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.

Contemporary fluid management, humidity, and patent ductus arteriosus management strategy for premature infants among 336 hospitals in Asia.

Objectives: The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries. Methods: AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status. Results: The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation (p < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation (p < 0.001) and on day 14 after birth for infants born at <29 weeks gestation (p < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth (p < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p = 0.012 and <80% vs. 90%-100%, OR of 5.31, p < 0.001). Conclusions: In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices.

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.

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.

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.