Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics.

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

The effects of N-acetylcysteine on lung alveolar epithelial cells infected with respiratory syncytial virus.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the most common causes of acute lower respiratory infection in infants and young children. Mucolytic agents, such as acetylcysteine and carbocysteine have reported benefits in alleviating acute upper or lower respiratory infections. Among these, N-acetylcysteine (NAC) has cyto-protective effects when cells are infected with the RSV. MATERIALS AND METHODS: Our study investigated primarily the dose-dependent effects of NAC on respiratory alveolar epithelial (A549) cells when co-cultured with RSV in vitro. Three different concentrations of NAC were used, 0.1 mM, 1 mM, and 10 mM. The cytotoxicity of RSV-infected cells was measured by lactate dehydrogenase and antiviral activity of NAC on cell cultures was evaluated by immunofluorescence. RESULTS: Pre-treatment with the highest dose, 10 mM NAC, resulted in features of cell injury even without RSV infection. The proportion of cells infected by RSV and RSV-induced cell death decreased by more than 3-fold when cells were pre-treated with 1 mM NAC. Pre-treatment at the lowest dose, 0.1 mM, did not show any significant changes. CONCLUSION: A moderate dose of NAC (1 mM) appeared protective of RSV infection to lung alveolar epithelial cells. However, a higher dose of NAC (10 mM) may be relatively toxic and injurious to these cells.

Evaluation of quantitative point-of-care test for measurement of glucose-6-phosphate dehydrogenase enzyme activity in Malaysia.

INTRODUCTION: The treatment of Plasmodium vivax malaria with 8-aminoquinolines is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals due to the risk of acute haemolytic anaemia. Effective G6PD screening is paramount to avoid adverse drug reactions. This study aimed to evaluate the performance of novel quantitative point-of-care (POC) tests as a new screening method for G6PD deficiency in Malaysia. MATERIALS AND METHODS: A total of 153 neonatal cord blood, 99 peripheral blood of older children aged between 1 month to 12-years old, and 62 peripheral adult blood were screened for G6PD deficiency using two quantitative POC tests, CareStartTM biosensor (Carestart) and CareStartTM Biosensor 1 (S1). The results were compared with OSMMR2000D kit as a reference assay. Two statistical analyses were performed in this study to evaluate the POC test performances, the Spearman's correlation test and the Cohen's kappa method. RESULTS: Both Carestart and S1 tests showed significant positive correlations to OSMMRS000D with r2 = 0.7916 and r2 = 0.7467. Their measurement of agreement showed a kappa (κ) value of 0.805 (p<0.001, 95% CI), and 0.795 (p<0.001, 95% CI), respectively. Analysis of the area under the Receiver Operating Curve (ROC) at 60% cut-off illustrated that the Carestart had 90.2% sensitivity, 98.9% specificity, 98.3% positive predictive value (PPV), and 93.8% negative predictive value (NPV). The corresponding values for the S1 were 95.2%, 100%, 100%, and 96.8%, respectively. CONCLUSION: This study showed that the Carestart and S1 biosensors have high-performance reliability for screening of G6PD deficiency, which can guide safe prescriptions of anti-malaria medications and hence, eradication of Plasmodium vivax malaria.

COVID-19 vaccination for children in Malaysia - A position statement by the College of Paediatrics, Academy of Medicine of Malaysia.

The availability of COVID-19 vaccines and mass vaccination programmes in adults have significantly reduced the case attack rates and disease burden. COVID-19 vaccination successfully decreases the population at risk of infection, allowing for the safer re-opening of economies and reducing the pandemic's crippling impact on healthcare systems. However, the rapidly mutating severe acute respiratory syndrome-coronavirus-2 poses challenges in diminishing vaccine-induced immunity and vaccinating a significant proportion of adults to achieve herd immunity. These challenges necessitated adolescent vaccination. With the recent emergence of the highly transmissible Omicron variant and the increasing COVID-19 hospitalisation rates of children below 12 years old, many countries opted to also vaccinate younger children. Phase II/III clinical trials and real-world experience demonstrate that COVID-19 vaccinations are effective and safe for younger children and adolescents. Before Malaysia introduced its national COVID-19 vaccination programme for children 5-11 years old (which ran between March and June 2022), an expert advisory statement was issued by the College of Paediatrics, Academy of Medicine of Malaysia, to highlight the benefits and importance of vaccinating children. The advisory statement included clarifications about vaccine-related side effects such as post-vaccination myocarditis and allergic reactions to encourage informed decision making by healthcare providers and parents. This paper, which was prepared based on the critical appraisal of the current evidence, evaluation of the international experiences and the positive impact of COVID-19 vaccination in children, collectively sums up the rationale to support and ensure the success of the nationwide vaccination programme for children. Hence, the College recommends COVID-19 vaccination for children in Malaysia.

Correction to 'Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation'.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation.

G6PD deficiency is the commonest enzyme deficiency found in humans. Current diagnostic methods lack sensitivity to detect all cases of G6PD deficiency. We evaluated the reverse dot blot flow-through hybridisation assay designed to detect simultaneously multiple known G6PD mutations in a group of Malaysian neonates. Archival DNA samples from 141 G6PD-deficient neonates were subjected to reverse dot blot flow-through hybridisation assay using the GenoArray Diagnostic Kit (Hybribio Limited, Hong Kong) and DNA sequencing. The method involved PCR amplification of 5 G6PD exons using biotinylated primers, hybridisation of amplicons to a membrane containing oligoprobes designed for G6PD mutations known to occur in the Malaysian population and colour detection by enzyme immunoassay. The assay detected 13 of the 14 G6PD mutations and genotyped 133 (94.3%) out of 141 (102 males, 39 females) cases. Among the 39 female G6PD-deficient neonates, there were 7 homozygous and 6 compound heterozygous cases. The commonest alleles were G6PD Viangchan 871G > A (21%) and G6PD Mahidol 487G > A(20%) followed by G6PD Mediterranean 563C > T, (14%), G6PD Vanua Lava 383T > C (12%), G6PD Canton 1376G > T (10%), G6PD Orissa 131C > G (6.3%) G6PD Coimbra 592C > T (5.6%) plus 6 other mutations. DNA sequencing of remaining cases revealed 6 cases of intron 11 nt 93C > T not previously reported in Malaysia and two novel mutations, one case each of nt 1361G > T and nt 1030G > A. We found the reverse dot blot assay easy to perform, rapid, accurate and reproducible, potentially becoming an improved diagnostic test for G6PD deficiency.

Severe acute respiratory syndrome-Coronavirus-2 infection: A review of the clinical-pathological correlations of Coronavirus disease-19 in children.

The coronavirus disease-19 (COVID-19) has become a global pandemic of acute respiratory disease in just less than a year by the middle of 2020. This disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has resulted in significant mortality especially among the older age population and those with health co-morbidities. In contrast, children are relatively spared of this potentially ravaging disease that culminates in the acute respiratory distress syndrome, multi-organ failure and death. SARS-CoV-2 infection induces exuberant release of pro-inflammatory mediators, causing a "cytokine storm" and hypercoagulable states that underlie these complications. The SARS-CoV-2 infection median incubation is 5.1 days, with most developing symptoms by 11.5 days. It is highly infectious, spreading via the horizontal mode of transmission, but there is yet very limited evidence of vertical transmission to the newborn infant occurring either transplacentally or through breastfeeding. This said, various immune factors during childhood may modulate the expression of COVID-19, with the multisystem inflammatory syndrome in children (MIS-C) at the severe end of the disease spectrum. This article gives an overview of the SARS-CoV-2 infection, clinical presentation and laboratory tests of COVID-19 and correlating with the current understanding of the pathological basis of this disease in the paediatric population.

Gardnerella vaginalis in perinatology: An overview of the clinicopathological correlation.

Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1ß and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.

Tracheal agenesis: a rare cause of unsuccessful tracheal intubation during resuscitation.

Tracheal agenesis is a rare congenital airway anomaly that usually results in a fatal outcome. The diagnosis is usually made through post-mortem examination. In the current literature, there has been no reported long-term survival although a few reports claimed prolongation of life of several hours to days. This condition is commonly associated with premature birth, polyhydramnios and a male predominance. In 90% of the cases, it is associated with multiple cardiovascular, gastrointestinal and genitourinary tract anomalies which are incompatible with life. We report a case of a premature newborn with severe respiratory distress, absent cry and cyanosis soon after birth. Attempts at endotracheal intubation failed as it was no possible to negotiate the tube beyond the vocal cords. Needle cricothyrotomy and attempted tracheostomy also failed to secure the airway. The diagnosis was confirmed at post-mortem examination.

The role of serum insulin-like growth factor I (IGF-I) in neonatal outcome.

AIMS: To determine the role of serum insulin-like growth factor I (IGF-I) in predicting the occurrence of septal hypertrophic cardiomyopathy in infants of mothers with diabetes. METHODS/MATERIALS: In this prospective study, 100 pregnant women (50 with diabetes and 50 controls), matched for age and race, were studied. One intrapartum blood sample was taken at 28 weeks of gestation from both groups of mothers and another sample at delivery. All samples were analysed for maternal IGF-I by an enzyme linked immunosorbent assay method. A chest radiograph and an electrocardiogram were performed on the babies of the mothers with diabetes within the first 24 hours of life. An echocardiogram was performed in the first 3 days of life to look for septal hypertrophy and to measure the myocardial thickness. RESULTS: In the six cases of neonatal septal hypertrophic cardiomyopathy, all the mothers had greatly raised IGF-I concentrations of more than 400 ng/ml at the time of delivery compared with a mean (SD) of 302 (25) ng/ml in control mothers. CONCLUSIONS: In the present study a crude analysis revealed that increased IGF-I concentrations correlate with neonatal septal hypertrophic cardiomyopathy.

Chylothorax after repair of congenital diaphragmatic hernia--a case report.

Chylothorax is a rarely recognised post-operative complication following repair of congenital diaphragmatic hernia. We report here a newborn infant with this condition which resolved with percutaneous chest drainage, total parenteral nutrition and enteral feeding of a formula high in medium-chain triglycerides.

ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency presenting as Hydrops Foetalis.

ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency G6PD are common haematological problems affecting the newborn. The resulting haemolytic disease of foetus and newborn (HDFN) caused by either of these pathologies generally follows a benign course. It is typically characterized by mild jaundice without significant anaemia. ABO incompatibility alone as a cause of foetal hydrops is extremely rare. We report a case of a newborn baby girl with an anti-B isoimmunisation and G6PD deficiency manifesting with hydrops foetalis, anaemia and hyperbilirubinaemia, born to a mother with blood group O.

A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.

INTRODUCTION: This study aimed to determine the rates of non-adherence to standard steps of medication administration and medication administration errors committed by registered nurses in a neonatal intensive care unit before and after intervention. METHODS: A baseline assessment of compliance with ten standard medication administration steps by neonatal intensive care unit nurses was carried out over a two-week period. Following this, a re-education programme was launched. Three months later, they were re-assessed similarly. RESULTS: The baseline assessment showed that the nurses did not carry out at least one of the ten standard administrative steps during the administration of 188 medication doses. The most common steps omitted were having another nurse to witness drug administration (95 percent); labelling of individual medication prepared prior to administration (88 percent), checking prescription charts against patients' identification prior to administration (85 percent) and visually inspecting a patient's identification tag (71 percent) . Medication administration errors occurred in 31 percent (59/188) of doses administered, all due to imprecise timing of medication administration. There were no resultant adverse outcomes. Following implementation of remedial measures, there was a significant reduction in non-adherence of seven of the ten medication administration steps and the rate of medication administration errors (p-value is less than 0.001). However, in 94 percent of doses administered, the nurses still did not get a witness to countercheck calculations of drug dosages before administration. CONCLUSION: Non-compliance with the standard practice of medication administration by nurses is common but can be improved by continuing re-education and monitoring, plus the implementation of a standard operating procedure.

Intraperitoneal extravasation of total parental nutrition infusate from an umbilical venous catheter.

A preterm male infant who had an umbilical venous catheter (UVC) in situ for infusion of total parenteral nutrition (TPN) subsequently developed abdominal distension. He was initially diagnosed to have necrotising enterocolitis. However, a diagnostic abdominal paracentesis yielded fluid which biochemical analysis found to be consistent with TPN. TPN is often infused through a UVC, in the first few days of life, for the nutritional support of a premature infant. Various complications have been reported to be associated with this path of delivery, one of which will be illustrated in this case report.

Risk factors associated with neonatal hypothermia during cleaning of newborn infants in labour rooms.

Cleaning newborn infants with coconut oil shortly after birth is a common practice in Malaysian labour rooms. This study aimed: (1) to determine whether this practice was associated with a significant decrease in the core temperature of infants; and (2) to identify significant risk factors associated with neonatal hypothermia. The core temperature of 227 randomly selected normal-term infants immediately before and after cleaning in labour rooms was measured with an infrared tympanic thermometer inserted into their left ears. Their mean post-cleaning body temperature (36.6 degrees C, SD = 1.0) was significantly lower than their mean pre-cleaning temperature (37.1 degrees C, SD = 1.0; p < 0.001). Logistic regression analysis showed that the risk factors significantly associated with pre-cleaning hypothermia (< 36.5 degrees C) were: (1) not being placed under radiant warmer before cleaning p = 0.03); and (2) lower labour room temperature (p < 0.001). Logistic regression analysis also showed that the risk factors significantly associated with post-cleaning hypothermia were: (1) lower labour room temperature (p < 0.001); (2) lower pre-cleaning body temperature (p < 0.001); and (3) longer duration of cleaning (p = 0.002). In conclusion, to prevent neonatal hypothermia, labour room temperature should be set at a higher level and cleaning infants in the labour room should be discouraged.

Randomized controlled trial of heparin for prevention of blockage of peripherally inserted central catheters in neonates.

AIM: To determine whether the addition of heparin to total parenteral nutrition (TPN) fluid would prevent blockage of peripherally inserted central catheters (PICCs) in neonates. METHODS: This was a randomized, double-blind, controlled study of 66 eligible neonates with PICCs inserted for the administration of TPN. Infants were randomized to receive TPN containing either 1 IU ml(-1) of heparin (n = 35) or no heparin (n = 31). RESULTS: There was no significant difference in the incidence of blocked catheters between the two groups of infants (heparin: 14.3%; no-heparin: 22.6%, p = 0.4). Although a higher percentage (62.9%) of infants in the heparin group received a complete course of TPN successfully via PICC than those in the no-heparin group (48.4%), the difference was not statistically significant (p = 0.3). There were no significant differences in the incidence of catheter-related sepsis, hypertriglyceridaemia, hyperbilirubinaemia, coagulopathy or intraventricular haemorrhage between the two groups. CONCLUSION: Addition of heparin to TPN fluid was not associated with a significant reduction in the incidence of blocked PICCs. However, the sample size of this study was too small to exclude even rather marked differences between the groups.

Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses.

OBJECTIVE: To determine whether intravenous infusion of low dose of streptokinase was effective in lysing umbilical arterial catheter (UAC)-associated aortic thrombi. METHOD: A prospective cohort study of 31 consecutive newborn infants with UAC-associated aortic thrombi which were detected by abdominal ultrasonography after removal of UAC. Twenty-two infants were treated with intravenous infusion of low dose (1000 U/h) streptokinase, while nine others were not treated due to various contra-indications. Thrombolysis occurred after a mean interval of 2.2 days (standard deviation (SD) = 1.8) in the treated infants. In the untreated infants, spontaneous thrombolysis occurred significantly later, after a mean interval of 16.9 days (SD = 14.7) (95% confidence intervals of difference between mean intervals - 26.0, - 3.4; P = 0.02). Only one treated infant developed mild bleeding directly attributed to streptokinase therapy. CONCLUSION: Low dose streptokinase infusion was effective and safe in thrombolysing UAC-associated aortic thrombi.