Genetic Factors and Delayed TSB Monitoring and Treatment as Risk Factors Associated with Severe Hyperbilirubinemia in Term Neonates Admitted for Phototherapy.

OBJECTIVES: This study aimed to determine whether maternal-fetal blood group isoimmunization, breastfeeding, birth trauma, age when first total serum bilirubin (TSB) was measured, age of admission, and genetic predispositions to hemolysis [due to genetic variants of glucose-6-phosphate dehydrogenase (G6PD) enzyme], and reduced hepatic uptake and/or conjugation of serum bilirubin [due to genetic variants of solute carrier organic anion transporter protein family member 1B1 (SLCO1B1) and uridine diphosphate glucuronosyltransferase family 1 member A1 (UGT1A1)] were significant risk factors associated with severe neonatal hyperbilirubinemia (SNH, TSB ≥ 342µmol/l) in jaundiced term neonates admitted for phototherapy. METHODS: The inclusion criteria were normal term neonates (gestation ≥ 37 weeks). Parents/care-givers were interviewed to obtain data on demography, clinical problems, feeding practice and age when first TSB was measured. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect common G6PD, UGT1A1 and SLCO1B1 variants on each neonate's dry blood specimens. RESULTS: Of 1121 jaundiced neonates recruited, 232 had SNH. Logistic regression analysis showed that age (in days) when first TSB was measured [adjusted odds ratio (aOR) = 1.395; 95% confidence interval (CI) 1.094-1.779], age (in days) of admission (aOR = 1.127; 95% CI 1.007-1.260) and genetic mutant UGT1A1 promoter A(TA)7TAA (aOR = 4.900; 95% CI 3.103-7.739), UGT1A1 c.686C>A (aOR = 6.095; 95% CI 1.549-23.985), SLCO1B1 c.388G>A (aOR = 1.807; 95% CI 1.242-2.629) and G6PD variants and/or abnormal G6PD screening test (aOR = 2.077; 95% CI 1.025-4.209) were significantly associated with SNH. CONCLUSION: Genetic predisposition, and delayed measuring first TSB and commencing phototherapy increased risk of SNH.

The point-of-care Bilistick method has very short turn-around-time and high accuracy at lower cutoff levels to predict laboratory-measured TSB.

BACKGROUND: This study aimed to determine the accuracy of a point-of-care Bilistick method for measuring total serum bilirubin (TSB) and its turn-around-time (TAT) against hospital laboratory methods. METHODS: This prospective study was carried out on 561 term-gestation jaundiced neonates in two Malaysian hospitals. Venous blood sample was collected from each neonate for contemporary measurement of TSB by hospital laboratories and Bilistick. TAT was the time interval between specimen collection and TSB result reported by each method. RESULTS: The mean laboratory-measured TSB was 194.85 (±2.844) µmol/L and Bilistick TSB was 169.37 (±2.706) µmol/L. Pearson's correlation coefficient was: r = 0.901 (p < 0.001). The mean difference of [laboratory TSB- Bilistick TBS] was 26.48 (±29.41) µmol/L. The Bland-Altman plots show that the 95% limits of agreement (-31.1577, 84.11772) contain 94.7% (=531/561) of the difference in TSB readings. Bilistick has a 99% accuracy and 100% sensitivity to predict laboratory TSB levels of ≥80 µmol/L and ≥360 µmol/L at lower Bilistick TSB levels of ≥55 and ≥315 µmol/L, respectively. TAT of Bilistick TSB (2.0 min) was significantly shorter than TAT (105 min) of laboratory TSB (p < 0.001). CONCLUSIONS: Bilistick has shorter TAT. The accuracy and sensitivity of Bilistick TSB for predicting laboratory TSB is high at lower cutoff levels.

Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels.

Risk factors associated with outcomes of very low birthweight infants in four Asian countries.

AIM: The study aims to determine the risk factors associated with mortality and necrotising enterocolitis (NEC) among very low birthweight infants in 95 neonatal intensive care units in the Asian Network on Maternal and Newborn Health. METHODS: This is a cross-sectional study using an international collaborative database of 17,595 very low birthweight infants admitted within 28 days of birth between 2003 and 2006 in four Asian countries. Information on the mortality and morbidity of neonates admitted to the neonatal intensive care units was recorded. Factors associated with the death and diseases of infants were estimated using multilevel multivariate logistic regression. Random effects were included to account for the clustering of the observations. RESULTS: Overall discharge mortality was 15% and it was significantly different by countries and units. The mortality rate was found to be significantly higher in neonates with pulmonary haemorrhage (odds ratio 1.83, 95% confidence interval 1.63-2.04) and air leak syndrome (odds ratio 1.51, 95% confidence interval 1.30-1.72). The incidence of NEC was 4.3% and was strongly associated with other morbidities. Multivariate logistic regression showed that patent ductus arteriosus was the most significant risk factor associated with NEC. CONCLUSIONS: Our analysis has highlighted the great potential that multi-country, collaborative datasets have in terms of epidemiologic research when it comes to identifying issues in perinatal health that are common throughout Asia, and in relation to particular issues pertaining to specific countries and neonatal units. Establishing collaborative networks, conducting analyses of common datasets and further epidemiologic research are now essential measures to improve newborn health in Asia.

Risk factors associated with unconjugated neonatal hyperbilirubinemia in Malaysian neonates.

OBJECTIVE: To investigate the risk factors associated with neonatal hyperbilirubinemia in Malaysian neonates. METHODS: A prospective study was conducted to investigate the effects of glucose-6-phosphate dehydrogenase (G6PD) mutation, variant uridine diphosphate glucuronosyltransferase UGT1A1 gene and hepatic organic anion transporter protein (OATP2) gene on a group of neonates. Hyperbilirubinemia was defined as a total serum bilirubin level of ≥250 µmol/l. RESULTS: Of 318 neonates, 52 (16.4%) had hyperbilirubinemia. The incidence of G6PD mutation was 5.4% (15/280) among these infants. The incidence of G6PD mutation was significantly higher in the male neonates with hyperbilirubinemia (7.8%) when compared with the normal male neonates without hyperbilirubinemia (1.8%; p = 0.03). Logistic regression analysis showed that the significant risk factors for neonatal hyperbilirubinemia were Malay ethnicity [adjusted odds ratio (OR), 2.77; 95% confidence interval (CI): 1.31-5.86; p = 0.007] and G6PD mutation (adjusted OR, 3.29; 95% CI: 1.06-10.1820; p = 0.039). The gender, birth weight and gestation age of neonates, variant c.211G > A and variant of OATP2 gene were not significant. CONCLUSIONS: Neonates with Malay ethnicity and G6PD mutation were at risk for hyperbilirubinemia.

Admission hypothermia among VLBW infants in Malaysian NICUs.

This study aimed to determine the prevalence of admission hypothermia (AH) among very-low-birth-weight (≤1500 g) infants in 32 Malaysian neonatal intensive care units (NICUs). This was a retrospective analysis of prospectively collected data of all very-low-birth-weight infants admitted and a questionnaire survey of the practice of AH prevention. Of the 3768 (99.8%) infants with admission temperature recorded, 64.8% (n = 2440) were hypothermic: 40.3% (n = 983) mildly (36.0-36.4°C), 58.5% (n = 1428) moderately (32.0-35.9°C) and 1.2% (n = 29) severely (<32.0°C). Mean ambient temperature of these NICUs was 22.8°C (SD = 2.7, n = 28) in labour rooms and 20.1°C (SD = 1.6, n = 30) in operation theatres. None of the NICUs practised complete care bundle against AH at birth (i.e. use of pre-warmed radiant warmer and cling wrap, ambient temperature of at least 25°C and use of pre-warmed transport incubator). Care bundle against neonatal hypothermia should be actively promoted in Malaysian labour rooms and operation theatres.

Neural tube defects in Malaysia: data from the Malaysian National Neonatal Registry.

UNLABELLED: This study aimed to determine the prevalence and early outcome of neural tube defects (NTDs) in Malaysia. This prospective study included all neonates with NTDs (spina bifida, anencephaly, encephalocoele) born in 2009 in 32 Malaysian hospitals in the Malaysian National Neonatal Network. The prevalence of NTDs was 0.42 per 1000 live births, being highest among the indigenous people of Sarawak (1.09 per 1000 live births) and lowest among Malaysians of Chinese descent (0.09 per 1000 live births). The most common type of NTDs was anencephaly (0.19 per 1000 live births), followed by spina bifida (0.11 per 1000 live births) and encephalocoele (0.07 per 1000 live births). Majority of the infants with anencephaly (94.5%, n = 51), 45.8% (n = 11) with encephalocoele and 9.5% (n = 4) with spina bifida died. The median duration of hospital stay was 4 (range: 0-161) days. CONCLUSION: NTDs were common in Malaysia. Mortality was high. Long-term monitoring of NTD prevalence following folic fortification of food is recommended.

Cerebral palsy and developmental intellectual disability in children younger than 5 years: Findings from the GBD-WHO Rehabilitation Database 2019.

Objective: Children with developmental disabilities are associated with a high risk of poor school enrollment and educational attainment without timely and appropriate support. Epidemiological data on cerebral palsy and associated comorbidities required for policy intervention in global health are lacking. This paper set out to report the best available evidence on the global and regional prevalence of cerebral palsy (CP) and developmental intellectual disability and the associated "years lived with disability" (YLDs) among children under 5 years of age in 2019. Methods: We analyzed the collaborative 2019 Rehabilitation Database of the Global Burden of Disease (GBD) Study and World Health Organization for neurological and mental disorders available for 204 countries and territories. Point prevalence and YLDs with 95% uncertainty intervals (UI) are presented. Results: Globally, 8.1 million (7.1-9.2) or 1.2% of children under 5 years are estimated to have CP with 16.1 million (11.5-21.0) or 2.4% having intellectual disability. Over 98% resided in low-income and middle-income countries (LMICs). CP and intellectual disability accounted for 6.5% and 4.5% of the aggregate YLDs from all causes of adverse health outcomes respectively. African Region recorded the highest prevalence of CP (1.6%) while South-East Asia Region had the highest prevalence of intellectual disability. The top 10 countries accounted for 57.2% of the global prevalence of CP and 62.0% of the global prevalence of intellectual disability. Conclusion: Based on this Database, CP and intellectual disability are highly prevalent and associated with substantial YLDs among children under 5 years worldwide. Universal early detection and support services are warranted, particularly in LMICs to optimize school readiness for these children toward inclusive education as envisioned by the United Nations' Sustainable Development Goals.

Risk factors associated with pneumothorax in Malaysian neonatal intensive care units.

AIMS: This study aimed to determine the risk factors associated with the development of pneumothorax among infants admitted to the Malaysian neonatal intensive care units (NICUs). METHODS: Twenty-nine of forty NICUs in Malaysian public hospitals participated in the 2006 Malaysian National Neonatal Registry (MNNR). Data of infants from this registry with and without pneumothorax were analysed. A diagnosis of pneumothorax was made in the presence of extra-pleural air detected by chest radiograph or needle aspiration. RESULTS: There were 10,387 infants admitted to these NICUs who met the MNNR inclusion criteria and were included in this study. Pneumothorax developed in 505 (4.9%) of them. Pneumothorax was most common (7.3%) among the extremely low birthweight infants (birthweight equal or less than 1000 g) and the extremely preterm infants of gestation equal or less than 26 weeks (6.8%). Logistic regression analysis showed that the significant risk factors associated with increased risk of development of pneumothorax were: meconium aspiration syndrome (adjusted odds ratio (OR) = 2.1, 95% confidence intervals (CI): 1.7, 2.7), intermittent mandatory ventilation (adjusted OR = 1.5, 95% CI: 1.2, 2.0), high-frequency oscillatory ventilation (adjusted OR = 3.9, 95% CI: 3.0, 5.2) and confirmed sepsis (adjusted OR = 1.6, 95% CI: 1.3, 2.1). Infants on nasal continuous positive airway pressure (nCPAP) therapy were associated with significantly lower risk of pneumothorax (adjusted OR = 0.5, 95% CI: 0.4, 0.6). CONCLUSION: Meconium aspiration syndrome, mechanical ventilation and sepsis were associated with increased risk and the use of nCPAP with decreased risk of pneumothorax in Malaysian NICUs.

Global Burden of Childhood Epilepsy, Intellectual Disability, and Sensory Impairments.

BACKGROUND: Estimates of children and adolescents with disabilities worldwide are needed to inform global intervention under the disability-inclusive provisions of the Sustainable Development Goals. We sought to update the most widely reported estimate of 93 million children <15 years with disabilities from the Global Burden of Disease Study 2004. METHODS: We analyzed Global Burden of Disease Study 2017 data on the prevalence of childhood epilepsy, intellectual disability, and vision or hearing loss and on years lived with disability (YLD) derived from systematic reviews, health surveys, hospital and claims databases, cohort studies, and disease-specific registries. Point estimates of the prevalence and YLD and the 95% uncertainty intervals (UIs) around the estimates were assessed. RESULTS: Globally, 291.2 million (11.2%) of the 2.6 billion children and adolescents (95% UI: 249.9-335.4 million) were estimated to have 1 of the 4 specified disabilities in 2017. The prevalence of these disabilities increased with age from 6.1% among children aged <1 year to 13.9% among adolescents aged 15 to 19 years. A total of 275.2 million (94.5%) lived in low- and middle-income countries, predominantly in South Asia and sub-Saharan Africa. The top 10 countries accounted for 62.3% of all children and adolescents with disabilities. These disabilities accounted for 28.9 million YLD or 19.9% of the overall 145.3 million (95% UI: 106.9-189.7) YLD from all causes among children and adolescents. CONCLUSIONS: The number of children and adolescents with these 4 disabilities is far higher than the 2004 estimate, increases from infancy to adolescence, and accounts for a substantial proportion of all-cause YLD.

Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia.

BACKGROUND: The aim of the present study was to compare, in a case-control study, the prevalence of nucleotide 211 guanine to adenine (G-->A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 micromol/L during first 48 h of life or > or =300 micromol/L thereafter), and to determine whether this mutation was a significant risk factor associated with severe hyperbilirubinemia. METHODS: Seventy-four term infants of Chinese descent admitted with severe hyperbilirubinemia were recruited. Infants without severe hyperbilirubinemia (n = 125) were randomly selected from among healthy Chinese term infants. UGT1A1 nucleotide 211 polymorphism was assayed using the Taqman single nucleotide polymorphism genotyping method. Using gestational age, types of feeds, G6PD mutation, G6PD enzyme levels, and UGT1A1 gene mutation status as independent variables, logistic regression analysis was carried out to determine the significant risk factors associated with severe hyperbilirubinemia. RESULTS: UGT1A1 gene mutation was significantly more common among hyperbilirubinemic infants (39.2%) than controls (25.6%; P = 0.04). Gestational age (adjusted odds ratio [OR], 0.7; 95% confidence intervals [CI]: 0.5-0.9; P = 0.01), G6PD mutation (adjusted OR, 7.2; 95%CI: 2.7-19.0; P < 0.0001), exclusive breast-feeding (adjusted OR, 11.7; 95%CI: 2.7-49.9; P = 0.001), and homozygous variant of UGT1A1 gene mutation (adjusted OR, 32.2; 95%CI: 3.8-273.2; P = 0.001) were significant risk factors. Heterozygous variant of UGT1A1 gene mutation, actual levels of G6PD enzyme, and mixed feeding were not. CONCLUSION: Homozygous variant of nucleotide 211 G-->A mutation of UGT1A1 gene is a significant risk factor associated with severe hyperbilirubinemia among Malaysian Chinese newborns.

Variants of organic anion transporter polypeptide 2 gene are not risk factors associated with severe neonatal hyperbilirubinemia.

OBJECTIVES: This study aimed to determine the prevalence of four variants of organic anion transporter polypeptide 2 (OATP2) gene, and their association with severe hyperbilirubinemia. DESIGN: Observational study. SETTING: A tertiary university unit. PATIENTS: Term infants of Chinese descent. METHODS: 175 infants, consisting of 65 admitted for treatment of severe hyperbilirubinemia (with serum bilirubin levels > 250 mmol/L at age 1-2 days or > 300 micromol/L at age > or = 3 days) and 110 randomly selected inborn infants without severe hyperbilirubinemia during their first month of life, were recruited. Their blood samples were subjected to sequencing analysis of exon 4 and exon 5 of OATP2 gene for detection of c.388A > G, c.521T > C, c.571T > C and c.597C > T variants. RESULTS: The c.388A > G variant was the most common, and the c.521 T > C was least common, being present in 90.9% and 26.9% of the infants, respectively. Forward logistic regression analysis showed that the only significant risk factors associated with severe hyperbilirubinemia among these Chinese infants were: exclusive breast feeding (adjusted odds ratio (OR) = 12.5, 95% C.I.: 2.9, 53.4; p = 0.001), infants with homozygous 211 variant of the UDPG 1A1 gene (adjusted OR = 37.7, 95% C.I.: 4.4, 324.1; p = 0.001), and G6PD enzyme level < 8.5 IU/g Hb (adjusted OR = 7.3, 95% C.I.: 3.1, 17.5; p < 0.00001). Gestational age, G6PD mutation status, actual G6PD enzyme level, and the 4 variants of the OATP2 gene mutation were not significant risk factors. CONCLUSION: Variants of OATP2 gene were not significant risk factors associated with severe hyperbilirubinemia in Malaysian Chinese infants.

The burden of hypoxic-ischaemic encephalopathy in Malaysian neonatal intensive care units.

INTRODUCTION: This study aimed to determine the incidence of hypoxic-ischaemic encephalopathy (HIE) and predictors of HIE mortality in Malaysian neonatal intensive care units (NICUs). METHODS: This was a retrospective study of data from 37 NICUs in the Malaysian National Neonatal Registry in 2012. All newborns with gestational age ≥ 36 weeks, without major congenital malformations and fulfilling the criteria of HIE were included. RESULTS: There were 285,454 live births in these hospitals. HIE was reported in 919 newborns and 768 of them were inborn, with a HIE incidence of 2.59 per 1,000 live births/hospital (95% confidence interval [CI] 2.03, 3.14). A total of 144 (15.7%) affected newborns died. Logistic regression analysis showed that the significant predictors of death were: chest compression at birth (adjusted odds ratio [OR] 2.27, 95% CI 1.27, 4.05; p = 0.003), being outborn (adjusted OR 2.65, 95% CI 1.36, 5.13; p = 0.004), meconium aspiration syndrome (MAS) (adjusted OR 2.16, 95% CI 1.05, 4.47; p = 0.038), persistent pulmonary hypertension of the newborn (PPHN) (adjusted OR 4.39, 95% CI 1.85, 10.43; p = 0.001), sepsis (adjusted OR 4.46, 95% CI 1.38, 14.40; p = 0.013), pneumothorax (adjusted OR 4.77, 95% CI 1.76, 12.95; p = 0.002) and severe HIE (adjusted OR 42.41, 95% CI 18.55, 96.96; p < 0.0001). CONCLUSION: The incidence of HIE in Malaysian NICUs was similar to that reported in developed countries. Affected newborns with severe grade of HIE, chest compression at birth, MAS, PPHN, sepsis or pneumothorax, and those who were outborn were more likely to die before discharge.

Factors associated with inter-institutional variations in sepsis rates of very-low-birth-weight infants in 34 Malaysian neonatal intensive care units.

INTRODUCTION: This study aimed to determine whether patient loads, infant status on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis rates in very-low-birth-weight (VLBW) infants in the Malaysian National Neonatal Registry (MNNR). METHODS: This was a retrospective study of 3,880 VLBW (≤ 1,500 g) infants admitted to 34 neonatal intensive care units (NICUs) in the MNNR. Sepsis was diagnosed in symptomatic infants with positive blood culture. RESULTS: Sepsis developed in 623 (16.1%) infants; 61 (9.8%) had early-onset sepsis (EOS) and 562 (90.2%) had late-onset sepsis (LOS). The median EOS rate of all NICUs was 1.0% (interquartile range [IQR] 0%, 2.0%). Compared with NICUs reporting no EOS (n = 14), NICUs reporting EOS (n = 20) had significantly higher patient loads (total live births, admissions, VLBW infants, outborns); more mothers with a history of abortions, and antenatal steroids and intrapartum antibiotic use; more infants requiring resuscitation procedures at birth; higher rates of surfactant therapy, pneumonia and insertion of central venous catheters. The median LOS rate of all NICUs was 14.5% (IQR 7.8%, 19.2%). Compared with NICUs with LOS rates below the first quartile (n = 8), those above the third quartile (n = 8) used less intrapartum antibiotics, and had significantly bigger and more mature infants, more outborns, as well as a higher number of sick infants requiring ventilator support and total parenteral nutrition. CONCLUSION: Patient loads, resuscitation at birth, status of infants on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis.

Impact and Challenges of Early Continuous Positive Airway Pressure Therapy for Very Low Birth Weight Neonates in a Developing Country.

BACKGROUND: Early nasal continuous positive airway pressure (EnCPAP) therapy after birth for very low birth weight (VLBW; <1,500 g) neonates has been reported to be beneficial in developed countries. Its benefits in developing countries, such as Malaysia, are unknown. OBJECTIVES: This study aimed to determine EnCPAP rates in 36 neonatal intensive care units of the Malaysian National Neonatal Registry (MNNR) in 2013, to compare the outcomes of VLBW neonates with and without EnCPAP, and to determine whether the availability of CPAP facilities and unit policies played a significant role in EnCPAP rates. METHODS: First, a retrospective cohort study was conducted of VLBW neonates born in the hospitals participating in the study without major congenital abnormalities in the MNNR. This was followed by a questionnaire survey of these hospitals focussed on CPAP facilities and unit policies. RESULTS: Of the 2,823 neonates, 963 (34.1%) received EnCPAP. Amongst EnCPAP neonates significantly fewer deaths were recorded (10.9 vs. 21.7%; p < 0.001), less bronchopulmonary dysplasia was observed (BPD; 8.0 vs. 11.7%; p = 0.002) and fewer mechanical ventilation days were necessary (p < 0.001) than in non-EnCPAP neonates. Logistic regression analysis showed that EnCPAP was significantly associated with a lower mortality (adjusted OR 0.623; 95% CI 0.472, 0.824; p = 0.001) and BPD among survivors (adjusted OR 0.585; 95% CI 0.427, 0.802; p = 0.001). The median EnCPAP rate of the 36 hospitals was 28.4% (IQR 14.3-38.7). Hospitals with CPAP facilities in the delivery suites (p = 0.001) and during transport (p = 0.001) and a policy for EnCPAP (p = 0.036) had significantly higher EnCPAP rates. CONCLUSION: EnCPAP reduced mortality and BPD in Malaysian VLBW neonates. Resource-strapped developing countries should prioritise the use of this low-cost therapy.

Neonatal Jaundice in Low- and Middle-Income Countries: Lessons and Future Directions from the 2015 Don Ostrow Trieste Yellow Retreat.

Severe neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥20 mg/dl, is associated with a higher risk of permanent neurological sequelae and death. Jaundice can and should be promptly diagnosed and treated. Reliable methods for TSB assay are not always readily available, particularly in low- and middle-income countries, making the true incidence of severe neonatal jaundice (NNJ) difficult to estimate. To gather a more comprehensive picture, a symposium addressing NNJ worldwide was organized during the 2015 Don Ostrow Trieste Yellow Retreat. Data collected by several researchers in different regions of the world were presented and differences/similarities discussed. This report points out the need for: (1) a coordinated worldwide effort to define the burden and the causes of severe NNJ and its consequences; (2) aggressive educational programs for families and health personnel to facilitate timely care-seeking, and (3) accurate diagnostics and effective phototherapy.

Circulating tissue factor, tissue factor pathway inhibitor and D-dimer in umbilical cord blood of normal term neonates and adult plasma.

The investigation of many hemostatic defects in newborns is restricted by the lack of normal reference values. The coagulation system of the neonate differs in many ways from that of the adult. The present study was designed to compare the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and D-dimer (DD) in the umbilical cord blood of healthy newborns and in adult plasma. TF antigen was quantified using an in-house enzyme-linked immunosorbent assay, whereas TFPI and DD levels were measured with commercial kits. The mean TF level in cord blood (mean standard deviation, 183.94 103.63 pg/ml) was significantly higher ( = 0.008) than that in adults (136.64 65.09 pg/ml). Cord blood exhibited enhanced fibrinolysis, as was reflected by a significantly higher level of DD (924.57 733.87 ng/ml, 0.001) than that in adults (45.57 17.21 ng/ml). Conversely, cord blood (30.88 10.16 ng/ml) demonstrated significantly lower ( 0.001) TFPI levels than that in adults (55.77 21.16 ng/ml). However, no significant differences of these three hemostatic markers were noted between both gender groups in newborns and adults. Our findings indicate that an active and dynamic state of hemostasis exists in cord blood, as the fluidity of cord blood remains preserved in the presence of birth injury.

Risk factors associated with necrotising enterocolitis in very low birth weight infants in Malaysian neonatal intensive care units.

INTRODUCTION: This study aimed to identify the risk factors associated with necrotising enterocolitis (NEC) in very low birth weight (VLBW; weight < 1,501 g) infants in Malaysian neonatal intensive care units (NICUs). METHODS: This was a retrospective study based on data collected in a standardised format for all VLBW infants born in 2007 (n = 3,601) and admitted to 31 NICUs in Malaysian public hospitals. A diagnosis of NEC was made based on clinical, radiological and/or histopathological evidence of stage II or III, according to Bell's criteria. Logistic regression analysis was performed to determine the significant risk factors associated with NEC. RESULTS: 222 (6.2%) infants developed NEC (stage II, n = 197; stage III, n = 25). 69 (31.3%) infants died (stage II, n = 58; stage III, n = 11). The significant risk factors associated with NEC were: maternal age (adjusted odds ratio [OR] 1.024, 95% confidence interval [CI] 1.003-1.046; p = 0.027), intrapartum antibiotics (OR 0.639, 95% CI 0.421-0.971; p = 0.036), birth weight (OR 0.999, 95% CI 0.998-0.999; p < 0.001), surfactant therapy (OR 1.590, 95% CI 1.170-2.161; p = 0.003), congenital pneumonia (OR 2.00, 95% CI 1.405-2.848; p < 0.001) and indomethacin therapy for the closure of patent ductus arteriosus (PDA) (OR 1.821, 95% CI 1.349-2.431; p = 0.001). CONCLUSION: Increasing maternal age, decreasing birth weight, surfactant therapy, congenital pneumonia and indomethacin therapy for the closure of PDA were associated with an increased risk of NEC in Malaysian VLBW infants. Infants that received intrapartum antibiotics were associated with a reduced risk of developing NEC.

Current understanding of auditory neuropathy.

Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention.