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Neuronal apoptosis in sudden infant death syndrome.

Although evidence shows that victims of sudden infant death syndrome (SIDS) suffer repetitive episodes of hypoxemia, only subtle abnormalities have been found in their brains by light microscopy. The aim of the present study was to determine whether apoptosis, a form of cell death that can be triggered by hypoxemia and that leaves no scarring detectable by light microscopy, would be present in hypoxia-sensitive brain regions of SIDS victims. We looked for the presence of apoptosis with an in situ end-labeling method that detects DNA fragmentation. We studied 29 SIDS victims who were age-matched to nine control cases. We found significant neuronal apoptosis in 79% of the SIDS cases: 55% of the cases positive in the hippocampus and 96% positive in the brainstem. Whereas the distribution of apoptosis in the hippocampus was in hypoxia-sensitive subregions, the distribution in the brainstem was mostly in dorsal nuclei, including those involved with sensation in the face and position of the head (nucleus of the spinal trigeminal tract and vestibular nuclei). The control cases showed no significant apoptosis in the hippocampus and a mild degree in the brainstem in three cases. Our results indicate the occurrence of an acute insult at least several hours before death, an insult from which the infants had apparently recuperated. This suggests that SIDS victims suffered repeated apoptosis resulting in significant neuronal damage and, thus, functional loss in key brain regions. The involvement of specific nuclei in the brainstem may be linked to the fact that prone sleeping is a significant risk factor for SIDS. Enhanced neuronal death by apoptosis may thus have major implications for understanding the sequence of events leading to SIDS.

Frequency and timing of recurrent events in infants using home cardiorespiratory monitors

OBJECTIVE To determine the incidence, type, timing, and factors predictive of recurrent significant events in infants with home cardiorespiratory monitors. STUDY DESIGN We reviewed data accumulated for 147 patients with an event-recorder type of monitor. The infants were allocated to one of four diagnostic categories: apparent life-threatening events (ALTE, n = 73), former premature infants with persistent apnea and bradycardia (n = 29), siblings of victims of sudden infant death syndrome (SIDS) (n = 24), and parental anxiety after a nonsignificant event (n = 21). RESULTS Compliance with monitoring was excellent; the monitors were used on 94% of the prescribed days. Fifty-three (36%) of 147 infants had significant events; of those, 46 (87%) experienced their first event during the first month of monitoring, and 69% of the events occurred during that first month. The most prevalent event type was a bradycardic event. Among infants in the ALTE group, events during the initial investigation period predicted the likelihood of events at home; 2 of the 47 infants (4%) with negative results for an investigation and no events recorded in hospital had apnea, and 4 had a bradycardic event (9%). In contrast, when significant events were recorded in hospital, the events were likely to recur at home (69% and 35% of the infants had apnea or bradycardia, respectively; p < 0.001). CONCLUSION Because most apnea, bradycardia, and recurrent clinical events began during the first month of monitoring, we emphasize the need for vigilant follow-up care of infants immediately after institution of home monitoring. Readmission for investigation is warranted in infants with severe or multiple recurrent events.

Sudden unexpected deaths in infancy: what are the causes?

OBJECTIVES To determine the incidence of various causes of sudden unexpected death (SUD) within an entire population and to assess the relative importance of an expert autopsy, as well as age of demise, in predicting the likelihood of finding a cause of death. METHODS We reviewed all cases of SUD in infants aged 1 week to 18 months that occurred in the province of Quebec (Canada) between 1987 and 1996. RESULTS We identified 623 cases of SUD; in 80% the diagnosis was sudden infant death syndrome (SIDS). Infection was the most common non-SIDS diagnosis (7.1% of all SUDs), followed by cardiovascular anomalies (2.7%), child abuse or negligence (2.6%), and metabolic or genetic disorders (2.1%). The percentage of non-SIDS deaths was much higher for autopsies performed in centers with expertise in pediatric pathology (18% vs 6%, P <.005). The likelihood of a non-SIDS diagnosis was much higher at age ranges atypical, as compared with typical, for SIDS (33% at 7 to 27 days, 19% at 6 to 12 months, and 64% at 12 to 18 months [atypical] vs 15% at 1 to 6 months [typical]; P =.003). CONCLUSION The study of an entire population provides more reliable data regarding causes of SUDs than does the study of small groups. We recommend that in addition to a thorough investigation of each SUD, autopsies be performed in centers with expertise in pediatric pathology. This recommendation takes on added significance in this era of decreasing SIDS rates.

Pierre Robin sequence: Review of diagnostic and treatment challenges

Pierre Robin sequence is not a rare condition and paediatric specialists caring for respiratory related issues are likely to encounter cases in their practice. There have been a few recent reviews on the topic, mostly focusing on the surgical interventions performed for cases with severe airway obstruction. In the present review, we will highlight the different challenges that remain today in the global evaluation of infants afflicted with this condition through a thorough review of the medical literature, giving the clinician a full scope of the disease and of the various management options. The need for an improved objective evaluation of airway obstruction and for a better classification will be emphasized. We are therefore proposing a novel classification scheme that will better account for respiratory and feeding difficulties in these infants. Finally, many knowledge gaps persist regarding this condition, underlining the necessity for further research both in the genetic field and regarding the outcome of therapy.

International comparison of sudden unexpected death in infancy rates using a newly proposed set of cause-of-death codes

Background Comparing rates of sudden unexpected death in infancy (SUDI) in different countries and over time is difficult, as these deaths are certified differently in different countries, and, even within the same jurisdiction, changes in this death certification process have occurred over time. Aims To identify if International Classification of Diseases-10 (ICD-10) codes are being applied differently in different countries, and to develop a more robust tool for international comparison of these types of deaths. Methods Usage of six ICD-10 codes, which code for the majority of SUDI, was compared for the years 2002–2010 in eight high-income countries. Results There was a great variability in how each country codes SUDI. For example, the proportion of SUDI coded as sudden infant death syndrome (R95) ranged from 32.6% in Japan to 72.5% in Germany. The proportion of deaths coded as accidental suffocation and strangulation in bed (W75) ranged from 1.1% in Germany to 31.7% in New Zealand. Japan was the only country to consistently use the R96 code, with 44.8% of SUDI attributed to that code. The lowest, overall, SUDI rate was seen in the Netherlands (0.19/1000 live births (LB)), and the highest in New Zealand (1.00/1000 LB). SUDI accounted for one-third to half of postneonatal mortality in 2002–2010 for all of the countries except for the Netherlands. Conclusions The proposed set of ICD-10 codes encompasses the codes used in different countries for most SUDI cases. Use of these codes will allow for better international comparisons and tracking of trends over time.

Outcome Following Surgical Interventions for Micrognathia in Infants with Pierre Robin Sequence: A Systematic Review of the Literature.

Background Tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), and subperiosteal release of the floor of the mouth (SPRFM) are the most commonly performed surgical procedures to treat severe airway obstruction in infants born with Pierre Robin sequence (PRS). Objectives To determine the rate of failure of each type of procedure, in terms of mortality and the need for tracheostomy, and to determine what proportion of infants have significant airway obstruction postoperatively as determined by polysomnography (PSG) and compare the data by procedure type. Method A comprehensive literature search (1981 through June 2015) was done of the National Library of Medicine database using PubMed. Extracted data included diagnosis, type of surgery, and outcome including mortality, need for postoperative tracheostomy and details of PSG. Persistence of significant airway obstruction was defined as an apnea-hypopnea index > 15 events/h on PSG. Results Both mortality rate and need for tracheostomy were low for all procedures. Many studies lacked sufficient detail to identify significant airway obstruction postoperatively. In studies with sufficient data, MDO was associated with the lowest percentage of significant airway obstruction postprocedure (3.6%) compared to 50% for infants who underwent TLA. Insufficient PSG data was available for patients who were treated with SPRFM. Conclusions There is a paucity of objective PSG data to definitively assess postoperative airway outcomes for PRS. MDO appears to be the most effective technique based on the available PSG data. Standardized use of PSG may lead to better identification and treatment of patients at risk for suboptimal airway outcomes postoperatively.

Pediatric home mechanical ventilation: A Canadian Thoracic Society clinical practice guideline executive summary

ABSTRACT Over the last 30 to 40 years, improvements in technology, as well as changing clinical practice regarding the appropriateness of long-term ventilation in patients with “non-curable” disorders, have resulted in increasing numbers of children surviving what were previously considered fatal conditions. This has come but at the expense of requiring ongoing, long-term prolonged mechanical ventilation (both invasive and noninvasive). Although there are many publications pertaining to specific aspects of home mechanical ventilation (HMV) in children, there are few comprehensive guidelines that bring together all of the current literature. In 2011 the Canadian Thoracic Society HMV Guideline Committee published a review of the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. This current document is intended to be a companion to the 2011 guidelines, concentrating on the issues that are either unique to children on HMV (individuals under 18 years of age), or where common pediatric practice diverges significantly from that employed in adults on long-term home ventilation. As with the adult guidelines,1 this document provides a disease-specific review of illnesses associated with the necessity for long-term ventilation in children, including children with chronic lung disease, spinal muscle atrophy, muscular dystrophies, kyphoscoliosis, obesity hypoventilation syndrome, and central hypoventilation syndromes. It also covers important common themes such as airway clearance, the ethics of initiation of long-term ventilation in individuals unable to give consent, the process of transition to home and to adult centers, and the impact, both financial, as well as social, that this may have on the childs families and caregivers. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.

Section 4: Home monitoring and follow-up of home-ventilated children

Children receiving home mechanical ventilation (HMV) are at risk of acute deterioration and adverse events. Although caregivers represent the first-line monitoring for the child to identify acute events that could be potentially life threatening, monitoring equipment is often used. This section reviews the literature on the use of home monitoring. The objective of the review is to focus on the use of external monitoring devices; however, as ventilators used in the home environment have their own internal alarm system to alert caregivers, we will also briefly review this topic. Randomized controlled studies evaluating the usefulness of monitoring devices do not exist and will be very difficult to pursue; therefore, consensus or expert opinion is the highest level of evidence available. In addition, studies pertaining to monitor use in children receiving HMV with evaluation of benefits and pitfalls are likely scarce. To gain an insight on the potential need for monitoring at home for these complex children, it is therefore important to know the incidence of adverse events (morbidity and mortality).