Corrigendum: Protocol for a prospective multicenter longitudinal randomized controlled trial (CALIN) of sensory-tonic stimulation to foster parent child interactions and social cognition in very premature infants.

[This corrects the article DOI: 10.3389/fped.2022.913396.].

3q29 duplications: A cohort of 46 patients and a literature review.

Duplications of the 3q29 cytoband are rare chromosomal copy number variations (CNVs) (overlapping or recurrent ~1.6 Mb 3q29 duplications). They have been associated with highly variable neurodevelopmental disorders (NDDs) with various associated features or reported as a susceptibility factor to the development of learning disabilities and neuropsychiatric disorders. The smallest region of overlap and the phenotype of 3q29 duplications remain uncertain. We here report a French cohort of 31 families with a 3q29 duplication identified by chromosomal microarray analysis (CMA), including 14 recurrent 1.6 Mb duplications, eight overlapping duplications (>1 Mb), and nine small duplications (<1 Mb). Additional genetic findings that may be involved in the phenotype were identified in 11 patients. Focusing on apparently isolated 3q29 duplications, patients present mainly mild NDD as suggested by a high rate of learning disabilities in contrast to a low proportion of patients with intellectual disabilities. Although some are de novo, most of the 3q29 duplications are inherited from a parent with a similar mild phenotype. Besides, the study of small 3q29 duplications does not provide evidence for any critical region. Our data suggest that the overlapping and recurrent 3q29 duplications seem to lead to mild NDD and that a severe or syndromic clinical presentation should warrant further genetic analyses.

Effect of tactile and/or kinesthetic stimulation therapy of preterm infants on their parents' anxiety and depressive symptoms: A systematic review.

BACKGROUND: In the case of preterm birth, the idealized postnatal period is replaced by an anxious and even traumatic experience for parents. Higher prevalence of parental anxiety, postnatal depression, and posttraumatic stress disorder has been observed in mothers of preterm infants up to 18 months after childbirth. There is increasing evidence that proprioceptive stimulation has a beneficial effect on preterms' short-term outcomes. Could this care also have an impact on parental anxiety and depressive symptoms? We reviewed recent publications on the impact on parents' anxiety and depressive symptoms of delivering tactile and/or kinesthetic stimulation to their premature newborn. METHODS: We conducted a systematic review by searching the PubMed, PsycInfo, Scopus, ScienceDirect and Google Scholar databases for English-language publications from the past 10 years. We focused on the mothers or fathers of infants born preterm (before 37 weeks of gestation) who provided tactile and/or kinesthetic stimulation to their premature newborn in the neonatal intensive care unit. Relevant outcomes were the parents' anxiety, stress, depressive symptoms, and symptoms of posttraumatic stress disorder, assessed with reliable standardized inventories. RESULTS: Eleven articles were included in the systematic review. Results suggested a beneficial effect of parents' early tactile and kinesthetic stimulation of their preterm infants. CONCLUSIONS: These interventions may act as protective factors against the occurrence of anxiety and depressive symptoms in parents and deserve to be studied further in this population.

Inhaled Nitric Oxide Promotes Angiogenesis in the Rodent Developing Brain.

Inhaled nitric oxide (iNO) is a therapy used in neonates with pulmonary hypertension. Some evidence of its neuroprotective properties has been reported in both mature and immature brains subjected to injury. NO is a key mediator of the VEGF pathway, and angiogenesis may be involved in the reduced vulnerability to injury of white matter and the cortex conferred by iNO. Here, we report the effect of iNO on angiogenesis in the developing brain and its potential effectors. We found that iNO promotes angiogenesis in the developing white matter and cortex during a critical window in P14 rat pups. This shift in the developmental program of brain angiogenesis was not related to a regulation of NO synthases by exogenous NO exposure, nor the VEGF pathway or other angiogenic factors. The effects of iNO on brain angiogenesis were found to be mimicked by circulating nitrate/nitrite, suggesting that these carriers may play a role in transporting NO to the brain. Finally, our data show that the soluble guanylate cyclase/cGMP signaling pathway is likely to be involved in the pro-angiogenetic effect of iNO through thrombospondin-1, a glycoprotein of the extracellular matrix, inhibiting soluble guanylate cyclase through CD42 and CD36. In conclusion, this study provides new insights into the biological basis of the effect of iNO in the developing brain.

Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort.

OBJECTIVES: To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes. STUDY DESIGN: We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location. RESULTS: In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11). CONCLUSIONS: Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging. TRIAL REGISTRATION: NCT02676063.

Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort.

Initiation of therapeutic hypothermia (TH) within 6 h of life is a major concern for treating neonatal hypoxic ischemic encephalopathy (HIE). We aimed to determine clinical and healthcare organizational factors associated with delayed TH in a French population-based cohort of neonates with moderate/severe HIE. Time to reach a rectal temperature of 34 °C defines optimal and delayed (within and over 6 h, respectively) TH. Clinical and healthcare organizational factors associated with delayed TH were analysed among neonates born in cooling centres (CCs) and non-cooling centres (non-CCs). Among 629 neonates eligible for TH, 574 received treatment (91.3%). TH was delayed in 29.8% neonates and in 20.3% and 36.2% of those born in CCs and non-CCs, respectively. Neonates with moderate HIE were more exposed to delayed TH in both CCs and non-CCs. After adjustment for HIE severity, maternal and neonatal characteristics and circumstances of birth were not associated with increased risk of delayed TH. However, this risk was 2 to 5 times higher in maternities with < 1999 annual births, when the delay between birth and call for transfer (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] [1.03 to 5.96]) or between call for transfer and admission (aOR 6.06, 95%CI [2.60 to 14.12]) was > 3 h and when an undesirable event occurred during transfer (aOR 2.66, 95%CI [1.11 to 6.37].  Conclusion: Increasing early identification of neonates who could benefit from TH and access to TH in non-CCs before transfer are modifiable factors that could improve care of neonates with HIE.  Trial registration: The trial was registered at ClinicalTrials.gov (NCT02676063). What is Known: • International recommendations are to initiate therapeutic hypothermia before 6 h of life in neonates with moderate or severe hypoxic ischemic encephalopathy. What is New: •In this French population-based cohort of infants with hypoxic ischemic encephalopathy, nearly one-third of neonates eligible for treatment did not have access to hypothermia in the therapeutic window of 6 h of life. . • Among infants born in non-cooling centres, healthcare organizational factors involved in delayed care were the small size of maternities (1999 annual births), a time interval of more than 3 h between birth and call for transfer and between call for transfer and admission in neonatology, and the occurrence of an undesirable event during transfer.

Assessment of brain two-dimensional metrics in infants born preterm at term equivalent age: Correlation of ultrasound scans with magnetic resonance imaging.

Context: Developing brain imaging is a critical subject for infants born preterm. Impaired brain growth is correlated with poor neurological outcomes, regardless of overt brain lesions, such as hemorrhage or leukomalacia. As magnetic resonance imaging (MRI) remains a research tool for assessing regional brain volumes, two-dimensional metrics (2D metrics) provide a reliable estimation of brain structures. In neonatal intensive care, cerebral ultrasound (cUS) is routinely performed to assess brain integrity. This prospective work has compared US and MRI accuracy for the measurement of 2D brain metrics and identification of overt injuries. Methods: MRI and cUS were performed at term equivalent age (TEA) in infants born before 32 weeks of gestation (GW). Demographical data and results of serial cUS (Neonatal Intensive Care Unit [NICU]-US) performed during hospitalization were gathered from medical charts. Blinded, experienced senior doctors reviewed the scans for both standard analysis and standardized, 2D measurements. The correlation of 2D metrics and inter-/intraobserver agreements were evaluated using Pearson's coefficient, Bland-Altman plots, and intraclass coefficient (ICC), respectively. Results: In total, 102 infants born preterm were included. The performance of "TEA-cUS and NICU-cUS" when compared to "TEA-MRI and NICU-cUS" was identical for the detection of high-grade hemorrhages and close for low-grade ones. However, TEA-MRI only detected nodular lesions of the white matter (WM). No infant presented a cerebellar infarct on imaging. Intra- and inter-observer agreements were excellent for all 2D metrics except for the corpus callosum width (CCW) and anteroposterior vermis diameter. MRI and cUS showed good to excellent correlation for brain and bones biparietal diameters, corpus callosum length (CCL), transcerebellar diameters (TCDs), and lateral ventricle diameters. Measures of CCW and vermis dimensions were poorly correlated. Conclusion and perspective: The cUS is a reliable tool to assess selected 2D measurements in the developing brain. Repetition of these metrics by serial cUS during NICU stay would allow the completion of growth charts for several brain structures. Further studies will assess whether these charts are relevant markers of neurological outcome.

Case reports of large and symptomatic abdominal tumors in newborns: Pitfalls, difficulties in management, and surgical decision making.

BACKGROUND: Large and rapidly growing abdominal tumors may result in fatal outcomes in newborns. In some cases, a rapidly worsening clinical condition requires surgical decision-making despite the absence of a precise histological diagnosis. In these situations, there is neither a guide nor consensus. CASE: We highlight our experience with five patients with large abdominal tumors and assess the available literature for the best possible management of a rare condition. CONCLUSION: In these cases, laparostomy should be considered as a life-saving procedure. If the liver is involved and coagulopathy is present, prognosis is often compromised.

Amplitude-Integrated EEG Monitoring in Pediatric Intensive Care: Prognostic Value in Meningitis before One Year of Age.

Pediatric morbidity from meningitis remains considerable. Preventing complications is a major challenge to improve neurological outcome. Seizures may reveal the meningitis itself or some complications of this disease. Amplitude-integrated electroencephalography (aEEG) is gaining interest for the management of patients with acute neurological distress, beyond the neonatal age. This study aimed at evaluating the predictive value of aEEG monitoring during the acute phase in meningitis among a population of infants hospitalized in the pediatric intensive care unit (PICU), and at assessing the practicability of the technique. AEEG records of 25 infants younger than one year of age hospitalized for meningitis were retrospectively analyzed and correlated to clinical data and outcome. Recording was initiated, on average, within the first six hours for n = 18 (72%) patients, and overall quality was considered as good. Occurrence of seizure, of status epilepticus, and the background pattern were significantly associated with unfavorable neurological outcomes. AEEG may help in the management and prognostic assessment of pediatric meningitis. It is an easily achievable, reliable technique, and allows detection of subclinical seizures with minimal training. However, it is important to consider the limitations of aEEG, and combinate it with conventional EEG for the best accuracy.

An Updated Overview of MRI Injuries in Neonatal Encephalopathy: LyTONEPAL Cohort.

BACKGROUND: Brain magnetic resonance imaging (MRI) is a key tool for the prognostication of encephalic newborns in the context of hypoxic-ischemic events. The purpose of this study was to finely characterize brain injuries in this context. METHODS: We provided a complete, descriptive analysis of the brain MRIs of infants included in the French national, multicentric cohort LyTONEPAL. RESULTS: Among 794 eligible infants, 520 (65.5%) with MRI before 12 days of life, grade II or III encephalopathy and gestational age ≥36 weeks were included. Half of the population had a brain injury (52.4%); MRIs were acquired before 6 days of life among 247 (47.5%) newborns. The basal ganglia (BGT), white matter (WM) and cortex were the three predominant sites of injuries, affecting 33.8% (n = 171), 33.5% (n = 166) and 25.6% (n = 128) of participants, respectively. The thalamus and the periventricular WM were the predominant sublocations. The BGT, posterior limb internal capsule, brainstem and cortical injuries appeared more frequently in the early MRI group than in the late MRI group. CONCLUSION: This study described an overview of brain injuries in hypoxic-ischemic neonatal encephalopathy. The basal ganglia with the thalamus and the WM with periventricular sublocation injuries were predominant. Comprehensive identification of brain injuries in the context of HIE may provide insight into the mechanism and time of occurrence.

Advanced Brain Imaging in Preterm Infants: A Narrative Review of Microstructural and Connectomic Disruption.

Preterm birth disrupts the in utero environment, preventing the brain from fully developing, thereby causing later cognitive and behavioral disorders. Such cerebral alteration occurs beneath an anatomical scale, and is therefore undetectable by conventional imagery. Prematurity impairs the microstructure and thus the histological process responsible for the maturation, including the myelination. Cerebral MRI diffusion tensor imaging sequences, based on water's motion into the brain, allows a representation of this maturation process. Similarly, the brain's connections become disorganized. The connectome gathers structural and anatomical white matter fibers, as well as functional networks referring to remote brain regions connected one over another. Structural and functional connectivity is illustrated by tractography and functional MRI, respectively. Their organizations consist of core nodes connected by edges. This basic distribution is already established in the fetal brain. It evolves greatly over time but is compromised by prematurity. Finally, cerebral plasticity is nurtured by a lifetime experience at microstructural and macrostructural scales. A preterm birth causes a negative and early disruption, though it can be partly mitigated by positive stimuli based on developmental neonatal care.

Cerebral injuries in neonatal encephalopathy treated with hypothermia: French LyTONEPAL cohort.

BACKGROUND: Hypothermia is widely used for infants with hypoxic-ischemic neonatal encephalopathy but its impact remains poorly described at a population level. We aimed to describe brain imaging in infants born at ≥36 weeks' gestation, with moderate/severe encephalopathy treated with hypothermia. METHODS: Descriptive analysis of brain MRI and discharge neurological examination for infants included in the French national multicentric prospective observational cohort LyTONEPAL. RESULTS: Among 575 eligible infants, 479 (83.3%) with MRI before 12 days of life were included. MRI was normal for 48.2% (95% CI 43.7-52.8). Among infants with brain injuries, 62.5% (95% CI 56.2-68.5) had damage to more than one structure, 19.8% (95% CI 15.0-25.3) showed a pattern-associating injuries of basal ganglia/thalami (BGT), white matter (WM) and cortex. Overall, 68.4% (95% CI 62.0-74.3) of infants with normal MRI survived with a normal neurological examination. The rate of death was 15.4% (95% CI 12.3-19.0), predominantly for infants with the combined BGT, cortex, and/or WM injuries. CONCLUSIONS: Among infants with neonatal encephalopathy treated with hypothermia, two-thirds of those with normal MRI survived with a normal neurological examination at discharge. When present, brain injuries often involved more than one structure. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT02676063). IMPACT: In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge. In total, 10% of newborns showed a pattern associating injuries of the basal ganglia-thalami, white matter, and cortex, which was correlated with a high risk of death at discharge. The evolution of MRI techniques and sequences in the era of hypothermia calls for a revisiting of imaging protocol in neonatal encephalopathy, especially for the timing. The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.

Protocol for a prospective multicenter longitudinal randomized controlled trial (CALIN) of sensory-tonic stimulation to foster parent child interactions and social cognition in very premature infants.

Introduction: Premature birth is associated with long-term somatic and neurological disorders, including cognitive, social and behavioral impairments. Moreover, the mothers of infants born preterm exhibit a higher prevalence of anxiety and depressive symptoms after birth. Early rehabilitation, developmental care, and parenting support have already been shown to have a positive impact on neurological outcome. However, no randomized controlled study has so far assessed the effects on parenting and long-term neurological outcomes of proprioceptive stimulation to trigger positive brain plasticity in very preterm babies. The CALIN project will therefore investigate the impact of sensory-tonic stimulation (STS) of extremely preterm infants by their parents on child parent interactions, infants' morphological and functional brain development and subsequent cognition (including social cognition), and parents' anxiety and depressive symptoms in the postpartum period. Methods and analysis: Infants born between 25 and 32 weeks of gestation will be randomly assigned to the "STS + Kangaroo care" or "Kangaroo care" group. The primary endpoint, child and parent interactions, will be rated at 12 months corrected age using the Coding Interactive Behavior system. Secondary endpoints include: 1/functional and anatomical brain maturation sequentially assessed during neonatal hospitalization using electroencephalogram (EEG), amplitude-integrated EEG (aEEG), cranial ultrasound and MRI performed at term-corrected age, 2/social and cognitive outcomes assessed at 15 months, 2, 4 and 6 years, and 3/parents' anxiety and depressive symptoms assessed at 7 ± 1 weeks after birth, using dedicated questionnaires. Ethics and dissemination: This study was approved by the French Ethics Committee for the Protection of Persons on 18 October 2021. It is registered with the French National Agency for the Safety of Medicines and Health Products (ANSM; no. 2020-A00382-37). The registry number on ClinicalTrials.gov is NCT04380051.

Association Between Early Amino Acid Intake and Full-Scale IQ at Age 5 Years Among Infants Born at Less Than 30 Weeks' Gestation.

Importance: An international expert committee recently revised its recommendations on amino acid intake for very preterm infants, suggesting that more than 3.50 g/kg/d should be administered only to preterm infants in clinical trials. However, the optimal amino acid intake during the first week after birth in these infants is unknown. Objective: To evaluate the association between early amino acid intake and cognitive outcomes at age 5 years. Design, Setting, and Participants: Using the EPIPAGE-2 (Epidemiologic Study on Small-for-Gestational-Age Children-Follow-up at Five and a Half Years) cohort, a nationwide prospective population-based cohort study conducted at 63 neonatal intensive care units in France, a propensity score-matched analysis was performed comparing infants born at less than 30 weeks' gestation who had high amino acid intake (3.51-4.50 g/kg/d) at 7 days after birth with infants who did not. Participants were recruited between April 1 and December 31, 2011, and followed up from September 1, 2016, to December 31, 2017. Full-scale IQ (FSIQ) was assessed at age 5 years. A confirmatory analysis used neonatal intensive care unit preference for high early amino acid intake as an instrumental variable to account for unmeasured confounding. Statistical analysis was performed from January 15 to May 15, 2021. Exposures: Amino acid intake at 7 days after birth. Main Outcomes and Measures: The primary outcome was an FSIQ score greater than -1 SD (ie, ≥93 points) at age 5 years. A complementary analysis was performed to explore the association between amino acid intake at day 7 as a continuous variable and FSIQ score at age 5 years. Data from cerebral magnetic resonance imaging at term were available for a subgroup of preterm infants who participated in the EPIRMEX (Cerebral Abnormalities Detected by MRI, Realized at the Age of Term and the Emergence of Executive Functions) ancillary study. Results: Among 1789 preterm infants (929 boys [51.9%]; mean [SD] gestational age, 27.17 [1.50] weeks) with data available to determine exposure to amino acid intake of 3.51 to 4.50 g/kg/d at 7 days after birth, 938 infants were exposed, and 851 infants were not; 717 infants from each group could be paired. The primary outcome was known in 396 of 646 exposed infants and 379 of 644 nonexposed infants who were alive at age 5 years and was observed more frequently among exposed vs nonexposed infants (243 infants [61.4%] vs 206 infants [54.4%], respectively; odds ratio [OR], 1.33 [95% CI, 1.00-1.71]; absolute risk increase in events [ie, the likelihood of having an FSIQ score >-1 SD at age 5 years] per 100 infants, 7.01 [95% CI, 0.06-13.87]; P = .048). In the matched cohort, correlation was found between amino acid intake per 1.00 g/kg/d at day 7 and FSIQ score at age 5 years (n = 775; ß = 2.43 per 1-point increase in FSIQ; 95% CI, 0.27-4.59; P = .03), white matter area (n = 134; ß = 144 per mm2; 95% CI, 3-285 per mm2; P = .045), anisotropy of the corpus callosum (n = 50; ß = 0.018; 95% CI, 0.016-0.021; P < .001), left superior longitudinal fasciculus (n = 42; ß = 0.018; 95% CI, 0.010-0.025; P < .001), and right superior longitudinal fasciculus (n = 42; ß = 0.014 [95% CI, 0.005-0.024; P = .003) based on magnetic resonance imaging at term. Confirmatory and sensitivity analyses confirmed these results. For example, the adjusted OR for the association between the exposure and the primary outcome was 1.30 (95% CI, 1.16-1.46) using the instrumental variable approach among 978 participants in the overall cohort, and the adjusted OR was 1.35 (95% CI, 1.05-1.75) using multiple imputations among 1290 participants in the matched cohort. Conclusions and Relevance: In this cohort study, high amino acid intake at 7 days after birth was associated with an increased likelihood of an FSIQ score greater than -1 SD at age 5 years. Well-designed randomized studies with long-term follow-up are needed to confirm the benefit of this nutritional approach.

Impact of Executive Functions and Parental Anxiety on the Development of Social Cognition in Premature Children: A Cross-Sectional Case-Control Protocol.

Background: Recent research has identified neuropsychological disorders, specifically executive function disorders, in premature children. Executive functions support goal-oriented mental activity and play a role in the development of social cognition. This underlies the social and emotional behavior of individuals. Parental anxiety is also an important environmental factor that can influence the psycho-emotional development of children. Objectives: The present protocol aims to compare the development of social cognition in school-age children born prematurely to that of school-age children born full-term, and to determine the impact of executive (dys)function and parental anxiety on such development. Methods/Design: In this cross-sectional protocol, 28 prematurely born children aged 7-10 years ("preterm") and 28 full-term born children aged 7-10 years ("control") will be included. The "preterm" and "control" groups will be matched for sex and age. The neuropsychological evaluation will include that of non-verbal intellectual efficiency (Raven's colored progressive matrices), verbal level (WISC-IV subtests), and executive functions (NEPSY II subtests and the opposite worlds of TEA-CH). The evaluation of social cognition will be conducted via tests of the theory of cognitive and affective mind. Several dimensions of the level of parental anxiety will be collected through the Spielberg Trait Anxiety Inventory Form Y, Beck Depression Inventory, Social Support Questionnaire-6, Parental Stress Index and, specifically for mothers, the Modified Perinatal Post-Traumatic Stress Disorder Questionnaire. Discussion: The results of this protocol will aid our understanding of the development of social cognition in premature children and to determine the factors that influence such development. This clinical research project, although following a fundamental approach, will have clinical implications because a more precise description of the development of social cognition in this school-age population will make it possible to better determine the cognitive targets of therapeutic actions and to search for predictive indices of the efficacy of practices. Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03007095, identifier: NCT03007095.

COVID-19 Associated With Life-Threatening Apnea in an Infant Born Preterm: A Case Report.

A pandemic linked to the new coronavirus strain (SARS-CoV-2) has been raging for several months. Pediatric populations are less impacted than adults, and critical respiratory diseases seem rare (1, 2). We report the case of an infant, who presented with life-threatening apneas at home requiring basic life support. SARS-CoV-2 was subsequently identified in the patient's nasopharyngeal aspirate. He did not present with bronchiolitis or hypoxic failure as described in severe forms of COVID-19. The outcome was favorable in a few hours. The occurrence of apneas is not uncommon during viral respiratory infections in early infancy; however, there are very few descriptions related to a documented SARS-CoV-2 respiratory tract infection. In light of this clinical case, it seems necessary to quickly bring up a potential COVID-19 contamination in infants admitted for life-threatening apnea, in order to properly report and isolate these patients to avoid further nosocomial dissemination of SARS-CoV-2.

Interrater Agreement Between Critical Care Providers for Background Classification and Seizure Detection After Implementation of Amplitude-Integrated Electroencephalography in Neonates, Infants, and Children.

PURPOSES: Amplitude-integrated EEG (aEEG) has been widely developed in neonatal intensive care unit, but few studies focused on pediatric intensive care unit. Furthermore, reliability of aEEG under real-life conditions is unknown. METHODS: Participants were nurses from a 12-bed pediatric intensive care unit in a referral university hospital in France. Amplitude EEG was implemented after standardized training, including e-learning course, individual feedback and bedside teaching concerning monitoring installation, background classification patterns recognition, artefact analysis, and seizure detection. The primary judgment criterion was the agreement (Cohen Kappa) between nurses and aEEG experts for the detection of abnormal aEEG traces (moderately or severely altered background pattern according to Hellström-Westas classification and/or seizure activity). RESULTS: During the study period, 196 consecutives traces from 79 patients were analyzed by 51 nurses. According to expert's classification, 53% of traces were abnormal, including 17.5% of severely abnormal traces (severely altered traces and/or seizure activity) and 14% exhibiting seizure activity. Moderate agreement between experts and nurses was found for detection of any abnormal trace (k = 0.53; 95% confidence interval [CI]: 0.39-0.67). Substantial agreement was found for severely altered traces (k = 0.71; 95% CI: 0.57-0.85). Finally, fair agreement was found for seizure detection (irrespective of background classification, k = 0.40; 95% CI: 0.25-0.54). CONCLUSIONS: These results suggest that aEEG monitoring may be implemented in routine nursing care in pediatric intensive care unit. Further training courses are needed to enhance nurses' skill in detecting seizures activity at the bedside.

The Prognostic Value of Early Amplitude-Integrated Electroencephalography Monitoring After Pediatric Cardiac Arrest.

OBJECTIVES: To assess the ability of amplitude-integrated electroencephalography monitoring within 24 hours of the return of spontaneous circulation to prognosticate neurologic outcomes in children following cardiac arrest DESIGN:: Retrospective review of prospectively recorded data. An amplitude-integrated electroencephalography background score was calculated according to background activity during the first 24 hours after return of spontaneous circulation, a higher score correlating with more impaired background activity. The primary endpoint was the neurologic outcome as defined by the Pediatric Cerebral Performance Category at PICU discharge (Pediatric Cerebral Performance Category 1-3: a good neurologic outcome; Pediatric Cerebral Performance Category 4-6: a poor neurologic outcome). SETTING: A referral PICU. PATIENTS: Thirty children with a median age of 10 months (2-38 mo) and a male/female sex ratio of 1.3 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighteen patients were assigned to the favorable outcome group and 12 to the unfavorable outcome group. The median time between return of spontaneous circulation and amplitude-integrated electroencephalography initiation was 4 hours (3-9 hr). The amplitude-integrated electroencephalography score within 24 hours after return of spontaneous circulation was significantly higher in the children with poor outcomes compared with those with good outcomes (12 ± 4 vs 25 ± 8; p < 0.001). Background activity during amplitude-integrated electroencephalography monitoring was able to predict poor neurologic outcomes at PICU discharge, with an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.81-1.00). CONCLUSIONS: Early amplitude-integrated electroencephalography monitoring may help predict poor neurologic outcomes in children within 24 hours following cardiac arrest.

New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.

BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. METHODS: This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3 populations with a low rate of rebound effect. Gradual withdrawal of NO combined with pulmonary vasodilators are current practices in this population. The use of last-generation NO devices allowed good compliance with recommendations.

Monitoring Cerebral and Renal Oxygenation Status during Neonatal Digestive Surgeries Using Near Infrared Spectroscopy.

BACKGROUND: Depending on the initial pathology, hypovolemia, intra-abdominal hypertension, and sepsis are often encountered in neonatal digestive surgery. Accurate newborn monitoring during and after surgery is essential to adapt resuscitation protocols. Near infrared spectroscopy (NIRS) is non-invasive and can detect hypoperfusion which indicates a low circulatory blood flow, regardless of the cause. OBJECTIVE: Evaluating changes in cerebral and renal regional oxygen saturation during neonatal digestive surgeries, conducted according to normal practices, with commonly used monitoring parameters. Analyzing retrospectively the inter-relationships between NIRS values and mean arterial pressure (MAP) values as well as pre-ductal SpO2. METHODS: Prospective, descriptive, monocentric study. All neonates referred for surgery were included. NIRS allows the measurement of cerebral and renal oxygenation fluctuations, as well as calculating difference in intraoperative and postoperative values. RESULTS: Nineteen patients were included. Cerebral regional oxygen saturation (C rSO2) values were stable while renal regional oxygen saturation (R rSO2) values tended to decrease with time during surgery. Indeed, 72% of rSO2 decline episodes occurred after the first 30 min of surgery, without any significant statistical differences for the next 90 min of surgery. After surgery, the lowest average C and R rSO2 values were evidenced during the first 6 h, with 60% of C rSO2 and R rSO2 anomalies occurring in that time frame. There was no significant statistical difference observed in the following 18 h. There was a significant correlation between R rSO2 and SpO2 values (p < 0.01), but not with C rSO2 values. There was no correlation with the MAP either for the C rSO2 values or R rSO2 ones. CONCLUSION: NIRS is a promising non-invasive bedside tool to monitor cerebral and tissue perfusion, analyzing tissue microcirculation. NIRS has its interest to guide neonatal digestive surgeries (bowel manipulation, viscera reduction) and may represent an early warning for identifying patients requiring resuscitation during or after these surgeries.