Trends in neonatal mortality and morbidity in very-low-birth-weight (VLBW) infants over a decade: Singapore national cohort study.

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.

Preparation and consideration for establishment of an isolation maternity unit in a tertiary hospital during COVID-19 pandemic.

The SARS-CoV-2 pandemic is rapidly evolving and remains a major health challenge worldwide. With an increase in pregnant women with COVID-19 infection, we recognized an urgent need to set up a multidisciplinary taskforce to provide safe and holistic care for this group of women. In this review of practice in a tertiary hospital in Singapore, we discuss the key considerations in setting up an isolation maternity unit and our strategies for peripartum and postpartum care. Through teleconsultation, we involve these women and their families in the discussion of timing and mode of birth, disposition of babies after birth and safety of breastfeeding to enable them to make informed decisions and individualize their care.

Guidance for the clinical management of infants born to mothers with suspected/confirmed COVID-19 in Singapore.

In this paper, we provide guidance to clinicians who care for infants born to mothers with suspected/confirmed COVID-19 during this current pandemic. We reviewed available literature and international guidelines based on the following themes: delivery room management; infection control and prevention strategies; neonatal severe acute respiratory syndrome coronavirus 2 testing; breastfeeding and breastmilk feeding; rooming-in of mother-infant; respiratory support precautions; visiting procedures; de-isolation and discharge of infant; outpatient clinic attendance; transport of infant; and training of healthcare staff. This guidance for clinical care was proposed and contextualised for the local setting via consensus by members of this workgroup and was based on evidence available as of 31 July 2020, and may change as new evidence emerges.

Being Prepared During the Evolving COVID-19 Pandemic: A Neonatal Experience in Training and Simulation.

Background: Rapid spread of the COVID-19 pandemic raised an urgent need for preparedness in the healthcare sector, including training of healthcare workers to cope with the burden of infected cases while ensuring proper protection of themselves. Improper infection prevention and control measures were key reasons for infection in healthcare workers during the early phase of the outbreak. Objectives/Methods: This paper describes the combined approach of 3 restructured hospitals in Singapore in preparing and training neonatal healthcare workers' during the COVID-19 pandemic crisis, as well as lessons learnt during this process. Results: Information sharing was conducted in the form of e-learning, emphasizing on topics like disease knowledge and infection prevention and control procedures. Skills and competency training were carried out in the form of simulation, with sessions scaled into 4 levels progressing from individual task training to larger group simulations involving multiple disciplines and departments. Challenges encountered included information fatigue by large amount of constantly changing information and multiple amendments to workflows as more information arose. Difficulties conducting training and simulation sessions included restriction of group size to mitigate infection risk amongst participants and the limited supply of personal protective equipment prioritized for direct patient care. Conclusion: Healthcare institutions should ensure adequate dissemination of conceptual knowledge as well as skills competency training of staff in infection control measures for the protection of healthcare workers and patient safety. Ongoing training for sustainability of knowledge and skills, while adapting to the rapidly evolving situation is important in the preparation for future outbreaks.

Degradation of Melt Electrowritten PCL Scaffolds Following Melt Processing and Plasma Surface Treatment.

Melt electrowriting (MEW) has been widely used to process polycaprolactone (PCL) into highly ordered microfiber scaffolds with controllable architecture and geometry. However, the integrity of PCL during specific processes involved in routine MEW scaffold development has not yet been thoroughly investigated. This study investigates the impact of MEW processing on PCL following exposure to high temperatures required for melt extrusion as well as atmospheric plasma, a widely used surface treatment for improving MEW scaffold hydrophilicity. The change in polymer molecular weight and melt temperature is characterized, in comparing unprocessed and processed samples, in addition to analysis of the mechanical and surface properties of the scaffolds. No significant difference in the molecular weight or mechanical properties of the PCL scaffolds is evident following 5 days of cyclic heating to 90 °C. Exposure to plasma for up to 5 min significantly increased hydrophilicity and surface adhesion force, characterized via contact angle and atomic force microscope, however, significant polymer degradation occurred evidenced by increased brittleness of the scaffolds. This study demonstrates the degradation of PCL following fabrication via MEW and surface treatment to guide the optimization of scaffold development for subsequent applications in tissue engineering and biofabrication.

Singapore Neonatal Resuscitation Guidelines 2021.

Neonatal resuscitation is a coordinated, team-based series of timed sequential steps that focuses on a transitional physiology to improve perinatal and neonatal outcomes. The practice of neonatal resuscitation has evolved over time and continues to be shaped by emerging evidence as well as key opinions. We present the revised Neonatal Resuscitation Guidelines for Singapore 2021. The recommendations from the International Liaison Committee on Resuscitation Neonatal Task Force Consensus on Science and Treatment Recommendations (2020) and guidelines from the American Heart Association and European Resuscitation Council were compared with existing guidelines. The recommendations of the Neonatal Subgroup of the Singapore Resuscitation and First Aid Council were derived after the work group discussed and appraised the current available evidence and their applicability to local clinical practice.

Use of web-based game in neonatal resuscitation - is it effective?

BACKGROUND: Knowledge and skills decline within months post simulation-based training in neonatal resuscitation. To empower 'Millennial' learners to take control of their own learning, a single-player, unguided web-based Neonatal Resuscitation Game was designed. The present study investigates the effectiveness of the game on retention of resuscitation knowledge and skills. METHODS: The study evaluated 162 healthcare professionals who attended simulation-based training in neonatal resuscitation. Following standard simulation-based training, participants were assigned to either a gaming group (Gamers) with access to the web-based Neonatal Resuscitation Game or a control group (Controls) with no access to the game. Although Gamers were given access, game utilization was completely voluntary and at will. Some Gamers chose to utilize the web-based game (Players) and others did not (Non-players). Knowledge and skills in neonatal resuscitation were assessed upon completion of training and 6 months post-training using a multiple-choice question test and a manikin-based skills test. Changes in scores were compared statistically between Gamers vs Controls, Players vs Controls, and Players vs Controls + Non-players using two-sample t-tests. RESULTS: At the final assessment, declines in knowledge scores were seen in all groups. Mean change from baseline in knowledge and skill performance scores at 6 months, adjusted for baseline skill performance and MCQ test scores, did not differ significantly between Players vs Controls and Players vs Controls + Non-players. CONCLUSION: The web-based game in its current format may not be effective in facilitating retention of knowledge and technical skills in neonatal resuscitation.

Eliminating MRSA transmission in a tertiary neonatal unit-A quality improvement initiative.

BACKGROUND: Health care facility-onset methicillin-resistant Staphylococcus aureus (HO-MRSA) colonization or infection is a major cause of health care-associated infection (HAI) worldwide. HAIs are preventable and considered a health care quality outcome indicator. A quality improvement project to eliminate HO-MRSA transmission was conducted in a tertiary care neonatal unit over a 9-month period, and sustainability data were monitored. The primary aim of this project was to achieve zero transmission of MRSA among all neonatal unit admissions, and secondary aims were to improve hand hygiene (HH) and environmental hygiene compliance to 100%. METHODS: Existing inpatient admission processes, staff HH, and environmental hygiene practices were critically analyzed. Sequential interventions were implemented, including reinforcing staff awareness on infection control practices through regular education and updates, providing "just in time" feedback, ensuring easy availability of cleaning equipment, individualizing items for all patients, keeping personal belongings away from clinical areas, and revising admission work flow for ex-utero transferred babies from other hospitals. RESULTS: The neonatal unit achieved zero MRSA transmission to previously noninfected and noncolonized patients over the 9-month period, and HH and environmental hygiene compliance improved from a preintervention median of 87.1% and 82.2%, respectively, to 100%, which has been sustained to date. CONCLUSIONS: Intensive reinforcement of infection control practices, strict cohorting of ex-utero transfers, universal surveillance on admission, and improvement in HH and environmental hygiene compliance were key to infection prevention and control measures, resulting in elimination of MRSA transmission in our neonatal unit.

Long-Term Neurodevelopmental Outcomes of Premature Infants in Singapore.

INTRODUCTION: Neonatal care advances have resulted in improved survival but have raised concerns of increase in neurodevelopmental impairment. This study looked at long-term neurodevelopmental outcomes at ages 5 and 8 years of very low birthweight infants born in the 2000s as compared to the 1990s. Neurodevelopmental assessment at 2 years old was compared to that at 5 and 8 years to determine if assessment at 2 years was predictive of later outcomes. MATERIALS AND METHODS: A retrospective cohort study of consecutive infants with birthweight less than 1250 grams admitted to a tertiary centre in Singapore between January 1994 to December 1995 (Epoch I) and January 2004 to December 2005 (Epoch II) were included. Neurodevelopmental impairment was defined as having intelligence quotient (IQ) of less than 70, cerebral palsy, legal blindness, or hearing impairment requiring hearing aids. RESULTS: Mean gestational age was lower for Epoch II compared to Epoch I (28.1 ± 2.5 vs 29.4 ± 2.7 weeks, P = 0.004). Death or neurodevelopmental impairment rates did not differ (24.3% and 17.1% at 5 years old, P = 0.398; 29.1% and 25.0% at 8 years old, P = 0.709). There was improvement in visual impairment rate at 8 years in Epoch II (10.7% vs 34.0%, P = 0.024). Mean IQ was better in Epoch II (109 and 107 vs 97 and 99 at 5 [P = 0.001] and 8 years [P = 0.047], respectively). All infants with no neurodevelopmental impairment at 2 years remained without impairment later on. CONCLUSION: Over a decade, neurodevelopmental outcomes did not worsen despite lower mean gestational age. Long- term improvement in IQ scores and a reduction in visual impairment rates were seen. Our data suggests that children without neurodevelopmental impairment at 2 years are without impairment later on; therefore, they may need only developmental monitoring with targeted assessments instead of routine formal IQ assessments.

A Comparison of the Short-term Morbidity and Mortality Between Late Preterm and Term Newborns.

INTRODUCTION: Late preterm babies are defined as those born between 34 to 36 completed weeks. There has been a recent increased awareness that this group of babies has a higher incidence of morbidity as compared to term babies. The aim of this study was to evaluate the short-term morbidities occurring in this group of babies managed in the neonatal unit at Singapore General Hospital (SGH). MATERIALS AND METHODS: A retrospective study was done of babies managed in the neonatal unit at SGH from January 2005 to December 2008. Maternal, perinatal and neonatal data were obtained from the departmental database. The outcomes of late preterm infants were compared with term infants. RESULTS: A total of 6826 babies were admitted. Ten percent (681 out of 6826) of babies were late preterm babies, making up 63% (681 out of 1081) of all preterm babies. Late preterm babies had significantly greater need for resuscitation at birth. They also had statistically significant increased risks of developing hyaline membrane disease (2.5% vs 0.1%), transient tachypnoea of the newborn (TTN) (8.1% vs 1.7%), pneumonia (7.0% vs 2.8%), patent ductus arteriosus (PDA) (4.3% vs 1.1%), hypotension (0.7% vs 0%), apnoea (3.7% vs 0%), gastrointestinal (GI) bleeding (1.5% vs 0.3%), polycythaemia (2.2% vs 1.0%), anaemia (3.4% vs 1.2%), thrombocytopenia (3.2% vs 0.6%), hypoglycaemia (6.6% vs 1.7%), neonatal jaundice requiring phototherapy (41.1% vs 12.2%) and sepsis (1.7% vs 0.6%). CONCLUSION: Late preterm infants are indeed a vulnerable group of infants with significant morbidities that need to be addressed and treated. Despite their relatively large size and being almost term, the understanding that late preterm infants are not similar to term infants is important to both obstetricians and neonatologists.

Restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants: a systematic review and meta-analysis.

AIM: A systematic review was conducted to examine the effects of restrictive versus liberal red blood cell (RBC) transfusion thresholds on clinically important outcomes in very low birth weight (VLBW) infants. METHODS: Randomised controlled trials (RCTs) of varying RBC transfusion thresholds in VLBW infants were identified by searching MEDLINE, EMBASE, CINAHL, all of the Cochrane Library and other supplementary sources. Selected studies included one of the following outcomes: total number of red blood cell transfusions, donor exposure rate, cranial ultrasonographically diagnosed brain injury, retinopathy of prematurity, bronchopulmonary dysplasia, necrotising enterocolitis or death. Studies to be included were selected by two reviewers who also assessed the risk of bias of each trial. Data extraction and analyses were independently performed by two reviewers. All data were analysed using RevMan 5. RESULTS: Six RCTs were identified. One trial did not meet the inclusion criteria, while two had inadequate methodological quality. Pooled analysis of two trials showed that the restrictive transfusion group received a significantly lower mean number of transfusions per infant (mean difference (MD) -1.35, 95% confidence interval (CI) [-2.61, -0.09]) and donor exposure rate (MD -0.54, 95% CI [-0.93, -0.15]). No other statistically significant differences were observed. CONCLUSION: Restrictive RBC transfusion thresholds in VLBW infants may be utilised without incurring clinically important increases in the risk of death or major short-term neonatal morbidities.

Short- and long-term outcomes at 2, 5 and 8 years old for neonates at borderline viability--an 11-year experience.

INTRODUCTION: Neurodevelopmental outcome of borderline viability neonates have lagged behind improvement in survival figures. Accurate figures based on local outcome allow us to better counsel parents and to prognosticate with greater accuracy on both short- and longterm outcomes. MATERIALS AND METHODS: A retrospective cohort study of 101 consecutively born neonates, born from 21 to 26 weeks gestation over an 11-year period from 1 January 1994 to 31 December 2005 was conducted. Long-term outcomes were assessed at 2, 5 and 8 years of age in terms of mental developmental index (MDI) or intelligence quotient (IQ) scores, hearing and visual impairments, handicaps and impairments, school placement and interventions required. RESULTS: Survival rates were 20.0%, 60.9%, 70.4% and 73.2% for neonates born at 21 to 23, 24, 25 and 26 weeks gestation respectively. Factors that predicted increased mortality included higher alveolar-arterial oxygen difference (AaDO2) with odds ratio (OR) 1.005 and lower birth weight OR 0.993. Rates of severe retinopathy of prematurity (ROP) (stage 3 or worse) were 100%, 57.1%, 42.1% and 26.7% for 21 to 23, 24, 25 and 26 weeks gestation respectively. Rates of bronchopulmonary dysplasia (BPD) were 100.0%, 57.1%, 63.2% and 60.0% respectively. Rates of severe intraventricular haemorrhage (IVH) were 0%, 7.1%, 5.3% and 10.0% respectively. Moderate to severe disability rates at 2 years old were 100%, 44.4%, 33.3% and 30.4% respectively. At 5 years old, moderate to severe disability rates were 16.7%, 22.2% and 14.3% respectively for those born at 24, 25 and 26 weeks gestation. Interpretation at 8 years was limited by small numbers. CONCLUSION: Our results indicated that local figures for mortality and morbidity remained high at the limits of viability, although they were comparable to outcomes for large scale studies in advanced countries.

Profile of children diagnosed with autistic spectrum disorder managed at a tertiary child development unit.

INTRODUCTION: There has been a rising trend in childhood developmental and behavioural disorders (CDABD). This study reports the profile of children with autistic spectrum disorders (ASD) initially referred for evaluation of CDABD. METHODS: The CDABD database prospectively collected data of all consenting children referred in 2003 to the then Child Development Unit at KK Women's and Children's Hospital. All received medical consultation, followed by further assessments and intervention. Patients were tracked for one year. RESULTS: Among 542 referred children, 32% (n = 170) received a diagnosis of ASD one year after the first consultation. Most were male, with a male to female ratio of 4.5:1. The median age at the first consultation was 41 (19,109) months. The main presenting concern was a delay in the development of speech and language skills in 78% of the children. A significant number had behavioural (63%) and social interaction (34%) issues. Criteria for the diagnosis of ASD according to the Diagnostic Statistical Manual IV-Revised were fulfilled in almost 90%. With the remaining refusing or deferring evaluation, only 74% received a psychological assessment. ASD was assessed to be severe or moderate in 86% of the children. Three-quarters remained on follow-up one year after the first consultation. The majority were referred for either centre- or school-based intervention programmes, with 70% assessed to have improved at the one-year mark. CONCLUSION: This is the first presentation of local data that aids programme planning and resource allocation. Children with ASD have varied outcomes. It is important to identify and intervene early in order to optimise development and functionality.

Children with developmental and behavioural concerns in Singapore.

INTRODUCTION: Childhood developmental and behavioural disorders (CDABD) have been increasingly recognised in recent years. This study evaluated the profiles and outcomes of children referred for developmental and behavioural concerns to a tertiary child developmental centre in Singapore. This is the first such regional database. METHODS: Baseline information, obtained through a questionnaire, together with history at first consultation, provided information for referral, demographic and presentation profiles. Clinical formulations were then made. Definitive developmental and medical diagnoses, as well as outcomes based on clinical assessment and standardised testing, were recorded at one year post first consultation. RESULTS: Out of 1,304 referrals between January 1, 2003 and December 1, 2004, 45% were 2-4 years old and 74% were boys. The waiting time from referral to first consultation exceeded four months in 52% of children. Following clinical evaluation, 7% were found to be developmentally appropriate. The single most common presenting concern was speech and language (S&L) delay (29%). The most common clinical developmental diagnosis was autism spectrum disorder (ASD) (30%), followed by isolated S&L disorder, global developmental delay (GDD) and cognitive impairment (CI). Recommendations included S&L therapy (57%), occupational therapy (50%) and psychological/behavioural services (40%). At one year, ASD remained the most common definitive developmental diagnosis (31%), followed by S&L disorder, CI and GDD. Most were children with high-prevalence, low-moderate severity disorders who could potentially achieve fair-good prognosis with early intervention. CONCLUSION: Better appreciation of the profile and outcome of children with CDABD in Singapore could enable better resource planning for diagnosis and intervention.

Virtual visitation in the neonatal intensive care: experience with the use of internet and telemedicine in a tertiary neonatal unit.

INTRODUCTION: Globally about 8% to 10% of newborns require neonatal intensive care (NICU) care. Families face emotional and financial difficulties when their sick newborns are hospitalized for prolonged periods in a NICU. METHODS: We conducted a study to assess the feasibility and acceptance of an Internet-based telemedicine program in an intensive care setting and to evaluate its impact on newborns' length of stay (LOS) in hospitals. We identified eligible newborns and obtained their parents' written consent before installing a Web camera by the babies' beds. Using child-specific, confidential passwords, families viewed real-time video images of their newborns through a secure portal via an Internet browser or 3G (third-generation) cell phone. Parents of study subjects completed a survey that detailed the performance of the system. Frequency of parental visits and LOS of babies were tracked and compared with the same data for similar high-risk newborns matched for gestation and birth weight. RESULTS: Parents responded favorably to the stability of the system and clarity of the image. Eighty percent requested a larger image frame. Frequencies of hospital visits made by parents of newborns in the study group and of those made by parents in the control group were not statistically different. LOS and postmenstrual age on discharge of study infants were not statistically different compared with infants in the control group. CONCLUSION: Virtual visitation is well accepted by families with sick newborns requiring prolonged hospitalization. Inclusion of information technology to optimize NICU visitation resulted in no significant decrease in duration of hospitalization; however, its role in improving post-discharge transition care must be evaluated further.

Smooth muscle cells cultured from human saphenous vein exhibit increased proliferation, invasion, and mitogen-activated protein kinase activation in vitro compared with paired internal mammary artery cells.

OBJECTIVE: Smooth muscle cell (SMC) proliferation, invasion, and matrix metalloproteinase (MMP) secretion are key events in the development of intimal hyperplasia, the lesion that causes coronary artery bypass graft (CABG) failure. Saphenous vein (SV) grafts are the most commonly used bypass conduits but are markedly more susceptible to intimal hyperplasia than internal mammary artery (IMA) grafts. We hypothesized that this may be due to inherent functional differences between SV-SMCs and IMA-SMCs. In this study we used paired cultures of SV-SMCs and IMA-SMCs from the same patients and compared their rates of proliferation, invasion, migration, and MMP-2 and MMP-9 secretion. METHODS: SMCs were cultured from explants of paired SV and IMA from 22 patients undergoing CABG. SMC populations of equivalent passage were used to determine proliferation in response to 10% fetal calf serum (FCS), 10 ng/mL platelet-derived growth factor (PDGF), and 10 ng/mL basic fibroblast growth factor (bFGF) by counting cells during a 7-day period. Immunoblotting was used to quantify phosphorylation of p44/42-mitogen-activated protein kinase (MAPK). Invasion and migration rates of paired SMCs were quantified using a modified Boyden chamber technique in the presence or absence of a Matrigel basement membrane barrier (BD Biosciences, Oxford, UK). Conditioned media from invasion assays were analyzed for secretion of MMP-2 and MMP-9 by gelatin zymography. RESULTS: Analysis of areas under curves for 7-day proliferation assays revealed that the number of SV-SMCs in response to FCS, PDGF, and bFGF was 2.1, 2.0, and 2.3 times higher, respectively, than that of paired IMA-SMCs. Basal MAPK activation in SV-SMCs was approximately double that of paired IMA-SMCs. SV-SMCs exhibited a 2.1-fold increase in invasion rate (Matrigel barrier) compared with IMA-SMCs, but migration rates (no Matrigel barrier) and MMP-2 and MMP-9 secretion were similar for the two cell types. CONCLUSIONS: Human SV-SMCs are inherently more proliferative and invasive than paired IMA-SMCs, likely due to a relative increase in p44/42-MAPK activation. These inherent functional differences between SMC of different origins may contribute to the increased prevalence of intimal hyperplasia in SV grafts compared with IMA grafts.