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BackgroundAn operational definition of organ dysfunction applicable to neonates that predicts mortality in the setting of infection is lacking. We determined the utility of an objective, electronic health record (EHR)-automated, neonatal sequential organ failure assessment (nSOFA) score to predict mortality from late-onset sepsis (LOS) in premature, very low birth weight (VLBW) infants.MethodsRetrospective, single-center study of bacteremic preterm VLBW newborns admitted between 2012 and 2016. nSOFA scores were derived for patients with LOS at multiple time points surrounding the sepsis evaluation.ResultsnSOFA scores at evaluation and at all points measured after evaluation were different between survivors and non-survivors. Among patients with an nSOFA score of >4, mortality was higher at evaluation (13% vs 67%, p < 0.001), +6 h (15% vs 64%, p = 0.002), and +12 h (7% vs 71%, p < 0.001) as compared to patients with a score of ≤4. Receiver operating characteristics area under the curve was 0.77 at evaluation (95% CI 0.62–0.92; p = 0.001), 0.78 at +6 h (0.66–0.92; p < 0.001), and 0.93 at +12 h (0.86–0.997; p < 0.001).ConclusionsThe nSOFA scoring system predicted mortality in VLBW infants with LOS and this automated system was integrated into our EHR. Prediction of LOS mortality is a critical step toward improvements in neonatal sepsis outcomes.

BACKGROUNDThe effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota.METHODSAntibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians’ discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home.RESULTSOne hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions.CONCLUSIONSAntibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.

Background Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. Methods A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. Results Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. Conclusions NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. Impact This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

BackgroundAssociations between screen media and child cognition are complex. This study aimed to examine whether age of onset of media exposure, cumulative effect of high media exposure, and verbal interaction during screen time in the first 2 years of life were associated with 4-year-old cognition by including parenting behaviors into the final construct.MethodsThere were 274 healthy participants who were followed up until age 4 years. Screen media data were collected at age 6, 12, 18 months, and 2 years. Cognition or early learning composite (ELC) was evaluated at age 2, 3, and 4 years, where the latter variable was the primary outcome. Positive parenting was obtained by Parenting Styles and Dimensions Questionnaire.ResultsELC at age 2 years was associated with later age of onset of media exposure (β = 0.113, p < 0.05), fewer months of high media exposure above the upper quartile (β = 0.282, p < 0.001), and more months of verbal interaction during screen time (β = 0.261, p < 0.001). ELC at age 4 years was associated with ELC and positive parenting at earlier ages.ConclusionDelayed introduction of screen media, appropriate screen time, and increased verbal interaction during media use in the first 2 years of life were associated with better cognitive development in preschoolers.ImpactAssociations between screen media exposure and children’s cognitive development in existing literature mainly focused on duration of screen media viewing or the content of electronic media in which other factors are rarely explored.Earlier age of onset of media exposure, more months of excessive screen media exposure (>6.5 h/day), and fewer months of verbal interaction with children during media use in the first 2 years of life had associations with decreased preschool cognition.To mitigate undesirable effects of inappropriate screen media use on cognition, delayed introduction of screen media, appropriate electronic media exposure, and increased verbal interaction during media use with children should be recommended at health supervision visits.Lower positive parenting was a mediator for the relationship between cumulative months of high screen media exposure and decreased child cognition.

Background Maternal metabolic disturbances and diet may influence long-term infantile neurodevelopment. We investigated whether maternal gestational diabetes mellitus (GDM), obesity, and diet could affect the neurodevelopment of 2-year-old children. Methods Neurodevelopment of children ( n  = 243) born to mothers with overweight or obesity was assessed with the Bayley Scales of Infant and Toddler Development–Third Edition, and the Hammersmith Infant Neurological Examination. Maternal adiposity was determined by air displacement plethysmography, and GDM with an oral glucose tolerance test. Dietary assessment included diet quality and fish consumption questionnaires, and three-day food diaries, from which dietary inflammatory index (DII ® ) scores were computed. Results GDM was associated with weaker expressive language skills (adj. β  = −1.12, 95% CI = −2.10;−0.15), and higher maternal adiposity with weaker cognitive, language, and motor skills in children (adj. p  < 0.05). Maternal good dietary quality (adj. β  = 0.87, 95% CI = 0.004;1.73) and higher fish consumption (adj. p  = 0.02) were related to better expressive language skills. DII scores were not associated with children’s neurodevelopment. Conclusions Findings suggest that GDM and higher maternal adiposity may lead to weaker neurodevelopmental skills, although still within the mean normative range in this population of children. Good dietary quality and higher fish consumption during pregnancy could benefit a child’s language development. Impact Gestational diabetes mellitus and maternal higher adiposity may have unfavorable effects on a 2-year-old child’s neurodevelopment. An overall good quality of diet and higher fish consumption during pregnancy may result in more favorable cognitive and language skills when the child is 2-year-old. Our findings reveal that women with overweight or obesity, a risk group for pregnancy complications, could benefit from dietary counseling to support their children’s neurodevelopment.

Background This study aimed to investigate the prevalence of and the factors associated with post-COVID-2019 condition in COVID-19 children and adolescents in Germany. Methods The present retrospective cohort study used data from the Disease Analyzer database (IQVIA), and included patients aged <18 years who were diagnosed with COVID-19 in one of 524 general and 81 pediatric practices in Germany between October 2020 and August 2021 (index date: first COVID-19 diagnosis). Post-COVID-19 condition was assessed between the index date and November 2021. Covariates included age, sex, type of practice, and chronic conditions documented in at least 1% of the population. Results There were 6568 children and adolescents included in this study (mean [SD] age 10.1 [4.9] years; 49.2% girls). The prevalence of post-COVID-19 condition was 1.7% in the population. Patients aged 13–17 years were more likely to be diagnosed with post-COVID-19 condition compared with those being aged ≤5 years (RR = 3.14). Anxiety disorders (RR = 2.53), somatoform disorders (RR = 2.11), and allergic rhinitis (RR = 2.02) were also significantly associated with post-COVID-19 condition. Conclusion Post-COVID-19 condition was rare in COVID-19 children and adolescents in Germany. Data from other settings are warranted to confirm these findings. Impact The prevalence of post-COVID-19 condition was 1.7% in this population of children and adolescents. Older children and adolescents were more likely to be diagnosed with post-COVID-19 condition than their younger counterparts. Anxiety disorders, somatoform disorders, and allergic rhinitis were significantly associated with post-COVID-19 condition. More data from other settings and countries are warranted to corroborate or refute these findings.

BackgroundExtremely preterm (EPT) birth is a major risk factor for neurodevelopmental impairments. The aim was to evaluate the predictive value of Prechtl General Movement Assessment (GMA), including the Motor Optimality Score—Revised (MOS-R), at 3 months corrected age (CA) for adverse neurodevelopmental outcome at the age of 12 years.MethodsThe GMA, including the MOS-R, was applied at 3 months CA and outcomes were assessed at 12 years by Touwen’s neurological examination, the Movement Assessment Battery for Children-2, and chart reviews.ResultsFifty-three infants born EPT (33 boys, mean GA 25 weeks, mean body weight 805 ± 156 g) were included. Forty-two (79%) children participated in the follow-up (mean age 12.3 ± 0.4) and 62% of these had adverse outcomes. The MOS-R differed between groups (p = 0.007). The respective predictive values of GMA, aberrant FMs, and the MOS-R cut-off of 21 for adverse outcomes were positive predictive values (PPVs) of 1.00 and 0.77, negative predictive value of 0.47 and 0.63, sensitivity of 0.31 and 0.77, and specificity of 1.00 and 0.77.ConclusionsUsing the Prechtl GMA, including the MOS-R, at 3 months CA predicted an overall adverse neurodevelopment at 12 years, with a high PPV, specificity, and sensitivity in children born EPT.ImpactThe Prechtl GMA, including the MOS-R, can improve early identification of long-term adverse neurodevelopmental outcomes.This is the first study to investigate the predictive value of the MOS-R for neurodevelopmental outcome at mid-school age in children born EPT.Using the GMA, including the MOS-R, is suggested as one important part of the neurological assessment at 3 months CA in children born EPT.Aberrant FMs in combination with a MOS of <21 is an indicator of an increased risk of future adverse neurodevelopment in children born EPT.

BackgroundThe impact of degree of prematurity at birth on premature infant gut microbiota has not been extensively studied in comparison to term infants in large cohorts.MethodsTo determine the effect of gestational age at birth and postnatal exposures on gut bacterial colonization in infants, we analyzed 65 stool samples from 17 premature infants in the neonatal intensive care unit, as well as 13 samples from 13 mostly moderate-to-late premature infants and 189 samples from 176 term infants in the New Hampshire Birth Cohort Study. Gut colonization patterns were determined with 16S rDNA microbiome profiling.ResultsGut bacterial alpha-diversity differed between premature and term infants at 6 weeks of age, after adjusting for exposures (p = 0.027). Alpha-diversity varied between extremely premature (<28 weeks gestation) and very premature infants (≥28 but <32 weeks, p = 0.011), as well as between extremely and moderate-to-late premature infants (≥32 and <37 weeks, p = 0.004). Newborn antibiotic use among premature infants was associated with lower Bifidobacterium and Bacteroides abundance (p = 0.015 and p = 0.041).ConclusionGestational age at birth and early antibiotic exposure have significant effects on the premature infant gut microbiota.

Background The ability to determine severity of encephalopathy is crucial for early neuroprotective therapies and for predicting neurodevelopmental outcome. The objective of this study was to assess a novel brain state of newborn (BSN) trend to distinguish newborns with presence of hypoxic ischemic encephalopathy (HIE) within hours after birth and predict neurodevelopmental outcomes at 2 years of age. Method This is a prospective cohort study of newborns at 36 weeks’ gestation or later with and without HIE at birth. The Total Sanart Score (TSS) was calculated based on a modified Sarnat exam within 6 h of life. BSN was calculated from electroencephalogram (EEG) measurements initiated after birth. The primary outcome at 2 year of age was a diagnosis of death or disability using the Bayley Scales of Infant Development III. Results BSN differentiated between normal and abnormal neurodevelopmental outcomes throughout the entire recording period from 6 h of life. Additionally, infants with lower BSN values had higher odds of neurodevelopmental impairment and HIE. BSN distinguished between normal ( n  = 86) and HIE ( n  = 46) and showed a significant correlation with the concomitant TSS. Conclusion BSN is a sensitive real-time marker for monitoring dynamic progression of encephalopathy and predicting neurodevelopmental impairment. Impact This is a prospective cohort study to investigate the ability of brain state of newborn (BSN) trend to predict neurodevelopmental outcome within the first day of life and identify severity of encephalopathy. BSN predicts neurodevelopmental outcomes at 2 years of age and the severity of encephalopathy severity. It also correlates with the Total Sarnat Score from the modified Sarnat exam. BSN could serve as a promising bedside trend aiding in accurate assessment and identification of newborns who may benefit from additional neuroprotection therapies.

Background About 10–20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features. Methods Data were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z -score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation. Results Five machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706–0.72] in the Korean cohort and 0.696 [IQR: 0.609–0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z -score, KD clinical signs, or both did not considerably improve the median AUC in either cohort. Conclusions Using commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility. Impact We demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.