Displaying publications 21 - 36 of 36 in total

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  1. Cheah FC, Presicce P, Tan TL, Carey BC, Kallapur SG
    Front Pediatr, 2021;9:614209.
    PMID: 33777863 DOI: 10.3389/fped.2021.614209
    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.
  2. Wong PK, Mohamad Zamberi NN, Syafruddin SE, Cheah FC, Azmi N, Law JX, et al.
    CRISPR J, 2023 Jun;6(3):196-215.
    PMID: 37219623 DOI: 10.1089/crispr.2023.0013
    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.
  3. Arsad N, Abd Razak N, Omar MH, Shafiee MN, Kalok A, Cheah FC, et al.
    PMID: 35564596 DOI: 10.3390/ijerph19095201
    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.

  4. Ahmad Kamar A, Cheah FC, Ismail H, Pejaver R, Ellwood DA, Mahdy ZA
    Front Surg, 2023;10:1291596.
    PMID: 37841814 DOI: 10.3389/fsurg.2023.1291596
  5. Shah NM, Charani E, Ming D, Cheah FC, Johnson MR
    J Intensive Med, 2024 Jan;4(1):46-61.
    PMID: 38263965 DOI: 10.1016/j.jointm.2023.07.006
    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.
  6. Wong PK, Syafruddin SE, Cheah FC, Azmi N, Ng PY, Chua EW
    Per Med, 2024;21(6):353-366.
    PMID: 39440484 DOI: 10.1080/17410541.2024.2412514
    Aim: Rs16851030, a single-nucleotide variant located in the 3'-untranslated region of the ADORA1 gene, has been proposed as a potential marker of caffeine sensitivity in apnea of prematurity. Besides, it is associated with aspirin-induced asthma and the development of acute chest syndrome. However, its functional significance is still unconfirmed. This study aimed to elucidate the functional impact of rs16851030 by using CRISPR/Cas9 approach to induce the DNA variant and attendant physiological changes.Methods: Rs16851030 was introduced into HEK293 cells via homology-directed repair (HDR). Edited cells were fluorescence-enriched, sorted, isolated, and expanded into single-cell-derived clones. The edit was confirmed by Sanger sequencing. RNA sequencing was used to analyze affected pathways.Results: Rs16851030-mutant cells showed increased susceptibility to hypoxia, a condition related to apnea of prematurity. After 24 h of hypoxia, the viability of mutant clones 1 and 2 was low compared with wild-type cells (75.45% and 74.47% vs. 96.34%). RNA sequencing revealed transcriptomic changes linked to this increased vulnerability.Conclusion: Rs16851030 impairs cellular resistance to hypoxia, suggesting its role in conditions like apnea of prematurity. Further research should investigate the molecular mechanisms and transcriptomic alterations caused by rs16851030 under hypoxic conditions.
  7. Liau LL, Al-Masawa ME, Koh B, Looi QH, Foo JB, Lee SH, et al.
    Front Pediatr, 2020;8:591693.
    PMID: 33251167 DOI: 10.3389/fped.2020.591693
    Mesenchymal stromal cells (MSCs) can be derived from various tissue sources, such as the bone marrow (BMSCs), adipose tissue (ADSCs), umbilical cord (UC-MSCs) and umbilical cord blood (UCB-MSCs). Clinical trials have been conducted to investigate the potential of MSCs in ameliorating neonatal diseases, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). In preclinical studies, MSC therapy has been tested for the treatment of various neonatal diseases affecting the heart, eye, gut, and brain as well as sepsis. Up to date, the number of clinical trials using MSCs to treat neonatal diseases is still limited. The data reported thus far positioned MSC therapy as safe with positive outcomes. However, most of these trials are still preliminary and generally smaller in scale. Larger trials with more appropriate controls and a longer follow-up period need to be conducted to prove the safety and efficacy of the therapy more conclusively. This review discusses the current application of MSCs in treating neonatal diseases, its mechanism of action and future direction of this novel therapy, including the potential of using MSC-derived extracellular vesicles instead of the cells to treat various clinical conditions in the newborn.
  8. Chia WK, Cheah FC, Abdul Aziz NH, Kampan NC, Shuib S, Khong TY, et al.
    Front Pediatr, 2021;9:615508.
    PMID: 33791258 DOI: 10.3389/fped.2021.615508
    Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.
  9. Lee LY, Muhardi L, Cheah FC, Supapannachart S, Teller IC, Bindels J, et al.
    J Paediatr Child Health, 2018 Apr;54(4):370-376.
    PMID: 29205630 DOI: 10.1111/jpc.13775
    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.

  10. Ng BK, Chuah JN, Cheah FC, Mohamed Ismail NA, Tan GC, Wong KK, et al.
    Front Surg, 2023;10:1084867.
    PMID: 36860946 DOI: 10.3389/fsurg.2023.1084867
    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.

  11. Jani P, Mishra U, Buchmayer J, Maheshwari R, D'Çruz D, Walker K, et al.
    World J Pediatr, 2023 Feb;19(2):139-157.
    PMID: 36372868 DOI: 10.1007/s12519-022-00625-2
    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.

  12. Jani P, Mishra U, Buchmayer J, Walker K, Gözen D, Maheshwari R, et al.
    Pediatr Res, 2023 May;93(6):1701-1709.
    PMID: 36075989 DOI: 10.1038/s41390-022-02297-0
    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.

  13. Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, et al.
    Pediatrics, 2017 01;139(1).
    PMID: 28034908 DOI: 10.1542/peds.2016-1452
    BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation.

    METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission.

    RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13).

    CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

  14. Thamrin V, Saugstad OD, Tarnow-Mordi W, Wang YA, Lui K, Wright IM, et al.
    J Pediatr, 2018 10;201:55-61.e1.
    PMID: 30251639 DOI: 10.1016/j.jpeds.2018.05.053
    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.

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