Population-based Cohort Of Children Research Articles

Prescriptions of respiratory medications in children aged 0–10 years: A longitudinal drug utilization study in the POMME database

IntroductionRespiratory tract disorders are common in children. However, there is no available data on the prescription of respiratory medications for children in France. This study aimed to provide an overview of medications for obstructive airway diseases prescriptions for children during the initial ten years of their lives within POMME, a French population-based cohort of children. Material and methodsThis longitudinal, population-based study used data from the French POMME birth cohort, comprising children born in Haute Garonne between July 2010 and June 2011. Anonymous medical information, including medication reimbursement data, was collected between ages 0 and 10 years. Exposure was defined as at least one prescription for respiratory medications (ATC code R03*), focusing on specific subclasses. Data were analyzed by age, season, and prescribing physicians' specialties. ResultsOut of 5956 children, 4951 (83.1 %) received respiratory medication prescriptions. Inhaled corticosteroids (ICSs) were the most prescribed (95.3 %), followed by short-acting β2-agonists (68.8 %). The number of prescriptions increased with age, except for ICSs alone, which peaked between 6 months and 2 years. The average number of prescriptions per child was relatively low. DiscussionThis study highlighted high prescription rates of respiratory medications in children under 10 years, with ICSs being the most prevalent. While these medications are primarily intended for asthma management, the findings suggested a significant proportion of off-label prescriptions, especially in young children. Further research and clinical guidance are warranted to ensure appropriate medication use in the pediatric population.

The incidence of pediatric dacryocystitis among a population-based cohort of infants with congenital nasolacrimal duct obstruction

PurposeTo report the incidence, clinical characteristics, and outcomes of acute dacryocystitis among a large, population-based cohort of children born with congenital nasolacrimal duct obstruction (CNLDO) over a 10-year period. MethodsThis multicenter retrospective, population-based cohort study included all patients diagnosed with acute dacryocystitis in a cohort of patients diagnosed with CNLDO before age 5 years in Olmsted County, Minnesota, United States of America from January 1, 1995, through December 31, 2004. ResultsOf 1,998 patients with CNLDO, there were 70 cases (36 female [(51%)]) of acute dacryocystitis during the study, yielding an incidence rate of 243 per 100,000 children (95% CI, 170-316). Mean age at diagnosis was 9.0 months. Patients who developed dacryocystitis were significantly less likely to be born via C-section (OR = 0.29, P = 0.009). Less than half of patients with dacryocystitis were treated with oral/intravenous antibiotics (46%), but whose who were had a significantly higher odds of requiring probing (OR = 8.50, P = 0.004). Spontaneous CNLDO resolution was significantly less likely to occur in patients diagnosed with acute dacryocystitis compared with those without (OR = 2.46, P = 0.001). The median age of spontaneous resolution in the dacryocystitis group (6.0 months) was significantly older than the uncomplicated CNLDO group (P = 0.012). ConclusionsPediatric acute dacryocystitis is an uncommon complication of CNLDO and is associated with both a lower likelihood of and older age at spontaneous resolution of CNLDO symptoms.

Child- and parent-related determinants for out-of-home care in a nationwide population with neurodevelopmental disorders: a register-based Finnish birth cohort 1997 study.

Neurodevelopmental disorders (NDDs) are among the most common health issues in childhood and adolescence. Psychiatric disorders are known to be overrepresented among children using child welfare services and placed in out-of-home care (OHC). Child- and parent-related determinants for OHC among a national population with NDDs were evaluated utilising longitudinal register data from the national Finnish Birth Cohort 1997 (n = 58,802) from birth to 18 years (1997-2015). The cohort members with NDDs (n = 5,143, 9% of total cohort) formed our study population. Based on their history of OHC, cohort members with NDD were categorised to OHC (n = 903) and non-OHC groups (n = 4,240). Of all cohort members with NDDs, 17.6% had a history of OHC. Within NDDs, a significant excess of ADHD diagnosis was observed in the OHC group compared to the non-OHC group (49% vs. 26%). The OHC group with NDDs was significantly characterised by having comorbid psychiatric diagnosis for conduct and oppositional disorders (adj. RR 2.21), substance use disorders (adj. RR 1.61) and depression and anxiety disorders (adj. RR 1.60). Of all parent-related determinants, the most prevailing in the OHC group compared to the non-OHC group, was social assistance received by parent (88% vs. 44.5%). The longer the period (in years) for received social assistance, the greater the likelihood for OHC (adj. RRs range from 2.41 for one year to 5.24 for over 4 years). Further, significantly associating determinants for OHC were parental psychiatric disorders (adj. RR 1.42) and parental death (adj. RR 1.23). Our findings from the population-based cohort of children and adolescents with NDDs highlight the importance of screening and assessment of family situation. Also, effective prevention and treating of comorbid psychiatric disorders, especially conduct and oppositional disorders is essential.

Place-Based Child Opportunity at Birth and Child Development from Infancy to Age 4

ObjectiveTo evaluate whether the children’s neighborhood quality, as a measure of place-based social determinants of health, is associated with the odds of developmental delay and developmental performance up to age 4 years. Study DesignMothers of 5702 children from the Upstate KIDS Study, a longitudinal population-based cohort of children born from 2008 through 2010, provided questionnaire data and a subset of 573 children participated in a clinic visit. The Child Opportunity Index 2.0 (COI) was linked to home census tract at birth. Probable developmental delays were assessed by the Ages and Stages Questionnaire© up to 7 times between 4 and 36 months, and developmental performance was assessed via the Battelle Developmental Inventory at age 4 years. ResultsIn unadjusted models, higher neighborhood opportunity was protective against developmental delays and was associated with slightly higher development scores at age 4. After adjusting for family-level confounding variables, ten-point higher COI (on a 100-point scale) remained associated with a lower odds of any developmental delay (OR = .966, 95%CI = .940-.992), and specifically delays in the personal-social domain (OR = .921, 95%CI = .886-.958), as well as better development performance in motor (B = 0.79, 95%CI = 0.11-1.48), personal-social (B = 0.64, 95%CI = 0.003-1.28), and adaptive (B = 0.69, 95%CI = 0.04-1.34) domains at age 4. ConclusionsCommunity-level opportunities are associated with some aspects of child development prior to school entry. A greater understanding of neighborhood quality may be helpful to pediatric providers to inform targeted developmental screening.

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting β2-agonists and the association inhaled corticosteroids/long-acting β2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

Effect of the COVID-19 pandemic on children: an analysis of the situation through a cross-sectional study

Amidst the COVID-19 pandemic in Vietnam, providing support for children has emerged as a significant challenge for social workers. However, there is a lack of research examining how social workers assess the pandemic's impact on children. In this study, we conducted a survey within a population-based cohort of children in Ho Chi Minh City, Vietnam. By employing the "Children’s Coping Strategies during COVID-19" scale, we evaluated the pandemic's multifaceted influence on children through the lens of the effectiveness of social work measures. The results revealed distinct and significant positive correlations between the impacts of COVID-19 on children, children’s coping strategies during COVID-19, the social work approach, and the effectiveness of the social work approach. Moreover, the impacts of COVID-19 on the effectiveness of the social work approach on children after the pandemic, encompassing aspects like ensuring primary care for children, personal intervention, discussions on the pandemic's impact on children's lives and activities, as well as school support, were all significantly and positively associated with the effectiveness of social work measures. Additionally, the analysis unveiled that social workers assessed the impact of the COVID-19 pandemic on Vietnamese children as yielding average effects. These findings underscore the significance of interdisciplinary support and rehabilitation for children grappling with the consequences of COVID-19. Nevertheless, for a more comprehensive understanding of the long-term effects, future longitudinal research is imperative. Please review the text for grammar and accuracy.

A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state

BackgroundIn children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. MethodsThe Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012–2017). Participants were 689 students in 4th grade (baseline; age=9.2 ± 0.4 years), and 647 students in 5th grade (age=10.5 ± 0.5 years). Nine salivary cortisol measures per child (2 awakening and 1 prior to bed for 3 sequential days) (n = 1336 child phenotype days; n = 7987 cortisol assays), 10 cytokines measured in morning and evening saliva samples (n = 202 child phenotype days), and lipids were measured. Clinical outcomes were blood pressure, weight and height (body mass index [BMI]; BMI = kg/m2), among others. FindingsUpon-waking cortisol levels were 0.28 ± 0.13 µg/dL, 30-minute post-waking 0.33 ± 0.15 µg/dL, and evening 0.08 ± 0.10 µg/dL. Salivary cytokine levels (n = 202) showed interleukins (IL) IL-1β and IL-8 were highest in early morning (upon awakening; AM), and IL-6 and tumor necrosis factor (TNF) TNF-α highest before bed (PM) (IL-1β AM > PM [−4.02 fold; p < 0.001]; IL-8 AM > PM [−1.36 fold; p < 0.001]; IL-6 AM < PM [+1.49 fold; p < 0.001]; TNF-α AM < PM [+1.73 fold; p = 0.03]. Regression modeling showed high morning cortisol was associated with high morning IL-1β (p = 3.82 ×10−6), but low evening IL-1β (p = 6.27 ×10−4). Regression modeling of BMI z-score as the response variable showed the expected significant relationships to high density lipoprotein (HDL) (negative; p < 0.001), mean arterial pressure (positive; p < 0.001), and morning cortisol (negative; p = 0.01) but only weak relationships to either evening cortisol (p = 0.1) or cytokine (positive; p = 0.02; from the model with smallest Rsquared) levels. InterpretationWe provide preliminary data on diurnal fluctuations of inflammatory cytokines in saliva in a population-based cohort of children. Correlation of morning and evening cortisol levels with inflammatory cytokines in the same saliva samples showed that high morning cortisol was associated with high morning IL-1β and low evening IL-1β. Future studies may test the hypothesis that strong diurnal cycling of IL-1β may serve as a homeostatic mechanism keeping the immune system in check, and that low morning cortisol (possible circadian misalignment) may lead to less stringent control of inflammatory networks.

Birth prevalence and characteristics of congenital corneal opacities.

To report the birth prevalence and natural history of congenital corneal opacities among a population-based cohort of children. The medical records of patients <5 years diagnosed with a congenital onset corneal opacity while residing in Olmsted County, Minnesota, from January 1, 1977, through December 31, 2016, were retrospectively reviewed. Fourteen patients were diagnosed with a congenital corneal opacity during the 40-year study period for a birth prevalence of 1 in 5188 live births. The mean age at diagnosis was 7.5 months (range 0-48 months) and 9 (64.3%) were males. Four patients had congenital glaucoma, 4 had limbal dermoids, 2 had sclerocornea, and 1 patient each had Descemet's tear from birth trauma, herpes simplex virus type 1 keratitis, corneal leukoma, and an undiagnosed scar. Six (42.8%) patients required treatment for their underlying corneal opacity including the four patients with congenital glaucoma. The other 8 (57.1%) patients had a clear central axis. Four (28.6%) of 14 patients required amblyopia therapy, and 4 (28.6%) developed strabismus. Four (28.6%) patients had associated systemic conditions. During a mean follow up of 5.4 years (range 1.3-27.0 years), the median best corrected visual acuity (BCVA) was logmar 0.16 (20/25) (range 20/20-hand motion) with one patient with unilateral BCVA less than 20/60 and one patient with bilateral BCVA less than 20/60. In this 40-year cohort, congenital corneal opacities were relatively rare and the result of a variety of disorders. Although amblyopia and strabismus occurred commonly, most patients had good visual outcomes.

Creating a population-based cohort of children born with and without congenital anomalies using birth data matched to hospital discharge databases in 11 European regions: Assessment of linkage success and data quality.

Linking routinely collected healthcare administrative data is a valuable method for conducting research on morbidity outcomes, but linkage quality and accuracy needs to be assessed for bias as the data were not collected for research. The aim of this study was to describe the rates of linking data on children with and without congenital anomalies to regional or national hospital discharge databases and to evaluate the quality of the matched data. Eleven population-based EUROCAT registries participated in a EUROlinkCAT study linking data on children with a congenital anomaly and children without congenital anomalies (reference children) born between 1995 and 2014 to administrative databases including hospital discharge records. Odds ratios (OR), adjusted by region, were estimated to assess the association of maternal and child characteristics on the likelihood of being matched. Data on 102,654 children with congenital anomalies were extracted from 11 EUROCAT registries and 2,199,379 reference children from birth registers in seven regions. Overall, 97% of children with congenital anomalies and 95% of reference children were successfully matched to administrative databases. Information on maternal age, multiple birth status, sex, gestational age and birthweight were >95% complete in the linked datasets for most regions. Compared with children born at term, those born at ≤27 weeks and 28-31 weeks were less likely to be matched (adjusted OR 0.23, 95% CI 0.21-0.25 and adjusted OR 0.75, 95% CI 0.70-0.81 respectively). For children born 32-36 weeks, those with congenital anomalies were less likely to be matched (adjusted OR 0.78, 95% CI 0.71-0.85) while reference children were more likely to be matched (adjusted OR 1.28, 95% CI 1.24-1.32). Children born to teenage mothers and mothers ≥35 years were less likely to be matched compared with mothers aged 20-34 years (adjusted ORs 0.92, 95% CI 0.88-0.96; and 0.87, 95% CI 0.86-0.89 respectively). The accuracy of linkage and the quality of the matched data suggest that these data are suitable for researching morbidity outcomes in most regions/countries. However, children born preterm and those born to mothers aged <20 and ≥35 years are less likely to be matched. While linkage to administrative databases enables identification of a reference group and long-term outcomes to be investigated, efforts are needed to improve linkages to population groups that are less likely to be linked.

Rates and predictors of visits to primary care physicians during and after treatment of childhood acute lymphoblastic leukemia: A population-based cohort study.

Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL). Children of age less than 18years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables. A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40-0.54; p<.0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2-1.6; p<.0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6-2.5; p<.0001). Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment.

Nutritional status and growth of children and adolescents with and without cerebral palsy in eastern Uganda: A longitudinal comparative analysis.

There is a need to understand the growth and burden of malnutrition in children with cerebral palsy (CP) in order to design appropriate inclusive nutrition strategies. We compared the nutritional status and four-year longitudinal growth of a population-based cohort of children and adolescents (C&A) with CP (n = 97; 2-17 years; 55/42 M/F), and an age and sex matched group without CP (n = 91; 2-17y; 50/41 M/F) in rural Uganda. The cohorts were assessed in 2015 and 2019 for weight, height, social demographic characteristics, and feeding related factors. Nutritional status was determined using the World Health Organization (WHO) Z-scores. Wilcoxon sign rank and Mann-Whitney tests were used to test within and between group differences. Multivariable linear regression was used to determine predictors of the change in growth. Approximately two thirds (62/97 (64%)) of C&A with CP were malnourished (with <-2SD in any of the WHO Z-scores), especially those with feeding difficulties (OR = 2.65; P = 0.032), and those who needed to be fed (OR = 3.8; P = 0.019). Both the CP and non-CP groups deviated negatively from the WHO reference growth curve for height, with a significantly slower growth in the CP group (median change score of height-for-age Z score (HAZ) between assessments = -0.80(-1.56, 0.31), p<0.01), than the non-CP group (median HAZ change score = -0.27(-0.92,0.34, p = 0.034). There was a statistically significant group difference in the median HAZ change score between the CP and non-CP groups (z = -2.21, p = 0.026). Severity of motor impairment measured by the Gross Motor Function Classification System (GMFCS-level) correlated negatively (r = -1.37,95%CI -2.67, -0.08) with the change in HAZ scores among the CP group. Children and adolescents with severe motor impairments exhibit an increased risk of malnutrition and growth retardation compared to their age matched peers without CP, which underscores the need to develop inclusive community-based nutrition strategies for children with cerebral palsy.

Developmental motor problems and health-related quality of life in 5-year-old children born extremely preterm: A European cohort study.

To measure the association between cerebral palsy (CP) and non-CP-related movement difficulties and health-related quality of life (HRQoL) among 5-year-old children born extremely preterm (<28 weeks gestational age). We included 5-year-old children from a multi-country, population-based cohort of children born extremely preterm in 2011 to 2012 in 11 European countries (n = 1021). Children without CP were classified using the Movement Assessment Battery for Children, Second Edition as having significant movement difficulties (≤5th centile of standardized norms) or being at risk of movement difficulties (6th-15th centile). Parents reported on a clinical CP diagnosis and HRQoL using the Pediatric Quality of Life Inventory. Associations were assessed using linear and quantile regressions. Compared to children without movement difficulties, children at risk of movement difficulties, with significant movement difficulties, and CP had lower adjusted HRQoL total scores (β [95% confidence interval] = -5.0 [-7.7 to -2.3], -9.1 [-12.0 to -6.1], and - 26.1 [-31.0 to -21.2]). Quantile regression analyses showed similar decreases in HRQoL for all children with CP, whereas for children with non-CP-related movement difficulties, reductions in HRQoL were more pronounced at lower centiles. CP and non-CP-related movement difficulties were associated with lower HRQoL, even for children with less severe difficulties. Heterogeneous associations for non-CP-related movement difficulties raise questions for research about mitigating and protective factors.

What is the role of puberty in the development of islet autoimmunity and progression to type 1 diabetes?

In many populations, the peak period of incidence of type 1 diabetes (T1D) has been observed to be around 10–14 years of age, coinciding with puberty, but direct evidence of the role of puberty in the development of T1D is limited. We therefore aimed to investigate whether puberty and the timing of its onset are associated with the development of islet autoimmunity (IA) and subsequent progression to T1D. A Finnish population-based cohort of children with HLA-DQB1-conferred susceptibility to T1D was followed from 7 years of age until 15 years of age or until a diagnosis of T1D (n = 6920). T1D-associated autoantibodies and growth were measured at 3- to 12-month intervals, and pubertal onset timing was assessed based on growth. The analyses used a three-state survival model. IA was defined as being either positive for islet cell antibodies plus at least one biochemical autoantibody (ICA + 1) or as being repeatedly positive for at least one biochemical autoantibody (BC1). Depending on the IA definition, either 303 (4.4%, ICA + 1) or 435 (6.3%, BC1) children tested positive for IA by the age of 7 years, and 211 (3.2%, ICA + 1)) or 198 (5.3%, BC1) developed IA during follow-up. A total of 172 (2.5%) individuals developed T1D during follow-up, of whom 169 were positive for IA prior to the clinical diagnosis. Puberty was associated with an increase in the risk of progression to T1D, but only from ICA + 1-defined IA (hazard ratio 1.57; 95% confidence interval 1.14, 2.16), and the timing of pubertal onset did not affect the association. No association between puberty and the risk of IA was detected. In conclusion, puberty may affect the risk of progression but is not a risk factor for IA.

Impact of the COVID-19 pandemic on children and adolescents: determinants and association with quality of life and mental health—a cross-sectional study

BackgroundThe medium-term impact of the COVID-19 pandemic on the wellbeing of children and adolescents remains unclear. More than 2 years into the pandemic, we aimed to quantify the frequency and determinants of having been severely impacted by the COVID-19 pandemic and estimate its impact on health-related quality of life (HRQoL) and mental health.MethodsData was drawn from a population-based cohort of children and adolescents, recruited between December 2021 and June 2022, in Geneva, Switzerland. The Coronavirus impact scale was used to assess the multidimensional impact of the pandemic on children through parent’s report. A score higher than one standard deviation above the mean was deemed a severe impact. Parents additionally reported about their offspring HRQoL and mental health with validated scales. Determinants of having been severely impacted were assessed with logistic models, as were the associations between having experienced a severe impact and poor HRQoL or mental health.ResultsOut of 2101 participants aged 2–17, 12.7% had experienced a severe pandemic impact. Having a lasting health condition, a pandemic-related worsening of lifestyle habits or an unfavorable family environment were associated with having been severely impacted by the pandemic, while a previous anti-SARS-CoV-2 infection was not. Participants who had experienced a severe pandemic impact were more likely to present poor HRQoL (aOR = 3.1; 95% CI 2.3–4.4) and poor mental health (aOR = 3.9; 95% CI 2.5–6.2).ConclusionThe COVID-19 pandemic may have persistent consequences on the wellbeing of children and adolescents, especially among those with health and family vulnerabilities.

Risk factors for cerebral palsy and movement difficulties in 5-year-old children born extremely preterm.

Motor impairment is common after extremely preterm (EPT, <28 weeks' gestational age (GA)) birth, with cerebral palsy (CP) affecting about 10% of children and non-CP movement difficulties (MD) up to 50%. This study investigated the sociodemographic, perinatal and neonatal risk factors for CP and non-CP MD. Data come from a European population-based cohort of children born EPT in 2011-2012 in 11 countries. We used multinomial logistic regression to assess risk factors for CP and non-CP MD (Movement Assessment Battery for Children - 2nd edition ≤5th percentile) compared to no MD (>15th percentile) among 5-year-old children. Compared to children without MD (n = 366), young maternal age, male sex and bronchopulmonary dysplasia were similarly associated with CP (n = 100) and non-CP MD (n = 224) with relative risk ratios (RRR) ranging from 2.3 to 3.6. CP was strongly related to severe brain lesions (RRR >10), other neonatal morbidities, congenital anomalies and low Apgar score (RRR: 2.4-3.3), while non-CP MD was associated with primiparity, maternal education, small for GA (RRR: 1.6-2.6) and severe brain lesions, but at a much lower order of magnitude. CP and non-CP MD have different risk factor profiles, with fewer clinical but more sociodemographic risk factors for non-CP MD. Young maternal age, male sex and bronchopulmonary dysplasia similarly increased risks of both cerebral palsy and non-cerebral palsy movement difficulties. Cerebral palsy was strongly related to clinical risk factors including severe brain lesions and other neonatal morbidities, while non-cerebral palsy movement difficulties were more associated with sociodemographic risk factors. These results on the similarities and differences in risk profiles of children with cerebral palsy and non-cerebral palsy movement difficulties raise questions for etiological research and provide a basis for improving the identification of children who may benefit from follow-up and early intervention.

Childhood exposure to non-persistent endocrine disrupting chemicals and multi-omic markers in a population-based child cohort

Childhood exposure to non-persistent endocrine disrupting chemicals and multi-omic markers in a population-based child cohort

Peripapillary Hyperreflective Ovoid Mass–like Structures (PHOMS) in Children: The Copenhagen Child Cohort 2000 Eye Study

To determine the prevalence of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in a population-based child cohort and to study their association with other optic nerve head features and myopia. Observational, population-based cohort study of 1407 children aged 11-12 years. Optical coherence tomography scans of optic nerve heads were graded for PHOMS, disc tilt, prelaminar hyperreflective lines, and scleral canal diameter and investigated for associated prenatal and ocular parameters. Children with optic disc drusen or optic disc edema were excluded. PHOMS were found in 8.9% of children. The location of PHOMS was predominantly in the superonasal section of the optic disc. Myopia and optic nerve head tilt were more common in children with PHOMS than in children without PHOMS (P < .001 and P < .001, respectively). Prelaminar hyperreflective lines were found in 17.9% of children with PHOMS compared to 7.3% of children without PHOMS (P < .001). Prelaminar hyperreflective lines with and without PHOMS were associated with a shorter axial length of the eye (P < .001). There were no prenatal factors associated with PHOMS. Prelaminar hyperreflective lines were associated with higher birth weight and continued maternal smoking during pregnancy (P=.01 and P=.02, respectively). PHOMS had a prevalence of 8.9% in healthy children without optic disc drusen or optic disc edema and was associated with increasing myopic refraction and the presence of a tilted optic nerve head and prelaminar hyperreflective lines. Given the high prevalence of PHOMS, they should not unreservedly be taken as evidence of optic neuropathy.

Redefining germline predisposition in children with molecularly characterized ependymoma: a population-based 20-year cohort

Ependymoma is the second most common malignant brain tumor in children. The etiology is largely unknown and germline DNA sequencing studies focusing on childhood ependymoma are limited. We therefore performed germline whole-genome sequencing on a population-based cohort of children diagnosed with ependymoma in Denmark over the past 20 years (n = 43). Single nucleotide and structural germline variants in 457 cancer related genes and 2986 highly evolutionarily constrained genes were assessed in 37 children with normal tissue available for sequencing. Molecular ependymoma classification was performed using DNA methylation profiling for 39 children with available tumor tissue. Pathogenic germline variants in known cancer predisposition genes were detected in 11% (4/37; NF2, LZTR1, NF1 & TP53). However, DNA methylation profiling resulted in revision of the histopathological ependymoma diagnosis to non-ependymoma tumor types in 8% (3/39). This included the two children with pathogenic germline variants in TP53 and NF1 whose tumors were reclassified to a diffuse midline glioma and a rosette-forming glioneuronal tumor, respectively. Consequently, 50% (2/4) of children with pathogenic germline variants in fact had other tumor types. A meta-analysis combining our findings with pediatric pan-cancer germline sequencing studies showed an overall frequency of pathogenic germline variants of 3.4% (7/207) in children with ependymoma. In summary, less than 4% of childhood ependymoma is explained by genetic predisposition, virtually restricted to pathogenic variants in NF2 and NF1. For children with other cancer predisposition syndromes, diagnostic reconsideration is recommended for ependymomas without molecular classification. Additionally, LZTR1 is suggested as a novel putative ependymoma predisposition gene.

Kidney outcomes in early adolescence following perinatal asphyxia and hypothermia-treated hypoxic-ischaemic encephalopathy

BackgroundAcute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007–2009 with a history of hypothermia-treated HIE.MethodsAt 10–12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI.ResultsForty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI.ConclusionRenal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited.

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy-not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy.