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Neonatal intrahepatic cholestasis associated with citrin deficiency (NICCD): a case series of 11 Malaysian patients

Chew HB, Ngu LH, Zabedah MY, Keng WT, Balasubramaniam S, Hanifah MJ, et al.

J Inherit Metab Dis, 2010 Dec;33 Suppl 3:S489-95.
PMID: 21161389 DOI: 10.1007/s10545-010-9248-6

Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.

Matched MeSH terms: Infant, Newborn
Anxiety of the mothers with referred baby during Universal Newborn Hearing Screening

Mohd Khairi MD, Rafidah KN, Affizal A, Normastura AR, Suzana M, Normani ZM

Int J Pediatr Otorhinolaryngol, 2011 Apr;75(4):513-7.
PMID: 21292333 DOI: 10.1016/j.ijporl.2011.01.009

To investigate the anxiety among mothers whom their babies have failed test results in the first stage of Universal Neonatal Hearing Screening Program.

Matched MeSH terms: Infant, Newborn
Fulltext A medication-estimated health status measure for predicting primary care visits: the Long-Term Therapeutic Groups Index

Dhabali AA, Awang R

Health Policy Plan, 2010 Mar;25(2):162-9.
PMID: 19923207 DOI: 10.1093/heapol/czp051

BACKGROUND: Managed care is one of the means advocated for health care reforms. The Malaysian government has proposed managed care for its citizens. In the Malaysian private health care sector, managed care is practised on a small scale with crude risk adjustment. The main determinant of an individual's health service utilization is their health status (HS). HS is used as a risk adjuster for capitation payment. Prescribed medications represent a useful source for HS estimation. We aimed to develop and validate a medication-based HS estimate and to incorporate it in the Andersen model of health service utilization. This is a preparatory step in studying the feasibility of developing a model for risk assessment in the Malaysian context.
METHODS: Data were collected retrospectively from an academic year from computerized databases in University Sains Malaysia (USM) about users of USM primary care services. A user is a USM health scheme beneficiary who made at least one visit in the academic year to USM-assigned primary care providers. Socio-demographic variables, enrolment period, medications prescribed and number of visits were also collected. Chronic illness medications and some non-chronic illness medications were used to calculate the Long-Term Therapeutic Groups Index (LTTGI) which is an estimate of the HS of users. Using a random 50% of users, weighted least square methods were used to develop a model that predicts a user's number of visits. The other 50% were used for validation.
RESULTS: Socio-demographic variables explained 15% of variability in number of primary care visits among users. Adding the LTTGI improved the explanatory power of the model to 36% (P < 0.001). A similar contribution of the LTTGI was noted in the validation.
CONCLUSIONS: The Long-Term Therapeutic Groups Index was successfully developed. Variability in number of primary care visits can be predicted by LTTGI-based models.

Matched MeSH terms: Infant, Newborn
Noninvasive ventilation in a tertiary pediatric intensive care unit in a middle-income country

Lum LC, Abdel-Latif ME, de Bruyne JA, Nathan AM, Gan CS

Pediatr Crit Care Med, 2011 Jan;12(1):e7-13.
PMID: 20190672 DOI: 10.1097/PCC.0b013e3181d505f4

To determine the factors that predict outcome of noninvasive ventilation (NIV) in critically ill children.

Matched MeSH terms: Infant, Newborn
Congenital disorder of glycosylation type Ia in a Malaysian family: clinical outcome and description of a novel PMM2 mutation

Thong MK, Fietz M, Nicholls C, Lee MH, Asma O

J Inherit Metab Dis, 2009 Dec;32 Suppl 1:S41-4.
PMID: 19165618 DOI: 10.1007/s10545-009-1031-1

There are few reports of congenital disorders of glycosylation (CDGs) in the Asian population, although they have been reported worldwide. We identified a Malaysian infant female at 2 days of life with CDG type Ia. The diagnosis was suspected on the basis of inverted nipples and abnormal fat distribution. She had cerebellar hypoplasia and developed coagulopathy, hypothyroidism and severe pericardial effusion and died at 7 months of life. The diagnosis was supported by abnormal serum transferrin isoform pattern that showed elevated levels of the disialotransferrin isoform and trace levels of the asialotransferrin isoform. Enzyme testing of peripheral leukocytes showed decreased level of phosphomannomutase (PMM) activity (0.6 nmol/min per mg protein, normal range 1.6-6.2) and a normal level of phosphomannose isomerase activity (19 nmol/min per mg protein, normal range 12-25), indicating a diagnosis of CDG type Ia. Mutation study of the PMM2 gene showed the patient was heterozygous for both the common p.R141H (c.422T>A) mutation and a novel sequence change in exon 7, c.618C>A. The latter change is predicted to result in the replacement of the highly conserved phenylalanine residue at position 206 with a leucine residue (p.F206L) and occurs in the same codon as the previously reported p.F206S mutation. Analysis of 100 control chromosomes has shown that the p.F206L sequence change is not present, making it highly likely that this change is functionally important. To the best of our knowledge, this is the first report of CDG in the Malay population. Prenatal diagnosis was successfully performed in a subsequent pregnancy for this family.

Matched MeSH terms: Infant, Newborn
The 50-g glucose challenge test and pregnancy outcome in a multiethnic Asian population at high risk for gestational diabetes

Tan PC, Ling LP, Omar SZ

Int J Gynaecol Obstet, 2009 Apr;105(1):50-5.
PMID: 19154997 DOI: 10.1016/j.ijgo.2008.11.038

OBJECTIVE:
To evaluate the 50-g glucose challenge test (GCT) on pregnancy outcome in a multiethnic Asian population at high risk for gestational diabetes (GDM).

METHODS:
GCT was positive if the 1-hour plasma glucose level was >or=7.2 mmol/L. GDM was diagnosed by a 75-g glucose tolerance test using WHO (1999) criteria. Of the 1368 women enrolled in the study, 892 were GCT negative, 308 were GCT false-positive, and 168 had GDM. Pregnancy outcomes were extracted from hospital records. Multivariable logistic regression analysis was performed with GCT negative women as the reference group.

RESULTS:
GCT false-positive status was associated with preterm birth (adjusted odds ratio [AOR] 2.1; 95% CI, 1.2-3.7) and postpartum hemorrhage (AOR 1.7; 95% CI, 1.0-2.7). GDM was associated with labor induction (AOR 5.0; 95% CI, 3.3-7.5), cesarean delivery (AOR 2.2; 95% CI, 1.6-3.2), postpartum hemorrhage (AOR 2.1; 95% CI, 1.2-3.7), and neonatal macrosomia (AOR 2.5; 95% CI, 1.0-6.0).

CONCLUSION:
GCT false-positive women had an increased likelihood of an adverse pregnancy outcome. The role and threshold of the GCT needs re-evaluation.

Matched MeSH terms: Infant, Newborn
Molecular characterization of influenza viruses circulating in Northern Italy during two seasons (2005/2006 and 2006/2007) of low influenza activity

Pariani E, Amendola A, Zappa A, Bianchi S, Colzani D, Anselmi G, et al.

J Med Virol, 2008 Nov;80(11):1984-91.
PMID: 18814246 DOI: 10.1002/jmv.21323

The influenza activity and circulation of influenza viruses in Lombardy (the most populous Italian region) were observed during two consecutive seasons (2005/2006 and 2006/2007) characterized by low influenza activity by the Italian Influenza Surveillance Network. The molecular characteristics of circulating viruses were analyzed to evaluate the introduction of new variants and emergence of vaccine-escape viruses. In both seasons, the epidemic in Lombardy was sustained almost exclusively by influenza A viruses, accounting for 80.5% and 93.6% of total detections, respectively, and the co-circulation of A/H3 viruses belonging to distinct phylogenetic groups was observed. The A/H1N1 viruses isolated during the 2005/2006 season were closely related to A/New Caledonia/20/99, while the hemagglutinin (HA) sequences of the A/H1N1 viruses from the 2006/2007 season exhibited a greater diversity. These viruses were A/Solomon Islands/3/2006-like and showed several variants. All B isolates were similar to B/Malaysia/2506/2004 belonging to the B/Victoria/2/87-lineage. Influenza B virus was the dominant virus in Europe in the 2005/2006 season and accounted for the 20% of total detections in Lombardy. Overall, the viruses studied presented heterogeneity in their HA sequences suggesting the circulation of a miscellaneous set of variants during the two seasons notwithstanding the medium-low activity of influenza. The importance of virological surveillance of influenza viruses is recognized widely and the molecular characterization of the viruses, especially in vaccinated subjects, is of particular importance to evaluate the introduction and circulation of new variants.

Matched MeSH terms: Infant, Newborn
Fulltext Trial of labor after one cesarean: role of the order and number of prior vaginal births on the risk of emergency cesarean delivery and neonatal admission

Tan PC, Subramaniam RN, Omar SZ

Taiwan J Obstet Gynecol, 2008 Sep;47(3):305-11.
PMID: 18935994 DOI: 10.1016/S1028-4559(08)60129-1

To evaluate the influences of mode of immediate preceding delivery and number of prior vaginal births on the risk of repeat cesarean and neonatal admission at attempted vaginal birth after cesarean.

Matched MeSH terms: Infant, Newborn
Growing wealth and growing pains: child and adolescent psychiatry in Hong Kong, Malaysia and Singapore

Tan S, Fung D, Hung SF, Rey J

Australas Psychiatry, 2008 Jun;16(3):204-9.
PMID: 18568628 DOI: 10.1080/10398560701874283

Several Asian regions have undergone a dramatic transformation, some becoming very affluent. This paper aims to ascertain how countries that are becoming wealthy have dealt with child and adolescent mental health issues.

Matched MeSH terms: Infant, Newborn
The association between maternal periodontitis and low birth weight infants among Malay women

Saddki N, Bachok N, Hussain NH, Zainudin SL, Sosroseno W

Community Dent Oral Epidemiol, 2008 Aug;36(4):296-304.
PMID: 19145718

OBJECTIVES: Maternal periodontitis has been suggested as one of the risk factors for low birth weight (LBW) infants. The objective of this study was to determine the association between maternal periodontitis and LBW infants among Malay women.
METHODS: Screening periodontal examinations were carried out on all eligible Malay pregnant women in the second trimester of pregnancy attending two randomly selected community maternal and child health clinics in Kota Bharu, Kelantan. Patients with four or more sites with pocket depth 4 mm or higher, and clinical attachment loss 3 mm or higher at the same site with presence of bleeding on probing were diagnosed as having periodontitis in this study. Using this definition, systematic random sampling was utilized for selection of 250 subjects for each exposed and non-exposed group. Of 500 subjects enrolled in the study, 28 (5.6%) were either dropped or lost to follow-up. Of the remaining 472 subjects, 232 with periodontitis were in the exposed group and 240 with healthy periodontium were in the nonexposed group.
RESULTS: The incidence of LBW was 14.2% (95% CI: 9.70-18.75) in women with periodontitis, and 3.3% (95% CI: 1.05-5.62) in women without periodontitis. The relative risk of having LBW infants was 4.27 times higher for women with periodontitis compared with those without periodontitis (95% CI: 2.01-9.04). After adjustment for potential confounders using multiple logistic regression analysis, significant association was found between maternal periodontitis and LBW (OR = 3.84; 95% CI: 1.34-11.05).
CONCLUSION: The results of this study provide additional evidence that pregnant women with periodontitis are at a significantly higher risk of delivering LBW infants.

Matched MeSH terms: Infant, Newborn
Fulltext Optimising reproductive and child health outcomes by building evidence-based research and practice in South East Asia (SEA-ORCHID): study protocol

Henderson-Smart DJ, Lumbiganon P, Festin MR, Ho JJ, Mohammad H, McDonald SJ, et al.

BMC Med Res Methodol, 2007;7:43.
PMID: 17892586

Disorders related to pregnancy and childbirth are a major health issue in South East Asia. They represent one of the biggest health risk differentials between the developed and developing world. Our broad research question is: Can the health of mothers and babies in Thailand, Indonesia, the Philippines and Malaysia be improved by increasing the local capacity for the synthesis of research, implementation of effective interventions, and identification of gaps in knowledge needing further research?

Matched MeSH terms: Infant, Newborn
High-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the N-terminal portion of the capsid protein VP1

Tan CS, Cardosa MJ

Arch Virol, 2007;152(6):1069-73.
PMID: 17318736

Human enterovirus 71 has emerged as an important pathogen of children in the Asia Pacific region, and it may be important to consider the development of a vaccine against this virus. Human cord serum was used as a source of neutralizing antibodies to determine whether the N- or C-terminal half of the VP1 capsid protein was more likely to harbour neutralizing determinants. Cord sera from 205 individuals were tested for neutralizing antibodies against human enterovirus 71 in an indirect ELISA against recombinant VP1 antigen as well as the N- and C-terminal portions of VP1 antigen. High-titred human neutralizing antibodies were significantly more reactive with the N-terminal half of VP1 than weak or negative sera. The N-terminal half of human enterovirus 71 is likely to have important neutralizing antibody determinants and should be investigated further in vaccine development efforts.

Matched MeSH terms: Infant, Newborn
Ethnic differences in the frequency of subtypes of childhood acute lymphoblastic leukemia: results of the Malaysia-Singapore Leukemia Study Group

Ariffin H, Chen SP, Kwok CS, Quah TC, Lin HP, Yeoh AE

J Pediatr Hematol Oncol, 2007 Jan;29(1):27-31.
PMID: 17230064

Childhood acute lymphoblastic leukemia (ALL) is clinically heterogeneous with prognostically and biologically distinct subtypes. Although racial differences in frequency of different types of childhood ALL have been reported, many are confounded by selected or limited population samples. The Malaysia-Singapore (MA-SPORE) Leukemia Study Group provided a unique platform for the study of the frequency of major subgroups of childhood ALL in a large cohort of unselected multiethnic Asian children. Screening for the prognostically important chromosome abnormalities (TEL-AML1, BCR-ABL, E2A-PBX1, and MLL) using multiplex reverse-transcription polymerase chain reaction was performed on 299 consecutive patients with ALL at 3 study centers (236 de novo, 63 at relapse), with the ethnic composition predominantly Chinese (51.8%) and Malay (34.8%). Reverse-transcription polymerase chain reaction was successful in 278 (93%) of cases screened. The commonest fusion transcript was TEL-AML1 (19.1%) followed by BCR-ABL (7.8%), MLL rearrangements (4.2%), and E2A-PBX1 (3.1%). Chinese have a significantly lower frequency of TEL-AML1 (13.3% in de novo patients) compared with Malays (22.2%) and Indians (21.7%) (P=0.04). Malays have a lower frequency of T-ALL (6.2%) compared with the Chinese and Indians (9.8%). Both Malays (7.4%) and Chinese (5.0%) have significantly higher frequency of BCR-ABL compared with the Indian population (P<0.05) despite a similar median age at presentation. Our study suggests that there are indeed significant and important racial differences in the frequency of subtypes of childhood ALL. Comprehensive subgrouping of childhood ALL may reveal interesting population frequency differences of the various subtypes, their risk factors and hopefully, its etiology.

Matched MeSH terms: Infant, Newborn
NAIP-deletion analysis in Malaysian patients with spinal muscular atrophy

Watihayati MS, M S W, Zabidi AM, A M H ZH, Tang TH, T H T, et al.

Kobe J Med Sci, 2007;53(4):171-5.
PMID: 17932457

Spinal Muscular Atrophy (SMA) is an autosomal recessive disease, which is characterized by degeneration of the anterior horn cells of the spinal cord. SMA is classified into 3 clinical subtypes, type I (severe), type II (intermediate), and type III (mild). Two genes, SMN1 and NAIP, have been identified as SMA-related genes. The SMN1 gene is now recognized as a responsible gene for the disease because it is deleted or mutated in most SMA patients. However, the role of the NAIP gene in SMA has not been fully clarified. To clarify the contribution of NAIP to the disease severity of SMA, we studied the relationship between NAIP-deletion and clinical phenotype in Malaysian patients. A total of 39 patients lacking SMN1 (12 type I, 19 type II, and 8 type III patients) were enrolled into this study. Seven out of 12 patients with type I SMA (approximately 60%) showed NAIP deletion. On the contrary, only 2 out of 20 type II patients and none of type III patients showed NAIP deletion. There was a statistically significant difference in NAIP-deletion frequency among the clinical subtypes (Fisher's exact probability test, p value = 0.014). In conclusion, according to our data that NAIP deletion was more frequent in type I SMA than in type II-III SMA, the NAIP gene may be a modifying factor for disease severity of SMA.

Matched MeSH terms: Infant, Newborn
Changes in the process of care and outcome over a 10-year period in a neonatal nursery in a developing country

Ho JJ, Chang AS

J Trop Pediatr, 2007 Aug;53(4):232-7.
PMID: 17578848

Over a 10-year period there was increasing involvement by clinicians in the generation and implementation of evidence-based practices in the neonatal intensive care unit (NICU). For two cohorts of very low birth weight (VLBW) babies admitted 10 years apart to a developing country, NICU were compared and changes occurring in process of care that might have contributed to any change in outcome were documented.

Matched MeSH terms: Infant, Newborn
Deletion analyses of SMN1 and NAIP genes in Malaysian spinal muscular atrophy patients

Watihayati MS, Zabidi-Hussin AM, Tang TH, Matsuo M, Nishio H, Zilfalil BA

Pediatr Int, 2007 Feb;49(1):11-4.
PMID: 17250498

The survival motor neuron 1 (SMN1) gene has been recognized to be responsible for spinal muscular atrophy (SMA) because it is homozygously deleted in more than 90% of SMA patients, irrespective of their clinical severity, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is now considered to be a modifying factor of the severity of SMA. In Malaysia, it remains to be elucidated whether deletion of the SMN1 gene is also a main cause of SMA or whether deletion of the NAIP gene is found in the SMA patients.

Matched MeSH terms: Infant, Newborn
Rotavirus and other enteropathogens in childhood acute diarrhoea: a study of two centres in Malaysia

Lee WS, Rajasekaran G, Pee S, Karunakaran R, Hassan HH, Puthucheary SD

J Paediatr Child Health, 2006 Sep;42(9):509-14.
PMID: 16925536

To study the role of rotavirus in children hospitalised for acute gastroenteritis (AGE) in two urban hospitals in Malaysia.

Matched MeSH terms: Infant, Newborn
Fulltext Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates

Ainoon O, Boo NY, Yu YH, Cheong SK, Hamidah HN, Lim JH

Malays J Pathol, 2004 Dec;26(2):89-98.
PMID: 16329560

We performed DNA analysis on cord blood samples of 128 Chinese male neonates diagnosed as G6PD deficiency in Hospital Universiti Kebangsaan Malaysia by a combination PCR-restriction enzyme digest technique, Single Stranded Conformation Polymorphism analysis and DNA sequencing. We found 10 different G6PD-deficient mutations exist. The two commonest alleles were G6PD Canton 1376 G>T (42.3%) and Kaiping 1388 G>A (39.4%) followed by G6PD Gaohe 592 G>A (7.0%), Chinese-5 1024 C>T, Nankang 517 T>C (1.5%), Mahidol 487 G>A (1.6%), Chatham 1003 G>T (0.8%), Union 1360 C>T (0.8%), Viangchan 871 G>A (0.8%) and Quing Yang 392 G>T (0.8%). Sixty eight percent (88/125) neonates in this study had neonatal jaundice and 29.7% developed hyperbilirubinemia >250 micromol/l. The incidence of hyperbilirubinemia >250 micromol/l was higher in G6PD Kaiping (43.8%) than G6PD Canton (22%) (p< 0.05). There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean duration of phototherapy between the two major variants. None of the 88 neonates required exchange transfusion. In conclusion we have completely characterized the molecular defects of a group of Chinese G6PD deficiency in Malaysia. The mutation distribution reflects the original genetic pool and limited ethnic admixture with indigenous Malays.

Matched MeSH terms: Infant, Newborn
The use of octyl cyanoacrylate (superglue) in hypospadias repair including its use as a fixator for urethral stents

Tan HL, Nah SA, Budianto II, Sehat S, Tamba R

J Pediatr Surg, 2012 Dec;47(12):2294-7.
PMID: 23217892 DOI: 10.1016/j.jpedsurg.2012.09.022

Octyl cyanoacrylate has been used for many years for simple skin closure, but its use in hypospadias repair and as a urethral stent fixator has not been previously reported. We report our experience.

Matched MeSH terms: Infant, Newborn
Fulltext Effect of pentoxifylline on tumor necrosis factor-alpha and interleukin-6 levels in neonatal sepsis

Selim K, Hüseyin C, Ibrahim KH, Hasan BU, Kazim U, Hüseyin K

Med J Malaysia, 2004 Aug;59(3):391-4.
PMID: 15727386

Several pharmacological agents have been found to alter systemic concentrations and/or the activity of different cytokines via a variety of mechanisms, including changes in biosynthesis, secretion, and/or stability. Pentoxifylline (PTX), which is a methylxanthine derivative for example, has multiple effects on the immune system, but inhibition of pro-inflammatory cytokine release predominates. In this study we aimed to evaluate the influence of PTX on plasma levels of tumor necrosis factor (TNF) alpha and interleukin (IL)-6 in newborn infants with sepsis. The study included 20 infants with neonatal sepsis. In all subjects blood samples for serum C-reactive protein, TNF alpha and IL-6 determinations were received before giving PTX and at the 12th and 24th hours following PTX. In addition, white blood cell was counted before giving PTX and on the 3rd and 7th day following PTX. The infants were randomly divided into two groups. Firstly, PTX was used in infants who were successively admitted to the clinic and the subsequent infants were accepted as a control group. Of 20 infants, 13 infants received PTX and seven infants did not. We did not find any difference in the leukocyte count, serum C-reactive protein level, TNF alpha and IL-6 levels between the two groups of patients (P>0.05). While three infants died in the group of receiving PTX, death was not recorded in the group of non-receiving PTX (P>0.05). Our findings showed that PTX treatment did not affect leukocyte counts, serum CRP levels, TNF alpha and IL-6 levels and death ratio in newborn infants with sepsis. The last result may be due to the fact that the number of patients in the study was very small. We think that more extensive and controlled studies should be performed about this subject.

Matched MeSH terms: Infant, Newborn

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