Unusual cerebral intraventricular hemorrhage and cardiomyopathy related to congenital cytomegalovirus from non-primary maternal infection: a case report.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection, resulting from non-primary maternal infection or reactivation during pregnancy, can cause serious fetal abnormalities, complications in the immediate neonatal period, and severe sequelae later in childhood. Maternal non-primary cytomegalovirus infection in pregnancy is transmitted to the fetus in 0.5-2% of cases (1). CASE PRESENTATION: An African full term male newbornwas delivered by emergency caesarean section. Due to signs of asphyxia at birth and clinical moderate encephalopathy, he underwent therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 h, however, soon after rewarming, he presented refractory status epilepticus due to an intracranial hemorrhage, related to severe thrombocytopenia. The patient also presented signs of sepsis (hypotension and signs of reduced perfusions). An echocardiography revealed severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. Research for CMV DNA Polymerase Chain Reaction (PCR) on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions was positive.The mother had positive CMV IgG with negative IgM shortly before pregnancy. Serology for CMV was therefore not repeated during pregnancy, but CMV DNA performed on the Guthrie bloodspot taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. The baby was discharged in good general condition and follow up showed a normal neurodevelopmental outcome at 9 months. CONCLUSION: Although uncommon, congenital cytomegalovirus infection should be included in the differential diagnosis of intraventricular hemorrhage and cardiomyopathy. Furthermore, this case highlights the possible severity of congenital cytomegalovirus infection, even in cases of previous maternal immunity.

Cyanoacrylate glue as part of a new bundle to decrease neonatal PICC-related complications.

A "bundle" is defined as a combination of evidence-based interventions that, if followed collectively and reliably, improve patient outcomes. The aim of this quasi-experimental study, conducted in a level-III NICU in Belgium, was to assess the impact of central line dressing and maintenance bundle implementation on the rate of catheter-related mechanical complications. We performed a quality improvement (QI) project. Prior to bundle implementation, neonatal PICC lines were secured by Steri-Strip® and occlusive dressing. We implemented a new PICC bundle consisting of the use of glue, sutureless device (Griplock®), and a transparent dressing to secure the catheter to the skin. We compared the rate of infections, mechanical complications, and dislocations before and after bundle implementation (periods 1 and 2, respectively). The use of glue resulted in a significantly decreased rate of central line-associated bloodstream infection (CLABSI) (p < 0.001), dislocations, and mechanical complications (p < 0.0001). During period 2, there was a significant increase for the average number of days the catheter stayed in place (p < 0.05). We did not observe catheter breakage or patient skin irritations attributable to the use of glue (not even in ELBW infants). CONCLUSION: The implementation of the new bundle to secure neonatal PICCs in our NICU was associated with a significant reduction in CLABSI and dislodgment rates, without glue-related complications. Active surveillance of CVC placement procedure, positioning, and management, as well as analysis of related complications is crucial for improving patient safety. Continuous implementation of up-to-date central line bundles based on best practice recommendations is a key for quality improvement in NICUs. WHAT IS KNOWN: • Stable vascular access is crucial in the NICU. Neonatal PICC securement issues can have serious consequences and are associated with device failure. WHAT IS NEW: • Catheter securement with tissue adhesive is safe and effective in reducing failure and complication rates in the neonatal population.

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial).

BACKGROUND: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. METHODS: The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18-24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. DISCUSSION: Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020.

Atrial fibrillation in a pediatric patient caused by an unusual malignant etiology: A case report.

This case report describes a 15-year-old patient with a known congenital malformation syndrome and immune deficiency, presenting with new-onset atrial fibrillation (AF) after a recent diagnosis of an intrathoracic mass. Transthoracic echocardiography showed a structurally and functionally normal heart and workup confirmed a primary diffuse large B-cell lymphoma, with pericardial and left atrial involvement on cardiac magnetic resonance imaging. Electrical cardioversion was successfully performed to convert the AF and chemotherapy was promptly started. Antiarrhythmic treatment was continued for 6 weeks, without recurrent AF. We discuss the pathogenesis of AF in the setting of malignancies as well as the management strategies of AF, mainly based on adult guidelines.

Clinical and Neurophysiologic Phenotypes in Neonates With BRAT1 Encephalopathy.

BACKGROUND AND OBJECTIVES: BRAT1 encephalopathy is an ultra-rare autosomal recessive neonatal encephalopathy. We delineate the neonatal electroclinical phenotype at presentation and provide insights for early diagnosis. METHODS: Through a multinational collaborative, we studied a cohort of neonates with encephalopathy associated with biallelic pathogenic variants in BRAT1 for whom detailed clinical, neurophysiologic, and neuroimaging information was available from the onset of symptoms. Neuropathologic changes were also analyzed. RESULTS: We included 19 neonates. Most neonates were born at term (16/19) from nonconsanguineous parents. 15/19 (79%) were admitted soon after birth to a neonatal intensive care unit, exhibiting multifocal myoclonus, both spontaneous and exacerbated by stimulation. 7/19 (37%) had arthrogryposis at birth, and all except 1 progressively developed hypertonia in the first week of life. Multifocal myoclonus, which was present in all but 1 infant, was the most prominent manifestation and did not show any EEG correlate in 16/19 (84%). Video-EEG at onset was unremarkable in 14/19 (74%) infants, and 6 (33%) had initially been misdiagnosed with hyperekplexia. Multifocal seizures were observed at a median age of 14 days (range: 1-29). During the first months of life, all infants developed progressive encephalopathy, acquired microcephaly, prolonged bouts of apnea, and bradycardia, leading to cardiac arrest and death at a median age of 3.5 months (range: 20 days to 30 months). Only 7 infants (37%) received a definite diagnosis before death, at a median age of 34 days (range: 25-126), and almost two-thirds (12/19, 63%) were diagnosed 8 days to 12 years postmortem (median: 6.5 years). Neuropathology examination, performed in 3 patients, revealed severely delayed myelination and diffuse astrogliosis, sparing the upper cortical layers. DISCUSSION: BRAT1 encephalopathy is a neonatal-onset, rapidly progressive neurologic disorder. Neonates are often misdiagnosed as having hyperekplexia, and many die undiagnosed. The key phenotypic features are multifocal myoclonus, an organized EEG, progressive, persistent, and diffuse hypertonia, and an evolution into refractory multifocal seizures, prolonged bouts of apnea, bradycardia, and early death. Early recognition of BRAT1 encephalopathy allows for prompt workup, appropriate management, and genetic counseling.

Partial wavelet coherence as a robust method for assessment of neurovascular coupling in neonates with hypoxic ischemic encephalopathy.

In neonates with hypoxic ischemic encephalopathy, the computation of wavelet coherence between electroencephalogram (EEG) power and regional cerebral oxygen saturation (rSO2) is a promising method for the assessment of neurovascular coupling (NVC), which in turn is a promising marker for brain injury. However, instabilities in arterial oxygen saturation (SpO2) limit the robustness of previously proposed methods. Therefore, we propose the use of partial wavelet coherence, which can eliminate the influence of SpO2. Furthermore, we study the added value of the novel NVC biomarkers for identification of brain injury compared to traditional EEG and NIRS biomarkers. 18 neonates with HIE were monitored for 72 h and classified into three groups based on short-term MRI outcome. Partial wavelet coherence was used to quantify the coupling between C3-C4 EEG bandpower (2-16 Hz) and rSO2, eliminating confounding effects of SpO2. NVC was defined as the amount of significant coherence in a frequency range of 0.25-1 mHz. Partial wavelet coherence successfully removed confounding influences of SpO2 when studying the coupling between EEG and rSO2. Decreased NVC was related to worse MRI outcome. Furthermore, the combination of NVC and EEG spectral edge frequency (SEF) improved the identification of neonates with mild vs moderate and severe MRI outcome compared to using EEG SEF alone. Partial wavelet coherence is an effective method for removing confounding effects of SpO2, improving the robustness of automated assessment of NVC in long-term EEG-NIRS recordings. The obtained NVC biomarkers are more sensitive to MRI outcome than traditional rSO2 biomarkers and provide complementary information to EEG biomarkers.

Implementing intact cord resuscitation in very preterm infants: feasibility and pitfalls.

The purpose of this study is to evaluate the feasibility of intact cord resuscitation (ICR) in very preterm infants using a custom-equipped mobile resuscitation trolley (LifeStart®). We collected maternal and neonatal data of all inborn infants < 32 weeks eligible for ICR per our protocol over 9 months from ICR implementation. We compared rates of ICR between the beginning and the end of the study period. We reviewed maternal and neonatal adverse events related to the procedure and direct outcomes. In order to assess potential quality improvements related to the procedure, we collected the same data in the infants born in the 9-month period preceding ICR implementation. Out of 44 infants born < 32 weeks during the period, 27 were eligible for ICR. Failure to initiate ICR occurred in 9/27, exclusively in the first 5.5 months of the study. In one infant, ICR was interrupted prior to 2 min due to placental abruption. No ICR procedure had to be interrupted due to insufficient cord length. Among the 18 infants who completed ICR, cord clamping timing increased significantly over the study period, from 3.0 [2.5-3.5] to 4.2 min [3.1-8.3] (p = 0.02). No significant maternal blood loss or wound complications were noted. No infant deaths were attributable to failure or direct consequence of ICR, and no infant experienced hypoxic respiratory failure (intubation, FiO2 ≥ 0.4), asphyxia (pH < 7.2), or blood pressure instability (< 2 SD) following stabilization. Hemoglobin level after cord clamping was higher in the ICR cohort than in the pre-implementation group. Seven out of 18 infants exposed to ICR had a temperature < 36.5 °C on admission.   Conclusion: ICR is feasible in very preterm infants. Temperature management requires special attention. Multidisciplinary simulation training before implementation and systematic post-implementation quality improvement meetings may significantly increase ICR program success. What is Known: • Because infants born < 32 weeks often require cardiorespiratory resuscitation at birth, they are not offered delayed cord clamping in the majority of neonatal intensive care units. • Recently, fully equipped mobile trolleys have been developed in order to allow bedside resuscitation with an intact cord. What is New: • Variable timing of cord clamping based on the infant's transition and respiratory stability, i.e., "physiology-based cord clamping," is safely achievable in very preterm infants. • Intact cord resuscitation requires specific equipment, operational protocols, and a high level of preparation from both obstetrical and neonatal teams, with a learning curve that can be streamlined by multidisciplinary simulation training.

Assessing Neurovascular Coupling Using Wavelet Coherence in Neonates with Asphyxia.

Brain monitoring is important in neonates with asphyxia in order to assess the severity of hypoxic ischaemic encephalopathy (HIE) and identify neonates at risk of adverse neurodevelopmental outcome. Previous studies suggest that neurovascular coupling (NVC), quantified as the interaction between electroencephalography (EEG) and near-infrared spectroscopy (NIRS)-derived regional cerebral oxygen saturation (rSO2) is a promising biomarker for HIE severity and outcome. In this study, we explore how wavelet coherence can be used to assess NVC. Wavelet coherence was computed in 18 neonates undergoing therapeutic hypothermia in the first 3 days of life, with varying HIE severities (mild, moderate, severe). We compared two pre-processing methods of the EEG prior to wavelet computation: amplitude integrated EEG (aEEG) and EEG bandpower. Furthermore, we proposed average real coherence as a biomarker for NVC. Our results indicate that NVC as assessed by wavelet coherence between EEG bandpower and rSO2 can be a valuable biomarker for HIE severity in neonates with peripartal asphyxia. More specifically, average real coherence in a very low frequency range (0.21-0.83 mHz) tends to be high (positive) in neonates with mild HIE, low (positive) in neonates with moderate HIE, and negative in neonates with severe HIE. Further investigation in a larger patient cohort is needed to validate our findings.

A Metabolomic Approach in Search of Neurobiomarkers of Perinatal Asphyxia: A Review of the Current Literature.

Perinatal asphyxia and the possible sequelae of hypoxic-ischemic encephalopathy (HIE), are associated with high morbidity and mortality rates. The use of therapeutic hypothermia (TH) commencing within the first 6 h of life-currently the only treatment validated for the management of HIE-has been proven to reduce the mortality rate and disability seen at follow up at 18 months. Although there have been attempts to identify neurobiomarkers assessing the severity levels in HIE; none have been validated in clinical use to date, and the lack thereof limits the optimal treatment for these vulnerable infants. Metabolomics is a promising field of the "omics technologies" that may: identify neurobiomarkers, help improve diagnosis, identify patients prone to developing HIE, and potentially improve targeted neuroprotection interventions. This review focuses on the current evidence of metabolomics, a novel tool which may prove to be a useful in the diagnosis, management and treatment options for this multifactorial complex disease. Some of the most promising metabolites analyzed are the group of acylcarnitines: Hydroxybutyrylcarnitine (Malonylcarnitine) [C3-DC (C4-OH)], Tetradecanoylcarnitine [C14], L-Palmitoylcarnitine [C16], Hexadecenoylcarnitine [C16:1], Stearoylcarnitine [C18], and Oleoylcarnitine [C18:1]. A metabolomic "fingerprint" or "index," made up of 4 metabolites (succinate × glycerol/(ß-hydroxybutyrate × O-phosphocholine)), seems promising in identifying neonates at risk of developing severe HIE.

How to minimize central line-associated bloodstream infections in a neonatal intensive care unit: a quality improvement intervention based on a retrospective analysis and the adoption of an evidence-based bundle.

Central line-associated bloodstream infection (CLABSI) is a significant cause of morbidity and mortality in neonatal intensive care units (NICUs). A "bundle" is defined as a combination of evidence-based interventions that provided they are followed collectively and reliably, are proven to improve patient outcomes. The aim of this quasi-experimental study was to assess the impact of new central line insertion, dressing, and maintenance "bundles" on the rate of CLABSI and catheter-related complications. We performed a quality improvement (QI), prospective, before-after study. In the first 9-month period, the old "bundles" and pre-existing materials were used/applied. An intervention period then occurred with changes made to materials used and the implementation of new "bundles" related to various aspects of central lines care. A second 6-month period was then assessed and the CLABSI rates were measured in the NICU pre- and post-intervention period. The QI measures were the rate of CLABSI and catheter-related complications. Data are still being collected after the study to verify sustainability. The implementation of the new "bundles" and the change of certain materials resulted in a significantly decreased rate of CLABSI (8.4 to 1.8 infections per 1000 central venous catheter (CVC) days, p = 0.02,) as well as decreased catheter-related complications (47 to 10, p < 0.007).Conclusions: The analysis of pre-existing "bundles" and the implementation of updated central line "bundles" based on best practice recommendations are crucial for reducing the rate of CLABSI in the NICU. The implementation of the new evidence-based central line "bundles" was associated with a significant reduction in CLABSI rate in our unit soon after implementation. What is Known: • Central line-associated bloodstream infection (CLABSI) is a major cause of morbidity and mortality in the neonatal population. • The implementation of evidence-based "bundles" in the NICU is associated with a reduction in the incidence of CLABSI. What is New: • For the improvement in quality care in the NICU, audits are necessary to assess the existing systems. • The "Plan-Do-Study-Act cycle" is an effective tool to use when tackling challenges in an existing system. Using this tool assisted in the approach to reducing CLABSI in our NICU.

An interesting case of 'strange lines' a neonate with oesophageal atresia, tracheo-oesophageal fistula, situs inversus abdominalis and azygos continuation.

We describe the case of a term baby boy born via vaginal delivery at 39 weeks gestation with oesophageal atresia, tracheaoesophageal fistula, situs inversus abdominalis and azygos continuation. The azygos continuation was diagnosed after cardiac echo and confirmed on cardiac catherisation after an unexpected umbilical line position on thoracoabdominal X-ray. The baby underwent a right-sided thoracotomy on day 1 of life for repair of the oesophageal atresia. A double fistula, of both the proximal and distal segments, of the oesophagus with short segment stenosis was confirmed. The tracheo-oesophageal fistulae were ligated and divided and the oesophageal atresia repaired by primary anastomosis without complications. The azygos vein was not ligated.