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Background: Very preterm infants are at risk for neurodevelopmental impairment because of postnatal morbidities. This study aims to (1) compare the outcomes of very-low-birth-weight (VLBW) infants in Singapore during two time periods over a decade; 2) compare performances among Singaporean neonatal intensive care units (NICUs); and 3) compare a Singapore national cohort with one from the Australian and New Zealand Neonatal Network (ANZNN)., Methods: Singapore national data on VLBW infants born during two periods, 2007-2008 (SG2007, n = 286) and 2015-2017 (SG2017, n = 905) were extracted from patient medical records. The care practices and clinical outcomes among three Singapore NICUs were compared using SG2017 data. Third, using data from the ANZNN2017 annual report, infants with gestational age (GA) ≤29 weeks in SG2017 were compared with their Oceania counterparts., Results: SG2017 had 9.9% higher usage of antenatal steroids (p < 0.001), 8% better survival for infants ≤26 weeks (p = 0.174), and used 12.7% lesser nonsteroidal anti-inflammatory drugs for patent ductus arteriosus closure (p < 0.001) than those of SG2007 cohort. Rate of late-onset sepsis (LOS) was almost halved (7.4% vs. 14.0%, p < 0.001), and exclusive human milk feeding after discharge increased threefold (p < 0.001). SG2017, in contrast, had a higher rate of chronic lung disease (CLD) (20.0% vs. 15.1%, p = 0.098). Within SG2017, the rates of LOS, CLD, and human milk feeding varied significantly between the three NICUs. When compared with ANZNN2017, SG2017 had significantly lower rates of LOS for infants ≤25 weeks (p = 0.001), less necrotizing enterocolitis for infants ≤27 weeks (p = 0.002), and less CLD across all GA groups., Conclusion: Postnatal morbidities and survival rates for VLBW infants in Singapore have improved over a decade. Outcomes for VLBW infants varied among three Singapore NICUs, which provide a rationale for collaboration to improve clinical quality. The outcomes of Singaporean VLBW infants were comparable to those of their ANZNN counterparts., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain., Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD)., Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020., Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met., Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately., Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group., Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded., Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Objective: To evaluate TIMP in preterm very low birth weight (VLBW) infants, analyze risk factors, for atypical TIMP (aTIMP) scores, and explore TIMP's predictive relationship with Bayley-III at 2 years., Method: A prospective study of 288 VLBW infants, with TIMP assessment between 34 weeks postmenstrual age and 16 weeks age, corrected for prematurity., Result: aTIMP scores were observed in 58/288(20%) infants, whose mean birth weight (BW) and gestational age were 1122 ± 257 g and 29.2 ± 2.12 weeks respectively. Risk factors included BW < 750 g (OR 4.8, 95% CI 1.3-17.7) and 750-1000 g (OR 2.9, 95% CI 1.2-6.9), presence of necrotizing enterocolitis ≥ stage 2; or focal intestinal perforation (OR 4.6, 95% CI 1.4-14.4), periventricular leukomalacia (OR 22.4,95% CI 2.0-246.2), and need for intensive resuscitation at birth (OR 2.7, 95% CI 1.3-5.5). aTIMP scores correlated with Bayley-III Score <85 in motor and cognitive domains with high specificity (80-82%) and negative predictive value (85-94%)., Conclusion: Identification of the risk factors for aTIMP scores will enable targeted intervention to optimize resources and outcomes in VLBW infants., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aim: To describe nutritional practices among preterm extremely low-birthweight (ELBW) infants and their impact on growth and to compare differences in nutritional intervention and comorbidities between those with limited growth velocity (GV < 25th percentile) and those with GV > 25th percentile., Methods: A prospective cohort study was conducted to assess total protein and energy intake for week 1, days 14, 21 and 28 of life. Post-natal growth was calculated by measuring GV using an exponential model. Univariable analysis was applied to identify the potential risk factors associated with poor GV at day 28 and at discharge from hospital., Results: The median GV from birth to day 28 was 9.84 g/kg/day and 11.87 g/kg/day for GV from birth to discharge. Increased protein and energy intake was associated with higher GV at discharge. Hypotension needing inotropes, necrotising enterocolitis (NEC), patent ductus arteriosus and chronic lung disease were significantly associated with reduced GV at discharge. Infants with NEC, hypotension needing inotropes and sepsis took a significantly longer time to achieve full enteral nutrition. A longer time to attain full enteral feeds was associated with slower GV at discharge. Small-for-gestational-age babies increased from 22% at birth to 66.6% at discharge., Conclusions: GV at discharge was positively correlated with increasing protein and energy intake in the first 28 days and adversely affected by the presence of neonatal morbidities. There was strong evidence of extra-uterine growth restriction, with the majority of preterm ELBW infants having lower z scores at discharge compared to at birth., (© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Medications added to preterm milk feeds have the potential to raise osmolality, causing feed intolerance and necrotizing enterocolitis., Objective: The aim of this study was to evaluate changes in the osmolality of milk feeds and water with 14 medications and the diluent amounts required to keep the osmolality below the safety threshold of ≤450 mOsm/kg. Changes in the osmolality of milk with medications while on continuous infusion over 2 and 4 h were determined., Methods: This study was designed to measure the osmolality of 14 commonly used medications in preterm infants both neat and when supplemented with expressed breast milk (EBM), EBM with fortifier (EBMF), preterm formula (PTF), and water. Dose-effect curves were plotted, and the volume of each diluent was calculated to keep the osmolality ≤450 mOsm/kg. Time-effect curves were plotted at 2 and 4 h for each medication for both EBM and EBMF., Results: Neat osmolality of all except 5 medications were above 2,000 mOsm/kg. The osmolality rose with decreasing proportions of diluents used, depicting an indirect curvilinear relationship between the increasing dilution and osmolality for all except 2 medications. As a diluent, EBM was required in lower dilutions than EBMF. Dilutions needed for additives with PTF were very similar to those of EBM. The change in osmolality over time with additives was statistically significant for EBMF., Conclusions: EBM and PTF were found to be safer diluents than EBMF for enteral additives. The practice of keeping milk feeds with medications for continuous feeding is safe for a period of 4 h in EBM., (© 2016 S. Karger AG, Basel.)

Background: Meconium retention is associated with feeding intolerance. Trials using glycerol and Gastrografin to expedite the evacuation of meconium have failed to generate clinically valid results for efficacy and safety., Objective: We assessed the feasibility of aggressive meconium evacuation with saline rectal washout (RW) in very-low-birth-weight infants to reduce the time it took them to reach full enteral feeds., Methods: We conducted an open-label, pilot, randomized controlled trial (RCT) (birth weight stratified, i.e., to 750-999 g and 1,000-1,500 g) of early aggressive meconium evacuation with twice-daily normal saline RW compared to conventional management with glycerin suppositories (GS), until full enteral feeds (110 mL/kg/day) were reached. Primary outcome was time to reach full enteral feeds. Safety, process, and secondary efficacy outcomes were also evaluated., Results: Sixty-one infants were randomized, 28 to RW and 33 to GS. The process and feasibility outcomes were met. RW was found to be safe; none of the RW-randomized infants developed necrotizing enterocolitis (≥ stage II) or complications secondary to RW. Evidence of efficacy was supported: in the 750-999 g stratum (n = 15), the median time to full enteral feeds was shorter with RW (11.0 days, 95% CI: 10.4-11.6) than with GS (15.6 days, 95% CI: 13.0-18.2) by a reduction of 4.6 days (p = 0.027). In the 1,000-1,500 g stratum (n = 46), there was no evidence of benefit: RW 10.2 days (95% CI 8.3-12.1) and GS 10.1 days (95% CI 9.3-10.9, p = 0.304)., Conclusion: Our protocol was feasible and an adequately powered RCT is required to confirm the findings of this trial., (© 2017 S. Karger AG, Basel.)

Objective: Patent ductus arteriosus is very commonly seen in very low birth weight (VLBW) infants, affecting about one-third. The present review tries to identify the group of VLBW infants who need active intervention in day-to-day practice and to determine the mode of intervention, based on current published literatures., Methods: We searched the Cochrane library, MEDLINE, EMBASE and CINAHL databases, and reference that of identified trials., Results and Conclusions: Preterm infants with a birth weight of <800g are at risk of significant morbidity and mortality from PDA; it would be reasonable to treat them when symptomatic or if requiring positive pressure ventilator support. Those weighing >800g are unlikely to need treatment unless they are ventilator-dependent or show evidence of congestive heart failure.

Introduction: Parainfluenza type 3 virus (PIV-3) is an important nosocomial pathogen which causes pneumonia and bronchiolitis in infants. We report an outbreak of PIV-3 respiratory infection which occurred in the neonatal unit of KK Hospital in June 2005. This is the second PIV-3 outbreak in our unit after the fi rst in December 1994., Materials and Methods: The clinical characteristics and outcome of 7 infants tested positive for PIV-3 on nasopharyngeal aspirate in June 2005 were reviewed retrospectively., Results: Seven cases were infected with PIV-3 during this outbreak. The median birthweight of affected infants was 970 g (range, 740 to 2585 g), gestational age was 27 weeks and 4 days (range, 24 to 35 weeks), and postnatal age was 84 days (range, 28 to 250 days). Apnoeas and bradycardias were significant symptoms in 3 infants, 5 infants had progressive respiratory distress while the remaining 2 infants had flu-like illness. Five infants required ventilatory support and there were no deaths. The index case was an infant with chronic lung disease who was on oxygen supplementation and subsequently required ventilatory support with nasal CPAP. Despite implementation of control measures to prevent the spread of infection through early identification with strict cohorting of infected cases, contact tracing/screening, and reinforcement of hand hygiene precautions, the outbreak lasted for 24 days., Conclusion: PIV-3 respiratory infection in preterm infants can present with non-specific symptoms, leading to significant morbidity especially in those with underlying pulmonary pathology. Early recognition of symptoms and diagnosis by physicians, and prompt institution of control measures are necessary to prevent the spread of infection.

Aim: To characterise and compare the nutritional management and growth in infants <33 weeks' gestation in two tertiary centres., Methods: An audit of daily intake and growth from birth to discharge home was undertaken in two neonatal units: The KK Women's and Children's Hospital Singapore and the Adelaide Women's and Children's Hospital, South Australia. Mixed models were used to model intake and daily weight (g/day) accounting for repeated day per subject., Results: The clinical characteristics of the two cohorts were similar. The Adelaide cohort had a higher initial energy intake in the first 5 days compared with the Singapore cohort, and a significantly greater weekly increase of 21.0 kcal/week (95% CI 7.7-34.3; P = 0.002). The Adelaide cohort also had a higher initial protein intake and a significantly greater weekly increase of 0.88 g/week (95% CI 0.5, 1.3), P < 0.001) compared with the Singapore cohort. The weight gain of the Adelaide cohort was 9 g/day more than the Singapore cohort (95% CI 7.3, 10.7; P < 0.001). Post-natal growth failure was evident in 32% (n = 64) of the Adelaide cohort and 64% (n = 94) of the Singapore cohort., Conclusions: The two centres showed distinct differences in nutritional management. A higher energy and protein intake was associated with improved growth yet growth in both cohorts was still below current recommendations.

This randomized cross over study aimed to compare the severity and incidences of desaturation and bradycardia between the partially ventilated endotracheal suction method (PVETS) and closed tracheal suction system (CTSS) in extremely preterm neonates. Fifteen intubated and ventilated extremely low birth weight preterm infants (mean birth weight 689g) randomly underwent both suction techniques within a 12-h period to obtain a paired reading group. The process was repeated 24-48h apart until three pairs of reading groups were collected. Changes in oxygen saturation measured with pulse oximetry and heart rate changes measured with electrocardiogram were recorded using Hewlett-Packard m240A monitor trending software. The mean of each parameter's variation from baseline was obtained using SPSS descriptive statistics and analyzed using SPSS repeated measures ANOVA. Fisher Exact Test was used to analyze the incidence of desaturation and bradycardia. The closed tracheal suction system reported a significantly smaller degree of oxygen saturation fall (P<0.005) and significantly fewer incidences of desaturation. There was also a significantly smaller degree of heart rate reduction although episodes of bradycardia were not significantly different between the two methods. Oxygen saturation and heart rate were significantly more stable during the use of CTSS compared to PVETS in the extremely low birth weight preterm population.

Objective: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the effect of low-dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance., Methods: Two groups of preterm infants (birth weight

In sick preterm neonates receiving intensive care a spectacular rise in monocyte count has frequently been observed in sequential full blood examinations. The etiology of this has not previously been investigated and this study examines clinical factors that may contribute to this finding. Thirty (5.1%) of the 587 neonates who required intensive care during the study period had significant monocytosis (absolute count greater than 1700/mm3). Their mean gestation was 29 weeks (range 26-32 weeks). Monocytic response occurred at an age of 5.5 +/- 3 (mean +/- S.D.) days with 20% occurring at birth, 57% in the first week and 23% in the second week of life and lasted for 19.8 +/- 16 days (mean +/- S.D.). Most reached peak levels within two weeks and these ranged between 2,170 and 7176 per mm3. Analysis of the clinical variables against 37 controls revealed lower mean birth weight and gestational age, and higher incidence of leukocytosis, multiple transfusions, albumin infusions and theophylline therapy in the study group in comparison to the controls (P less than 0.001). No significant difference was found in maternal risk factors (pre-eclampsia, diabetes and amnionitis), birth asphyxia, respiratory disease, parenteral nutrition, proven infection and antibiotic therapy. An unexpected association with maternal steroid therapy was demonstrated. It is speculated that monocytosis represents a physiological though immature response of the marrow of small premature infants to a variety of exogenous stimuli including drugs and foreign protein infusions.