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 Median deviation analysis identified the peak publication years, including the most cited historical references.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.

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.

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.

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.

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.

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.

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.

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.

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.

Unit policies and breast milk feeding at discharge of very preterm infants: The EPIPAGE-2 cohort study.

BACKGROUND: Facilitating factors and barriers to breast milk feeding (BMF) very preterm (VP) infants have been widely studied at the individual level. We aimed to describe and analyse factors associated with BMF at discharge for VP infants, with a special focus on unit policies aiming to support BMF. METHODS: We described BMF at discharge in 3108 VP infants enrolled in EPIPAGE-2, a French national cohort. Variables of interest were kangaroo care during the 1st week of life (KC); unit's policies supporting BMF initiation (BMF information systematically given to mothers hospitalised for threatened preterm delivery and breast milk expression proposed within 6 hours after birth) and BMF maintenance (availability of protocols for BMF and a special room for mothers to pump milk); the presence in units of a professional trained in human lactation and regional BMF initiation rates in the general population. Associations were investigated by multilevel logistic regression analysis, with adjustment on individual factors. RESULTS: In total, 47.2% of VP infants received BMF at discharge (range among units 21.1%-84.0%). Unit policies partly explained this variation, regardless of individual factors. BMF at discharge was associated with KC (adjusted odds ratio (aOR) 2.26 (95% confidence interval (CI) 1.40, 3.65)), with policies supporting BMF initiation (aOR 2.19 (95% CI 1.27, 3.77)) and maintenance (aOR 2.03 (95% CI 1.17, 3.55)), but not with BMF initiation rates in the general population. CONCLUSION: Adopting policies of higher performing units could be an effective strategy for increasing BMF rates at discharge among VP infants.

The impact of neonatal unit policies on breast milk feeding at discharge of moderate preterm infants: The EPIPAGE-2 cohort study.

Facilitating factors and barriers to breast milk feeding (BMF) for preterm infants have been mainly studied in very preterm populations, but little is known about moderate preterm infants. We aimed to analyze hospital unit characteristics and BMF policies associated with BMF at discharge for infants born at 32 to 34 weeks' gestation. EPIPAGE-2, a French national cohort of preterm births, included 883 infants born at 32 to 34 weeks' gestation. We investigated kangaroo care in the first 24 hr, early involvement of parents in feeding support, volume of the unit, BMF information given to mothers hospitalized for threatened preterm delivery, protocols for BMF, presence of a professional trained in human lactation, unit training in neurodevelopmental care, and regional BMF initiation rates in the general population. Multilevel logistic regression analysis was used to investigate associations between unit policies and BMF at discharge, adjusted for individual characteristics and estimating odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 59% (490/828) of infants received BMF at discharge (27% to 87% between units). Rates of BMF at discharge were higher with kangaroo care (adjusted OR 2.03 [95% CI 1.01, 4.10]), early involvement of parents in feeding support (1.94 [1.23, 3.04]), unit training in a neurodevelopmental care programme (2.57 [1.18, 5.60]), and in regions with a high level of BMF initiation in the general population (1.85 [1.05, 3.28]). Creating synergies by interventions at the unit and population level may reduce the variability in BMF rates at discharge for moderate preterm infants.

Vaccine-preventable severe morbidity and mortality caused by meningococcus and pneumococcus: A population-based study in France.

BACKGROUND: In a context of suboptimal vaccination coverage and increasing vaccine hesitancy, we aimed to study morbidity and mortality in children related to missing or incomplete meningococcal C and pneumococcal conjugate vaccines. METHODS: We conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1 month to 16 years who died before admission or were admitted to an intensive care unit for a community-onset bacterial infection. Vaccine-preventable infection was defined as an infection with an identified serotype included in the national vaccine schedule at the time of infection and occurring in a non- or incompletely vaccinated child. Death and severe sequelae were studied at hospital discharge. Frequencies of vaccine-preventable morbidity and mortality caused by meningococcus and pneumococcus were calculated. RESULTS: Among the 124 children with serotyped meningococcal (n = 75) or pneumococcal (n = 49) severe infections included (median age 26 months), 20 (16%) died and 12 (10%) had severe sequelae. Vaccine-preventable infections accounted for 18/124 infections (15%, 95% CI 9, 22), 5/20 deaths (25%, 95% CI 9, 49), and 3/12 severe sequelae cases (25%, 95% CI 0, 54). The vaccine schedule for meningococcal C and pneumococcal conjugate vaccinations was incomplete for 71/116 (61%) children targeted by at least one of these two vaccination programs. CONCLUSIONS: Mortality and morbidity rates related to vaccine-preventable meningococcal or pneumococcal infection could be reduced by one quarter with better implementation of immunisation programs. Such information could help enhance the perception of vaccine benefits and fight vaccine hesitancy.

A Population and Developmental Pharmacokinetic Analysis To Evaluate and Optimize Cefotaxime Dosing Regimen in Neonates and Young Infants.

Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regimens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimize the dosing regimen. An opportunistic sampling strategy combined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimize the dose. The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two-compartment model with first-order elimination. The median values for clearance and the volume of distribution at steady state were 0.12 liter/h/kg of body weight and 0.64 liter/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age (PNA) had significant impacts on cefotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%. We determined the population pharmacokinetics of cefotaxime and established a model-based dosing regimen to optimize treatment for neonates and young infants.

Actigraphy is not a reliable method for measuring sleep patterns in neonates.

AIM: Polysomnography is the gold standard for studying sleep, but it is complex to use, and this can be problematic in clinically unstable preterm infants. We evaluated the reliability of actigraphy and polysomnography in detecting sleep-wake patterns in newborn infants. METHODS: A prospective, monocentric study was conducted that measured the sleep patterns of 48 infants: 24 late preterm neonates born at 34-36 weeks of gestational age and 24 term neonates. We used both polysomnography and the Actiwatch Mini during a three-hour period and then compared the results from the two methods. RESULTS: The baseline measurements for the preterm and terms groups were as follows: gestational age (34.5 weeks and 39.2 weeks), birthweight (2368 g and 3393 g) and age (6.4 days and 0.72 days). With the Actiwatch Mini, sensitivity for the late preterm and full-term infants was 78% and 87% for the leg actigraph and 78% and 93% for the arm actigraph. For specificity, the respective figures were 42% and 31% for the leg and 34% and 20% for the arm. CONCLUSION: Actigraphy using the Actiwatch Mini was not a reliable method for measuring sleep patterns in healthy late preterm and term neonates a few days after birth.

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.

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.

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.

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).