Polygenic risk scores and the need for pharmacotherapy in neonatal abstinence syndrome.

BACKGROUND: The aim of this study was to identify genetic variants associated with NAS through a genome-wide association study (GWAS) and estimate a Polygenic Risk Score (PRS) model for NAS. METHODS: A prospective case-control study included 476 in utero opioid-exposed term neonates. A GWAS of 1000 genomes-imputed genotypes was performed to identify variants associated with need for pharmacotherapy for NAS. PRS models for estimating genetic predisposition were generated via a nested cross-validation approach using 382 neonates of European ancestry. PRS predictive ability, discrimination, and calibration were assessed. RESULTS: Cross-ancestry GWAS identified one intergenic locus on chromosome 7 downstream of SNX13 exhibiting genome-wide association with need for pharmacotherapy. PRS models derived from the GWAS for a subset of the European ancestry neonates reliably discriminated between need for pharmacotherapy using cis variant effect sizes within validation sets of European and African American ancestry neonates. PRS were less effective when applying variant effect sizes across datasets and in calibration analyses. CONCLUSIONS: GWAS has the potential to identify genetic loci associated with need for pharmacotherapy for NAS and enable development of clinically predictive PRS models. Larger GWAS with additional ancestries are needed to confirm the observed SNX13 association and the accuracy of PRS in NAS risk prediction models. IMPACT: Genetic associations appear to be important in neonatal abstinence syndrome. This is the first genome-wide association in neonates with neonatal abstinence syndrome. Polygenic risk scores can be developed examining single-nucleotide polymorphisms across the entire genome. Polygenic risk scores were higher in neonates receiving pharmacotherapy for treatment of their neonatal abstinence syndrome. Future studies with larger cohorts are needed to better delineate these genetic associations.

FREQUENCY OF HOSPITAL ACQUIRED HYPONATREMIA IN A PEDIATRIC TERTIARY CARE SETTING.

BACKGROUND: Hyponatremia is the most commonly encountered electrolyte disorder in children. In our country the epidemiology of hospital acquired hyponatremia has hardly ever been explored whereas the administration of hypotonic IV fluids is widely practiced here. Therefore we pioneered to conduct this study to determine the frequency of hospital acquired hyponatremia. METHODS: This was a cross sectional study carried out at Aga Khan University Hospital, Karachi in paediatric ward and ICU over a period of 12 months. All children (>1 month and <15 years of age) admitted in paediatric units and on maintenance IV fluids who had serum sodium level measured on admission were included in the study and followed to identify patients who had a drop in serum sodium during hospitalization. Informed consent was taken from parents and collected data was recorded on a pro forma. RESULTS: A total of 865 patients were enrolled in the study. Hyponatremia was recorded in 405 patients on admission (46.8%) while hospital acquired hyponatremia was documented in 240. children (27.7%). Out of these 142 (59.2%) were male and 98 (40.8%) were female. Mean age of children in hospital acquired hyponatremia group was 60.67 months. Severity of hospital acquired hyponatremia was recorded as mild in 191 (79.6%), moderate in 35 (14.6%) and severe in 14 (5.8%) children. Major disease categories included gastrointestinal disorder (30.4 %), respiratory illness (12.5%), oncological disease (16.3%), cardiovascular disease (11.7%), infectious disease (9.2%) and neurological illness (8.3%). CONCLUSION: Hospital acquired hyponatremia is frequently encountered in our hospitalized children with majority of them receiving hypotonic IV solutions.

Aetiological profile of acquired anaemia in a paediatric tertiary care setting.

BACKGROUND: Anaemia is the commonest haematological disorder frequently faced by clinicians worldwide. The multi-factorial aetiology of the disorder warrants a comprehensive search for the different causes as management plans differ for different disorders. The objective of this study was to identify the different acquired causes of anaemia in our paediatric population. METHODS: The study was conducted at the Department of Paediatrics, Ayub Teaching Hospital from April 2009 to April 2010. It was a cross-sectional study. A total of 110 patients were included in the study who presented with anaemia secondary to acquired aetiologies and were assessed clinically using general physical and systemic examination. The salient clinical and laboratory data was retrieved in designed protocol. RESULTS: Out of a total of 110 patients, 61 (55.5%) were male and 49 (44.5%) were female. Mean age of the participants was 48 months. Nutritional anaemia comprising iron deficiency anaemia and megaloblastic anaemia was the leading cause being present in 49 (44.5%) patients followed by Visceral Leishmaniasis in 28 (25.5%) patients. Mean haemoglobin was 4.36 g/dl. CONCLUSION: Anaemia secondary to acquired causes is a disorder with grave consequences ranging from cognitive and psychomotor dysfunction to mortality in severe cases. Identification of the different acquired causes is important in preventing the disorder by guiding appropriate interventions.

Spectrum Of Congenital Heart Disease In Full Term Neonates.

BACKGROUND: Congenital heart disease is a significant problem world over especially in neonates. Early diagnosis and prompt interventions in neonatal period precludes the mortality associated with this disorder. The objective of this study was to highlight the diversity of congenital cardiac defects in our region so that appropriate interventions are devised to minimize significant morbidity and mortality associated with this disorder. METHODS: This descriptive cross-sectional study was conducted at the Neonatology Unit of Department of Paediatrics, Ayub Teaching Hospital from January 2015 to December 2016. Approval of ethical committee was taken. All fullterm neonates of either gender who presented in department of neonatology including those delivered in hospital or received from other sources (private settings, home deliveries), diagnosed as having congenital heart disease on echocardiography were included in the study. Preterm neonates of either gender were excluded from the study. Patient characteristics were recorded in a designed proforma. Data was entered in SPSS version 20 and analysed. RESULTS: A total of 89 neonates were included in the study. Mean age of presentation was 6.34±7.058 days and range of 1-28 days. There was a male preponderance with 57 (64%) male patients as compared to 32 (36%) female patients. Ventricular septal defect (VSD) was the commonest cardiac lesion being present in 34 (38.2%) patients. Other defects included complex congenital heart disease in 8 (9%), atrial septal defect (ASD) and transposition of great arteries (TGA) in 7 (7.9%) each, atrioventricular septal defect (AVSD) in 6 (6.7%) and Fallots's tetralogy (TOF) and hypoplastic left heart syndrome in 5 (5.6%) each.. CONCLUSIONS: Congenital heart disease is a problem of profound importance. It constitutes approximately one third of the total major congenital malformations. There is a diversity of cardiac lesions in our region that warrant early and prompt interventions so that the disease is recognized and treated at the earliest to reduce morbidity and mortality.