Noraida Ramli

Frequencies of A(TA)7TAA, G71R, and G493R Mutations of the UGT1A1 Gene in the Malaysian Population

Background: Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice. Objectives: The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls. Methods: The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography. Results: Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p = 0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p = 0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p = 0.476). Conclusions: The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population.

Comparison of antimicrobial resistance in neonatal and adult intensive care units in a tertiary teaching hospital

Intrahospital variations in antimicrobial profiles may be related to many factors. This study compared causative agents of nosocomial bloodstream infections between a neonatal intensive care unit (NICU) that adopted a ward-tailored antibiotic policy and adult intensive care units (ICUs). Data on organisms from blood cultures obtained from the respective wards between 2005 and 2009 were analyzed. Compared with the adult ICUs, the NICU had a higher frequency of Enterobacteriacae and lower frequencies of typical hospital-acquired pathogens (eg, Klebsiella pneumoniae, 17.4% vs 10.0% [P < .001]; Acinetobacter baumannii, 3.9% vs 11.6% [P < .001]). Antibiotic resistance of gram-negative organisms was also significantly lower in the NICU, including resistance to imipenem (5.7% vs 32.1%; P < .001), amikacin (8.8% vs 30.3%), and ceftriaxone (36.1% vs 74.6%; P < .001). This could possibly be due to the ward-tailored antibiotic policy adopted by the NICU but not by the other ICUs.

Randomised controlled trial of single phototherapy with reflecting curtains versus double phototherapy in term newborns with hyperbilirubinaemia

The use of reflecting curtains with single phototherapy has not yet been directly compared with double phototherapy (DP). The objective of this study is to compare the efficacy of single phototherapy with reflecting curtains (SPRC) and DP in treating neonatal jaundice.

Two-hourly versus 3-hourly feeding for very low birthweight infants: a randomised controlled trial

Objective To determine whether feeding with 2-hourly or 3-hourly feeding interval reduces the time to achieve full enteral feeding and to compare their outcome in very low birthweight preterm infants. Design Parallel-group randomised controlled trial with a 1:1 allocation ratio. Setting Two regional tertiary neonatal intensive care units. Patients 150 preterm infants less than 35 weeks gestation with birth weight between 1.0 and 1.5 kg were recruited. Interventions Infants were enrolled to either 2-hourly or 3-hourly interval feeding after randomisation. Blinding was not possible due to the nature of the intervention. Main outcome measures The primary outcome was time to achieve full enteral feeding (≥100 mL/kg/day). Secondary outcomes include time to regain birth weight, episode of feeding intolerance, peak serum bilirubin levels, duration of phototherapy, episode of necrotising enterocolitis, nosocomial sepsis and gastro-oesophageal reflux. Results 72 infants were available for primary outcome analysis in each group as three were excluded due to death—three deaths in each group. The mean time to full enteral feeding was 11.3 days in the 3-hourly group and 10.2 days in the 2-hourly group (mean difference 1.1 days; 95% CI −0.4 to 2.5; p=0.14). The mean time to regain birth weight was shorter in 3-hourly group (12.9 vs 14.8 days, p=0.04). Other subgroup analyses did not reveal additional significant results. No difference in adverse events was found between the groups. Conclusion 3-hourly feeding was comparable with 2-hourly feeding to achieve full enteral feeding without any evidence of increased adverse events. Trial registration number ACTRN12611000676910, pre-result.

High resolution melting analysis of the NR1I3 genetic variants: Is there an association with neonatal hyperbilirubinemia?

Constitutive androstane receptor (CAR) encoded by the nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene regulates the elimination of bilirubin through activating the components of the bilirubin clearance pathway. Hence, NR1I3 genetic variants may affect bilirubin metabolism and result in neonatal hyperbilirubinemia. Thus far, research which investigates the association between NR1I3 variants and neonatal hyperbilirubinemia has not been undertaken in any population. The present study aimed to evaluate the influence of MPJ6_1I3008 (rs10157822), IVS8+116T>G (rs4073054) and 540A>G (rs2307424) on neonatal hyperbilirubinemia development in the Malay population. Buccal swabs were collected from 232 hyperbilirubinemia and 277 control term newborns with gestational age ≥37weeks and birth weight ≥2500g. The NR1I3 variants were genotyped by using high resolution melting (HRM) assays and verified by DNA sequencing. Gender, mode of delivery and birth weight did not differ between hyperbilirubinemia and control groups. The genotypic and allelic frequencies of MPJ6_1I3008, IVS8+116T>G and 540A>G were not significantly different between the groups. However, stratification by gender revealed a significant inverse association between homozygous variant genotype of MPJ6_1I3008 and risk of neonatal hyperbilirubinemia in the females (OR, 0.44; 95% CI, 0.20-0.95; p=0.034). This study demonstrates that the homozygous variant genotype of MPJ6_1I3008 was associated with a significant reduced risk of neonatal hyperbilirubinemia in the females.

A Psychologist-Led Educational Intervention Results in a Sustained Reduction in Neonatal Intensive Care Unit Infections

Even though in the corporate world psychological science has been widely used, the formal use of evidence-based psychology in important areas of clinical medicine has been scanty at best. It was the aim of this study to determine the efficacy of a psychologist-led 2-week nurse educator training on the infection rate in the neonatal intensive care unit (NICU). Materials and methods: In 2007, six senior neonatal nurses underwent a training course focusing on the retrieval of evidence and knowledge of psychological principles that would allow them to share the evidence in such a way that evidence is effectively brought into practice. The course was led by a psychologist. The nurses created and delivered their own teaching modules, all focused on infection control. The rates of bacteremia, 2 years prior to intervention were analyzed and compared with the rate following the intervention for 3 years. Results: The immediate output of the course included three teaching modules: hand washing, sterile procedures, and general measures to control infection. These modules were subsequently administered to the NICU nurses in regular structured continuous nursing education sessions. The psychological techniques taught in the course were applied. Bacteremia in the NICU significantly decreased in the year of the course and the subsequent years when compared to previous years (from more than 17 in 2005 and 2006 to less than 10 per 100 admissions to the NICU in 2008 and 2009). Conclusion: This study suggests that a psychologist-led course, followed by a structured CNE can lead to a sustainable reduction in infection rates in a NICU.

Hemolytic disease of the fetus and newborn caused by anti-E

Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mothers red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.