Perinatal mortality rates have been gradually declining in all countries. The initial decline mainly resulted from improvements in the late foetal mortality rates. Later with improvements in neonatal care, early neonatal mortality rates also improved. The developed countries have consistently shown better results than the developing countries, an indication of the higher standard of living, general health as well as the delivery of health care in these countries. In the Singapore situation, a rapid improvement in perinatal mortality was initially observed due to improvements in the late foetal mortality, followed later by reduction in the early neonatal mortality due to upgrading of neonatal intensive care. The perinatal mortality rate is lowest in the Chinese compared to the Indians and Malays, most likely due to the dietary practices of the three ethnic groups in Singapore; while the Chinese encourage extra nutrition in the pregnant female, the Malays and Indians tend to practise dietary restriction during this period. The improved nutrition of the pregnant mother is a factor in improving the perinatal mortality.
100 patients were registered at the Diabetic Clinic in 1981, where they were managed by a team of physician, obstetrician and paediatrician, based on a preset protocol. Only 92 patients were eventually analysed. The study showed a 1.3% incidence of pregnancies complicated by diabetes mellitus. The mean birthweights of infants of both gestational and established diabetics were heavier than that of the general population by race and gestation. 25% of the 92 infants of diabetic mothers have birthweight exceeding the 90th centile of population. Further division of the 92 patients into the "true gestational" diabetics, as shown by an oral glucose tolerance test performed 6 weeks post-natally, also showed a 25% incidence of macrosomia. Late antenatal booking, delayed detection of abnormal glucose tolerance and treatment attributed to the high incidence of macrosomia. Only one infant had birthweight below the tenth centile. There were no perinatal mortality in the 92 patients studied. Macrosomia is a common complication in infants of diabetic mothers despite a physician-obstetrician joint-care system. Also, the risk of having macrosomia amongst gestational diabetics is high.
225 women with diabetes in pregnancy were managed by a team of obstetricians, physicians (endocrinologists) and paediatricians from the National University of Singapore. A protocol of management was formulated and followed. The incidence of 1.1% or 1 in 90 pregnancies was found, with significantly higher incidence in Indians and lower in Malays. There were 37 established diabetics and 188 diagnosed during pregnancy. Of these (188), 74 were gestational diabetics. All the women were treated with Insulin and Diet or Diet alone. 177 (79%) were treated with Insulin and Diet. Blood sugar profiles were done for monitoring diabetic control. 72.8% of the women were between para 0 and 1 and 85.2% between the ages of 20 and 34. 72.5% of the women delivered at 38 weeks gestation or later. 48.9% went into spontaneous labour, 32.4% were induced and 18.7% had elective caesarean section. 62.2% of the women had labour of less than 12 hours. The overall caesarean section rate was 41.7%. There were 3 stillbirths and 2 neonatal deaths. The perinatal mortality rate was 2.2%. Thirteen babies had congenital malformations (5.8%). 77.8% of the babies had Apgar score of 7 or more at 5 minutes after delivery. 79.1% of the babies weighed between 2.5 kgm and 3.9 kgm. Pre-eclamptic toxaemia was the commonest complication in pregnancy followed by Urinary Tract Infection and Polyhydramnios. Postpartum complications in the mother were confined to 14 women (6.2%), and wound infection or breakdown was the commonest cause.
The use of the colloidal-gold technique in electron microscopy immunocytochemistry has provided important information on the in situ localisation of intracellular antigens. We have developed a post-embedding technique for prolactin localisation on resin-embedded human pituitary tissue sections by the use of the protein-A gold conjugate. Human pituitary tissue obtained at autopsy was processed for electron microscopical study without post-osmication and then embedded in Epon. The indirect immunoperoxidase method was used for light microscopical targetting of lactotroph cells for subsequent electron microscopical antigen localisation. Ultra-thin sections were labelled with human anti-human prolactin followed by protein-A gold conjugate. Specific labelling was observed over secretory granules with a density of 15-30 particles per granule, as determined by the Quantimet 570 image analysis system. This technique provides a means of studying the pathophysiology of hormonal secretion at ultrastructural level and can be a useful tool in diagnostic and research investigations.
In order to assess the usefulness of immunohistochemistry in the diagnosis of melioidosis, an infection by Burkholderia pseudomallei, polyclonal antibodies were applied to tissues from known cases of melioidosis and to other infected tissues. Formalin-fixed, paraffin-embedded tissues were stained by a modified immunoperoxidase technique. In autopsy tissues with inflammatory lesions of melioidosis, the cytoplasm of phagocytes and intact bacilli, both intra- and extracellular, were stained very strongly positive. Relatively more focal positive staining was observed in some but not all surgical biopsies from proven cases of melioidosis. In granulomas staining was mainly found in the central necrotic areas, with little staining of peripheral phagocytes. All control materials stained negative. Immunohistochemistry appears to be a useful diagnostic tool in melioidosis.
The incidence of congenital dislocation of the hip (CDH) in Singapore and Malaysia has been reported as being lower than in the West. In our hospital, we have seen an increasing number of congenital hip dislocation as well as dysplastic hips. We undertook a prospective study from December 1989 to December 1994 of 20,000 live births. The neonates were all screened by a consultant neonatologist and the findings were confirmed by a consultant paediatric orthopaedic surgeon. All babies had plain X-rays at 3 months and an acetabular index (AI) of 30 degrees or more was considered dysplastic. All babies with positive signs were followed up for 1 year and again had radiographs taken at 1 year. Comparison of plain X-rays and ultrasound assessment in a subgroup of 130 neonates showed that 64% of patients with AI > 20 degrees had hip dysplasia by ultrasonographic (alpha angle < 60 degrees) The incidence of dysplastic hips was 16.8 per 1000 live births. The overall incidence of neonates with dislocated hips was 4.7 per 1000 live births. The Malays were most affected with an incidence of 5.4 per 1000 live births. The incidence of developmental dysplasia of the hip in Singapore is higher than previously reported, with the Malays having the highest incidence. A significant number of babies with clicking hips have radiological evidence of acetabular dysplasia (AI > 30 degrees). One-third of the babies' hips were still dysplastic at 1 year of age. A well-organised screening programme with experienced examiners has proved to be useful in making early and accurate clinical diagnosis.
Beta-thalassemia major patients have chronic anemia and are dependent on blood transfusions to sustain life. Molecular characterization and prenatal diagnosis of beta3-thalassemia is essential in Malaysia because about 4.5% of the population are heterozygous carriers for beta-thalassemia. The high percentage of compound heterozygosity (47.62%) found in beta-thalassemia major patients in the Thalassaemia Registry, University of Malaya Medical Centre (UMMC), Malaysia, also supports a need for rapid, economical, and sensitive protocols for the detection of beta-thalassemia mutations. Molecular characterization of beta-thalassemia mutations in Malaysia is currently carried out using ARMS, which detects a single beta-thalassemia mutation per PCR reaction. We developed and evaluated Combine amplification refractory mutation system (C-ARMS) techniques for efficient molecular detection of two to three beta-thalassemia mutations in a single PCR reaction. Three C-ARMS protocols were evaluated and established for molecular characterization of common beta-thalassemia mutations in the Malay and Chinese ethnic groups in Malaysia. Two C-ARMS protocols (cd 41-42/IVSII #654 and -29/cd 71-72) detected the beta-thalassemia mutations in 74.98% of the Chinese patients studied. The CARMS for cd 41-42/IVSII #654 detected beta-thalassemia mutations in 72% of the Chinese families. C-ARMS for cd 41-42/IVSI #5/cd 17 allowed detection of beta-thalassemia mutations in 36.53% of beta-thalassemia in the Malay patients. C-ARMS for cd 41-42/IVSI #5/cd 17 detected beta-thalassemia in 45.54% of the Chinese patients. We conclude that C-ARMS with the ability to detect two to three mutations in a single reaction provides more rapid and cost-effective protocols for beta-thalassemia prenatal diagnosis and molecular analysis programs in Malaysia.
Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
Haemoglobin Bart's hydrops foetalis syndrome (--SEA/--SEA) is not compatible with life and contributes to a majority of the hydropic foetuses in the Malaysian Chinese alpha-thalassaemia carriers who possess the 2-alpha-gene deletion in cis (--SEA/alphaalpha). A duplex-PCR which simultaneously amplifies a normal 136 bp sequence between the psialpha-alpha2-globin genes and a 730 bp Southeast Asian deletion-specific sequence (--SEA) between the psialpha2-theta1-globin genes was established. The duplex-PCR which detects the --SEA deletion in both chromosomes serves as a rapid and cost-effective confirmatory test in the antenatal diagnosis of Haemoglobin Bart's hydrops foetalis syndrome in Malaysia. In addition, the duplex-PCR is simple to perform as both the normal and deletion-specific alpha-globin gene sequences are amplified in the same PCR reaction.
beta-thalassaemia major, an autosomal recessive hemoglobinopathy, is one of the most common single gene disorders in multi-racial Malaysia. The control of beta-thalassaemia major requires a multi-disciplinary approach that includes population screening, genetic counselling, prenatal diagnosis and the option of termination of affected pregnancies. To achieve this objective, the molecular characterisation of the spectrum of beta-globin gene mutations in each of the affected ethnic groups is required. We studied 88 consecutive unrelated individuals and their respective families with beta-thalassaemia (74 beta-thalassaemia major, 12 HbE-beta-thalassaemia, 2 with HbE homozygotes) and four individuals with beta-thalassaemia trait that contributed a total 180 alleles for study. Using a 2-step molecular diagnostic strategy consisting of amplification refractory mutation system (ARMS) to identify the 8 most common mutations followed by other DNA-based diagnostic techniques, a total of 177 (98.3 per cent) of the 180 beta-thalassaemia alleles were characterised. One out of 91 (1 per cent) of the Chinese alleles, one out of 46 (2.2 per cent) Malay alleles and one out of two Indian alleles remained unknown. A 100 per cent success rate was achieved in studying the Kadazandusun community in this study. A strategy to identify beta-globin gene mutations in Malaysians with beta-thalassaemia is proposed based on this outcome.
Objectives: This study aimed to evaluate the UBI MAGIWELTM ζ-GLOBIN ELISA Kit for the presumptive diagnosis of αo-thalassaemia. The ELISA results obtained were confirmed by molecular characterisation of αo-thalassaemia using a Duplex-PCR. Methods: Routine peripheral blood counts and red cell indices were determined in 94 blood samples sent for Hb analysis. Hb subtypes were quantified by high performance liquid chromatography (HPLC) and Hb electrophoresis conducted on agarose gel at pH 8.5. Zeta-globin chain levels were determined using the UBI MAGIWELTM ζ-GLOBIN ELISA Kit. Molecular analysis was performed using a duplex-PCR which simultaneously amplifies
a normal 136 bp sequence between the ψα−α2-globin genes and a 730 bp Southeast Asian deletion-specific sequence (–SEA) between the ψα2−θ1-globin genes. Results: Using the ELISA assay kit, 20 blood samples were presumptively identified as α-thalassaemia carriers from elevated ζ-globin chains (OD>0.3) while the remaining 74 blood samples showed OD
This is a cohort study investigating the profile of children with disability registered with the primary health care clinics in Malaysia. The purpose of the study was to determine whether reassessment on the development of children with disability under rehabilitation should be done at three months interval or six months interval. Secondary data from the pilot project conducted by the Family Health Development Division, Ministry of Health Malaysia was used in this study. The study was carried out for seven months from 1st August 2004 until 28th February 2005. A total of 168 disabled children followed up for six months were selected in this study. Schedule of Growing Scale (SGS) II was the tool used for analysis. Results showed a statistically significant difference in the mean total SGS score at six months interval but not at three months interval. The result suggests that reassessment on children with Down Syndrome, Autism, Cerebral Palsy, mental retardation and delayed speech under rehabilitation should be carried out every six months while children with gross developmental delay and slow learner might need a longer interval for reassessment.
This is a cross-sectional study investigating the profile of children with disability registered with the primary health care clinics in Malaysia. The purpose of the study was to assess the developmental stage of children with disability. Secondary data from the pilot project conducted by the Family Health Development Division, Ministry of Health Malaysia was used in this study. The study period was for six months from 1st August 2004 until 31st January 2005. A total of 900 disabled children were selected in this study. Schedule of Growing Scale (SGS) II was used for analysis. Results showed more boys than girls were affected with a ratio of 6:4. The mean total SGS score increases as the age of the child increased. The score was highest in delayed speech cases and lowest in cerebral palsy cases. The performance among children with delayed speech was the highest while children with cerebral palsy were the lowest. There was a statistically significant difference between the major ethnic groups in delayed speech and attention deficit hyperactive disorder.
Questionnaire: Denver Developmental Assessment Test II chart; DSST; Schedule of Growing Scale II; SGS
BACKGROUND/AIMS: Individuals with double heterozygosity for alpha- and beta-thalassaemia and heterozygous beta-thalassaemia show a similar haematological picture. Co-inheritance of alpha- and beta-thalassaemia in both partners may result in pregnancies with either Hb Bart's hydrops foetalis or beta-thalassaemia major, or pregnancies with both disorders.
METHODS: The co-inheritance of alpha-thalassaemia in 322 beta-thalassaemia carriers in Malaysia was studied.
RESULTS: The frequency of alpha-thalassaemia in the beta-thalassaemia carriers was 12.7% (41/322), with a carrier frequency of 7.8% for the SEA deletion, 3.7% for the -alpha(3.7) deletion, 0.9% for Hb Constant Spring and 0.3% for the -alpha(4.2) deletion.
CONCLUSION: Double heterozygosity for alpha- and beta-thalassaemia was confirmed in 5 out of the 41 couples and the risk of the fatal condition Hb Bart's hydrops foetalis was confirmed in two of these couples. Detection of the Southeast Asian (SEA) deletion in the Malaysian Malays in this study confirms that Hb Bart's hydrops foetalis can occur in this ethnic group. Results of this study have provided new information on the frequency and different types of alpha-thalassaemia (--(SEA), -alpha(3.7) and -alpha(4.2) deletions, Hb Constant Spring) in Malaysian beta-thalassaemia carriers.