New Cohort Of Children Research Articles

Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial

ObjectivesTo validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. MethodsProspective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48–72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. ResultsA total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48–72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3–6) versus 3 (IQR 3–6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, −0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DiscussionWe validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

Перинатальні аспекти порушень раннього неонатального періоду в дітей при COVID-19, перенесеному матір’ю під час вагітності

through various mechanisms: increased rates of preterm birth, placental infection that can disrupt placental-fetal exchange, and through transmission of the virus in utero, during childbirth or after birth. Purpose - to determine the characteristics of the state of newborns and the neonatal period, depending on the severity of the mother’s illness with COVID-19. Materials and methods. Under observation were 14 newborns (group 1), whose mothers were ill with severe COVID-19 and needed intensive care in the department of anesthesiology and intensive care, and 46 children from mothers with moderate COVID-19, who were treated in the infectious diseases and obstetrics department (group 2). Results. In mothers with COVID-19, especially when the disease is severe, the fetus is exposed to direct and indirect negative effects of a viral infection, which is confirmed by signs of placental insufficiency in the vast majority of pregnant women (71.4%) and its clinical manifestations in the form of distress and fetal growth retardation (50.0% and 35.7%, respectively), placental dysfunction was confirmed pathohistologically. Dangerous for the fetus are oligohydramnios in 50.0% of women up to ahydramnios (14.3%), preeclampsia (14.3%), caesarean section (57.1%), premature rupture of fruit membranes (14.3%) and preterm birth (28.0%). 42.9% of children are born in a state of asphyxia, with 14.3% having severe asphyxia, 35.7% of children were born weighing less than 2500 g. A positive test for COVID-19 was observed in 7.1% of newborns. 21.4% of children were diagnosed with pneumonia, 35.7% had respiratory distress syndrome. Children from mothers with COVID-19 have a high incidence of maladaptation syndromes (64.3%). In addition to RDS, there was a high incidence of neurological disorders (57.1%) in the form of a syndrome of depression, gastrointestinal syndrome (50.0%), thermoregulation disorders (42.9%), and 35.7% had hypoglycemic and hemorrhagic syndromes. Necrotizing enterocolitis was diagnosed in children with pneumonia on the 5-7th day of life. Conclusions. Disorders in children from mothers with COVID-19 at birth and a high incidence of maladjustment syndromes, the risk of health and cognitive impairment in the future necessitate further scientific research, active follow-up of this new cohort of children and the development of prevention and rehabilitation measures. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Developmental and symptom profiles in early-onset psychosis

Psychotic disorders in children are more heterogeneous than is captured by categorical diagnoses. In a new cohort of children and adolescents, we evaluated the relationships among age at onset (AAO), clinical symptoms and developmental impairments. Patients with schizophrenia and other “spectrum” psychotic diagnoses (N = 88; AAO 6–17, mean 12.6) were evaluated with diagnostic interviews, a new clinical scale (Lifetime Dimensions of Psychosis Scale-Child and Adolescent), and neuropsychological and medical evaluations. Key findings were replicated in an adult cohort of 2420 cases, including 127 with retrospective AAO<13. Factor and cluster analyses were carried out to identify clinical profiles. Five clinical factors were identified in each cohort: Positive, Bizarre Positive, Negative/Formal Thought Disorder, Depression and Mania. Earlier AAO predicted severity of bizarre positive symptoms in children and of bizarre and other symptoms in adults. Four clinical clusters in the child cohort were characterized by: more severe bizarre positive symptoms (N = 31); negative symptoms (N = 15); premorbid autism spectrum features and developmental delay (N = 12); and depressive symptoms with heterogeneous diagnoses and mild positive/negative symptoms (N = 25). Previous factor-analytic studies of childhood psychosis did not specifically consider bizarre positive symptoms. Here, bizarre positive symptoms emerged as clinical markers of severe, childhood-onset psychosis similar to adult schizophrenia. The four clusters are clinically meaningful and useful for treatment planning and potentially for biological research. Childhood-onset cases are rare and thus difficult to study, but additional, larger cohorts may be useful in dissecting the biological and developmental heterogeneity of psychotic disorders.

Developing a new cohort of children born to women who used opioids in pregnancy using administrative data: insights into cohort creation and early results

Background with rationaleChildren born to opioid-dependent mothers are at a developmental disadvantage from pre-birth. They are additionally affected by the mother’s compromised ability to recognise and respond to the infant’s cues. Development is often compounded by environmental factors. Research to date has primarily focused on early infancy and small, clinical samples. This group is difficult to follow-up using traditional methods due to chaotic home environments, housing instability and parent-child separation. The use of administrative data circumnavigates such difficulties, allowing follow-up of children over longer periods, even when removed from the birth parent.&#x0D; Main AimThis paper will describe the complex creation of a cohort of children born to opioid-dependent women, using administrative data. It will also describe early results about pregnancy and neonatal outcomes.&#x0D; Methods/ApproachData were pooled from women who gave birth between 2007 and 2017 using five datasets (c.5,000 women): women who were recorded as using heroin, street methadone or opioid substitution therapy (OST) on the Drugs Misuse Database, or on OST prescription records; women admitted to hospital, or psychiatric care, for an opioid related reason; and/or women whose children were recorded as having Neonatal Abstinence Syndrome (NAS). Data on children’s neonatal outcomes will be described, including birth weight and gestation, congenital abnormalities, neonatal death and NAS treatment. Models will be fitted to investigate the associations between possible teratogenicity of prenatal opioids and developmental outcomes.&#x0D; ResultsThe development of this cohort using administrative data sources has been complex, requiring five different datasets to ensure all women of interest are captured. Descriptive results on outcomes will be available in the Autumn.&#x0D; ConclusionThis administrative data study demonstrates the value of using linked data sources to enhance our knowledge of the trajectories of this vulnerable group of children, and the additional support that they, and their carers, may require.

Are Schools (Still) a Great Equalizer? Replicating a Summer Learning Study Using Better Test Scores and a New Cohort of Children

When do children become unequal in reading and math skills? Some research claims that inequality grows mainly before school begins. Some research claims that schools cause inequality to grow. And some research—including the 2004 study “Are Schools the Great Equalizer?”—claims that inequality grows mainly during summer vacations. Unfortunately, the test scores used in the Great Equalizer study suffered from a measurement artifact which exaggerated estimates of inequality growth. In addition, the Great Equalizer study is dated and its participants are no longer school-aged. In this article, we replicate the Great Equalizer study using better test scores in both the original data and in a newer cohort of children. When we use the new test scores, we find that variance is substantial at the start of kindergarten, and does not grow, but actually shrinks, over the next two to three years. This finding, which was not evident in the original Great Equalizer study, implicates the years before kindergarten as the primary source of inequality in elementary reading and math. Total score variance grows during most summers and shrinks during most school years, suggesting that schools reduce inequality overall. Changes in inequality are small after kindergarten and do not replicate consistently across grades, subjects, or cohorts. That said, socioeconomic gaps tend to shrink during the school year and grow during the summer, while the black-white gap tends to follow the opposite pattern.

T30 - The Role Of Circulating Micrornas As Possible Biomarkers Predicting Response And Adverse Events In Depressed And Anxious Children And Adolescents Treated With Fluoxetine

Background Depression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, it has been reported that 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with serious adverse events (AE), including activation symptoms, manic switch and increased suicidal behavior. These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a black-box warning. Currently there is no way of knowing in advance who of the patients will respond or develop AE. The purpose of the current study is to examine the role of circulating small non-coding RNA's (ncRNA's) as a promising candidate biomarker for SSRI treatment response and AE in children and adolescents treated for depression and anxiety disorders. Methods Eighty patients who met DSM-IV criteria for major depressive disorder (MDD) or anxiety disorders participated in the study. Their age ranged from 6 to 18 (14.12 ± 2.30) years. The patients were treated with fluoxetine 20-40 mg/day for 8 weeks. Psychiatric evaluation was conducted using several standardized diagnostic instruments. The changes in depressive and anxiety symptoms from baseline to 8 weeks were assessed, and remitters and non-responders were compared. Suicidal events, as per convention in pharmacological trials, were defined as either a suicide attempt or an onset or worsening in suicidal ideation. Activation was assessed using a new scale devised by our group for the project and mania by the Young Mania Rating Scale. Blood samples from all the participants were collected before treatment initiation and after eight weeks. RNA was purified using QIAGEN kit and libraries were prepared for sequencing using the Illumina TruSeq Small RNA Library Preparation Kit. miRBase based quantification of miRNAs was carried out on each sample. Samples with less than 1,000,000 miRNA reads were excluded. DeSeq2 was performed for statistical analysis. Results The overall response rate was 67%. Seventeen children and adolescents (21%) responded with moderate or severe AE. In total 86 samples were analyzed. Ten differentially expressed miRNA’s were found between the responders with no AE vs. non-responders/responders + moderate or severe AE. Discussion Ongoing studies: A recruitment of a new cohort of children for validation of the finding in the first cohort will follow. The differentially regulated small ncRNA's will form the basis of a study in an animal model of juvenile depression which will hopefully enable us to gain insights into the mechanism of how these models are involved in the biology of response to treatment and perhaps even of juvenile depression.

Kid-Short Marfan Score (Kid-SMS) Is a Useful Diagnostic Tool for Stratifying the Pre-Test Probability of Marfan Syndrome in Childhood.

Due to age dependent organ manifestation, diagnosis of Marfan syndrome (MFS) is a challenge, especially in childhood. It is important to identify children at risk of MFS as soon as possible to direct those to appropriate treatment but also to avoid stigmatization due to false diagnosis. We published the Kid-Short Marfan Score (Kid-SMS) in 2012 to stratify the pre-test probability of MFS in childhood. Hence we now evaluate the predictive performance of Kid-SMS in a new cohort of children. We prospectively investigated 106 patients who were suspected of having MFS. At baseline, children were examined according to Kid-SMS. At baseline and follow-up visit, diagnosis of MFS was established or rejected using standard current diagnostic criteria according to the revised Ghent Criteria (Ghent-2). At baseline 43 patients were identified with a risk of MFS according to Kid-SMS whereas 21 patients had Ghent-2 diagnosis of MFS. Sensitivity was 100%, specificity 77%, negative predictive value 100% and Likelihood ratio of Kid-SMS 4.3. During follow-up period, three other patients with a stratified risk for MFS were diagnosed according to Ghent-2. We confirm very good predictive performance of Kid-SMS with excellent sensitivity and negative predictive value but restricted specificity. Kid-SMS avoids stigmatization due to diagnosis of MFS and thus restriction to quality of life. Especially outpatient pediatricians and pediatric cardiologists can use it for primary assessment.

Prospective Validation of a Risk Prediction Model for Severe Sepsis in Children With Cancer and High-risk Febrile Neutropenia

We previously created a risk prediction model for severe sepsis not clinically apparent during the first 24 hours of hospitalization in children with high-risk febrile neutropenia (HRFN), which identified 3 variables, age ≥ 12 years, serum C-reactive protein (CRP) ≥ 90 mg/L and interleukin-8 ≥ 300 pg/mL, evaluated at the time of admission and at 24 hours of hospitalization. The combination of these 3 variables identified a risk for severe sepsis ranging from 8% to 73% with a relative risk of 3.15 (95% confidence interval: 1.1-9.06). The aim of this study was to validate prospectively our risk prediction model for severe sepsis in a new cohort of children with cancer and HRFN. Predictors of severe sepsis identified in our previous model (age, CRP and interleukin-8) were evaluated at admission and at 24 hours of hospitalization in a new cohort of children with HRFN between April 2009 and July 2011. Diagnosis of severe sepsis, not clinically apparent during the first 24 hours of hospitalization, was made after discharge by a blind evaluator. A total of 447 HRFN episodes were studied, of which 76 (17%) had a diagnosis of severe sepsis. The combination of age ≥ 12 years, CRP ≥ 90 mg/L and interleukin-8 ≥ 300 pg/mL at admission and/or at 24 hours in the new cohort identified a risk for severe sepsis ranging from 7% to 46% with an RR of 6.7 (95% CI: 2.3-19.5). We validated a risk prediction model for severe sepsis applicable to children with HRFN episodes within the first 24 hours of admission. We propose to incorporate this model in the initial patient assessment to offer a more selective management for children at risk for severe sepsis.

Approaching the prevalence of the full spectrum of fetal alcohol spectrum disorders in a South African population-based study.

The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) were determined in this fourth study of first-grade children in a South African community. Active case ascertainment methods were employed among 747 first-grade pupils. The detailed characteristics of children within the continuum of FASD are contrasted with randomly selected, normal controls on (i) physical growth and dysmorphology; (ii) cognitive/behavioral characteristics; and (iii) maternal risk factors. The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world. The prevalence (per 1,000) is as follows: fetal alcohol syndrome (FAS)-59.3 to 91.0; partial fetal alcohol syndrome (PFAS)-45.3 to 69.6; and alcohol-related neurodevelopmental disorder (ARND)-30.5 to 46.8. The overall rate of FASD is therefore 135.1 to 207.5 per 1,000 (or 13.6 to 20.9%). Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for understanding the full spectrum of FASD in a community. The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total (mean) dysmorphology scores of the children: FAS = 18.9; PFAS = 14.3; ARND = 12.2; and normal controls, alcohol exposed = 8.2 and unexposed = 7.1. Documented drinking during pregnancy is significantly correlated with verbal (r = -0.253) and nonverbal ability (r = -0.265), negative behaviors (r = 0.203), and total dysmorphology score (r = 0.431). Other measures of drinking during pregnancy are significantly associated with FASD, including binge drinking as low as 3 drinks per episode on 2 days of the week. High rates of specific diagnoses within FASD were well documented in this new cohort of children. FASD persists in this community. The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD.

Low-level Pb and cardiovascular responses to acute stress in children: The role of cardiac autonomic regulation

Objective A number of studies suggest that Pb exposure increases cardiovascular disease risk in humans. As a potential mechanism for this effect, we recently reported a significant association between early childhood Pb levels and cardiovascular response to acute stress. The current study considers the association between current Pb levels and the autonomic nervous system activation pattern underlying the cardiovascular response to stress in a new cohort of children. Methods We assessed blood Pb levels as well as cardiovascular responses to acute stress in 9–11 year old children ( N = 140). Sympathetic activation (measured with pre-ejection period) and parasympathetic activation (measured with high frequency heart rate variability) were also assessed. Results In a sample with very low levels of blood Pb ( M = 1.01 μg/dL), we found that increasing blood Pb was associated with coinhibition of sympathetic and parasympathetic activation in response to acute stress. In addition, increasing Pb levels were associated with the hemodynamic stress response pattern typical of coinhibition — significantly greater vascular resistance and reduced stroke volume and cardiac output. Conclusions Blood Pb levels were associated with significant autonomic and cardiovascular dysregulation in response to acute psychological stress in children. Moreover, these effects were significant at Pb levels considered to be very low and notably well below the 10 μg/dL, the Centers for Disease Control and Prevention definition of an elevated blood Pb level. The potential for autonomic dysregulation at levels of Pb typical for many US children would suggest potentially broad public health ramifications.

Validation of Two Prognostic Models Predicting Outcome at Two Years after Diagnosis in a New Cohort of Children with Epilepsy: The Dutch Study of Epilepsy in Childhood

To validate two prognostic models for childhood-onset epilepsy designed to predict a terminal remission of <6 months at 2 years after diagnosis in children referred to the hospital. A hospital-based cohort of children with newly diagnosed epilepsy was recruited and followed up for 2 years to validate previously developed models. One model was based on variables collected at intake, and the other was based on intake variables plus variables collected during the first 6 months of follow-up. The accuracy of both models was estimated by measuring the area under the receiver-operant-characteristic curves (ROC area). The ROC area of the model developed with intake variables was 0.69 [95% confidence interval (CI), 0.64-0.74] for the original cohort and 0.62 (95% CI, 0.55-0.69) for the validation cohort. The best combination of sensitivity and specificity for the original cohort was 61.6% and 69.1%, whereas it was 60.0% and 61.4% for the validation cohort. For the model with intake and 6-month variables combined, the ROC area was 0.78 (95% CI, 0.73-0.82) for the original cohort and 0.71 (95% CI, 0.64-0.78) for the validation cohort. The sensitivity and specificity were 72.6% and 73.1%, respectively, for the original cohort and 67.4% and 60.2%, respectively, for the validation cohort. Although both models predict outcome better than chance, they are insufficiently accurate to be of practical value. Both models performed marginally less well with the validation cohort than with the original cohort, but in both instances, the model based on intake and 6-month variables was more accurate.

Outcomes of an emergent literacy intervention from Head Start through second grade.

The present investigation is a replication of an emergent literacy intervention in Head Start with a new cohort of children and includes a follow-up of both the original cohort and the replication cohort through the end of 2nd grade. Positive effects at the end of Head Start obtained in the original study were replicated, and effects on emergent literacy skills in both cohorts were maintained through the end of kindergarten. Effects of the emergent literacy intervention did not generalize to literacy outcomes at the end of 1st and 2nd grades. Growth in emergent literacy skills and literacy skills from year to year was strongly influenced by variation in the Head Start centers and school districts attended by children in the sample. Although children in the sample began formal reading instruction with relatively low levels of emergent literacy skills, they showed substantial gains with respect to national norms by the end of 2nd grade.