Agreement between Hammersmith Neonatal Neurological Examination (HNNE) and Test of Infant Motor Performance (TIMP) in neurodevelopmental assessment of preterm infants <32 weeks' gestation at term corrected age.

Objectives: To determine the agreement between HNNE and TIMP at TCA for preterm infants born <32 weeks' gestation, and to evaluate their correlation to PDMS-2 at 12-month corrected age (CA).

Methods: Infants born between November 2013 to June 2022 who had both HNNE and TIMP performed at TCA of 37-41 weeks gestation, and motor outcome assessed using the PDMS-2 at 12-month old were enrolled. The HNNE and 12-month PDMS-2 findings were categorized as optimal vs sub-optimal.

Comparison of the neurobehavioural profile of early-preterm infants against term and late-preterm infants using the Hammersmith neonatal neurological examination.

Aim: To compare the neurobehavioural profile of early-preterm infants (<32 weeks gestation) at term-corrected age (39 -41 weeks) versus late-preterm and full-term infants at similar term gestational ages.

Methods: Early-preterm infants were assessed neurologically at term-corrected age using the Hammersmith neonatal neurological examination. The raw scores of the 34 Hammersmith neonatal neurological examination items were converted to optimality scores.

Patent ductus arteriosus in a late preterm neonate: think congenital hypopituitarism.

A late preterm female neonate presented with initial respiratory distress and heart murmur attributed to a haemodynamically significant patent ductus arteriosus (hsPDA) not responding to two courses of ibuprofen. Thyroid function performed for prolonged neonatal jaundice at 3 weeks of life suggested central hypothyroidism. Subsequent adrenocorticotropic hormone stimulation test showing hypocortisolism and MRI revealing adenohypophysis hypoplasia confirmed the diagnosis of congenital hypopituitarism (CH).

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.

Parental bereavement - impact of death of neonates and children under 12 years on personhood of parents: a systematic scoping review.

Background: Losing a child tragically impacts the well-being and functioning of parents. With these effects extending beyond emotional, physical morbidity and compromising self-perceptions, appropriate, longitudinal, timely and personalised support is key to effective care of bereaved parents. However, in the absence of a comprehensive understanding of parental bereavement, effective support of bereaved parents remains suboptimal.

Pharmacokinetics of oral versus intravenous ibuprofen for closure of patent ductus arteriosus: A pilot randomised controlled study.

Aim: This pilot study aimed to compare the pharmacokinetic profiles of oral (PO) and intravenous (IV) ibuprofen for treatment of patent ductus arteriosus (PDA) in preterm neonates.

Methods: In a single-centre, parallel, randomised open-label trial, neonates ≤35 weeks, weight <1800 g with haemodynamically significant PDA during the first week of life were recruited between June 2017 and February 2019 and randomised to receive either PO or IV ibuprofen at standard dosage of 10, 5 and 5 mg/kg every 24 h for three consecutive days. Plasma concentrations of ibuprofen were quantified using a validated high-performance liquid chromatography method and pharmacokinetic parameters were calculated.

Impact of Dying Neonates on Doctors' and Nurses' Personhood: A Systematic Scoping Review.

Context: Caring for dying neonates is distressing for healthcare professionals (HCP)s. Yet, the extent of these effects is poorly understood, compromising support of HCPs. To better understand and support HCPs, a systematic scoping review (SSR) of prevailing data is proposed.

Varying clinical presentations of umbilical venous catheter extravasation: A case series.

Umbilical venous catheter insertion is a common procedure in the neonatal units performed for rapid vascular access. Though relatively safe and easy to perform, suboptimal position of the catheter tip is frequently encountered and can lead to wide range of complications from venous thrombosis, catheter extravasation with extravasation of infusate to intraperitoneal or intrapericardial space, liver injury and cardiac arrhythmias. Identification of catheter extravasation may be difficult and often confused with catheter related infection or necrotising enterocolitis.

Early entrapment of fourth ventricle following Pseudomonas meningitis in extreme prematurity: Case report.

Trapped fourth ventricle (TFV) as a complication of post-hemorrhagic hydrocephalus (PHH) is widely reported in the pediatric population with a prior history of ventriculo-peritoneal (VP) shunt placement. Characterized by disproportionate dilatation of the fourth ventricle on serial neuro-imaging, it is rarely encountered in the early course of preterm infants and the differentiating clinical features are subtle and non-specific. Clinical alertness and sonographic correlation hold the key to early diagnosis.

CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners.

Bone marrow (BM) niche cells help to keep adult hematopoietic stem cells (HSCs) in a quiescent state via secreted factors and induction of cell-cycle inhibitors. Here, we demonstrate that the adapter protein CABLES1 is a key regulator of long-term hematopoietic homeostasis during stress and aging. Young mice lacking Cables1 displayed hyperproliferation of hematopoietic progenitor cells.

In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis.

Antibody-drug conjugates (ADCs) are a new class of therapeutics that use antibodies to deliver potent cytotoxic drugs selectively to cancer cells. CD203c, an ecto-nucleotide pyrophosphatase-phosphodiesterase 3, is overexpressed on neoplastic mast cells (MCs) in systemic mastocytosis (SM), thus representing a promising target for antibody-mediated therapy. In this study, we have found that human neoplastic MC lines (ROSA and ROSA), which express high levels of CD203c, are highly and specifically sensitive to the antiproliferative effects of an ADC against CD203c (AGS-16C3F).

Evaluation of neurological behaviour in late-preterm newborn infants using the Hammersmith Neonatal Neurological Examination.

Aim: We hypothesise that clinically well late-preterm infants (LPI) (34 -36 weeks) are neurologically more immature than their term counterparts, and this immaturity persists even when these infants reach term-corrected age (TCA). The primary aim of our study was to characterise and contrast the neurodevelopmental profile of well LPI with full-term infants (FTI) (39 -41 weeks) using the Hammersmith Neonatal Neurological Examination (HNNE). Our secondary aim was to obtain local reference ranges for the 34 items in the HNNE in an Asian-dominant population.

Singapore Neonatal Resuscitation Guidelines 2016.

We present the revised Neonatal Resuscitation Guidelines for Singapore. The 2015 International Liaison Committee on Resuscitation Neonatal Task Force's consensus on science and treatment recommendations (2015), and guidelines from the American Heart Association and European Resuscitation Council were debated and discussed. The final recommendations of the National Resuscitation Council, Singapore, were derived after the task force had carefully reviewed the current available evidence in the literature and addressed their relevance to local clinical practice.

Parental perceptions of hypothermia treatment for neonatal hypoxic-ischaemic encephalopathy.

Aims: Hypothermia Treatment (HT) is now the standard care for neonatal hypoxic-ischaemic encephalopathy (HIE). We conducted a survey to explore parental perceptions of HT as there is little information about this in the current literature.

Methods: Postal questionnaire survey included families (n = 51) whose babies received HT at Princess Anne Hospital, Southampton, UK, with 23 questions covering communication, clinical management, follow-up, and care in general.

Differentiation of Mouse Enteric Nervous System Progenitor Cells Is Controlled by Endothelin 3 and Requires Regulation of Ednrb by SOX10 and ZEB2.

Background & Aims: Maintenance and differentiation of progenitor cells in the developing enteric nervous system are controlled by molecules such as the signaling protein endothelin 3 (EDN3), its receptor (the endothelin receptor type B [EDNRB]), and the transcription factors SRY-box 10 (SOX10) and zinc finger E-box binding homeobox 2 (ZEB2). We used enteric progenitor cell (EPC) cultures and mice to study the roles of these proteins in enteric neurogenesis and their cross regulation.

Methods: We performed studies in mice with a Zeb2 loss-of-function mutation (Zeb2) and mice carrying a spontaneous recessive mutation that prevents conversion of EDN3 to its active form (Edn3).

Endothelin-3 stimulates cell adhesion and cooperates with β1-integrins during enteric nervous system ontogenesis.

Endothelin-3 (EDN3) and β1-integrins are required for the colonization of the embryonic gut by enteric neural crest cells (ENCCs) to form the enteric nervous system (ENS). β1-integrin-null ENCCs exhibit migratory defects in a region of the gut enriched in EDN3 and in specific extracellular matrix (ECM) proteins. We investigated the putative role of EDN3 on ENCC adhesion properties and its functional interaction with β1-integrins during ENS development.

Principles of Clinical Management of Patent Ductus Arteriosus in Extremely Preterm Neonates.

The clinical management of a patent ductus arteriosus (PDA) in preterm newborns is a controversial topic, and despite nearly three decades of research, varying opinions remain. This dilemma stems from uncertain causal linkage between PDA and neonatal comorbidities, as well as the lack of clear evidence showing that benefits of treatment outweigh risks. There has been a general shift in the management of PDA in preterm newborns from early and aggressive closure to a more conservative approach of watchful waiting and spontaneous closure.

Subnuclear re-localization of SOX10 and p54NRB correlates with a unique neurological phenotype associated with SOX10 missense mutations.

SOX10 is a transcription factor with well-known functions in neural crest and oligodendrocyte development. Mutations in SOX10 were first associated with Waardenburg-Hirschsprung disease (WS4; deafness, pigmentation defects and intestinal aganglionosis). However, variable phenotypes that extend beyond the WS4 definition are now reported.

Minimal enteral nutrition during neonatal hypothermia treatment for perinatal hypoxic-ischaemic encephalopathy is safe and feasible.

Aim: The safety and efficacy of enteral feeding during hypothermia treatment following hypoxic-ischaemic encephalopathy has not been studied before, resulting in variations in practice. Our study compared the benefits and safety of both early minimal and delayed enteral feeding during hypothermia treatment.

Methods: Our retrospective cohort study, from January 2009 to December 2011, compared a Swedish cohort, who received early enteral feeding during hypothermia, and a UK cohort, who received delayed enteral feeding.

SOX10 mutations mimic isolated hearing loss.

Ninety genes have been identified to date that are involved in non-syndromic hearing loss, and more than 300 different forms of syndromic hearing impairment have been described. Mutations in SOX10, one of the genes contributing to syndromic hearing loss, induce a large range of phenotypes, including several subtypes of Waardenburg syndrome and Kallmann syndrome with deafness. In addition, rare mutations have been identified in patients with isolated signs of these diseases.

An impairment of long distance SOX10 regulatory elements underlies isolated Hirschsprung disease.

A deletion encompassing several SOX10 enhancers was recently identified in a patient presenting with Waardenburg syndrome type 4 (WS4), which is defined as a combination of Hirschsprung disease (HSCR, intestinal aganglionosis) and WS (deafness and pigmentation defects). The expression patterns of some of the known SOX10 enhancers in animal models led to the speculation that endophenotypes of WS4 may be linked to mutations within some of these sequences. The present study investigated deletions and point mutations within four SOX10 enhancers in 144 unexplained isolated HSCR cases.

Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.

Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS).

Sox10 and Itgb1 interaction in enteric neural crest cell migration.

SOX10 involvement in syndromic form of Hirschsprung disease (intestinal aganglionosis, HSCR) in humans as well as developmental defects in animal models highlight the importance of this transcription factor in control of the pool of enteric progenitors and their differentiation. Here, we characterized the role of SOX10 in cell migration and its interactions with β1-integrins. To this end, we crossed the Sox10(lacZ/+) mice with the conditional Ht-PA::Cre; beta1(neo/+) and beta1(fl/fl) mice and compared the phenotype of embryos of different genotypes during enteric nervous system (ENS) development.

Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings.

Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings.