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.

Risk Factors Associated with Sarcopenia Among Independently Mobile, Institutionalised Older People in the Klang Valley of Malaysia: A Cross-Sectional Study.

BACKGROUND: Studies on sarcopenia among Malaysian older people (OP ≥ 60 years of age) living in the community but not in long-term care (LTC) homes have been reported previously. This study aimed to determine the prevalence of sarcopenia and its risk factors in OP in Malaysian LTC homes. METHODS: This cross-sectional study was conducted with 202 independently mobile OP (males 32%) in seven LTC homes in the Klang Valley of Malaysia. Trained personnel measured their anthropometrics, body composition, gait speed, hand grip strength and timed up-and-go (TUG) duration. Criteria of the European Working Group on Sarcopenia in Older People (EWGSOP) and of the Asian Working Group for Sarcopenia were used to identify the presence of sarcopenia. The mini-nutritional assessment (MNA) was used to determine their nutritional status. Additionally, logistic regression analysis was performed to identify significant risk factors associated with pre-sarcopenia/sarcopenia. RESULTS: Pre-sarcopenia/sarcopenia was detected in 103 (51%) OP. The significant risk factors were body mass index (BMI, weight/height2; adjusted odds ratio [AOR] = 0.44, P < 0.001), percentage of body fat (PBF; AOR = 1.26, P < 0.001), age group (≥ 80 years; AOR = 3.63, P = 0.025) and 'at risk of malnutrition' status (AOR = 2.63, P = 0.049). CONCLUSION: Sarcopenia is common among OP in LCT homes. The risk increases with decreasing BMI, increasing PBF, age ≥ 80 years and suboptimal nutrition status.

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.

Retinopathy of Prematurity in Very Low Birthweight Neonates of Gestation Less Than 32 weeks in Malaysia.

OBJECTIVES: To determine the screening rates and incidence of retinopathy of prematurity (ROP), and risk factors associated with ROP in very low birthweight (VLBW, <1500 g) neonates of gestation <32 wk admitted to neonatal intensive care units (NICUs) in a middle-income country. METHODS: It was a retrospective cohort study of prospectively submitted data by 44 Malaysian NICUs participating in the Malaysian National Neonatal Registry. All VLBW neonates of gestation <32 wk born in 2015-2020 and survived to discharge were included. RESULTS: Of 11768 survivors, 90.5% (n = 10436) had ROP screening; 16.1% (1685/10436) had ROP. ROP was significantly more common in neonates <28 wk gestation (extremely preterm, EPT) than ≥28 wk gestation (37.7% vs. 9.7%; p <0.001), and more common in those with birthweight <1000 g (extremely low birthweight, ELBW) than ≥1000 g (32.9% vs. 9.1%; p <0.001). Multiple logistic regression analysis showed that the significant independent factors associated with increased risk of ROP were ELBW, EPT, Indian ethnic group, vaginal delivery, mechanical ventilation >5 d, high frequency ventilation, total parenteral nutrition, late-onset sepsis, bronchopulmonary dysplasia, and intraventricular hemorrhage. Receiving oxygen therapy at birth was associated with significantly lower risk of ROP. CONCLUSIONS: The incidence and severity of ROP increased with decreasing gestation and birthweight. Prolonged duration of oxygen therapy, infection, invasive respiratory support, and conditions commonly causing fluctuations of oxygenation were significant factors associated with increased risk of ROP. Receiving oxygen at birth did not increase risk.

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.

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.

Barriers to neonatal care in developing countries: parents' and providers' perceptions.

AIM: Hospital care and advanced medical technologies for sick neonates are increasingly available, but not always readily accessible, in many countries. We characterised parents' and providers' perceptions of barriers to neonatal care in developing countries. METHODS: We interviewed parents whose infant was hospitalised within the first month of life in Cambodia, Malaysia, Laos and Vietnam, asking about perceived barriers to obtaining newborn care. We also surveyed health-care providers about perceived barriers to providing care. RESULTS: We interviewed 198 parents and 212 newborn care providers (physicians, nurses, midwives, paediatric and nursing trainees). Most families paid all costs of newborn care, which they reported as a hardship. Although newborn care is accessible, 39% reported that hospitals are too distant; almost 20% did not know where to obtain care. Parents cited lack of cleanliness (46%), poor availability of medications (42%) or services (36%), staff friendliness (42%), poor infant outcome (45%), poor communications with staff (44%) and costs of care (34%) as significant problems during prior newborn care. Providers cited lack of equipment (74%), lack of staff training (61%) and poor infrastructure (51%) as barriers to providing neonatal care. Providers identified distance to hospital, lack of transportation, care costs and low parental education as barriers for families. CONCLUSIONS: Improving cleanliness, staff friendliness and communication with parents may diminish some barriers to neonatal care in developing countries. Costs of newborn care, hospital infrastructure, distance to hospital, staffing shortages, limited staff training and limited access to medications pose more difficult barriers to remedy.

An Observational Study of Therapeutic Hypothermia and Factors Associated With Mortality in Late-Preterm and Term Neonates With Hypoxic-Ischemic Encephalopathy in a Middle-Income Country.

Objectives: To investigate the types of therapeutic hypothermia (TH) used and risk factors associated with mortality in late-preterm and term neonates (LPTN, gestation of ≥35 weeks) with hypoxic-ischemic encephalopathy (HIE) in a middle-income country. Design: This was an observational retrospective cohort study. Setting: A total of 44 neonatal intensive care units (NICUs) in the Malaysian National Neonatal Registry participated in the study. Patients: All LPTN without major malformations and diagnosed to have HIE were included. Main Outcome Measures: Number of in-hospital mortality, and types of TH used [no TH, TH using commercially available servo-controlled devices (SCDs), passive TH by exposing neonates to NICU's air-conditioned ambient temperature with/without the use of cooled gel packs (P±CGPs)]. Results: Of a total of 2,761 HIE neonates, 66.3% received TH. All NICUs provided TH; 55.4% NICUs had SCDs, which was administered to 43.6% (248/569) of severe, 51.6% (636/1,232) of moderate, and 18.6% (179/960) of mild HIE neonates. P±CGPs was used on 26.9% of severe, 33.4% of moderate, and 21.1% of mild HIE neonates. There were 338 deaths. Multiple logistic regression analysis showed that 5-min Apgar scores <5 (aOR: 1.436; 95% CI: 1.019, 2.023), Cesarean section (aOR: 2.335; 95% CI: 1.700, 3.207), receiving no TH (aOR: 4.749; 95% CI: 3.201, 7.045), TH using P±CGPs (aOR: 1.553; 95% CI: 1.031, 2.338), NICUs admitted <50 HIE cases (aOR: 1.898; 95% CI: 1.225, 2.940), NICUs admitted 50-<100 HIE cases (aOR: 1.552; 95% CI: 1.065, 2.260), moderate HIE (aOR: 2.823; 95% CI: 1.495, 5.333), severe HIE (aOR: 34.925, 95% CI: 18.478, 66.012), Thompson scores of 7-13 (aOR: 1.776; 95% CI: 1.023,3.082), Thompson scores of ≥14 (aOR: 3.641; 95% CI: 2.000, 6.629), pneumothorax (aOR: 3.435; 95% CI: 1.996, 5.914), and foreigners (aOR: 1.646; 95% CI: 1.006, 2.692) were significant risk factors associated with mortality. Conclusion: Both SCD and P±CGP were used for TH. Moderate/severe HIE and receiving passive/no TH were among the risk factors associated with mortality.

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.

Reducing hypothermia in preterm infants with polyethylene wrap.

BACKGROUND: Occlusive plastic applied immediately after birth to reduce evaporative heat loss has been proven effective in preterm infants <28 weeks' gestation. However its effectiveness on preterm infants >28 weeks' gestation has not been shown. This study aimed to determine the effect of occlusive wrap at birth on the temperature at neonatal intensive care unit (NICU) admission among infants of greater than or equal to 24 weeks' and less than 34 weeks' gestation. METHODS: Study infants were randomly assigned to "wrap" or "control" groups. Newborns in the wrap group were wrapped with polyethylene plastic sheets within the first min after birth. Infants randomized to the control group were dried immediately after birth with warmed towels under a warmer, according to the guidelines of Neonatal Resuscitation. Infants' axillary temperatures were measured on admission to the NICU, and after having been stabilized in incubators in the NICU. RESULTS: A total of 110 infants were recruited into the study. The mean admission temperature was significantly higher in the wrap group (35.8 vs 34.8°C, P < 0.01). Admission hypothermia (axillary temperature <36.5°C) was present in 38 (78%) and 58 (98%) infants in the wrap and control groups, respectively. Among infants of <28 weeks' gestation, the post-stabilization temperature was significantly higher in the wrap group. CONCLUSIONS: Wrapping premature infants with gestational age <34 weeks in polyethylene plastics immediately after birth is associated with lower incidence of hypothermia.

Ten-year trend of care practices, morbidities and survival of very preterm neonates in the Malaysian National Neonatal Registry: a retrospective cohort study.

Objectives: To determine a 10-year trend of survival, morbidities and care practices, and predictors of in-hospital mortality in very preterm neonates (VPTN, gestation 22 to <32 weeks) in the Malaysian National Neonatal Registry. Design: Retrospective cohort study. Setting: 43 Malaysian neonatal intensive care units. Patients: 29 010 VPTN (without major malformations) admitted between 1 January 2009 and 31 December 2018. Main outcome measures: Care practices, survival, admission hypothermia (AH, <36.5°C), late-onset sepsis (LOS), pneumothorax, necrotising enterocolitis grade 2 or 3 (NEC), severe intraventricular haemorrhage (sIVH, grade 3 or 4) and bronchopulmonary dysplasia (BPD). Results: During this 10-year period, there was increased use of antenatal steroid (ANS), lower segment caesarean section (LSCS) and early continuous positive airway pressure (eCPAP); but decreased use of surfactant therapy. Survival had increased from 72% to -83.9%. The following morbidities had decreased: LOS (from 27.9% to 7.1%), pneumothorax (from 6.0% to 2.7%), NEC (from 8.1% to 4.7%) and sIVH (from 12.2% to 7.5%). However, moderately severe AH (32.0°C-35.9°C) and BPD had increased. Multiple logistic regression analyses showed that lower birth weight, no ANS, no LSCS, admission to neonatal intensive care unit with <100 VPTN admissions/year, no surfactant therapy, no eCPAP, moderate and severe AH, LOS, pneumothorax, NEC and sIVH were significant predictors of mortality. Conclusion: Survival and major morbidities had improved modestly. Failure to use ANS, LSCS, eCPAP and surfactant therapy, and failure to prevent AH and LOS increased risk of mortality.

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.