The 50 most-cited articles in Pediatric Research, 2023

BACKGROUND: In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear. METHODS: Infants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4-6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years. RESULTS: Of 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5-5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar…

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity.…

BACKGROUND: This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of intraventricular hemorrhage (IVH). METHODS: Four databases were searched for observational studies that were qualified using the Newcastle-Ottawa Scale. RESULTS: 37 studies involving 32,370 children were included. Compared to children without IVH, children with mild IVH had higher incidences of neurodevelopmental impairment (NDI), cerebral palsy (CP), motor/cognitive delay, hearing impairment and visual impairment, as well as lower scores of the mental development index (MDI) and psychomotor development (PDI). Moreover, compared to mild IVH, severe IVH increased susceptibilities of children to NDI, motor delay, CP, hearing impairment and visual impairment, with worse performances in MDI, PDI, motor score and IQ. Mild IVH was not associated with seizures or epilepsy. CONCLUSIONS: Adverse neurodevelopmental outcomes positively associated with the occurrence and severity of IVH in preterm or LBW infants,…

Transitional circulation is normally transient after birth but can vary markedly between infants. It is actually in a state of transition between fetal (in utero) and neonatal (postnatal) circulation. In the absence of definitive clinical trials, information from applied physiological studies can be used to facilitate clinical decision making in the presence of hemodynamic compromise. This review summarizes the peculiar physiological features of the circulation as it transitions from one phenotype into another in term and preterm infants. The common causes of hemodynamic compromise during transition, intact umbilical cord resuscitation, and advanced hemodynamic monitoring are discussed. IMPACT: Transitional circulation can vary markedly between infants. There are alterations in preload, contractility, and afterload during the transition of circulation after birth in term and preterm infants. Hemodynamic monitoring tools and technology during neonatal transition and utilization of bedside echocardiography during the neonatal transition are increasingly recognized. Understanding the…

BACKGROUND: Bifidobacterium infantis has special abilities to utilise human milk oligosaccharides. Hence we hypothesised that probiotic supplements containing B. infantis may confer greater benefits to preterm infants than probiotic supplements without B. infantis. METHODS: A systematic review with meta-analysis was conducted according to standard guidelines. We selected RCTs evaluating probiotics compared to placebo or no treatment in preterm and/or low birth weight infants. Probiotic effects on Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS) and Mortality were analysed separately for RCTs in which the supplemented probiotic product contained B. infantis and those that did not contain B. infantis. RESULTS: 67 RCTs were included (n = 14,606), of which 16 used probiotics containing B. infantis (Subgroup A) and 51 RCTs did not (Subgroup B) Meta-analysis of all RCTs indicated that probiotics reduced the risk of NEC, LOS, and mortality. The subgroup meta-analysis demonstrated greater reduction in the incidence of NEC in subgroup A than subgroup B [(relative risk in subgroup A:…

BACKGROUND: Ketogenic diet (KD) refers to any diet in which food composition induces a ketogenic state of human metabolism. OBJECTIVE: To assess short- and long-term efficacy, safety, and tolerability of KD [classic KD and modified Atkins diet (MAD)] in childhood drug-resistant epilepsy (DRE) and to investigate the effect of KD on electroencephalographic (EEG) features of children with DRE. METHODS: Forty patients diagnosed with DRE according to International League Against Epilepsy were included and randomly assigned into classic KD or MAD groups. KD was initiated after clinical, lipid profile and EEG documentation, and regular follow-up was done for 24 months. RESULTS: Out of 40 patients with DRE, 30 completed this study. Both classic KD and MAD were effective in seizure control as 60% in classic KD group and 53.33% in MAD group became seizure free, and the remaining showed ≥50% seizure reduction. Lipid profile remained within acceptable levels throughout the study period in both groups. Adverse effects were mild and managed medically with an improvement of growth parameters and…

Abstract Introduction Neonatal bronchopulmonary dysplasia (BPD) is associated with lifelong respiratory and neurological sequalae. Prediction models could identify infants at greatest risk of BPD and allow targeted preventative strategies. We performed a systematic review and meta-analysis with external validation of identified models. Methods Studies using predictors available before day 14 of life to predict BPD in very preterm infants were included. Two reviewers assessed 7,628 studies for eligibility. Meta-analysis of externally validated models was followed by validation using 62,864 very preterm infants in England and Wales. Results 64 studies using 53 prediction models were included totalling 274,407 infants (range 32–156,587/study). 35 (55%) studies predated 2010; 39 (61%) were single-centre studies. 46 (87%) models were developed for the first week of life. Overall, 97% of studies had a high risk of bias, especially in the analysis domain. Internal (25%) and external (30%) validation were performed infrequently in the 44 model derivation studies. Following meta-analysis of…

BACKGROUND: Early detection of cognitive disability is challenging. We assessed the domain-specific, concurrent validity of the ages and stages questionnaire (ASQ-3) and the Bayley Scales of Infant and Toddler Development (BSID-III), and their ability to predict cognitive delay at school age. METHODS: Within a longitudinal birth cohort study, a nested cohort of children was assessed using ASQ-3 and BSID-III at 24 months, and at 5 years using the Kaufmann brief IQ test (KBIT). RESULTS: 278 children were assessed using BSID-III and ASQ-3 at 24-months; mean(SD) BW = 3445(506) grams, M:F ratio=52:48. ASQ-3 had reasonable predictive ability (AUROC, p value, sensitivity:specificity) of same domain delay for motor (0.630, p = 0.008, 50%:76.1%) and language (0.623, p = 0.010, 25%:99.5%) at 2 years, but poor ability to detect cognitive delay compared to BSID-III (0.587, p = 0.124, 20.7%/96.8%;). 204/278 children were assessed at 5 years. BSID-III language and cognition domains showed better correlation with verbal and nonverbal IQ (R = 0.435, p < 0.001 and 0.388, p < 0.001 respectively).…

BACKGROUND: The first-pass meconium has been suggested as a proxy for the fetal gut microbiota because it is formed in utero. This systematic review and cohort study investigated how pre- and perinatal factors influence the composition of the meconium microbiota. METHODS: We performed the systematic review using Covidence by searching PubMed, Scopus, and Web of Science databases with the search terms "meconium microbiome" and "meconium microbiota". In the cohort study, we performed 16 S rRNA gene sequencing on 393 meconium samples and analyzed the sequencing data using QIIME2. RESULTS: Our systematic review identified 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition in relation to subsequent health of infants but gave only limited comparative evidence regarding factors related to the composition of the meconium microbiota. The cohort study pointed to a low-biomass microbiota consisting of the phyla Firmicutes, Proteobacteria and Actinobacteriota and the genera Staphylococcus, Escherichia-Shigella and Lactobacillus, and indicated that…

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…

Abstract 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)…

BACKGROUND: Poor literacy can impact achieving optimal health outcomes. The aim of this project was to assess the readability of parent information leaflets (PILs). METHODS: A single-centre study using paediatric PILs. Five readability tests were applied (Gunning Fog Index (GFI), Simple Measure of Gobbledygook (SMOG), Flesch Kincaid Grade Level (FKGL), Coleman-Liau Index (CLI) and Automated Readability Index (ARI)). Results were compared to standards and by subtype. RESULTS: A total of 109 PILs were obtained; mean (±SD) number of characters was 14,365 (±12,055), total words 3066 (±2541), number of sentences 153 (±112), lexical density 49 (±3), number of characters per word 4.7 (±0.1), number of syllables per word 1.6 (±0.1) and number of words per sentence 19.1 (±2.5). The Flesch reading ease score was 51.1 (±5.6), equating to reading age 16-17 years. The mean PIL readability scores were GFI (12.18), SMOG (11.94), FKGL (10.89), CLI (10.08) and ARI (10.1). There were 0 (0%) PILs classed as easy (score <6), 21 (19%) mid-range (6-10) and 88 (81%) were difficult (>10). They were…

BACKGROUND: Studies on mNGS application in pediatric oncology patients, who are at high risk of infection, are quite limited. METHODS: From March 2020 to June 2022, a total of 224 blood samples from 195 pediatric oncology patients who were suspected as bloodstream infections were enrolled in this study. Their clinical and laboratory data were retrospectively reviewed, and the diagnostic performance of mNGS was assessed. RESULTS: Compared to the reference tests, mNGS showed significantly higher sensitivity (89.8% vs 32.5%, P < 0.001) and clinical agreement (76.3% vs 51.3%, P < 0.001) in detecting potential pathogens and distinguishing BSI from non-BSI. Especially, mNGS had an outstanding performance for virus detection, contributing to 100% clinical diagnosed virus. Samples from patients with neutropenia showed higher incidence of bacterial infections (P = 0.035). The most identified bacteria were Escherichia coli, and the overall infections by gram-negative bacteria were significantly more prevalent than those by gram-positive ones (90% vs 10%, P < 0.001). Overall, mNGS had an…

BACKGROUND: The safety of coronavirus disease 2019 (COVID-19) vaccines during pregnancy is a particular concern. Here, we addressed the neonatal outcomes after maternal vaccination of COVID-19 during pregnancy. METHODS: We systematically searched PubMed, EMBASE, and the WHO COVID-19 Database for studies on neonatal outcomes after maternal COVID-19 vaccination from inception to 3 July 2022. Main neonatal outcomes were related to preterm, small for gestation (SGA), NICU admission, low Apgar score at 5 min (<7), and additional neonatal outcomes such as gestation <34 weeks, low birth weight and some neonatal morbidity were all also analyzed. RESULTS: A total of 15 studies were included. We found that maternal vaccination during pregnancy was related to the reduction rates of Preterm, SGA, Low Apgar score at 5 min (<7). In addition, there was no evidence of a higher risk of adverse neonatal outcomes after maternal vaccination of COVID-19 during pregnancy, including NICU admission, preterm birth with gestation <34 weeks, low birth weight, very low birth weight, congenital anomalies, and…

The twenty-first century has been marked by a surge in viral epidemics and pandemics, highlighting the global health challenge posed by emerging and re-emerging pediatric viral diseases. This review article explores the complex dynamics contributing to this challenge, including climate change, globalization, socio-economic interconnectedness, geopolitical tensions, vaccine hesitancy, misinformation, and disparities in access to healthcare resources. Understanding the interactions between the environment, socioeconomics, and health is crucial for effectively addressing current and future outbreaks. This scoping review focuses on emerging and re-emerging viral infectious diseases, with an emphasis on pediatric vulnerability. It highlights the urgent need for prevention, preparedness, and response efforts, particularly in resource-limited communities disproportionately affected by climate change and spillover events. Adopting a One Health/Planetary Health approach, which integrates human, animal, and ecosystem health, can enhance equity and resilience in global communities. IMPACT: We…

BACKGROUND: To describe pediatric Produce Prescription (PRx) interventions and their study designs, outcomes, and opportunities for future research. METHODS: A scoping review framework was used to describe PRx interventions published between January 2000 and September 2023. Articles from online databases were uploaded into Covidence. Data on study characteristics, outcomes of interest (health, food insecurity (FI), nutritional and culinary efficacy, and fruit and vegetable (F/V) consumption), and feasibility were extracted. The Mixed Methods Appraisal Tool (MMAT) was used for quality assessment. RESULTS: 19 articles met inclusion criteria. Ten studies were quantitative, five were qualitative, and four used mixed-methods. Interventions included food vouchers (n = 14) or food box/pantries (n = 5). Four studies allowed food items in addition to F/Vs. Six studies measured changes in FI and five reported a statistically significant decrease. Seven studies measured changes in F/V consumption and five reported a statistically significant increase. One study reported a statistically…

BACKGROUND: Approximately 50% of all neonatal endotracheal intubation attempts are unsuccessful and associated with airway injury and cardiorespiratory instability. The aim of this study was to describe intubation practice at a high-risk Neonatal Intensive Care Unit (NICU) and identify factors associated with successful intubation at the first attempt. METHODS: Retrospective cohort study of all infants requiring intubation within the Royal Children's Hospital NICU over three years. Data was collected from the National Emergency Airway Registry for Neonates (NEAR4NEOS). Outcomes were number of attempts, level of operator training, equipment used, difficult airway grade, and clinical factors. Univariate and multivariate analysis were performed to determine factors independently associated with first attempt success. RESULTS: Three hundred and sixty intubation courses, with 538 attempts, were identified. Two hundred and twenty-five (62.5%) were successful on first attempt, with similar rates at subsequent attempts. On multivariate analysis, increasing operator seniority increased the…

BACKGROUND: The aim was to study whether non-combustible nicotine (Swedish snuff) use in pregnancy is associated with elevated risk of post neonatal mortality, Sudden Infant Death Syndrome (SIDS), and Sudden Unexpected Infant Death (SUID) and to study how cessation before the antenatal booking influenced these risks. METHODS: This was a population-based register study of all infants with information on tobacco exposure in early pregnancy born in Sweden 1999-2019, n = 2,061,514. Self-reported tobacco use in early pregnancy was categorized as nonuse, snuff use, and moderate and heavy smoking. Multiple logistic regression models were used to estimate crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. The risks of snuff use and moderate smoking were of similar magnitude. Heavy smoking was associated with the highest risks. Cessation of smoking and snuff use before the antenatal booking was associated with lower risks of SIDS and SUID compared to that of…

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely…

BACKGROUND: The composition of the gut fungal microbiome, mycobiome, is likely associated with human health. Yet, the development of gut mycobiome is poorly understood in infants and children. Here we investigate how perinatal events influence the development of gut mycobiome. METHODS: In this prospective cohort study of 140 infants, we used ITS gene sequencing of fecal samples from birth to the age of 18 months. We compared gut mycobiome composition according to delivery mode and exposure to intrapartum antibiotics during vaginal delivery. RESULTS: At birth, gut mycobiome were dominated by the genus Candida, at 6-month stool samples by Malassezia and Cystofilobasidium, and the 18-month stool samples by Trichosporon and unidentified fungi. Perinatal factors altered mycobiome. At 18 months, gut mycobiome of infants born vaginally consisted mostly of Trichosporon (32%) and unidentified fungi (31%), while those born via Cesarean section delivery samples had mycobiome dominated by Saccharomyces (50%). At the age of 18 months, those exposed to intrapartum antibiotics had mycobiome…

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics. RESULTS: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child,…

BACKGROUND: ), by sociodemographic factors among a diverse sample of 10-to-14-year-old adolescents in the US. METHODS: over the course of 21 days. RESULTS: ). We found effect modification by household income for Black adolescents and by sex for Asian adolescents. CONCLUSIONS: , physical activity guidelines should focus on key populations and adopt strategies optimized for adolescents from diverse backgrounds. IMPACT: Sociodemographic disparities in physical activity have been documented but mostly rely on self-reported data, which can be limited by reporting and prevarication bias. In this demographically diverse sample of 10-14-year-old early adolescents in the U.S., we found notable and nuanced sociodemographic disparities in Fitbit steps per day. More daily steps were recorded for male versus female sex, Black versus White race, heterosexual versus sexual minority, >$100,000 versus <$25,000 household income, and having married/partnered versus unmarried/unpartnered parents. We found effect modification by household income for Black adolescents and by sex for Asian adolescents.

BACKGROUND: Energy drinks (EDs) are popular beverages among minors. To date, clinical studies investigating ED-induced effects on the pediatric cardiovascular system are sparse. This study aimed to investigate the effects of a single, bodyweight-adjusted ED dosage on 24-h ambulatory blood pressure monitoring (ABPM) in healthy children and adolescents. METHODS: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants received a single, bodyweight-adjusted ED amount or a placebo drink on 2 consecutive days at similar morning hours. Twenty-four-hour ABPM was assessed via an automated oscillometric blood pressure device after beverage consumption on both study days. RESULTS: A total of 17 healthy children and teenagers (13.90 (12.29-17.89) years) were included in the final analysis. The ED consumption led, compared to the placebo intake, to a significantly higher 24-h systolic (115.90 (110.22-118.04) vs. 110.64 (108.09-115.45) mmHg, p = 0.013) and diastolic blood pressure (66.08 (64.20-68.32) vs. 62.63 (61.40-66.46) mmHg, p = 0.005).…