Bibliometric analysis with reference publication year spectroscopy showed how key programmes drove developmental care in newborn infants.

AIM: We investigated the historical origins of developmental care for newborn infants using Reference Publication Year Spectroscopy (RPYS), an innovative method of bibliometric analysis. METHODS: A Web of Science search query that combined infant and intervention-related synonyms was performed on 2 February 2022. RPYS analysis was performed on this dataset to identify the most referenced historical publications for developmental care in newborn infants. Median deviation analysis identified the peak publication years, including the most cited historical references. Landmark publications were defined as those belonging to the top 10% of the most frequently referenced publications for at least 20 years. RESULTS: The RPYS peaks showed an early phase (1936-1986), during which infant development was studied and analysed, leading to a conceptualisation of developmental care for newborn infants. The following years (1987-2020), showed an explosion of interest in developmental care and highlighted two main programmes. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP) and the Infant Health and Development Program (IHDP) inspired numerous publications during those years, which strove to demonstrate evidence of their clinical benefits. CONCLUSION: Developmental care has become increasingly important, thanks to the implementation of NIDCAP and IHDP.

Prematurity has no impact on the quality of parents' sleep 6 months after birth.

AIM: Due to the stress that is classically associated with the premature birth of a child, these parents may be prone to sleep disorders. The aim of this study was to compare sleep quality of preterm infants' parents with that of term infants' parents. METHODS: Prospective observational cohort study conducted at the University Hospital of Brest between January 2019 and January 2021. The primary outcome criterion was the score obtained by the parents on the Pittsburg Sleep Quality Index (PSQI) 6 months after their child's birth. Each parent was recruited in the days following their child's birth and completed the PSQI online. RESULTS: Overall, 316 parents were included. The median gestational age at birth was 34.3 (31.6-35.5) weeks in the preterm infant group and 39.7 (38.6-40.7) weeks in the term infant group. Of the 948 expected questionnaires, 771 were completed and collected. On average, 59% of the parents obtained a PSQI global score >5. Six months after birth, no differences were reported between parents of preterm and full-term infants. CONCLUSION: This study did not reveal any difference between sleep quality of preterm infants' parents and term infants' parents.

Distribution, Consequences, and Determinants of Time to Antibiotics in Children With Community-Onset Severe Bacterial Infection: A Secondary Analysis of a Prospective Population-Based Study.

OBJECTIVES: To describe the distribution, consequences and potential determinants of time to antibiotics administration in children with community-onset severe bacterial infections (COSBIs). DESIGN: Secondary analysis of the available data from a prospective population-based study from 2009 to 2014. SETTING: An administrative area in western France accounting for 13% of the national pediatric population. PATIENTS: All children from 1 month to 16 years old admitted to a PICU or who died before admission and had a COSBI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The time to antibiotics was divided into patient interval (from first signs of COSBI to the first medical consultation) and medical interval (from the first consultation to appropriate antibiotics administration). The association between the medical interval and child outcome was studied by a multinomial logistic regression model and the potential determinants of the patient and medical intervals were by a Cox proportional-hazards model. Of the 227 children included (median age 2.1 yr), 22 died (9.7%), and 21 (9.3%) had severe sequelae at PICU discharge. Median patient and medical intervals were 7.0 hours (interquartile range [IQR], 2.0-16.5 hr) and 3.3 hours (IQR, 1.1-12.2 hr), respectively. The last quartile of medical interval was not associated with death (adjusted odds ratio [aOR], 3.7; 95% CI, 0.8-17.5) or survival with severe sequelae (aOR, 1.3; 95% CI, 0.4-4.0) versus survival without severe sequelae. Patient interval was shorter in younger children (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.92-0.99), and medical interval was reduced when the first consultation was conducted in a hospital (aHR, 1.5; 95% CI, 1.1-2.0) versus outpatient medicine. CONCLUSIONS: For children with COSBI, we found no significant association between medical interval and mortality or severe sequelae. An initial hospital referral could help reduce the time to antibiotics in COSBIs.

Early skin-to-skin contact and risk of late-onset-sepsis in very and extremely preterm infants.

BACKGROUND: To evaluate the association between exposure to early skin-to-skin contact (SSC) and incidence of late-onset sepsis (LOS) in extremely and very preterm infants. METHODS: Observational study using the national population-based EPIPAGE-2 cohort in 2011. A propensity score for SSC exposure was used to match infants with and without exposure to SSC before day 4 of life and binomial log regression used to estimate risk ratios and CIs in the matched cohort. The primary outcome was at least one episode of LOS during hospitalization. Secondary outcomes were the occurrence of any late-onset neonatal infection (LONI), LOS with Staphylococcus or Staphylococcus aureus, incidence of LOS and LONI per 1000 central venous catheter days. RESULTS: Among the 3422 included infants, 919 were exposed to early SSC. The risk ratio (RR) for LOS was 0.86 (95% CI, 0.67-1.10), for LONI was 1.00 (95% CI, 0.83-1.21), and for LOS with Coagulase-negative Staphylococcus or Staphylococcus aureus infection was 0.91 (95% CI, 0.68-1.21) and 0.77 (95% CI, 0.31-1.87). The incidence RR for LOS per-catheter day was 0.87 (95% CI, 0.64-1.18). CONCLUSION: Early SSC exposure was not associated with LOS or LONI risk. Thus, their prevention should not be a barrier to a wider use of SSC. IMPACT: Kangaroo Mother Care decreased neonatal infection rates in middle-income countries. Skin-to-skin contact is beneficial for vulnerable preterm infants but barriers exist to its implementation. In a large population-based study using a propensity score methods, we found that skin-to-skin contact before day 4 of life was not associated with a decreased risk of late-onset-sepsis in very and extremely preterm infants. Early skin-to-skin contact was not associated with an increased risk of any late-onset-neonatal-infection, in particular with staphylococcus. The fear of neonatal infection should not be a barrier to a wider use of early skin-to-skin contact in this population.

Prevalence, Characteristics, and Determinants of Suboptimal Care in the Initial Management of Community-Onset Severe Bacterial Infections in Children.

Importance: Assessment of the quality of initial care is necessary to target priority actions that can reduce the still high morbidity and mortality due to community-onset severe bacterial infections (COSBIs) among children. Objective: To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs. Design, Setting, and Participants: This prospective, population-based, cohort study and confidential enquiry was conducted between August 2009 and January 2014 in western France, a region accounting for 15% of the French pediatric population (1 968 474 children aged 1 month to 16 years) and including 6 pediatric intensive care units (PICUs) and 35 emergency departments. Participants included all children aged 1 month to 16 years who died before PICU admission or were admitted to a PICU with a COSBI (ie, bacterial sepsis, including meningitis, purpura fulminans, and pulmonary, osteoarticular, intra-abdominal, cardiac, and soft-tissue severe infections). Data were analyzed from March to June 2020. Exposures: Suboptimal care determined according to evaluation of 8 types of care: (1) the delay in seeking care by family, (2) the physician's evaluation of severity, (3) the patient's referral at the first consultation with signs of severity, (4) the timing and (5) dosage of antibiotic treatment, (6) the timing and (7) volume of fluid bolus administration, and (8) the clinical reassessment after fluid bolus. Main Outcomes and Measures: Two experts assessed the quality of care before death or PICU admission as optimal, possibly suboptimal, or certainly suboptimal. The consequences and determinants of certainly suboptimal care were identified with multinomial logistic regression and generalized linear mixed models. Results: Of the 259 children included (median [IQR] age, 24 [6-66] months; 143 boys [55.2%]), 27 (10.4%) died, and 25 (9.6%) had severe sequelae at PICU discharge. The quality of care was certainly suboptimal in 89 cases (34.4%). Suboptimal care was more frequent in children with sequelae (adjusted odds ratio [aOR], 5.61; 95% CI, 1.19-26.36) and less frequent in children who died (aOR, 0.16; 95% CI, 0.04-0.65) vs those surviving without sequelae. Factors independently associated with suboptimal care were age younger than 5 years (aOR, 3.15; 95% CI, 1.25-7.90), diagnosis of sepsis with no source (aOR, 5.77; 95% CI, 1.64-20.30) or meningitis (aOR, 3.39; 95% CI, 1.15-9.96) vs other severe infections, and care by a primary care physician (aOR, 3.22; 95% CI, 1.17-8.88) vs a pediatric hospital service. Conclusions and Relevance: This study found that suboptimal care is frequent in the initial management of COSBI and is associated with severe sequelae. The paradoxical association with reduced risk of death may be explained by an insufficient adjustment on bacterial or host intrinsic factors. Management could be optimized by improving the quality of primary care, especially for young children.

A review of the characteristics, mechanisms and clinical significance of habituation in foetuses and newborn infants.

Habituation has been a topic of interest since the early 20th century. We summarise the characteristics of habituation, the proposed habituation mechanisms, the associated cortical responses and the link between habituation and cognitive development. Behavioural and neuroimaging studies have highlighted the early sensory abilities of foetuses and newborn infants, with preterm newborn infants exhibiting decreased habituation and dishabituation capabilities that increase their environmental vulnerability. Habituation provides a foundation for the learning and cognition on which higher functions are constructed. It has been suggested that it is efficient for predicting cognitive developmental outcomes in term and preterm newborn infants.

Evaluation of Maturation in Preterm Infants Through an Ensemble Machine Learning Algorithm Using Physiological Signals.

This study was designed to test if heart rate variability (HRV) data from preterm and full-term infants could be used to estimate their functional maturational age (FMA), using a machine learning model. We propose that the FMA, and its deviation from the postmenstrual age (PMA) of the infants could inform physicians about the progress of the maturation of the infants. The HRV data was acquired from 50 healthy infants, born between 25 and 41 weeks of gestational age, who did not present any signs of abnormal maturation relative to their age group during the period of observation. The HRV features were used as input for a machine learning model that uses filtering and genetic algorithms for feature selection, and an ensemble machine learning (EML) algorithm, which combines linear and random forest regressions, to produce as output a FMA. Using HRV data, the FMA had a mean absolute error of 0.93 weeks, 95% CI [0.78, 1.08], compared to the PMA. These results demonstrate that HRV features of newborn infants can be used by an EML model to estimate their FMA. This method was also generalized using respiration rate variability (RRV) and bradycardia data, obtaining similar results. The FMA, predicted either by HRV, RRV or bradycardia, and its deviation from the true PMA of the infants, could be used as a surrogate measure of the maturational age of the infants, which could potentially be monitored non-invasively and in real-time in the setting of neonatal intensive care units.

Premedication before laryngoscopy in neonates: Evidence-based statement from the French society of neonatology (SFN).

Context: Laryngoscopy is frequently required in neonatal intensive care. Awake laryngoscopy has deleterious effects but practice remains heterogeneous regarding premedication use. The goal of this statement was to provide evidence-based good practice guidance for clinicians regarding premedication before tracheal intubation, less invasive surfactant administration (LISA) and laryngeal mask insertion in neonates. Methods: A group of experts brought together by the French Society of Neonatology (SFN) addressed 4 fields related to premedication before upper airway access in neonates: (1) tracheal intubation; (2) less invasive surfactant administration; (3) laryngeal mask insertion; (4) use of atropine for the 3 previous procedures. Evidence was gathered and assessed on predefined questions related to these fields. Consensual statements were issued using the GRADE methodology. Results: Among the 15 formalized good practice statements, 2 were strong recommendations to do (Grade 1+) or not to do (Grade 1-), and 4 were discretionary recommendations to do (Grade 2+). For 9 good practice statements, the GRADE method could not be applied, resulting in an expert opinion. For tracheal intubation premedication was considered mandatory except for life-threatening situations (Grade 1+). Recommended premedications were a combination of opioid + muscle blocker (Grade 2+) or propofol in the absence of hemodynamic compromise or hypotension (Grade 2+) while the use of a sole opioid was discouraged (Grade 1-). Statements regarding other molecules before tracheal intubation were expert opinions. For LISA premedication was recommended (Grade 2+) with the use of propofol (Grade 2+). Statements regarding other molecules before LISA were expert opinions. For laryngeal mask insertion and atropine use, no specific data was found and expert opinions were provided. Conclusion: This statement should help clinical decision regarding premedication before neonatal upper airway access and favor standardization of practices.

Longitudinal Trajectories of Hair Cortisol: Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Early Childhood.

The objective of this study was to examine if longitudinal trajectories of hair cortisol concentrations (HCC) measured at two or three yearly time points can identify 1-3 year old children at risk for altered hypothalamic-pituitary-adrenal (HPA)-axis function due to early life stress (ELS). HCC was measured (N = 575) in 265 children using a validated enzyme-linked immunosorbent assay. Hair was sampled in Clinic Visits (CV) centered at years 1, 2, and 3 (n = 45); 1 and 2 (n = 98); 1 and 3 (n = 27); 2 and 3 (n = 95). Log-transformed HCC values were partitioned using latent class mixed models (LCMM) to minimize the Bayesian Information Criterion. Multivariable linear mixed effects models for ln-HCC as a function of fixed effects for age in months and random effects for participants (to account for repeated measures) were generated to identify the factors associated with class membership. Children in Class 1 (n = 69; 9% Black) evidenced declining ln-HCC across early childhood, whereas Class 2 members (n = 196; 43% Black) showed mixed trajectories. LCMM with only Class 2 members revealed Class 2A (n = 17, 82% Black) with sustained high ln-HCC and Class 2B (n = 179, 40% Blacks) with mixed ln-HCC profiles. Another LCMM limited to only Class 2B members revealed Class 2B1 (n = 65, 57% Black) with declining ln-HCC values (at higher ranges than Class 1), and Class 2B2 (n = 113, 30% Black) with sustained high ln-HCC values. Class 1 may represent hair cortisol trajectories associated with adaptive HPA-axis profiles, whereas 2A, 2B1, and 2B2 may represent allostatic load with dysregulated profiles of HPA-axis function in response to varying exposures to ELS. Sequential longitudinal hair cortisol measurements revealed the allostatic load associated with ELS and the potential for developing maladaptive or dysregulated HPA-axis function in early childhood.

What Do We Know about Pruritus in Very Young Infants? A Literature Review.

In infants, pruritus is frequently considered as absent because they do not scratch themselves. Because pruritus could induce severe adverse effects in this vulnerable population, we aimed to review existing evidence on the ability of young infants to experience itch and on how to assess itch-related discomfort in this population. A literature review was performed (Pubmed, Google Scholar). Neurological itch pathways are well described. Skin development starts early during gestation. At 34 weeks of gestation, skin is almost complete while skin adaptations occur after birth. Newborn skin is neurologically functional, including the ability for young infants to feel pain. Similarities and interactions between pain and pruritus support the hypothesis that infants could feel pruritus. However, the existence of pruritus in infants has never been evidenced. Many itchy conditions can affect them, suggesting non-negligible prevalence of infant pruritus among which atopic dermatitis (AD) is the most studied disease. Studies reported a negative impact of AD on children and their families. There is no existing validated method to assess pruritus in infants, although they may feel pruritus and chronic pruritus can lead to serious adverse effects. To appropriately diagnose pruritus appears of great interest among young infants. Development of a method is required to this aim.

Frequency of Extracorporeal Membrane Oxygenation Support and Outcomes After Implementation of a Structured PICU Network in Neonates and Children: A Prospective Population-Based Study in the West of France.

OBJECTIVES: To describe the frequency and outcomes on the use of extracorporeal membrane oxygenation (ECMO) among critically ill neonates and children within a structured pediatric critical care network in the West of France. To assess the optimality of decision-making process for patients primarily admitted in non-ECMO centers. DESIGN: Observational prospective population-based study from January 2015 to December 2019. PATIENTS: Neonates over 34 weeks of gestational age, weighing more than 2,000 g and children under 15 years and 3 months old admitted in one of the 10 units belonging to a Regional Pediatric Critical Care Network. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight-thousand one hundred eighty-nine children and 3,947 newborns were admitted within one of the 10 units of the network over the study period. Sixty-five children (8.1% [95% CI, 6.2-10‰]) and 35 newborns (9.4% [95% CI, 6.4-12%]) required ECMO support. Of these patients, 31 were first admitted to a non-ECMO center, where 20 were cannulated in situ (outside the regional ECMO center) and 11 after transfer to the ECMO regional center. Cardiogenic shock, highest serum lactate level, and cardiac arrest prior to first phone call with the regional ECMO center were associated with higher rate of in situ cannulation. During the study period, most of the patients were cannulated for underlying cardiac issue (42/100), postoperative cardiac surgery instability (38/100), and pediatric (10/100) and neonatal (10/100) respiratory distress syndrome. Patients primarily admitted in non-ECMO centers or not had similar 28-day post-ICU survival rates compared with those admitted in the referral ECMO center (58% vs 51%; p = 0.332). Pre-ECMO cardiac arrest, ECMO, and lower pH at ECMO onset were associated with lower 28-day post-ICU survival. CONCLUSIONS: Our local results suggest that a structured referral network for neonatal and pediatric ECMO in the region of Western France facilitated escalation of care with noninferior (or similar) early mortality outcome. Our data support establishing referral networks in other equivalent regions.

COVID-19 preparedness-a survey among neonatal care providers in low- and middle-income countries.

OBJECTIVE: To evaluate COVID-19 pandemic preparedness, available resources, and guidelines for neonatal care delivery among neonatal health care providers in low- and middle-income countries (LMICs) across all continents. STUDY DESIGN: Cross-sectional, web-based survey administered between May and June, 2020. RESULTS: Of 189 invited participants in 69 LMICs, we received 145 (77%) responses from 58 (84%) countries. The pandemic provides significant challenges to neonatal care, particularly in low-income countries. Respondents noted exacerbations of preexisting shortages in staffing, equipment, and isolation capabilities. In Sub-Saharan Africa, 9/35 (26%) respondents noted increased mortality in non-COVID-19-infected infants. Clinical practices on cord clamping, isolation, and breastfeeding varied widely, often not in line with World Health Organization guidelines. Most respondents noted family access restrictions, and limited shared decision-making. CONCLUSIONS: Many LMICs face an exacerbation of preexisting resource challenges for neonatal care during the pandemic. Variable approaches to care delivery and deviations from guidelines provide opportunities for international collaborative improvement.

Association of Continuous Opioids and/or Midazolam During Early Mechanical Ventilation with Survival and Sensorimotor Outcomes at Age 2 Years in Premature Infants: Results from the French Prospective National EPIPAGE 2 Cohort.

OBJECTIVE: To evaluate the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age 2 years in very premature infants who were ventilated. STUDY DESIGN: This national observational study included premature infants born before 32 weeks of gestation intubated within 1 hour after birth and still intubated at 24 hours from the French EPIPAGE 2 cohort. Infants only treated with bolus were excluded. Treated infants received continuous opioid and/or midazolam infusion started before 7 days of life and before the first extubation. Naive infants did not receive these treatments before the first extubation, or received them after the first week of life, or never received them. This study compared treated (n = 450) vs naive (n = 472) infants by using inverse probability of treatment weighting after multiple imputation in chained equations. The primary outcomes were survival and survival without moderate or severe neuromotor or sensory impairment at age 2 years. RESULTS: Survival at age 2 years was significantly higher in the treated group (92.5% vs 87.9%, risk difference, 4.7%; 95% CI, 0.3-9.1; P = .037), but treated and naive infants did not significantly differ for survival without moderate or severe neuromotor or sensory impairment (86.6% vs 81.3%; risk difference, 5.3%; 95% CI -0.3 to 11.0; P = .063). These results were confirmed by sensitivity analyses using 5 alternative models. CONCLUSIONS: Continuous opioid and/or midazolam infusions in very premature infants during initial mechanical ventilation that continued past 24 hours of life were associated with improved survival without any difference in moderate or severe sensorimotor impairments at age 2 years.

Diagnosis of Neonatal Late-Onset Infection in Very Preterm Infant: Inter-Observer Agreement and International Classifications.

BACKGROUND: The definition of late-onset bacterial sepsis (LOS) in very preterm infants is not unified. The objective was to assess the concordance of LOS diagnosis between experts in neonatal infection and international classifications and to evaluate the potential impact on heart rate variability and rate of "bronchopulmonary dysplasia or death". METHODS: A retrospective (2017-2020) multicenter study including hospitalized infants born before 31 weeks of gestation with intention to treat at least 5-days with antibiotics was performed. LOS was classified as "certain or probable" or "doubtful" independently by five experts and according to four international classifications with concordance assessed by Fleiss's kappa test. RESULTS: LOS was suspected at seven days (IQR: 5-11) of life in 48 infants. Following expert classification, 36 of them (75%) were considered as "certain or probable" (kappa = 0.41). Following international classification, this number varied from 13 to 46 (kappa = -0.08). Using the expert classification, "bronchopulmonary dysplasia or death" occurred less frequently in the doubtful group (25% vs. 78%, p < 0.001). Differences existed in HRV changes between the two groups. CONCLUSION: The definition of LOS is not consensual with a low international and moderate inter-observer agreement. This affects the evaluation of associated organ dysfunction and prognosis.

Using sensor-fusion and machine-learning algorithms to assess acute pain in non-verbal infants: a study protocol.

INTRODUCTION: Objective pain assessment in non-verbal populations is clinically challenging due to their inability to express their pain via self-report. Repetitive exposures to acute or prolonged pain lead to clinical instability, with long-term behavioural and cognitive sequelae in newborn infants. Strong analgesics are also associated with medical complications, potential neurotoxicity and altered brain development. Pain scores performed by bedside nurses provide subjective, observer-dependent assessments rather than objective data for infant pain management; the required observations are labour intensive, difficult to perform by a nurse who is concurrently performing the procedure and increase the nursing workload. Multimodal pain assessment, using sensor-fusion and machine-learning algorithms, can provide a patient-centred, context-dependent, observer-independent and objective pain measure. METHODS AND ANALYSIS: In newborns undergoing painful procedures, we use facial electromyography to record facial muscle activity-related infant pain, ECG to examine heart rate (HR) changes and HR variability, electrodermal activity (skin conductance) to measure catecholamine-induced palmar sweating, changes in oxygen saturations and skin perfusion, and electroencephalography using active electrodes to assess brain activity in real time. This multimodal approach has the potential to improve the accuracy of pain assessment in non-verbal infants and may even allow continuous pain monitoring at the bedside. The feasibility of this approach will be evaluated in an observational prospective study of clinically required painful procedures in 60 preterm and term newborns, and infants aged 6 months or less. ETHICS AND DISSEMINATION: The Institutional Review Board of the Stanford University approved the protocol. Study findings will be published in peer-reviewed journals, presented at scientific meetings, taught via webinars, podcasts and video tutorials, and listed on academic/scientific websites. Future studies will validate and refine this approach using the minimum number of sensors required to assess neonatal/infant pain. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03330496).

The newborn infant parasympathetic evaluation index for acute procedural pain assessment in preterm infants.

BACKGROUND: Accurate assessments of pain in hospitalized preterm infants present a major challenge in improving the short- and long-term consequences associated with painful experiences. We evaluated the ability of the newborn infant parasympathetic evaluation (NIPE) index to detect acute procedural pain in preterm infants. METHODS: Different painful and stressful interventions were prospectively observed in preterm infants born at 25 + 0 to 35 + 6 weeks gestation. Pain responses were measured using the composite Premature Infant Pain Profile Revised (PIPP-R) scale, the NIPE index, and skin conductance responses (SCR). Outcome measures were correlations between the NIPE index, the PIPP-R score, and the SCR. Sensitivity/specificity analyses tested the accuracy of the NIPE index and SCR. RESULTS: Two hundred and fifty-four procedures were recorded in 90 preterm infants. No significant correlation was found between PIPP-R and the NIPE index. PIPP-R and SCR were positively correlated (r = 0.27, P < 0.001), with stronger correlations for painful procedures (r = 0.68, P < 0.001) and especially for skin-breaking procedures (r = 0.82, P < 0.001). The NIPE index and SCR had high sensitivity and high negative predictive values to predict PIPP-R > 10, especially for skin-breaking painful procedures. CONCLUSIONS: We found no significant correlation between the NIPE index and PIPP-R during routine painful or stressful procedures in preterm infants. IMPACT: Exposure to repetitive pain can lead to neurodevelopmental sequelae. Behavior-based pain scales have limited clinical utility, especially for preterm infants. New devices for monitoring physiological responses to pain have not been validated sufficiently in preterm infants. This study found that the NIPE index was not significantly correlated to the validated PIPP-R scale during acute procedural pain. Secondary analysis of this study showed that NIPE index and SCRs may help to exclude severe pain in preterm infants. In clinical practice, measurements of physiological parameters should be combined with behavior-based scales for multidimensional pain assessments.

Quiet Sleep Organization of Very Preterm Infants Is Correlated With Postnatal Maturation.

Background: Sleep is an important determinant of brain development in preterm infants. Its temporal organization varies with gestational age (GA) and post-menstrual age (PMA) but little is known about how sleep develops in very preterm infants. The objective was to study the correlation between the temporal organization of quiet sleep (QS) and maturation in premature infants without severe complications during their neonatal hospitalization. Methods: Percentage of time spent in QS and average duration of time intervals (ADI) spent in QS were analyzed from a cohort of newborns with no severe complications included in the Digi-NewB prospective, multicentric, observational study in 2017-19. Three groups were analyzed according to GA: Group 1 (27-30 weeks), Group 2 (33-37 weeks), Group 3 (>39 weeks). Two 8-h video recordings were acquired in groups 1 and 2: after birth (T1) and before discharge from hospital (T2). The annotation of the QS phases was performed by analyzing video recordings together with heart rate and respiratory traces thanks to a dedicated software tool of visualization and annotation of multimodal long-time recordings, with a double expert reading. Results are expressed as median (interquartile range, IQR). Correlations were analyzed using a linear mixed model. Results: Five newborns were studied in each group (160 h of recording). Median time spent in QS increased from 13.0% [IQR: 13-20] to 28.8% [IQR: 27-30] and from 17.0% [IQR: 15-21] to 29.6% [IQR: 29.5-31.5] in Group 1 and 2, respectively. Median ADI increased from 54 [IQR: 53-54] to 288 s [IQR: 279-428] and from 90 [IQR: 84-96] to 258 s [IQR: 168-312] in Group 1 and 2. Both groups reach values similar to that of group 3, respectively 28.2% [IQR: 24.5-31.3] and 270 s [IQR: 210-402]. The correlation between PMA and time spent in QS or ADI were, respectively 0.73 (p < 10-4) and 0.46 (p = 0.06). Multilinear analysis using temporal organization of QS gave an accurate estimate of PMA (r 2 = 0.87, p < 0.001). Conclusion: The temporal organization of QS is correlated with PMA in newborns without severe complication. An automated standardized continuous behavioral quantification of QS could be interesting to monitor during the hospitalization stay in neonatal units.

Automatic oxygen flow titration in spontaneously breathing children: An open-label randomized controlled pilot study.

INTRODUCTION: When children require supplemental oxygen due to acute hypoxemic respiratory distress (AHRD), manual control of the oxygen flow is often difficult and time-consuming, and carries the risk of unrecognized hypoxia and hyperoxia. To date, no automatic oxygen titration system has been developed and evaluated in spontaneously breathing children. METHODS: Children between 1 month and 15 years of age receiving supplemental oxygen due to AHRD were recruited within 24 hours following the onset of the O2 administration in a French University Department of Paediatrics. Patients were randomized to receive either automated oxygen administration using the FreeO2 device, or conventional manual oxygen administration over a maximum period of 6 hours. Stratification was performed to classify the patients into two age groups: 1 month to 2 years of age and 2 to 15 years of age. The primary outcome was % time spent within the SpO2 target range (92%-98%). RESULTS: 60 patients (30 infants, 30 children) were randomized and 55 could be analyzed for the primary outcome (28 automated, 27 manual). The automated O2 delivery using the FreeO2 device significantly increased the time spent within the predefined SpO2 range (94.6% ± 6% vs 76.3% ± 22%, difference [95% confidence interval {CI}] 18.4 [10.1; 26.7]) with less time spent with hypoxemia (1% ± 1.1% vs 15.1% ± 21.8%, difference [95% CI] -14.4 [-22.2; -6.7]). This difference was greater among (2-15 years of age) children, compared to (1 month-2 years of age) infants. CONCLUSIONS: The present randomized controlled pilot study indicates that the tested automated closed-loop O2 titration technology was safe and yielded improved oxygen parameters among spontaneously breathing children. Based on our pilot data, a full randomized controlled trial will be required to verify the potential clinical benefits.

A novel, short and easy-to-perform method to evaluate newborns' social olfactory preferences.

Humans' early olfactory perception has been studied mainly within the framework of mother-offspring interactions and only a few studies have focused on newborns' abilities to discriminate body odors per se. The aim of this study was to develop a method to evaluate olfactory social preferences of infants at term-equivalent age. Twenty dyads of infants (10 born preterm and 10 born at term) at term-equivalent age and their mothers were included. We analyzed the behavioral reactions of infants to their mother's upper-chest odor (that bears social, non-food related information). The two impregnated gauzes and a control gauze were presented to the infants for 10 s each, in a random order. We compared two durations of gauze impregnation: 30 min and 12 h. This study reveals that mothers' upper chest emits sufficient olfactory information to induce reactions in infants born full-term or born preterm and that a short impregnation is preferable to evaluate their perception of body odors, notably for those born preterm.

Epidemiology of Community-Onset Severe Bacterial Infections in Children and Its Evolution: A Population-Based Study in France.

OBJECTIVES: To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution. DESIGN: Prospective, observational, population-based study from 2009 to 2014. SETTING: An administrative area accounting for 13% of the French pediatric population. PATIENTS: All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period. CONCLUSIONS: The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.