Years Of Follow-up In Children Research Articles

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015–2020)

ObjectiveTo assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. MethodsAs part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. ResultsOut of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SignificanceThese findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Early GH Treatment Is Effective and Well Tolerated in Children With Turner Syndrome: NordiNet® IOS and Answer Program.

Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature. This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS. Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905). A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was -0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] -1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]). GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.

OP34 Enteral Nutrition Compared with Steroids in Children with Crohn’s Disease – In Israel: a nationwide study from the epi-IIRN

Abstract Background Studies have shown that exclusive enteral nutrition (EEN) treatment is as effective to corticosteroids (CS) for induction of remission in pediatric Crohn's disease (CD) with fewer side effects, but long-term outcome data are scarce. In this nationwide study we aimed to compare the risk of complicated disease course (CDC) after 2 years of follow-up in children with CD receiving EEN or CS as induction therapy. Methods Data of children diagnosed with CD in the epi-IIRN cohort between 2005-2020 were retrieved from the 4 Israeli Health-Maintenance-Organizations covering 98% of the population. The primary outcome was CDC defined as CD-related surgery, steroid-dependency, or need for more than one biologic class during 2 years post-diagnosis. Secondary outcomes included hospitalizations, and the use of biologics (any). Additionally, anthropometrics, labs reflecting nutrition (i.e., Alb and HGB), and growth were assessed at repeated visits until 2 years thereafter. To account for confounding by indication bias, we compared children with similar baseline characteristics based on Propensity Score (PS) individual matching. Time to CDC outcome was evaluated using Kaplan-Meier survival curves and compared by the log-rank test. A Cox proportional hazard model was sought to assess the relationship between the type of induction and time to CDC outcome. Results A total of 785 children with CD were induced after diagnosis with either EEN (n=410) or CS (n=375); mean age 13.3±3.5 years, 59% males. PS successfully matched 116 pairs of whom 85 (36%) had CDC. The survival probability of CDC at 6, 12,18, and 24 months was higher in the CS group compared to the EEN group at all time points (5%vs4%, 12% vs 10%, 22% vs 3%, and 27% vs.16%, respectively p=0.045; fig. 1). In a Cox multivariable model adjusted by year of diagnosis, CS induction treatment was similarly associated with higher hazard of CDC by 2 years (HR 1.8 [95%CI 1.01-3.25]). The survival probability of hospitalization was also higher in the CS group at 6,12,8, and 24 months (16% vs 9%, 20% vs 12%, 25% vs 14%, and 27% vs. 15%, respectively, p=0.024; fig.2). There was no difference in time to biologics (p=0.96, n=59 (51%) in EEN, n=57 (49%) in CS) and anthropometric data (Table 1). Significant improvements were observed in HGB and Alb levels for the EEN group during the first 3 months from diagnosis compared with the CS (p=0.046 and p=0.035 respectively) (table 1). Conclusion EEN as induction therapy in pediatric CD is associated with a lower long-term risk of complicated disease course and larger improvement in HGB and Alb but not in growth parameters compared with CS, even when adjusting to baseline disease severity and patients characteristics.

The leptin/adiponectin ratio as prognostic marker for dyslipidemia during 1 year of follow-up in pediatric patients receiving kidney replacement therapy.

Background: leptin and adiponectin are associated with cardiovascular disease in chronic kidney disease (CKD) patients and could be useful prognostic factors. Objectives. to explore the usefulness of the leptin/adiponectin ratio (LAR) to predict the presence or worsening of dyslipidemia during 1 year of follow-up in children receiving kidney replacement therapy (KRT). Material and methods: a prospective cohort study was performed. Pediatric KRT patients aged between 8 and 17 years who were undergoing hemodialysis or peritoneal dialysis were included. At enrollment, the lipid profile, adiponectin and leptin levels, and somatometric measurements, including body fat percentage, were determined. At the one-year follow-up, the lipid profile was reassessed. Results: of the 70 patients included, the median age was 13 years, and there was no sex predominance (52.8 % males). At the end of follow-up, the patients were divided into three groups: those without dyslipidemia (WOD), those who developed or experienced worsening of their dyslipidemia (DWD) and those with persistent dyslipidemia (PD). A LAR > 0.85 (OR, 16.7) and body fat percentage (OR, 1.46) were associated with an increased risk of PD and DWD at 12 months, independently of urea level, BMI Z-score, benzafibrate treatment, CKD progression time, and replacement treatment. Conclusions: a LAR > 0.85 and fat body percentage at the beginning of follow-up were strongly associated with the presence, persistence or worsening of dyslipidemia at the 12-month follow-up in children with KRT.

High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study

BackgroundIn this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. MethodsA total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. ResultsAt baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). ConclusionsThe prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly.

Avascular necrosis following closed reduction for treatment of developmental dysplasia of the hip: a systematic review.

BackgroundAvascular necrosis (AVN) is a significant and potentially devastating complication following the treatment of developmental dysplasia of the hip (DDH). The reported rate of AVN following closed reduction for DDH ranges from 4 to 60%, and the resultant influence on hip development remains unclear.PurposeA systematic review of the literature was undertaken to evaluate the frequency of AVN after more than 5 years of follow-up in children that underwent closed reduction at younger than 2-years of age for DDH.MethodsThe search strategy was formulated with key-concepts and keywords identified using the patient problem, intervention, comparison and outcome process. Searches were undertaken using Pubmed, Scopus and Web of Science up to and including May, 2016 to identify potential studies.ResultsA total of seven papers met the a priori inclusion and exclusion criteria of this review. The overall rate of significant AVN in 441 patients (538 hips) was 10% at a mean length of follow-up of 7.6 years (5–18.8) following closed reduction. This finding can be used to inform the feasibility of future intervention studies, and act as a baseline for which surgeons to compare their results to a ‘standard’.Electronic supplementary materialThe online version of this article (doi:10.1007/s11832-016-0776-y) contains supplementary material, which is available to authorized users.

Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children

BackgroundThe candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules.MethodsWe conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child’s home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group.ResultsOver 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], −17.0 to 21.9; P=0.66) in the intention-to-treat analysis and 7.0% (95% CI, −14.5 to 24.6; P=0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: −43.5%; 95% CI, −100.3 to −2.8 [P=0.03]; per-protocol analysis: −56.8%; 95% CI, −118.7 to −12.3 [P=0.008]).ConclusionsA three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.)

High adherence to a gluten-free diet in adolescents with screening-detected celiac disease.

The aim of the study was to evaluate the gluten-free diet (GFD) adherence after 1 year of follow-up in children with screening-detected celiac disease (CD) in a general population. A total of 18,325 twelve-year-olds were invited to participate in a population-based CD screening (Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This substudy included 210 children with TG2-IgA, evaluated both at the initial biopsy occasion and at 1-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). After 1 year, 85% (179/210) had normalized TG2-IgA levels (<5 U/mL). Among those who had >50 U/mL at diagnosis, 25% (16/63) still had elevated TG2-IgA, but for the majority their initial values were more than halved. Most reported a high level of GFD adherence ("always" 82% [158/193] and "often" 16% [30/193]), and 75% [145/193] reported always adhering combined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely; however, a majority of these initially had the highest TG2-IgA levels. GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12-year-olds. Almost all of them had normalized serology and reported GFD adherence at the 1-year follow-up. A few adolescents who reported GFD adherence, however, had elevated TG2-IgA levels, suggesting more severe disease and/or nonadherence.

Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1years of follow-up in children and adolescents and mean duration of 0.33years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.

Duration of vaccine efficacy against malaria: 5th year of follow-up in children vaccinated with RTS,S/AS02 in Mozambique

A primary concern for the RTS,S malaria vaccine candidate is duration of protection. The ongoing Phase III trial reported evidence of waning efficacy within the first year following vaccination. Multiple Phase IIb trials demonstrated early waning of efficacy. The longest duration of protection for RTS,S recorded to date was in a trial of a cohort of 1605 Mozambican children age 1–4 yr at the time of immunization (C1), which showed an overall efficacy against clinical malaria of 30.5% over 43 subsequent months of surveillance. A significant reduction in parasite prevalence in RTS,S vaccinees indicated that the vaccine continued to protect at the end of this period. Although follow-up for recording incident cases of clinical malaria was stopped at 45 months, we were interested in evidence of further durability of protection, and revisited the cohort at 63 months, recording the secondary trial endpoint, prevalence of asexual Plasmodium falciparum parasitemia, in the RTS,S and comparator vaccine groups as a proxy for efficacy. As a comparator, we also visited the contemporaneous cohort of 417 children (C2), which showed waning efficacy after 6 months of follow-up. We also assessed anti-circumsporozoite antibody titers. These results were compared with those of other Phase IIb trials. Prevalence of parasitemia was not significantly lower in the RTS,S/AS02 group compared to comparator groups in C1 (57 [119%] Vs 62 [128%]; p=0.696) or C2 (30 [226%] Vs 35 [276%]; p=0.391), despite elevated antibody titers, suggesting that protection did not extend to 5 years after vaccination. This is in contrast to the earlier assessment of parasitemia in C1, where a 34% lower prevalence of parasitemia was observed in the RTS,S/AS02 group at month 45. Comparison with other Phase II trials highlights a complex relationship between efficacy, age and transmission intensity. RTS,S/AS02 provided partial protection from clinical malaria for at least 3.5 years in C1. Duration of protection may depend on environmental circumstances, such as changing malaria transmission, and special attention should be given in the Phase III trial to identifying factors that modify longevity of protection.

Nutritional status of children and young adults with Ewing Sarcoma or osteosarcoma at diagnosis and during multimodality therapy

Objective Objective of our study was to evaluate the nutritional status and growth of children and adolescents with common malignancies of the musculoskeletal system at diagnosis, and undergoing multimodality therapy. Methods A retrospective analysis of data from 2001 to 2009 was conducted. Hospital charts were used as a source of clinical data. Primary endpoint of the analyses was to identify variations in anthropometric parameters at diagnosis and during the first 2 years of follow-up in children and adolescents with osteosarcoma or Ewing sarcoma. Factors contributing to disorders of growth in this population were sought. Results A total of 139 children were registered, 62 with Ewing sarcoma and 77 with osteosarcoma. At diagnosis 72.7% of all patients were classified as adequately nourished (BMI 5th to <85th percentiles). During treatment all anthropometric parameters were markedly reduced (P < 0.001) in both groups with extreme changes in body weight from −30% to +44%. This was pronounced in children affected by osteosarcoma (P < 0.05). During follow-up, recovery of body weight was noted in both groups. Height Z-scores remained low (P < 0.001) in comparison to the general population. After the observation period 43.4% of the children with osteosarcoma and 25.5% of the patients with Ewing sarcoma demonstrated an altered body mass. Conclusions Pediatric patients with Ewing sarcoma or osteosarcoma are at an increased risk for developing malnutrition, in the form of either over- or underweight during multimodality therapy. Early recognition of abnormal body mass is required to prevent and to treat long-term comorbidities caused by malnutrition. Pediatr Blood Cancer 2012;59:621–626. © 2011 Wiley Periodicals, Inc.

The impact of birth mode of delivery on childhood asthma and allergic diseases–a sibling study

BackgroundCaesarean section (CS) has been reported to increase the risk of asthma in offspring. This may be due to that infants delivered by CS are unexposed to vaginal flora, according to the ‘hygiene hypothesis’.ObjectiveOur aim was to investigate if CS increases risk of childhood asthma, and if the risk increase remains after adjustment for familial confounding using sibling design.MethodsA register-based cohort study with 87 500 Swedish sibling pairs was undertaken. Asthma outcome variables were collected from national health registers as diagnosis or asthma medication (ICD-10 J45-J46; ATC code R03) during the 10th or 13th year of life (year of follow-up). Mode of delivery and confounders were retrieved from the Medical Birth Register. The data were analysed both as a cohort and with sibling control analysis which adjusts for unmeasured familial confounding.ResultsIn the cohort analyses, there was an increased risk of asthma medication and asthma diagnosis during year of follow-up in children born with CS (adjusted ORs, 95% CI 1.13, 1.04–1.24 and 1.10, 1.03–1.18 respectively). When separating between emergency and elective CS the effect on asthma medication remained for emergency CS, but not for elective CS, while both groups had significant effects on asthma diagnosis compared with vaginal delivery. In sibling control analyses, the effect of elective CS on asthma disappeared, while similar but non-significant ORs of medication were obtained for emergency CS.Conclusions and Clinical RelevanceAn increased risk of asthma medication in the group born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora. A more probable explanation should be sought in the indications for emergency CS.

Nutritional status of children and young adults with Ewing sarcoma or osteosarcoma at diagnosis and during multimodality therapy

Objective of our study was to evaluate the nutritional status and growth of children and adolescents with common malignancies of the musculoskeletal system at diagnosis, and undergoing multimodality therapy. A retrospective analysis of data from 2001 to 2009 was conducted. Hospital charts were used as a source of clinical data. Primary endpoint of the analyses was to identify variations in anthropometric parameters at diagnosis and during the first 2 years of follow-up in children and adolescents with osteosarcoma or Ewing sarcoma. Factors contributing to disorders of growth in this population were sought. A total of 139 children were registered, 62 with Ewing sarcoma and 77 with osteosarcoma. At diagnosis 72.7% of all patients were classified as adequately nourished (BMI 5th to <85th percentiles). During treatment all anthropometric parameters were markedly reduced (P < 0.001) in both groups with extreme changes in body weight from -30% to +44%. This was pronounced in children affected by osteosarcoma (P < 0.05). During follow-up, recovery of body weight was noted in both groups. Height Z-scores remained low (P < 0.001) in comparison to the general population. After the observation period 43.4% of the children with osteosarcoma and 25.5% of the patients with Ewing sarcoma demonstrated an altered body mass. Pediatric patients with Ewing sarcoma or osteosarcoma are at an increased risk for developing malnutrition, in the form of either over- or underweight during multimodality therapy. Early recognition of abnormal body mass is required to prevent and to treat long-term comorbidities caused by malnutrition.

Efficacy of a Low-Cost, Inactivated Whole-Cell Oral Cholera Vaccine: Results from 3 Years of Follow-Up of a Randomized, Controlled Trial

BackgroundKilled oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials.Methods/Principal FindingsWe conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound = 53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound = 44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1–4 years and in the third year in older age groups.Conclusions/SignificanceThe killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine's duration of protection.Trial RegistrationClinicalTrials.gov NCT00289224.