Thermoregulation and golden hour practices in extremely preterm infants: an international survey.

BACKGROUND: Are thermoregulation and golden hour practices in extremely preterm (EP) infants comparable across the world? This study aims to describe these practices for EP infants based on the neonatal intensive care unit's (NICUs) geographic region, country's income status and the lowest gestational age (GA) of infants resuscitated. METHODS: The Director of each NICU was requested to complete the e-questionnaire between February 2019 and August 2021. RESULTS: We received 848 responses, from all geographic regions and resource settings. Variations in most thermoregulation and golden hour practices were observed. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission, and having local protocols were the most consistent practices (>75%). The odds for the following practices differed in NICUs resuscitating infants from 22 to 23 weeks GA compared to those resuscitating from 24 to 25 weeks: respiratory support during resuscitation and transport, use of polyethylene plastic wrap and servo-control mode, commencing ambient humidity >80% and presence of local protocols. CONCLUSION: Evidence-based practices on thermoregulation and golden hour stabilisation differed based on the unit's region, country's income status and the lowest GA of infants resuscitated. Future efforts should address reducing variation in practice and aligning practices with international guidelines. IMPACT: A wide variation in thermoregulation and golden hour practices exists depending on the income status, geographic region and lowest gestation age of infants resuscitated. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission and having local protocols were the most consistent practices. This study provides a comprehensive description of thermoregulation and golden hour practices to allow a global comparison in the delivery of best evidence-based practice. The findings of this survey highlight a need for reducing variation in practice and aligning practices with international guidelines for a comparable health care delivery.

Tailoring an online breastfeeding course for Southeast Asian paediatric trainees- A qualitative study of user experience from Malaysia and Thailand.

BACKGROUND: This study explored the user experiences of paediatric postgraduate trainees in Malaysia and Thailand in using a 2 h and 15 min online module for breastfeeding developed for Southeast Asia, which was adapted from existing European online modules for European and German Continuing Medical Education (CME) credits. METHODS: A qualitative study using focus group discussions (FGDs) was conducted with paediatric postgraduate trainees who used an online English-language breastfeeding module in two Thai universities (May 2020, done online) and two Malaysian universities (Sept- Nov 2019, in-person). FGDs explored module usability and utility. Sessions were transcribed verbatim and analysed thematically. The process of coding was done collaboratively by Thai and Malaysian researchers. RESULTS: Twenty Six resident trainees participated (Thai, n = 13; Malaysian, n = 13). Ages ranged from 29-34 years old, with 21 females. Nineteen participants had never used online learning modules prior to this. Participants took between 1 to 5 sessions to complete the breastfeeding module. Four themes emerged from their experience. 1) The online learning module was more engaging and detailed than previous lectures, courses and/or books, but lacked hands-on training. 2) Using an online platform facilitated learning as eased navigation and resource searching, however, problems were encountered navigating the module on some devices. 3) Learners preferred less words and more graphics, as this helped them capture key messages. 4) Regionally tailored content elicited a mixed reaction from participants. CONCLUSIONS: Users found that the adapted module compared favourably with previous learning experiences. However, online learning modules lack hands-on training, and implementation should ideally incorporate a mix of both. Consideration of device diversity and preferences for how content was adapted for local settings are needed for tailoring.

Nutritional therapies in the neonatal intensive care unit and post-natal growth outcomes of preterm very low birthweight Asian infants.

AIM: A collaborative study was conducted between two Southeast Asian university hospitals to compare the nutritional intervention and growth outcomes and evaluate the extent of post-natal growth faltering (PNGF) among very low birthweight (VLBW) infants. METHODS: Data of all infants admitted during the 2011-2012 period to the two hospitals at Singapore (SG) and Malaysia (MY) were pooled and analysed. RESULTS: Of the 236 infants, SG infants received lower total protein and energy intake than MY infants (2.69 vs. 3.54 g/kg/day and 92.4 vs. 128.9 kcal/kg/day respectively; P < 0.001) in enteral feeds, with Singaporean infants predominantly fed fortified breast milk than Malaysian infants (45/48 vs. 10/41; P < 0.01). The mean weight z-score from birth to 36 weeks corrected age was significantly different (SG,-2.2 (0.9) vs. MY, -1.4 (0.7); P = 0.001). More SG than MY extremely low birthweight (ELBW) infants had severe PNGF >-2 SDS (55 vs. 16%; P = 0.001). The greater use of a diuretic in SG to treat haemodynamically significant patent ductus arteriosus (hsPDA) may have contributed to the higher PNGF rate. Mean growth velocity of at least 15 g/kg/day was attained by VLBW infants only from Day 14 and by ELBW infants only from Day 28 post-natally. Overall, severe PNGF rates (z-score change >-2 SDS at 36 weeks' corrected age) were 28.8 and 36.5% for VLBW and ELBW infants, respectively. CONCLUSIONS: Being very preterm, ELBW with hsPDA and receiving insufficient protein and energy were risk factors for severe PNGF. Increasing protein and energy content, augmenting fortification of breast milk and concentrating feed volumes, especially if there is an hsPDA, may curb severe PNGF among these infants.

Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0.

OBJECTIVE: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0. STUDY DESIGN: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat. RESULTS: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03). CONCLUSIONS: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.

Health-care professionals' approach in feeding term small-for-gestational age infants and its potential implications to later growth outcomes.

AIM: To understand feeding practices, nutrition management and postnatal growth monitoring of term small-for-gestational age (tSGA) infants in Southeast Asia. METHODS: Anonymous questionnaires to assess practices on feeding, nutrition management and post-natal growth monitoring of tSGA infants were distributed among health-care professionals (HCPs) participating in regional/local perinatology symposia in Malaysia, Thailand and Singapore. RESULTS: Three hundred seventy-seven respondents from Malaysia (37%), Thailand (27%), Singapore (18%) and other Asian countries (19%) participated in the survey. Respondents were neonatologists (35%), paediatricians (25%) and other HCPs (40%) including nurses and midwives. Exclusive human milk feeding was reported the most preferred feeding option for tSGA infants, followed by fortified human milk feeding (60% and 20%, respectively). This was consistent among the different countries. The perceived nutrient requirements of tSGA infants varied between countries. Most respondents from Malaysia and Singapore reported requirements to be similar to preterm infants, while the majority from Thailand reported that it was less than those of preterm infants. The World Health Organization Growth Chart of 2006 and Fenton Growth Charts of 2013 were the most frequently used charts for growth monitoring in the hospital and after discharge. CONCLUSIONS: Nutrition management and perceived nutrient requirements for tSGA infants among practising HCPs in Southeast Asia showed considerable variation. The impetus to form standardised and evidence based feeding regimens is important as adequate nutritional management and growth monitoring particularly in this population of infants will have long term impact on population health.

Glucose-6-phosphate dehydrogenase (G6PD)-deficient infants: Enzyme activity and gene variants as risk factors for phototherapy in the first week of life.

AIM: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a recognised cause of severe neonatal hyperbilirubinaemia, and identifying which infants are at risk could optimise care and resources. In this study, we determined if G6PD enzyme activity (EA) and certain gene variants were associated with neonatal hyperbilirubinaemia requiring phototherapy during the first week after birth. METHODS: Newborn infants with G6PD deficiency and a group with normal results obtained by the fluorescent spot test were selected for analyses of G6PD EA and the 10 commonly encountered G6PD mutations in this region, relating these with whether the infants required phototherapy before discharge from the hospital in the first week. RESULTS: A total of 222 infants with mean gestation and birth weight of 38.3 ± 1.8 weeks and 3.02 ± 0.48 kg, respectively, were enrolled. Of these, n = 121 were deficient with EA ≤6.76 U/g Hb, and approximately half (43%) received phototherapy in the first week after birth. The mean EA level was 3.7 U/g Hb. The EA had good accuracy in predicting phototherapy use, with area under the receiver-operating-characteristic curve of 0.81 ± 0.05. Infants on phototherapy more commonly displayed World Health Organization Class II mutations (<10% residual EA). Logistic regression analysis showed that deficiency in EA and mutation at c.1388G>A (adjusted odds ratio, 1.5 and 5.7; 95% confidence interval: 1.31-1.76 and 1.30-25.0, respectively) were independent risk factors for phototherapy. CONCLUSION: Low G6PD EA (<6.76 U/g Hb) and the G6PD gene variant, c.1388G>A, are risk factors for the need of phototherapy in newborn infants during the first week after birth.

Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase-deficient erythrocytes from newborn infants.

Erythrocytes require glucose-6-phosphate dehydrogenase (G6PD) to generate NADPH and protect themselves against hemolytic anemia induced by oxidative stress. Peroxiredoxin 2 (Prx2) is a major antioxidant enzyme that requires NADPH to recycle its oxidized (disulfide-bonded) form. Our aims were to determine whether Prx2 is more highly oxidized in G6PD-deficient erythrocytes and whether these cells are able to recycle oxidized Prx2 after oxidant challenge. Blood was obtained from 61 Malaysian neonates with G6PD deficiency (average 33% normal activity) and 86 controls. Prx2 redox state was analyzed by Western blotting under nonreducing conditions. Prx2 in freshly isolated blood was predominantly reduced in both groups, but the median level of oxidation was significantly higher (8 vs 3%) and the range greater for the G6PD-deficient population. When treated with reagent H2O2, the G6PD-deficient erythrocytes were severely compromised in their ability to recycle oxidized Prx2, with only 27 or 4% reduction after 1 h treatment with 0.1 or 1 mM H2O2 respectively, compared with >97% reduction in control erythrocytes. The accumulation of oxidized Prx2 in oxidatively stressed erythrocytes with common G6PD variants suggests that impaired antioxidant activity of Prx2 could contribute to the hemolysis and other complications associated with the condition.-Cheah, F.-C., Peskin, A. V., Wong, F.-L., Ithnin, A., Othman, A., Winterbourn, C. C. Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase deficient erythrocytes from newborn infants.

Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis.

Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide. Moreover, severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis. In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis, the implications for the neonate, as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment. Finally, we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.

The expectant management of a rare neonatal disease: transient neonatal myasthenia gravis.

BACKGROUND: Transient neonatal myasthenia gravis (TNMG) is an acquired disease which occurs in 10 to 20% of infants born to a mother with myasthenia gravis. Even though it is a self-limiting disorder, it may potentially be life-threatening if prompt diagnosis is not made, and expedient supportive respiratory management is not initiated when required. CASE: Here we describe three infants with TNMG. Two of them developed symptoms of TNMG within 24 hours of life, but one developed symptoms at 43 hours of life. One of the patients had an atypical form of TNMG with contracture and hypotonia. The other two infants survived a typical form of TNMG with hypotonia and poor sucking. All cases resolved spontaneously by one to two weeks of life with conservative management. CONCLUSIONS: Infants born to mothers with myasthenia gravis need to be monitored closely for symptoms of TNMG for the first 48 to 72 hours of life. However, the majority of infants with TNMG traverse a benign course and resolve spontaneously with expectant care.

The Promises and Pitfalls of CRISPR-Mediated Base Editing in Stem Cells.

Stem cells such as induced pluripotent stem cells, embryonic stem cells, and hematopoietic stem and progenitor cells are growing in importance in disease modeling and regenerative medicine. The applications of CRISPR-based gene editing to create a mélange of disease and nondisease stem cell lines have further enhanced the utility of this innately versatile group of cells in the studies of human genetic disorders. Precise base edits can be achieved using a variety of CRISPR-centric approaches, particularly homology-directed repair and the recently developed base editors and prime editors. Despite its much-touted potential, editing single DNA bases is technically challenging. In this review, we discuss the strategies for achieving exact base edits in the creation of various stem cell-based models for use in elucidating disease mechanisms and assessing drug efficacy, and the unique characteristics of stem cells that warrant special considerations.

Maternal and fetal outcomes of pregnant women with bacterial vaginosis.

Background: Bacterial vaginosis (BV) is a common infection in women of reproductive age group because of vaginal dysbiosis. The impact of BV during pregnancy is still not well defined. The objective of this study is to assess the maternal-fetal outcome in women with BV. Materials and Methods: A prospective cohort study over one-year duration was conducted from December, 2014 until December, 2015, involving 237 women who presented with abnormal vaginal discharge, preterm labour or preterm prelabour rupture of membrane between 22- and 34-weeks period of gestation. Vaginal swabs were sent for culture and sensitivity, BV® Blue testing and PCR for Gardnerella vaginalis (GV). Results: BV was diagnosed in 24/237 (10.1%) cases. The median gestational age was 31.6 weeks. GV was isolated from 16 out of 24 (66.7%) in the BV positive group. There was a significantly higher preterm birth rate, below 34 weeks (22.7% vs. 6.2%, p = 0.019) in women with BV. There was no statistically significant difference in maternal outcome such as clinical chorioamnionitis or endometritis. However, placental pathology revealed more than half (55.6%) of women with BV had histologic chorioamnionitis. Neonatal morbidity was significantly higher with exposure to BV, with a lower median birth weight, higher rate of neonatal intensive care unit admission (41.7% vs. 19.0%, p = 0.010), increased intubation for respiratory support (29.2% vs. 7.6%, p = 0.004) and respiratory distress syndrome (33.3% vs. 9.0%, p = 0.002). Conclusion: More research is needed to formulate guidelines for prevention, early detection and treatment of BV during pregnancy to reduce intrauterine inflammation and the associated adverse fetal outcomes.

Global variation in skin injures and skincare practices in extremely preterm infants.

BACKGROUND: Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them. METHODS: A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions. RESULTS: Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45-0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45-0.96; local skin infections: OR = 0.41, 95% CI = 0.26-0.65; chemical burns: OR = 0.46, 95% CI = 0.26-0.83; thermal burns: OR = 0.51, 95% CI = 0.27-0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33-0.67; pressure: aOR = 0.51, 95% CI = 0.34-0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51-0.99; perineal: aOR = 0.52, 95% CI = 0.36-0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed. CONCLUSIONS: Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a prevalent condition worldwide and is caused by loss-of-function mutations in the G6PD gene. Individuals with deficiency are more susceptible to oxidative stress which leads to the classical, acute hemolytic anemia (favism). However, G6PD deficiency in newborn infants presents with an increased risk of hyperbilirubinemia, that may rapidly escalate to result in bilirubin induced neurologic dysfunction (BIND). Often with no overt signs of hemolysis, G6PD deficiency in the neonatal period appears to be different in the pathophysiology from favism. This review discusses and compares the mechanistic pathways involved in these two clinical presentations of this enzyme disorder. In contrast to the membrane disruption of red blood cells and Heinz bodies formation in favism, G6PD deficiency causing jaundice is perhaps attributed to the disruption of oxidant-antioxidant balance, impaired recycling of peroxiredoxin 2, thus affecting bilirubin clearance. Screening for G6PD deficiency and close monitoring of affected infants are important aspects in neonatal care to prevent kernicterus, a permanent and devastating neurological damage. WHO recommends screening for G6PD activity of all infants in countries with high prevalence of this deficiency. The traditional fluorescent spot test as a screening tool, although low in cost, misses a significant proportion of cases with moderate deficiency or the partially deficient, heterozygote females. Some newer and emerging laboratory tests and diagnostic methods will be discussed while developments in genomics and proteomics contribute to increasing studies that spatially profile genetic mutations within the protein structure that could predict their functional and structural effects. In this review, several known variants of G6PD are highlighted based on the location of the mutation and amino acid replacement. These could provide insights on why some variants may cause a higher degree of phenotypic severity compared to others. Further studies are needed to elucidate the predisposition of some variants toward certain clinical manifestations, particularly neonatal hyperbilirubinemia, and how some variants increase in severity when co-inherited with other blood- or bilirubin-related genetic disorders.

Antenatal Corticosteroids to Asian Women Prior to Elective Cesarean Section at Early Term and Effects on Neonatal Respiratory Outcomes.

This exploratory study aimed to evaluate the effects of antenatal corticosteroids in singleton pregnancies of Asian women prior to elective cesarean section (CS) at early term on neonatal respiratory outcomes. METHODS: This is a pilot and pragmatic randomized trial conducted at a university hospital in Malaysia. Women with singleton pregnancies planned for elective CS between 37+0 and 38+6 weeks gestation were randomly allocated into the intervention group, where they received two doses of IM dexamethasone 12 mg of 12 h apart, 24 h prior to surgery OR into the standard care, control group, and both groups received the normal routine antenatal care. The primary outcome measures were neonatal respiratory illnesses, NICU admission and length of stay. RESULTS: A total of 189 patients were recruited, 93 women in the intervention group and 96 as controls. Between the steroid and control groups, the mean gestation at CS was similar, 266.1 ± 3.2 days (38 weeks) vs. 265.8 ± 4.0 days (37+6 weeks), p = 0.53. The mean birthweight of infants was 3.06 ± 0.41 kg vs. 3.04 ± 0.37 kg, p = 0.71. Infants with respiratory morbidities were primarily due to transient tachypnea of newborn (9.7% vs. 6.3%), and congenital pneumonia (1.1% vs. 3.1%) but none had respiratory distress syndrome. Only four infants required NICU admission (2.2% vs. 3.1%, p = 0.63). Their average length of stay was not statistically different; 3.5 ± 2.1 days vs. 5.7 ± 1.5 days, p = 0.27. CONCLUSIONS: Elective CS at early term before 39 weeks was associated with a modest overall incidence of neonatal respiratory illness (10.1%) in this Asian population. Antenatal dexamethasone did not diminish infants needing respiratory support, NICU admission and length of stay.

Gardnerella vaginalis infection in pregnancy: Effects on placental development and neonatal outcomes.

INTRODUCTION: Gardnerella vaginalis (GV)-associated bacterial vaginosis is recognised for its detrimental effects on pregnancy resulting in poor obstetric and neonatal outcomes. There is limited knowledge of the effects on placental histomorphology following GV infection in pregnancy. We investigated the effects of GV infection on the placenta, particularly with regards to the syncytiotrophoblasts and vascular development, and related these to neonatal outcomes. METHODS: A prospective cohort study involving GV-positive pregnant women presented with abnormal vaginal discharge, with gestational age-matched healthy pregnant women controls. Placental sampling was performed upon delivery and examined histologically. Vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) mRNA and protein expression were analysed by real-time PCR and immunohistochemistry respectively. The standard measures in neonatal outcomes were recorded. RESULTS: Placentas from GV-positive mothers were found to have significant histological evidence of maternal and/or fetal inflammatory response compared with the controls (17/28: 60.7% vs 2/20: 10%) (p = 0.0011). There was an increase in the percentage of syncytial nuclear aggregates (SNAs) per villus (47.4 ± 11.09%) in placentas from GV-positive mothers (p < 0.0001). VEGF-A was significantly increased in specifically, the villous endothelial cells of placentas with GV infection, but no difference in the immunoexpression of HIF-1α in these cells between groups. However, these were not associated with adverse neonatal outcomes. DISCUSSION: Increased placental VEGF-A expression associated with increased SNAs in pregnant women with GV infection of the genital tract may be an intrauterine response towards placental vascular remodeling, that may also serve as a protective role in moderating birth outcomes.

Transdermal Maltose-Based Microneedle Patch as Adjunct to Enhance Topical Anesthetic before Intravenous Cannulation of Pediatric Thalassemic Patients Receiving Blood Transfusion: A Randomized Controlled Trial Protocol.

Intravenous cannulation is experientially traumatic to children. To minimize this, EMLA® is applied on the would-be-cannulated area before IV cannula insertion. However, the time to achieve its maximum efficacy may be affected due to incomplete cutaneous absorption and the duration of application. The latter may be a limiting factor in a busy healthcare facility. The usage of dissolvable maltose microneedles may circumvent this problem by introducing micropores that will facilitate EMLA® absorption. A randomized phase II cross-over trial will be conducted to compare the Visual Analogue Scale (VAS) pain scores and skin conductance algesimeter index between 4 different interventions (1 fingertip unit (FTU) of EMLA® with microneedle patch for 30 min before cannulation; 0.5 FTU of EMLA® with microneedle patch for 30 min; 1 FTU of EMLA® with microneedle for 15 min; 1 FTU of EMLA® with sham patch for 30 min). A total of 26 pediatric patients with thalassemia aged between 6 and 18 years old and requiring blood transfusion will be recruited in this trial. During the visits, the VAS scores and skin conductance algesimeter index at venous cannulation will be obtained using the VAS rulers and PainMonitor™ machine, respectively. The trial will commence in August 2021 and is anticipated to end by August 2022.

Biomarkers of neutrophil-mediated glutathione and protein oxidation in tracheal aspirates from preterm infants: association with bacterial infection.

Bronchopulmonary dysplasia is associated with neutrophil infiltration into the lungs and oxidative injury. However, the pathological importance of neutrophil oxidants is still not clear. Nosocomial pneumonia is also implicated, but the evidence is limited, in part because of the difficulty of distinguishing genuine infection from bacterial colonization. Good biomarkers of neutrophil oxidant activity and lung infection are needed. We tested whether glutathione sulfonamide, a product of glutathione oxidation by myeloperoxidase-derived hypochlorous acid (HOCl) and a potential new neutrophil oxidant biomarker, is detectable in endotracheal aspirates from ventilated preterm infants. As infectious organisms stimulate neutrophils to generate HOCl, we determined whether levels of HOCl-specific biomarkers were increased in samples that were bacterial culture positive. Glutathione sulfonamide was detected in 66 of 87 endotracheal aspirate samples. Levels correlated with myeloperoxidase activity and another HOCl-specific marker, chlorotyrosine. Median levels of glutathione sulfonamide (4-fold) and other biomarkers (2-fold) were significantly higher in culture positive aspirates. Staphylococcus epidermidis, a frequent colonizer, was associated with glutathione sulfonamide levels no different from those in negative samples. Glutathione sulfonamide showed good sensitivity and specificity for detecting bacterial growth and has promise for detecting lung infection.

Simulation-Based Education in the Training of Newborn Care Providers-A Malaysian Perspective.

Simulation-based education (SBE) is increasingly used as an education tool to improve learning for healthcare providers. In newborn care practice, SBE is used in the Neonatal Resuscitation Program (NRP) and training in procedural skills. The NRP is a mandatory course in Malaysia for all house officers (interns) and medical officers (residents) during their pediatric rotation. Almost 30,000 of NRP providers have been trained over the last 5 years. The recent establishment of the Allied Healthcare Center of Excellence (AHCoE), an organization dedicated to promoting SBE, and Malaysian Society for Simulation in Healthcare (MaSSH) aims to enhance the integration of SBE into the healthcare training curriculum and set up a local healthcare simulation educator training program. Our experience in implementing SBE necessitated that we made several important choices. As there was no strong evidence to favor high-fidelity over low-fidelity simulation, and because simulation centers can be very costly to set up with limited resources, we chose SBE mainly in the form of low-fidelity and in situ simulation. We also identified an important developmental goal to train Malaysian instructors on structured debriefing, a critical activity for learning in SBE. Currently, debriefing is often carried out in our centers at an ad hoc basis because of time limitation and the lack of personnel trained. Finally, we aim to implement SBE further in Malaysia, with two axes: (1) the credentialing and recertification of physicians and nurses, and (2) the education of lay caregivers of high-risk infants before discharge from the neonatal intensive care unit.

Studying the Effects of Granulocyte-Macrophage Colony-Stimulating Factor on Fetal Lung Macrophages During the Perinatal Period Using the Mouse Model.

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine that is increased in the amniotic fluid in chorioamnionitis and elevated in the fetal lung with endotoxin exposure. Although GM-CSF has a pivotal role in fetal lung development, it stimulates pulmonary macrophages and is associated with the development of bronchopulmonary dysplasia (BPD). How antenatal GM-CSF results in recruitment of lung macrophage leading to BPD needs further elucidation. Hence, we used a transgenic and knock-out mouse model to study the effects of GM-CSF focusing on the fetal lung macrophage. Methods: Using bitransgenic (BTg) mice that conditionally over-expressed pulmonary GM-CSF after doxycycline treatment, and GM-CSF knock-out (KO) mice with no GM-CSF expression, we compared the ontogeny and immunophenotype of lung macrophages in BTg, KO and control mice at various prenatal and postnatal time points using flow cytometry and immunohistology. Results: During fetal life, compared to controls, BTg mice over-expressing pulmonary GM-CSF had increased numbers of lung macrophages that were CD68+ and these were primarily located in the interstitium rather than alveolar spaces. The lung macrophages that accumulated were predominantly CD11b+F4/80+ indicating immature macrophages. Conversely, lung macrophages although markedly reduced, were still present in GM-CSF KO mice. Conclusion: Increased exposure to GM-CSF antenatally, resulted in accumulation of immature macrophages in the fetal lung interstitium. Absence of GM-CSF did not abrogate but delayed the transitioning of interstitial macrophages. Together, these results suggest that other perinatal factors may be involved in modulating the maturation of alveolar macrophages in the developing fetal lung.