Long-term Outcome Of Children Research Articles

Comprehensive Care and Education Can Improve Nutritional and Growth Outcomes in Children with Persistent Cow's Milk, Egg, or Peanut Allergies: A Five-Year Follow-Up Study of Nutritional Status.

Data suggest that food allergies greatly impact a child's health and growth due to inadequate nutrient intake. Our study aimed to establish the long-term outcome of children with food allergies compared to a control group. This study was a retrospective cohort study with longitudinal follow-up with a mean period of 4.85 years from the diagnosis to the last study visit. The patients' nutritional intake was assessed using a three-day food diary and analysed by a dietitian. Patients (61 boys and 33 girls, mean age 6.9 years) had a single food allergy including 21 patients with cow's milk, 34 with egg, and 39 with peanut allergies. The control group included 36 children (19 boys and 17 girls, mean age 8.03 years). Blood analysis was performed on all participants. Data from our study showed that patients with cow's milk, egg or peanut allergies had normal growth and achieved catch-up growth from the diagnosis until the last study visit. In the cow's milk allergy group, the allergy was shown to affect calcium intake (p < 0.05), while egg and peanut allergies did not impact the dietary intake of nutrients. None of the investigated food allergies affected blood results (p < 0.05). In the present study, we showed that single food allergies do not compromise growth in children if they are provided with appropriate support and that the affected children reach catch-up growth from the diagnosis.

Gross motor development in children with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of rare, congenital skin disorders, characterized by skin fragility and formation of blisters. The gross motor outcomes of children with EB are not known. The primary objective of the study was to measure the proportion of gross motor delay in children with EB. The secondary objectives were to measure the difference in gross motor outcomes between EB sub-types and change in gross motor outcomes over time. Children with EB, aged between one month and five and a half years of age, attending the Sydney Children's Hospital, Epidermolysis Bullosa Clinic, were eligible. Carers completed Ages and Stages Questionnaires, Third Edition, on behalf of their children. Questionnaires were scored, and outcomes were compared to age-expected norms. There were 24 participants to complete a questionnaire. Eleven participants completed additional questionnaires over the 24 month study duration. The proportion of children with EB with gross motor delay was greater than age-expected norms (29.17% vs. 2.5%). The delay occurred in children with recessive dystrophic (80%) and epidermolysis bullosa simplex (33.33%) sub-types, but not dominant dystrophic (0%). No children with Junctional EB or Kindler EB joined this study. This study demonstrates a difference in gross motor outcomes in children with EB. Children with recessive dystrophic and epidermolysis bullosa simplex should be prioritized for monitoring of, and intervention for, gross motor outcomes through multidisciplinary care. Further research investigating long-term outcomes for children with EB and the effectiveness of interventions would be beneficial.

Surgical Treatments and Long-Term Outcomes for Pediatric Patients With Lumbar Spinal Tumors.

Retrospective case‒control study. This study aimed to report the effects of surgical intervention on spinal stability recovery and to assess the long-term outcomes of children and adolescents with lumbar tumors. From January 2016 to June 2021, 42 pediatric patients with lumbar tumors were selected and separated into different groups based on the surgical method used (total en bloc resection (TER) group, n = 21; piecemeal resection (PR) group, n = 21; titanium mesh (TM) group n = 23; artificial vertebrae (AV) group n = 19). The clinicopathological characteristics, treatments and related outcomes were described in detail and compared between groups, with P value ≤.05 indicating statistically significant differences. The average follow-up duration was 24.89 months, and the mean age was 14.89 ± 2.41years. There were no significant differences in the mean operation time, average blood loss, complication rate, or length of hospital stay between the groups. The ODI, VAS and JOA scores at the final follow-up (FF) were elevated after surgery in all groups. The FF local angular drift (LOD) and lumbar angular drift (LUD) were greater in the TM group than in the AV group (P = .03, P = .001). After surgery, pediatric patients with lumbar tumors can obtain satisfactory spinal stability, effective relief of pain symptoms and substantial improvements in neurological function. There was no significant difference in the invasiveness, safety or timeliness between the 2 surgical methods, so TER is recommended due to its low postoperative recurrence rate and good local control. Spinal fusion in the AV group resulted in better spinal stability.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

What to Expect on the Long-term Follow-up of Pediatric Pyeloplasty: Critical Time Intervals and Risk Factors

BackgroundStandard protocol for post-pyeloplasty monitoring in children and natural course of hydronephrosis resolution have not been well defined. We aimed to analyze critical time intervals and risk factors in the long-term clinical outcomes of children who were operated for ureteropelvic junction obstruction. MethodsFiles of patients who underwent open dismembered pyeloplasty between January 2000 and December 2012 and had a ≥10 years follow-up were retrospectively reviewed. Changes in SFU hydronephrosis grade, pelvis anteroposterior diameter (APD), renal parenchymal thickness, split renal functions (SRF) on MAG-3 scan as well as development of hypertension and proteinuria were noted. Complete resolution was defined as SFU grade 0–1 or APD≤10 mm or ≥50 % APD decrease. ResultsOverall, 223 patients (161 boys, 72.1 %) with a median age of 9 (range 1–185) months underwent unilateral pyeloplasty, whereas 14 patients (13 boys, 92.8 %) with a median age of 4 (range 2–39) months underwent bilateral pyeloplasty. Median follow-up was 13 (range 10–22) years. Complete resolution was observed in 190 patients (85.2 %). None of the cases required re-do pyeloplasty. Regarding unilateral cases, postoperative changes in hydronephrosis reached a plateau at the 60th month. Also, there was no significant difference regarding SRF between the 12th month and the 60th month (p > 0.05). Hypertension developed after a median period of 12 years in 13 (5.4 %) of the patients, while proteinuria developed in four (1.6 %) patients. Bilateral disease (HR: 2.518, p = 0.034) was found to be a significant determinant for development of hypertension and/or proteinuria. ConclusionsOur results indicated that ultrasonographic findings stabilized after the 60th month postoperatively, and SRF remained stable between the postoperative 12th and the 60th months. The risk of developing hypertension and/or proteinuria was 2.5 times greater in bilateral cases. Level of EvidenceLevel II.

Efficacy of Treatment Options for Children with Steroid-Refractory Acute Gvhd

Background: Approximately half of patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (alloHCT) experience steroid-refractory aGVHD (SR-aGVHD) disease. Patients with SR-aGVHD require intense and prolonged immunosuppression resulting in high risk of severe opportunistic infections and risk of relapse of malignancy which ultimately results in significant increase in short- and long-term morbidity and mortality, poor quality of life for children and their families and increases financial burden on families and health care system. Corticosteroids have been the mainstay of therapy for new onset acute GVHD. However, treatment for SR-GVHD in children is a serious unmet need. To date, few therapies have been investigated for SR-aGVHD in robust clinical trials for children. Moreover, long-term benefits and survival data from these trials are often lacking or unclear. A systematic literature review (SLR) was conducted to better understand the efficacy of therapies under investigation in this population. Methods: Literature database searches of Embase, MEDLINE, Cochrane, and Econlit, were performed on 22 May 2023 according to Cochrane guidelines to identify randomized and non-randomized clinical trials in which the pediatric population with SR-aGVHD represented at least 50% of the trial population. Clinical trials extensions and long-term follow-up reports were also included. Studies published in English from 2009 onwards were retrieved. Additional manual searches of relevant conference abstracts published in the past 3 years were performed. Results: Overall, 29 publications (23 unique studies) met the selection criteria, representing a total of 801 patients aged 18 years or younger with SR-aGVHD. A limited number of interventions were investigated in this population and most studies had a non-randomized design (19 out of 23 studies). Overall survival (OS) and response rates (ORR) were analyzed from studies enrolling more than 20 pediatric patients with SR-aGVHD (9 studies, Table), which investigated therapies such as mesenchymal stromal cells (MSC), remestemcel-L (MSC manufactured by Mesoblast), ruxolitinib, etanercept and extracorporeal photopheresis. At least 80% of patients treated with cellular therapies (remestemcel-L/MSC) and etanercept had grade III or IV disease. ORR on day 28 was 92% with etanercept, 77% to 91% with ruxolitinib, 61% to 92% with mesenchymal stromal cells, 61% to 70% with remestemcel-L, and 55% with extracorporeal photopheresis. Durable response rates of 69% at day 56 and 70% at day 100 and were noted for remestemcel-L and ruxolitinib, respectively. OS at 6 months was 69% with remestemcel-L, and 71% with mesenchymal stromal cells. OS at 1 year was reported for remestemcel-L (63%) and etanercept (59%). Long-term survival data beyond 1 year of patients enrolled in the clinical trial was available only for remestemcel-L and showed an OS rate of 51% at 2 years and 49% at 3 and 4 years. 4-year OS probability for patients with grade III or IV (48% in both cases) was similar to that for the overall population. Conclusions: Only a few small size clinical trials were conducted for children with SR-aGVHD which poses a unique challenge for FDA to approve new therapies for SR-aGVHD. Despite a small number (n=9: 5 ruxolitinib arm and 4 control arm) of children (12-18 years) enrolled in REACH II study, ruxolitinib was FDA approved for children&amp;gt;12 years of age. Long-term efficacy outcomes of children enrolled in clinical trials were reported only for remestemcel-L and showed that approximately half survived beyond 3 years. While other reports showed that grade III/IV disease is associated with poorer outcomes compared to grade I/II, similar survival rates were noted for patients with grade II, III and IV treated with remestemcel-L. In children with SR-aGVHD, other therapies such as ruxolitinib or etanercept demonstrated good response rates, however, the associated survival benefit is unclear.

A Single Dose of PEG-Asparaginase at the Beginning of Induction Not Only Accelerates MRD Clearance but Also Improves Long-Term Outcome in Children with B-Lineage ALL

This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 of induction therapy in children with B-lineage ALL. Methods. Conventional induction therapy consisted of dexamethasone, vincristine, and daunorubicin. MRD data was available in 502 patients who were randomized at the start of induction therapy, standard-risk (SR) patients into three (conventional induction without PEG, induction with additional PEG and with PEG but without daunorubicin) and intermediate-risk (ImR) patients into two groups (with additional PEG and without PEG). Results. The single administration of PEG resulted in a significantly higher proportion of rapid responders, in SR patients even when no anthracyclines were used for induction. In the SR group, the event-free survival of the MFC-MRD fast responders was similar in the PEG− and PEG+ arms (92.0 ± 3.1% vs. 96.2 ± 1.5%, respectively), and the same unfavorable trend was observed for MFC-MRD slow responders (57.5 ± 12.3% vs. 66.7 ± 15.7%, respectively). Results were similar in ImR patients: (94.3 ± 3.2% vs. 95.1 ± 2.4%, for fast responders and 63.3 ± 7.6% vs. 78.1 ± 7.9%, for slow responders in PEG− and PEG+ arms, respectively). However, there is a large difference between the proportion of MFC-MRD slow responders in the PEG− and PEG+ groups (18.3% vs. 5.2% for the SR group and 44.2% vs. 25.0% for the ImR group). Conclusions. Therefore, early use of PEG-ASP not only leads to an accelerated reduction of blasts, but also to an excellent outcome in a significantly larger proportion of patients in both risk groups.

Long-term Childhood Outcomes for Babies Born at Term Who were Exposed to Antenatal Corticosteroids

(Am J Obstet Gynecol. 2023;228:80) Antenatal corticosteroids (ACS) are recommended for mothers at risk for preterm delivery to reduce infant mortality and increase lung maturation. It is possible that ACS can decrease lung function for individuals later in life. This study aimed to compare the difference in lung function for individuals ages 5 and above whose mothers received ACS and those whose mothers did not.

Educational Outcomes for Children at 7 to 9 Years of Age After Birth at 39 vs 40 to 42 Weeks’ Gestation

Birth at 39 weeks' gestation is common and thought to be safe for mother and neonate. However, findings of long-term outcomes for children born at this gestational age have been conflicting. To evaluate the association of birth at 39 weeks' gestation with childhood numeracy and literacy scores at ages 7 to 9 years compared with birth at 40 to 42 weeks' gestation. In this Australian statewide, population-based cohort study using a causal inference framework based on target trial emulation, perinatal data on births between January 1, 2005, and December 31, 2011, were linked to educational outcomes at 7 to 9 years of age. Statistical analyses were performed from December 2022 to June 2023. Birth at 39 weeks' gestation compared with birth at 40 to 42 weeks' gestation. Numeracy and literacy outcomes were assessed at 7 to 9 years of age using Australian National Assessment Program-Literacy and Numeracy data and defined by overall z score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Multiple imputation and doubly robust inverse probability weighted regression adjustment were used to estimate population average causal effects. The study population included 155 575 children. Of these children, 49 456 (31.8%; 24 952 boys [50.5%]) were born at 39 weeks' gestation and were compared with 106 119 (68.2%; 52 083 boys [49.1%]) born at 40 to 42 weeks' gestation. Birth at 39 weeks' gestation was not associated with altered educational outcomes for children aged 7 to 9 years compared with their peers born at 40 to 42 weeks' gestation (mean [SE] z score, 0.0008 [0.0019] vs -0.0031 [0.0038]; adjusted risk difference, -0.004 [95% CI, -0.015 to 0.007]). Each educational domain was investigated, and no significant difference was found in grammar and punctuation (risk difference [RD], -0.006 [95% CI, -0.016 to 0.005]), numeracy (RD, -0.009 [95% CI, -0.020 to 0.001]), spelling (RD, 0.001 [95% CI, -0.011 to 0.0013]), reading (RD, -0.008 [95% CI, -0.019 to 0.003]), or writing (RD, 0.006 [95% CI, -0.005 to 0.016]) scores for children born at 39 weeks' gestation compared with those born at 40 to 42 weeks' gestation. Birth at 39 weeks' gestation also did not increase the risk of scoring below national minimum standards in any of the 5 tested domains. Using data from a statewide linkage study to emulate the results of a target randomized clinical trial, this study suggests that there is no evidence of an association of birth at 39 weeks' gestation with numeracy and literacy outcomes for children aged 7 to 9 years.

A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex

BackgroundTuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients.MethodsThis cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation.ResultsThirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05).ConclusionsThe results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.

Is refugee experience in childhood a risk for poorer health in adulthood?-A Swedish national survey study.

Studies on experiences of migration in childhood and subsequent health in adulthood report conflicting results. While there is limited research on the long-term health outcomes of refugee children as they transition into adulthood, it is often observed that refugee children experience adverse health conditions upon their arrival in the host country. We examined whether adults with a childhood refugee experience were more likely to have poorer mental health, general health, and risk-behaviours compared to non-refugee migrants and Swedish-born peers We included a nationally representative sample of 18-64-year-olds who answered the Swedish National Public Health survey in 2018 or 2020. Using official register data, we categorized individuals as: 1) refugees in childhood (<age 18 years); 2) migrants in childhood; or 3) Swedish-born. Associations between childhood status (refugee, migrant, or Swedish-born) and all outcomes in adulthood were analyzed using logistic regression. The final model was adjusted for age, sexual- and gender-minority (SGM) identity, and stratified by sex. We also analysed the above and all outcomes stratified by age (18-25, 26-64), adjusted for sex and SGM-identity. We found that a childhood refugee experience was not associated with worse self-rated general or mental health, or more risk behaviours in adulthood, compared to non-refugee migrants or Swedish-born individuals. Additionally, adults with a childhood refugee experience had lower odds of at-risk alcohol use and substance use than Swedish-born peers. In general, a childhood refugee experience was not associated with worse self-rated health or risk behaviours in adulthood when considering age and sexual- and gender-minority status.

LONG-TERM HEALTH OUTCOMES OF PAEDIATRIC MULTIFOCAL MUSCULOSKELETAL SEPSIS: A 15-YEAR REVIEW

This study aimed to identify long-term physical and psychosocial health outcomes in children with overwhelming musculoskeletal sepsis.Children admitted to the Paediatric Intensive Care Unit (PICU) from 1st January 2002 to 31st December 2017 with a musculoskeletal focus of infection were identified. A medical notes review was completed to determine survival and morbidity. Present-day clinical assessment of the musculoskeletal and respiratory systems along with questionnaires on health-related quality of life, mental health and sleep were performed.70 patients were identified over 15 years. Seven children died acutely (five Pasifika and two Māori children) indicating 10% mortality. Recurrence/chronic infection affected 23%. Growth disturbance affected 18%. The hip joint and proximal femur suffered the worst long-term complications. Children under 2 years most at risk of long-term disability. No patients had chronic respiratory illness beyond 90 days. Fifteen children had symptoms of acute neurological impairment, three of whom had permanent acquired brain injury. Twenty-six survivors (41%) were assessed a mean of 8.2 years (SD 4.5, range 2– 18 years) after discharge. Health-related quality of life scores were on par with normative data. All patients who underwent pulmonary function tests had normal results. Six patients and eight parents screened positive for moderate to severe post-traumatic stress disorder.Paediatric multifocal musculoskeletal sepsis can result in complex illness with multi-organ complications for some children. Māori and Pasifika children are most at risk. Children under 2 years and those with proximal femur and/or hip involvement are most likely to have chronic musculoskeletal sequelae and permanent disability. Other outcomes are favourable with no evidence of chronic lung disease or mean reduced quality of life. A period of rehabilitation for children with identified acquired brain injury should be part of discharge planning.

Predicting long-term neurocognitive outcome after pediatric intensive care unit admission for bronchiolitis—preliminary exploration of the potential of machine learning

PurposeFor successful prevention and intervention, it is important to unravel the complex constellation of factors that affect neurocognitive functioning after pediatric intensive care unit (PICU) admission. This study aims (1) to elucidate the potential relevance of patient and PICU-related characteristics for long-term adverse neurocognitive outcome after PICU admission for bronchiolitis, and (2) to perform a preliminary exploration of the potential of machine learning as compared to linear regression to improve neurocognitive outcome prediction in a relatively small sample of children after PICU admission.MethodsThis cross-sectional observational study investigated 65 children aged 6–12 years with previous PICU admission for bronchiolitis (age ≤ 1 year). They were compared to demographically comparable healthy peers (n = 76) on neurocognitive functioning. Patient and PICU-related characteristics used for the prediction models were as follows: demographic characteristics, perinatal and disease parameters, laboratory results, and intervention characteristics, including hourly validated mechanical ventilation parameters. Neurocognitive outcome was measured by intelligence and computerized neurocognitive testing. Prediction models were developed for each of the neurocognitive outcomes using Regression Trees, k-Nearest Neighbors, and conventional linear regression analysis.ResultsThe patient group had lower intelligence than the control group (p < .001, d = −0.59) and poorer performance in neurocognitive functions, i.e., speed and attention (p = .03, d = −0.41) and verbal memory (p < .001, d = −0.60). Lower intelligence was predicted by lower birth weight and lower socioeconomic status (R2 = 25.9%). Poorer performance on the speed and attention domain was predicted by younger age at follow-up (R2 = 53.5%). Poorer verbal memory was predicted by lower birth weight, younger age at follow-up, and greater exposure to acidotic events (R2 = 50.6%). The machine learning models did not reveal added value in terms of model performance as compared to linear regression.Conclusion: The findings of this study suggest that in children with previous PICU admission for bronchiolitis, (1) lower birth weight, younger age at follow-up, and lower socioeconomic status are associated with poorer neurocognitive outcome; and (2) greater exposure to acidotic events during PICU admission is associated with poorer verbal memory outcome. The findings of this study provide no evidence for the added value of machine learning models as compared to linear regression analysis in the prediction of long-term neurocognitive outcome in a relatively small sample of children.What is Known:• Adverse neurocognitive outcomes are described in PICU survivors, which are known to interfere with development in other major domains of functioning, such as mental health, academic achievement, and socioeconomic success, highlighting neurocognition as an important outcome after PICU admission.• Machine learning is a rapidly growing field of artificial intelligence that is increasingly applied in health care settings, with great potential to capture the complexity of outcome prediction.What is New:• This study shows that lower birth weight, lower socioeconomic status, and greater exposure to acidotic events during PICU admission for bronchiolitis are associated with poorer long-term neurocognitive outcome after PICU admission. Results provide no evidence for the added value of machine learning models in a relatively small sample of children.• As bronchiolitis seldom manifests neurologically, the relation between acidotic events and neurocognitive outcome may reflect either potentially harmful effects of acidosis itself or related processes such as hypercapnia or hypoxic and/or ischemic events during PICU admission. This study further highlights the importance of structured follow-up to monitor long-term outcome of children after PICU admission.

AHOD2131: A Randomized Phase 3 Response-Adapted Trial Comparing Standard Therapy with Immuno-Oncology Therapy for Children and Adults with Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma

Background: Chemotherapy in combination with radiotherapy (RT) is the standard for early-stage (ES) Hodgkin lymphoma (cHL). Despite high cure rates (12-year overall survival (OS) &amp;gt;93%), there is room to improve short and long-term outcomes for children and adults with ES cHL. Incorporation of immunotherapy (IO) into front line treatment of ES cHL is an opportunity to both improve progression-free survival (PFS) and maintain OS, while minimizing long-term morbidity and mortality by reducing exposure to RT and high-dose chemotherapy. Study Design and Methods: HL leaders of the NCTN groups, expert HL researchers and physicians, and representatives from the Cancer Therapy Evaluation Program (CTEP) formed a working group in April 2020 with the goals of harmonizing treatment approaches for ES cHL across pediatric and adult patients and reaching consensus regarding the optimal study design for incorporating IO therapy into frontline treatment. Study champions identified from each of the North American cooperative groups [Children's Oncology Group (COG), SWOG, ECOG-ACRIN, Alliance, NRG] and experts in imaging, radiation oncology, lymphoma biology and patient-reported outcomes (PROs) were included. The resulting COG-led clinical trial, AHOD2131, represents the largest ES cHL trial in the history of North American cooperative groups and the first to enroll patients across the age continuum. AHOD2131 (NCT05675410; Figure) is a randomized, phase 3 trial enrolling patients ages 5 to 60 years with newly diagnosed, previously untreated stage I and II cHL and will investigate the addition of the CD30-antibody drug conjugate brentuximab vedotin (Bv) with PD-1 blockade (nivolumab) compared to standard chemotherapy +/- RT. Since the April 2023 activation, 97 North American sites have activated the trial, and 21 participants have enrolled. Target enrollment is 1875 patients over 5 years of accrual, for an estimated 1782 eligible and evaluable patients. The primary objective is to compare the 3-year PFS of patients with ES cHL treated through a response-adapted, superiority design with either standard therapy or with an IO approach (BV + nivolumab). All patients will be stratified as favorable or unfavorable based on disease risk features at enrollment. Based on initial response assessment by PET/CT (via central review) after 2 cycles of ABVD, patients were classified to PET2 positive (SER, defined as 5 Point Score 4 or 5, ~15% of patients) and PET negative (RER). Those who are PET positive will receive involved site RT (ISRT). The SER and RER patients will be randomized to standard chemotherapy vs. IO therapy respectively. In addition to the primary outcome of PFS, there are 11 secondary and 10 exploratory aims. The secondary aims focus on OS, PFS of subgroups, and event-free survival at 12 years, physician-reported treatment-related adverse event (AE) rates, patient-reported AE using pediatric and adult versions of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the capture of representation by self-report and the use of electronic PRO data collections. The exploratory aims include the assessment of imaging central review as compared to local institutional review and the use of convolutional neural networks through artificial-intelligence machine learning. The study will examine the effect of therapy on acute and long-term adverse effects including health-related quality of life (HRQoL) and OS for up to 12 years. The study will compare patient self-report and provider AE reports and evaluate the associations of self-reported race/ethnicity and social determinants of health (SDOH)and post-progression/post-relapse OS. AHOD2131 strengthens the effort between the North American cooperative groups to conduct collaborative clinical trials and aims to harmonize an improved standard of care for ES cHL across the age continuum.

2 Infant Imitation: Detecting Risk in the First Year with PediaTrac™

Objective:Imitation has pervasive associations with social and communicative development. However, few methods have been developed to measure this construct in typically developing infants, and even less is available for at-risk populations, such as infants born preterm. Autism spectrum disorder (ASD), a particular risk of premature birth, is associated with atypical imitation and social communication. Although imitation emerges in infancy, most current screening and diagnostic tools for ASD cannot be utilized prior to 12 months. The present study aimed to develop and validate a caregiver-report measure of infant imitation, characterize imitation profiles at 4, 6, and 9 months in term and preterm infants, and explore the relationship between imitation and scores on an ASD screening questionnaire at 18 months.Participants and Methods:Participants (N = 571) were recruited from a larger multi-site study of PediaTrac™ v3.0, a web-based tool for monitoring and tracking infant development, and were surveyed longitudinally at birth, 2, 4, 6, 9, 12, 15, and 18 months. Participants completed the online PediaTrac™ survey and several reliable and validated questionnaires via pen-and-paper format. For the purposes of this study, only the Ages and Stages Questionnaire (3rd ed.; ASQ-3), Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP), Brief Infant Sleep Questionnaire (BISQ), and the Modified Checklist for Autism in Toddlers - Revised with Follow-Up (M-CHAT-R/F) were examined. The following hypotheses were tested: (1) proposed imitation items will represent a unitary latent construct, for which convergent and discriminant validity will be demonstrated, (2) there will be measurement invariance between term status groups at each assessment period, (3) preterm infants will obtain lower caregiver-reported imitation scores compared to term infants, and (4) imitation abilities at the assessment period with the most robust imitation factor will predict M-CHAT-R/F scores at 18 months.Results:Distinct imitation factors at 4, 6, and 9 months were modeled with confirmatory and exploratory factor analyses. Relationships between the factors and established measures of infant communication (CSBS; ASQ) and sleep (BISQ) revealed convergent and discriminant validity, respectively. Strict measurement invariance was demonstrated for the 4- and 9-month factors, and metric invariance for the 6-month measure. Full term infants scored higher on imitation at 9 months, though variance in this outcome was related to term status differences in sensorimotor skills. Lastly, the 9-month imitation factor, coupled with 6-month sensorimotor skills, predicted 18-month ASD risk over and above gestational age.Conclusions:This study provides support for the assessment of infant imitation, utilizing imitation to detect risk in preterm infants, and extending the age of identification for ASD risk into the first year. PediaTrac™ imitation, in combination with the PediaTrac™ sensorimotor domain, may be useful in detecting developmental risk, and specifically risk for ASD, within the first year, leading to earlier initiation of intervention. Further, with its minimal completion time and ease of dissemination through digital platforms, this measure can expand access to care and improve long-term outcomes for children and families.

Perinatal Trajectories of Maternal Depressive Symptoms in Prospective, Community-Based Cohorts Across 3 Continents

Depressive symptoms during pregnancy influence the development and health of the offspring, underscoring the need for timely intervention. However, the course of depressive symptoms across the perinatal period remains unclear, thus complicating screening and referral guidelines. To examine the course and stability of depressive symptoms across the perinatal period in multiple, ethnically diverse independent observational cohorts. This cohort study included self-reported depressive symptoms at multiple time points from 7 prospective cohorts spanning 3 continents (United Kingdom: Avon Longitudinal Study of Parents and Children from 1991 to 1995; Canada: Maternal Adversity, Vulnerability and Neurodevelopment from 2003 to 2007; Montreal Antenatal Well-being Study from 2019 to 2022; Alberta Pregnancy Outcomes and Nutrition from 2009 to 2014; and Singapore: Growing Up in Singapore Toward Healthy Outcomes from 2009 to 2013; Singapore Preconception Study of Long-Term Maternal and Child Outcomes from 2015 to 2019; and Mapping Antenatal Maternal Stress from 2019 to 2022). Participants were recruited either during preconception or pregnancy and observed into the postnatal period. All data from each cohort were analyzed from July 2022 to April 2023. Self-reported depressive symptoms from pregnancy to 2 years following childbirth using either the Edinburgh Postnatal Depression Scale or the Center for Epidemiological Studies Depression were analyzed independently within each cohort using item response theory (IRT) techniques. K-means clustering was used to identify groups of participants with similar trajectories. A total of 11 563 pregnant women (mean [SD] age, 29 [5] years; 569 [4.9%] East Asian women; 304 [2.6%] Southeast Asian women; 10 133 [87.6%] White women) self-reported depressive symptoms from pregnancy to 2 years following childbirth. Analytic methods from Item Response Theory identified 3 groups of mothers based on depressive symptoms: low, mild, and high levels in each of the 7 cohorts. Mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onwards. Mothers with clinical levels of depressive symptoms likewise showed stable trajectories from pregnancy into the postnatal period. In this study, trajectories of depressive symptoms remained stable from pregnancy across the perinatal period, a finding that conflicts with a continuing emphasis on postpartum or postnatal onset of depression that persists in some health policy guidelines. Interventions and public health initiatives should focus on reducing depressive symptoms during pregnancy in addition to following birth.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI

BackgroundExisting literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PurposeTo implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. Material and methodsMRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). ResultsThe proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. ConclusionConvolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

A - 111 Neuropsychological Performance in CDK-13 Related Disorder: a Multi-Year Case Study.

CDK13-related disorder (CDK13-RD) is a rare genetic condition first described in 2016 as involving congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Few studies have reported clinical presentations. There is very minimal information about cognitive and neuropsychological outcomes; however, developmental delays and intellectual disability are common. This study presents longitudinal neuropsychological outcomes of one adolescent with CKD13-RD. A female patient underwent five neuropsychological evaluations over eight years due to learning concerns. Pregnancy complications included recurrent maternal infections/treatment and fetal heart deceleration. The patient was born at full-term with average birthweight. Patient's history includes developmental delays, cerebral palsy, learning disabilities, anxiety, atrial septal defect, abnormal MRI and EEG, submucous cleft palate, velopharyngeal insufficiency, and craniofacial dysmorphisms. Genetic tests confirmed a likely pathogenetic variant in the CDK13-gene at 9-years-old. Patient's intellectual functioning varied during the five evaluations, with heterogeneous performance across indices. Verbal comprehension was often a strength in the low average to average ranges. Visual perception, nonverbal reasoning, fine motor coordination/planning, attention, and aspects of executive functioning were consistently impaired. Memory across evaluations was variable but broadly average. Caregiver reports revealed increasing executive and adaptive functioning concerns and fluctuating mood/behavioral concerns across evaluations. Patient's overall intellectual functioning is generally stronger than expected compared to the few available studies. This case adds to the scarce literature on neuropsychological outcomes in children with CKD13-RD and helps elucidate developmental trends given these serial results. Additional research is needed to better understand neuropsychological presentations and long-term outcomes in children with CKD13-RD.

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. URL: https://www. gov; Unique identifier: NCT0245531.

SAT445 Exposure To Perfluoroalkyl Substances At Preconception In Association With Metabolic Phenotype In Women From Singapore

Abstract Disclosure: N.J. Cohen: None. M. Yao: None. V. Midya: None. S. India-Aldana: None. S.S. Andra: None. S. Narasimhan: None. A.K. Meher: None. M. Arora: None. J.K. Chan: None. S.Y. Chan: None. Y. Kway: None. N. Michael: None. S.A. Sadanathan: None. J.G. Eriksson: None. S.S. Velan: None. T.K. Hian: None. Y. Oulhote: None. J. Huang: None. D. Valvi: None. Background and Aim: Exposure to perfluoroalkyl substances (PFAS) may result in adverse metabolic health outcomes, but few studies have focused on preconception PFAS exposures and metabolic dysregulation which could impact pregnancy. We assessed cross-sectional and prospective associations between preconception PFAS concentrations and glucose regulation, insulin sensitivity, and magnetic resonance imaging (MRI) based adiposity measures in a Singaporean cohort of women who were actively attempting to conceive. Methods: Our analyses included 384 participants from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), from which 126 underwent abdominal MRI at preconception. 15 different PFAS in preconception plasma samples were measured, and metabolic measures were cross-sectionally assessed at preconception (waist-to-height ratio [WHtR], 2-hour oral glucose tolerance test [OGTT] indices, and MRI-based measures of abdominal adiposity and liver fat), and prospectively at 24-28 weeks of gestation (2-hour OGTT indices). We used linear regression models to assess associations between individual PFAS and metabolic phenotype at preconception and pregnancy. In addition, we used Bayesian weighted quantile sum (BWQS) regression to assess the joint associations of the PFAS mixture with study outcomes. Results: We observed negative associations between perfluorononanoic acid (PFNA) concentrations and visceral adipose tissue (VAT; log2-transformed) volume (β per doubling of PFNA=-0.12 cm3, 95% CI -0.24, 0.00) and log2-transformed liver fat percentage (β=-0.28%, 95% CI -0.52, -0.04). Inverse associations were observed between the individual PFAS and most mid-pregnancy OGTT indices and insulin resistance, but were not statistically significant. Associations were not statistically significant for all preconception OGTT indices. Conclusions: We did not find strong evidence for an association between preconception PFAS concentrations and prenatal metabolic outcomes in young women in Singapore. Cross-sectional analyses indicated reduced adiposity in VAT volume and liver fat percentage with increasing PFAS concentration, which requires further investigation in prospective, more diverse, and larger studies. Presentation: Saturday, June 17, 2023