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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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to articles in a 2015 issue including "Corticosteroid Exposure in Pediatric Acute Respiratory Distress Syndrome," by N. Yehya and colleagues and "Corticosteroids for Paediatric ARDS: Unjustified--Even Unjustifiable?," by M. J. Peters and colleagues.

Normative ranges for cortisol levels in children remain controversial, because of diurnal variations, effects of age, sex, stressful experiences before sampling (blood, saliva), intercurrent illnesses/immunizations, sample preparation and analytical methods. Measuring hair cortisol concentrations (HCC) is unaffected by diurnal variations or many of these factors, and presents a summative measure of chronic stress. Depending on hair growth rates, approximately 1 cm of hair represents cortisol release over the past month. HCC does not fluctuate frequently and therefore represents cumulative stress over time. It is vitally important to establish normative cortisol levels in children, so that both maladaptive and toxic stress levels can be measured. Pilot data from children in the CANDLE Study (Conditions Affecting Neurocognitive Development & Learning in Early childhood) were analyzed to identify the 25th, 50th and 75th percentiles for HCC in 1-4 year-old children. Significantly higher HCC were noted in black vs. white children at 1, 2, 3, and 4-years (P<0.001, for all ages). When measuring HCC we must also study the biochemical composition of an individual's hair, primarily its lipid content. This lipid content is significantly different depending on one's racial background and may account for some of the observed racial differences in HCC (Robbins, 2012). Establishing age-, sex-, and racespecific normative levels for HCC are essential for investigating the cumulative effects of chronic stress or "allostatic load" across the lifespan. If the normative ranges for HCC can be established, both the causes and effects of maladaptive and toxic stress can be subsequently identified, prevented and/or treated. [ABSTRACT FROM AUTHOR]

Objective: Child survival after intensive care unit (ICU) hospitalization has increased, yet many children experience acute stress that may precipitate mental/behavioral health comorbidities. Parents report stress after their child's hospitalization. Little is known about the individual and family characteristics that may moderate intergenerational relationships of acute stress. Design: Following ICU admission at a large academic medical center, a prospective cross-sectional cohort study assessed the associations between intergenerational characteristics and acute stress among children and families. Patients: Parent–child dyads (N = 88) were recruited from the pediatric ICU and pediatric cardiovascular ICU (CVICU) following ICU discharge. Eligible children were between 8 and 18 years old with ICU stays longer than 24 hours. Children with developmental delays were excluded. Caregivers were proficient in English or Spanish. Surveys were collected before hospital discharge. Measurements/Main Results: The primary outcome was "child stress" defined as a score≥17, measured by the Children's Revised Impact of Events Scale (CRIES-8). "Parent stress" was defined as an elevated composite score on the Stanford Acute Stress Reaction Questionnaire. We used validated scales to assess the child's clinical and family social characteristics. Acute stress was identified in 34 (39.8%) children and 50 (56.8%) parents. In multivariate linear regression analyses adjusting for social characteristics, parent stress was associated with increased risk of child stress (adjusted odds ratio 2.58, 95% confidence interval 0.69, 4.46, p <.01). In unadjusted analyses, Hispanic ethnicity was associated with greater child stress. In adjusted analyses, race, income, ICU length of stay, and language were not associated with child stress and did not moderate the parent–child stress relationship. Conclusions: Parent stress is closely correlated with child stress during ICU hospitalization. Hispanic ethnicity may be associated with increased risk for child stress, but further studies are required to define the roles of other social and clinical measures. [ABSTRACT FROM AUTHOR]

Background. Early childhood experiences have long-lasting effects on subsequent mental and physical health, education, and employment. The measurement of these effects relies on insensitive behavioral signs, subjective assessments by adult observers, neuroimaging or neurophysiological studies, or retrospective epidemiologic outcomes. Despite intensive research, the underlying mechanisms of these long-term changes in development and health status remain unknown. Methods. We analyzed scalp hair from healthy children and their mothers using an unbiased proteomics platform combining tandem mass spectrometry, ultra-performance liquid chromatography, and collision-induced dissociation to reveal commonly observed hair proteins with a spectral count of 3 or higher. Results. We observed 1368 non-structural hair proteins in children and 1438 non-structural hair proteins in mothers, with 1288 proteins showing individual variability. Mothers showed higher numbers of peptide spectral matches and hair proteins compared to children, with important age-related differences between mothers and children. Age-related differences were also observed in children, with differential protein expression patterns between younger (2 years and below) and older children (3–5 years). We observed greater similarity in hair protein patterns between mothers and their biological children compared with mothers and unrelated children. The top 5% of proteins driving population variability represented biological pathways associated with brain development, immune signaling, and stress response regulation. Conclusions. Non-structural proteins observed in scalp hair include promising biomarkers to investigate the long-term developmental changes and health status associated with early childhood experiences. [ABSTRACT FROM AUTHOR]

The article highlights the absence of race and ethnicity data in healthcare, acknowledging the biases it creates, particularly for underserved populations, affecting Artificial Intelligence applications. It also discusses the proposal to consider AI-generated patterns as artifacts to better understand societal values and injustices.

Highlights • Maternal traumas prior to mid-gestation are associated with offspring hair cortisol. • This association is evident in the older subset of children (ages 3 and 4). • Additional research is necessary to identify biological and social pathways. Abstract Background and Objective Maternal trauma can have intergenerational consequences but little is known about whether maternal traumas affect key biological domains associated with mental health in their offspring. The objective of this study was to examine maternal lifetime history of traumatic events through mid-gestation in relation to offspring cortisol production in early childhood. Methods The sample was comprised of 660 children (49.9% Black, 44.4% White) from a longitudinal study of mother-offspring dyads in Shelby County, Tennessee, followed from mid-gestation to child age 4 years (enrolled 2006–2011). Maternal lifetime history of traumatic life events were assessed mid-gestation using the Traumatic Life Events Questionnaire. Total cortisol output among offspring was measured using hair cortisol concentrations at ages 1 to 4 years. Results Associations of maternal trauma history with child hair cortisol varied by child's age. No association was observed at age 1 or 2. In adjusted regression models, at ages 3 and 4, offspring of mothers in the third (β = 0.99, P <.01), fourth (β=0.72, P <.05), and fifth (β=0.83, P <.01) quintiles of trauma exposure history had elevated (natural log) hair cortisol concentrations, relative to mothers in the lowest quintile (P- trend = 0.003). The associations were not attenuated after adjustment for theorized pathways, including premature birth, maternal postpartum depression, and maternal parenting stress. Conclusions Maternal lifetime trauma exposures are associated with offspring hair cortisol concentrations. Future research is needed to determine intermediary mechanisms and functional significance of elevated hair cortisol concentration in young children. [ABSTRACT FROM AUTHOR]

This report describes the clinical course and treatment of a C. perfringens infection in a child following an injury to the knee that resulted in sepsis and multi-organ system failure. Diagnosis of the causative agent and systemic nature of the infection was delayed because of the non-traditional presentation, in which the patient appeared to have a localized necrotizing fasciitis and did not display symptoms consistent with severe systemic involvement. He was treated with vancomycin, wound debridement and fasciotomy. After identification of C. perfringens, vancomycin therapy was discontinued in favor of penicillin and clindamycin. With intensive supportive care, the patient recovered fully and resumed regular activities within two months. These infections are rare in children, but they can be life threatening. It is important to include systemic Clostridium infection in a differential so it can be recognized early and appropriate treatment begun as soon as possible. [ABSTRACT FROM AUTHOR]

The CANDLE Study aims to uncover factors experienced during pregnancy and early life that affect cognition, behavior, and health of children. External stressors and socioeconomic status (SES) influence the fetus through "prenatal programming". However, comprehensive measures of SES do not exist, except those based on income and education. We selected 53 variables from the CANDLE study including annual household income, headcount, marital status, health insurance, parental occupation and education. Singular value decomposition imputation (SVDI), a principal components analysis approach unaffected by the 24.4% missing data in our variables, was applied to all 53 variables (Troyanskaya, 2001). All variables were distilled into 3 principal components explaining 93% of the variability. These components were combined to develop the Family Poverty Index (FPI, range 1-10). All subjects were separated into deciles based on FPI scores. Individuals with FPI=1 were the "poorest" with 79% individuals having annual incomes <$15,000. Those with FPI=9 or 10 were "rich", since most individuals (98.7%, 73.3%) had annual incomes >$55,000. With FPI=1-3, 95% had Medicaid insurance and 4.8% had employer/private insurance, whereas with FPI=8-10, 86% had employer/private insurance and 11.8% had Medicaid. Other variables showed similar distributions across FPI categories. FPI appears to be a robust measure of SES in the CANDLE Study population. Further research should test the validity of the FPI in other datasets. [ABSTRACT FROM AUTHOR]

Stress physiology contributes to health outcomes. Hair cortisol concentration (HCC) is an objective measure of cumulative cortisol secretion associated with health, including pain. The aim of the current study was to describe associations between pre-injury stress physiology (as measured by HCC), acute pain characteristics and relevant demographic factors (i.e., BMI, age, sex, days since injury) in youth with an acute musculoskeletal (MSK) injury. Participants were 58 youth aged 11 to 17 with acute MSK pain. Participants completed self-report measures assessing pain intensity, pain catastrophizing, and pain interference. Hair was collected within 1 month after injury using hair cortisol collection procedures adapted from published research protocols. Correlations examining associations among HCC values and clinical/demographic factors revealed that higher HCC was associated with lower body mass index (BMI) and male sex. HCC was not associated with pain variables or age. Additional research is needed to clarify the relation between HCC and psychosocial variables to aid researchers in studying the role of pre-injury stress in acute MSK injury and pain recovery in youth., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: Health care inequities are common among individuals who speak languages other than English (LOE). Within our PICU, LOE families prefer communication via in-person interpreters (IPI). Spanish-speaking patient families are our largest LOE population; therefore, we sought to increase Spanish IPI utilization for medical updates in the PICU., Methods: A quality improvement initiative in a 36-bed PICU included: the addition of a dedicated weekday Spanish-speaking IPI, the creation of communication tools, staff education, optimized identification of LOE families, and development of a language dashboard across multiple Plan, Do, Study, Act cycles. The primary outcome was IPI utilization rates for daily medical updates., Results: Spanish IPI utilization for daily weekday medical updates among 442 Spanish-speaking patient families increased from a median of 39.4% at baseline to a new centerline median of 51.9% during implementation, exhibiting 66.3% (465 of 701) utilization in the final 6 months of implementation. The greatest sustained increases in Spanish IPI utilization occurred after PICU-based IPI implementation, staff education, electronic health record optimization, and a split work week between 2 PICU-based IPIs., Conclusions: This quality improvement initiative increased Spanish IPI utilization for daily weekday medical updates in the PICU across multiple Plan, Do, Study, Act cycles. Future work will adapt these interventions to other languages and other hospital-based units., (Copyright © 2024 by the American Academy of Pediatrics.)

Introduction: Despite increasing survival of children following hospitalization, hospitalization may increase iatrogenic risk for mental health (MH) disorders, including acute stress, post-traumatic stress, anxiety, or depression. Using a population-based retrospective cohort study, we assessed the rates of new MH diagnoses during the 12 months after hospitalization, including the moderating effects of ICU exposure., Study Design/methods: This was a retrospective case control study using the Truven Health Analytics insurance database. Inclusion criteria included children aged 3-21 years, insurance enrollment for >12 months before and after hospital admission. We excluded children with hospitalization 2 years prior to index hospitalization and those with prior MH diagnoses. We extracted admission type, ICD-10 codes, demographic, clinical, and service coordination variables from the database. We established age- and sex-matched cohorts of non-hospitalized children. The primary outcome was a new MH diagnosis. Multivariable regression methods examined the risk of incident MH disorder(s) between hospitalized and non-hospitalized children. Among hospitalized children, we further assessed effect modification from ICU (vs. non-ICU) stay, admission year, length of stay, medical complexity, and geographic region., Results: New MH diagnoses occurred among 19,418 (7%) hospitalized children, 3,336 (8%) ICU-hospitalized children and 28,209 (5%) matched healthy controls. The most common MH diagnoses were anxiety (2.5%), depression (1.9%), and stress/trauma (2.2%) disorders. Hospitalization increased the odds of new MH diagnoses by 12.3% (OR: 1.123, 95% CI: 1.079-1.17) and ICU-hospitalization increased these odds by 63% (OR: 1.63, 95% CI: 1.483-1.79) as compared to matched, non-hospitalized children. Children with non-complex chronic diseases (OR: 2.91, 95% CI: 2.84-2.977) and complex chronic diseases (OR: 5.16, 95% CI: 5.032-5.289) had a substantially higher risk for new MH diagnoses after hospitalization compared to patients with acute illnesses., Conclusion: Pediatric hospitalization is associated with higher, long-term risk of new mental health diagnoses, and ICU hospitalization further increases that risk within 12 months of the acute episode. Acute care hospitalization confers iatrogenic risks that warrant long-term mental and behavioral health follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Daughtrey, Ruiz, Felix, Saynina, Sanders and Anand.)

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., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Human scalp hair is a validated bio-substrate for monitoring various exposures in childhood including contextual stressors, environmental toxins, prescription or non-prescription drugs. Linear hair growth rates (HGR) are required to accurately interpret hair biomarker concentrations., Methods: We measured HGR in a prospective cohort of preschool children (N = 266) aged 9-72 months and assessed demographic factors, anthropometrics, and hair protein content (HPC). We examined HGR differences by age, sex, race, height, hair pigment, and season, and used univariable and multivariable linear regression models to identify HGR-related factors., Results: Infants below 1 year (288 ± 61 μm/day) had slower HGR than children aged 2-5 years (p = 0.0073). Dark-haired children (352 ± 52 μm/day) had higher HGR than light-haired children (325 ± 50 μm/day; p = 0.0019). Asian subjects had the highest HGR overall (p = 0.016). Younger children had higher HPC (p = 0.0014) and their HPC-adjusted HGRs were slower than older children (p = 0.0073). Age, height, hair pigmentation, and HPC were related to HGR in multivariable regression models., Conclusions: We identified age, height, hair pigment, and hair protein concentration as significant determinants of linear HGRs. These findings help explain the known hair biomarker differences between children and adults and aid accurate interpretation of hair biomarker results in preschool children., Impact: Discovery of hair biomarkers in the past few decades has transformed scientific disciplines like toxicology, pharmacology, epidemiology, forensics, healthcare, and developmental psychology. Identifying determinants of hair growth in children is essential for accurate interpretation of hair biomarker results in pediatric clinical studies. Childhood hair growth rates define the time-periods of biomarker incorporation into growing hair, essential for interpreting the biomarkers associated with environmental exposures and the mind-brain-body connectome. Our study describes age-, sex-, and height-based distributions of linear hair growth rates and provides determinants of linear hair growth rates in a large population of children. Age, height, hair pigmentation, and hair protein content are determinants of hair growth rates and should be accounted for in child hair biomarkers studies. Our findings on hair protein content and linear hair growth rates may provide physiological explanations for differences in hair growth rates and biomarkers in preschool children as compared to adults., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Social isolation and conflict due to structural racism may result in human suffering and loneliness across the life span. Given the rising prevalence of these problems in the United States, combined with disruptions experienced during the COVID-19 pandemic, the neurobiology of affiliative behaviors may offer practical solutions to the pressing challenges associated with structural racism. Controlled experiments across species demonstrate that social connections are critical to survival, although strengthening individual resilience is insufficient to address the magnitude and impact of structural racism. In contrast, the multilevel construct of social resilience, defined by the power of groups to cultivate, engage in, and sustain positive relationships that endure and recuperate from social adversities, offers unique insights that may have greater impact, reach, and durability than individual-level interventions. Here, we review putative social resilience-enhancing interventions and, when available, their biological mediators, with the hope to stimulate discovery of novel approaches to mitigate structural racism. We first explore the social neuroscience principles underlying psychotherapy and other psychiatric interventions. Then, we explore translational efforts across species to tailor treatments that increase social resilience, with context and cultural sensitivity in mind. Finally, we conclude with some practical future directions for understudied areas that may be essential for progress in biological psychiatry, including ethical ways to increase representation in research and developing social paradigms that inform dynamics toward or away from socially resilient outcomes., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Artificial Intelligence (AI)-based methods allow for automatic assessment of pain intensity based on continuous monitoring and processing of subtle changes in sensory signals, including facial expression, body movements, and crying frequency. Currently, there is a large and growing need for expanding current AI-based approaches to the assessment of postoperative pain in the neonatal intensive care unit (NICU). In contrast to acute procedural pain in the clinic, the NICU has neonates emerging from postoperative sedation, usually intubated, and with variable energy reserves for manifesting forceful pain responses. Here, we present a novel multi-modal approach designed, developed, and validated for assessment of neonatal postoperative pain in the challenging NICU setting. Our approach includes a robust network capable of efficient reconstruction of missing modalities (e.g., obscured facial expression due to intubation) using an unsupervised spatio-temporal feature learning with a generative model for learning the joint features. Our approach generates the final pain score along with the intensity using an attentional cross-modal feature fusion. Using experimental dataset from postoperative neonates in the NICU, our pain assessment approach achieves superior performance (AUC 0.906, accuracy 0.820) as compared to the state-of-the-art approaches.

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.

An increasing prevalence of early childhood adversity has reached epidemic proportions, creating a public health crisis. Rather than focusing only on adverse childhood experiences (ACEs) as the main lens for understanding early childhood experiences, detailed assessments of a child's social ecology are required to assess "early life adversity." These should also include the role of positive experiences, social relationships, and resilience-promoting factors. Comprehensive assessments of a child's physical and social ecology not only require parent/caregiver surveys and clinical observations, but also include measurements of the child's physiology using biomarkers. We identify cortisol as a stress biomarker and posit that hair cortisol concentrations represent a summative and chronological record of children's exposure to adverse experiences and other contextual stressors. Future research should use a social-ecological approach to investigate the robust interactions among adverse conditions, protective factors, genetic and epigenetic influences, environmental exposures, and social policy, within the context of a child's developmental stages. These contribute to their physical health, psychiatric conditions, cognitive/executive, social, and psychological functions, lifestyle choices, and socioeconomic outcomes. Such studies must inform preventive measures, therapeutic interventions, advocacy efforts, social policy changes, and public awareness campaigns to address early life adversities and their enduring effects on human potential. IMPACT: Current research does not support the practice of using ACEs as the main lens for understanding early childhood experiences. The social ecology of early childhood provides a contextual framework for evaluating the long-term health consequences of early life adversity. Comprehensive assessments reinforced with physiological measures and/or selected biomarkers, such as hair cortisol concentrations to assess early life stress, may provide critical insights into the relationships between early adversity, stress axis regulation, and subsequent health outcomes.

Background: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU., Methods: An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines., Results: This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are also described., Conclusion: Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing this data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world., Impact: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2. Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae. These guidelines can be adapted to both high- and limited-resource settings.