balochistan while the second patient was from Northern Pakistan. Both presented with a prolonged history of fever, massive hepatosplenomegaly, anaemia and thrombocytopenia. Visceral leishmaniasis was diagnosed with bone marrow studies. Amphotericin B was first started in the first patient; however severe hypokalaemia and allergic reaction occurred. Oral miltefosine was then administered. The child showed clinical improvement with regards to signs of leishmania infection but succumbed to a nosocomial infection during the hospital stay. In the second patient, miltefosine was started in the first instance. He showed remarkable clinical improvement. At 2 months follow-up, the child showed adequate weight gain along with successful resolution of hepatosplenomegaly and fever. Miltefosine has the potential to be considered a first line therapy for visceral leishmaniasis in developing countries; however larger studies are warranted to validate the trends observed in this small case series.

Newborn screening in Pakistan - lessons from a hospital-based congenital hypothyroidism screening programme.

We are living in a time of unprecedented increase in knowledge and rapidly changing technology. Such biotechnology especially when it involves human subjects raises complex ethical, legal, social and religious issues. The establishment of newborn screening programmes in developing countries poses major challenges as it competes with other health priorities like control of infectious diseases, malnutrition and immunization programmes. Despite this, it is imperative that the importance of newborn screening programmes is recognised by developing countries as it has been proven through decades of experience that it saves thousands of babies from mental retardation, death and other serious complications. Pakistan has an estimated population of 167 million inhabitants, 38.3% of whom are under 15 years of age. Pakistan lacks a national programme for newborn screening. However, as individual practice at the local level, Aga Khan University Hospital (AKUH) and a few other hospitals are doing newborn screening for congenital hypothyroidism. The main hurdle in the implementation of newborn screening in Pakistan is the lack of good infrastructure for health. Eighty percent of deliveries take place at home. Moreover, little resources are available for children identified with a genetic condition due to the non-existence of genetic and metabolic services in Pakistan. In a 20-year audit of congenital hypothyroid screening at AKUH we found 10 babies with congenital hypothyroidism. However due to missing data links spanning several years, we were unable to calculate its true incidence during this period. In order to estimate the incidence of congenital hypothyroidism (CH) we reviewed in detail data over 10 months in 2008, a period where there was better compliance for repeat thyroid stimulating hormone (TSH) testing, and found 2 babies with CH. This gave an estimated incidence of 1 in 1600 live births.