Meaningful Patient Engagement in Adolescent and Young Adult (AYA) Cancer Research: A Framework for Qualitative Studies.

Over the last two decades, patient engagement in cancer research has evolved significantly, especially in addressing the unique challenges faced by adolescent and young adult (AYA) cancer populations. This paper introduces a framework for meaningful engagement with AYA cancer patient research partners, drawing insights from the "FUTURE" Study, a qualitative study that utilizes focus groups to explore the impact of cancer diagnosis and treatment on the sexual and reproductive health of AYA cancer patients in Canada. The framework's development integrates insights from prior works and addresses challenges with patient engagement in research specific to AYA cancer populations. The framework is guided by overarching principles (safety, flexibility, and sensitivity) and includes considerations that apply across all phases of a research study (collaboration; iteration; communication; and equity, diversity, and inclusion) and tasks that apply to specific phases of a research study (developing, conducting, and translating the study). The proposed framework seeks to increase patient engagement in AYA cancer research beyond a supplementary aspect to an integral component for conducting research with impact on patients.

Sexual health outcomes among adolescent and young adult cancer patients: a systematic review and meta-analysis.

BACKGROUND: Sexual health outcomes (SHO), which entail the physical, emotional, mental, and social impacts, are an important consideration for adolescent and young adults (AYA, ages 15-39) affected by cancer. The objective of this systematic review and meta-analysis is to summarize the current literature and evaluate AYA cancer impact on SHO. METHODS: EMBASE and MEDLINE were searched from January 1, 2000 to September 28, 2022 to identify epidemiologic studies that used an analytic observational design, included individuals with AYA cancer and non-cancer control participants, and evaluated SHO. Odds ratios and prevalence ratios were calculated; random effects models were used to obtain pooled measures where possible. RESULTS: Of 2621 articles, 8 were included that investigated 23 SHO in 9038 AYA cancer patients. Based on the sexual response cycle, outcomes were categorized as those occurring among males (desire = 1, arousal = 1, orgasm = 4, other = 3) and females (desire = 2, arousal = 1, orgasm = 2, pain = 6, other = 3). It was feasible to conduct meta-analysis for 3 female SHO and 5 male SHO. There were associations between AYA cancer and 3 SHO: vaginal dryness (pooled odds ratio = 3.94; 95% confidence interval (CI) = 2.02 to 7.70), ejaculatory dysfunction (pooled odds ratio = 3.66; 95% CI = 2.20 to 6.08), and testosterone level (pooled mean difference = -2.56 nmol/liter; 95% CI = -3.46 to -1.66; P = .00001). CONCLUSION: This study found increased ejaculatory dysfunction and reduced testosterone levels in male AYA cancer patients and increased vaginal dryness in female AYA cancer patients, highlighting the need for sexual health resources in this population.

Reproductive Health Outcomes among Adolescent and Young Adult Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis (SRMA) aimed to synthesize the current literature on the impacts of adolescent and young adult (AYA, ages 15-39 years) cancer on reproductive health outcomes. METHODS: EMBASE and Medline were searched from 1 January 2000 to 26 January 2022 for observational studies that included individuals with AYA cancer and controls which evaluated reproductive health outcomes. We used random effects models and 95% confidence intervals to obtain pooled measures of associations between AYA cancer, cancer treatment, and reproductive health outcomes. RESULTS: The search identified 8625 articles; 21 were included. 62 reproductive outcomes were assessed and classified according to a sex-based framework as fetal/neonatal (n = 26), maternal (n = 11), fetal/neonatal-maternal (n = 23), and maternal-paternal (n = 2). Meta-analyses of crude estimates showed significant associations between AYA cancer and outcomes including preterm birth (pooled odds ratio [pOR] 1.31; 95% CI: 1.22, 1.42), gestational diabetes (pOR 1.43; 95% CI: 1.03, 1.99), and fertility treatment (pOR 2.66; 95% CI 1.71, 4.11). We also found higher odds of preterm birth (pOR 1.65; 95% CI: 1.21, 2.26) and low APGAR score at birth (pOR 2.03; 95% CI: 1.32, 3.13) among AYA cancer patients who received radiation compared to controls. CONCLUSIONS: Our SRMA quantified impacts of AYA cancers and treatments on several reproductive health outcomes.

Prognostic factors and outcomes of infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, and mixed-phenotype acute leukemia (MPAL) in Canada: a report from CYP-C.

The epidemiology of infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, and mixed-phenotype acute leukemia (MPAL) in Canada is unknown. The main objective was to describe the prevalence, prognostic factors, and outcomes of three rare and high-risk ALL subtypes in Canada. This is a retrospective study using the Cancer in Young People-Canada (CYP-C) database. Event-free survival (EFS) and overall survival (OS) were described by the Kaplan-Meier method and compared using the log-rank test. Among 2626 children aged 0-14 years diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) between 2001 and 2018, 227 (8.6%) patients were identified to be infant ALL (n = 139), hypodiploid ALL (n = 43), or MPAL (n = 45). The 5-year EFS/OS was significantly worse in the infant ALL subgroup compared to that of hypodiploid ALL and MPAL. For the entire cohort, presenting White blood cells (WBCs) ≥50 × 109/L was independently associated with worse EFS/OS.

Poor outcome after hematopoietic stem cell transplantation of patients with unclassified inherited bone marrow failure syndromes.

Classification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment of treatment. Unfortunately, 30% of patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified with a specific syndromic diagnosis. We analyzed the outcome of hematopoietic stem cell transplantation (HSCT) in unclassified IBMFSs (uIBMFSs) and the factors associated with outcome. Twenty-two patients with uIBMFSs and 70 patients with classified IBMFSs underwent HSCT. Five-year overall survival of uIBMFS patients after HSCT was inferior to that of patients with classified IBMFSs (56% vs 76.5%). The outcome of patients with uIBMFS who received cord blood was significantly lower than that of patients who received other stem cell sources (14.8% vs 90.9%). Engraftment failure was higher among patients with uIBMFS who received cord blood than those who received bone marrow. None of the following factors were significantly associated with poor survival: transfusion load, transplant indication, the intensity of conditioning regimen, human leukocyte antigen-identical sibling/alternative donor. We suggest that identifying the genetic diagnosis is essential to modulate the transplant procedure including conditioning agents and stem cell sources for better outcome and the standard cord blood transplantation (CBT) should be avoided in uIBMFS.

Incidence of childhood cancer in Canada during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years. METHODS: We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [ß], level 4.98, 95% CI -15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2]). INTERPRETATION: We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada.

Regional differences in access to hematopoietic stem cell transplantation among pediatric patients with acute myeloid leukemia.

INTRODUCTION: Indications for hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML) are primarily dependent on risk stratification at diagnosis and relapse status. We sought to determine whether access to HSCT is influenced by regional and socioeconomic factors. METHODS: Children with newly diagnosed AML aged < 15 years between 2001 and 2015 were identified using the Cancer in Young People in Canada national population-based registry. Factors potentially associated with the receipt of HSCT were studied using univariate and multivariable logistic regression models. RESULTS: Overall, 568 children with newly diagnosed AML were included and 262 (46%) received HSCT. A greater proportion of patients, 103/157 (65.6%), underwent HSCT after first or subsequent relapse compared to 159/411 (38.7%) patients who underwent transplant before relapse. Among patients for whom HSCT would be considered before relapse, factors associated with higher odds of HSCT in a multivariable analysis were: poor versus good-risk cytogenetics (Odds ratio [OR]: 30.0, 95% confidence interval [CI]: 7.7-117.0), diagnosis during 2012-2015 versus 2001-2006 (OR: 3.2, 95% CI: 1.6-6.3), diagnosis in eastern Canada versus central Canada (OR: 3.7, 95% CI: 1.9-7.3), and age 10-14 years versus age < 1 year (OR: 5.4, 95% CI: 2.3-12.8). Among patients for whom HSCT would be considered after first relapse, higher odds of HSCT was associated with diagnosis at a HSCT center (OR: 2.1, 95% CI: 1.1-4.1). CONCLUSION: Patients diagnosed at a HSCT performing center and patients from eastern Canada had higher odds of receiving HSCT. This may suggest preferential access to HSCT for certain patients.

Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry.

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.

Cellular and molecular architecture of hematopoietic stem cells and progenitors in genetic models of bone marrow failure.

Inherited bone marrow failure syndromes, such as Fanconi anemia (FA) and Shwachman-Diamond syndrome (SDS), feature progressive cytopenia and a risk of acute myeloid leukemia (AML). Using deep phenotypic analysis of early progenitors in FA/SDS bone marrow samples, we revealed selective survival of progenitors that phenotypically resembled granulocyte-monocyte progenitors (GMP). Whole-exome and targeted sequencing of GMP-like cells in leukemia-free patients revealed a higher mutation load than in healthy controls and molecular changes that are characteristic of AML: increased G>A/C>T variants, decreased A>G/T>C variants, increased trinucleotide mutations at Xp(C>T)pT, and decreased mutation rates at Xp(C>T)pG sites compared with other Xp(C>T)pX sites and enrichment for Cancer Signature 1 (X indicates any nucleotide). Potential preleukemic targets in the GMP-like cells from patients with FA/SDS included SYNE1, DST, HUWE1, LRP2, NOTCH2, and TP53. Serial analysis of GMPs from an SDS patient who progressed to leukemia revealed a gradual increase in mutational burden, enrichment of G>A/C>T signature, and emergence of new clones. Interestingly, the molecular signature of marrow cells from 2 FA/SDS patients with leukemia was similar to that of FA/SDS patients without transformation. The predicted founding clones in SDS-derived AML harbored mutations in several genes, including TP53, while in FA-derived AML the mutated genes included ARID1B and SFPQ. We describe an architectural change in the hematopoietic hierarchy of FA/SDS with remarkable preservation of GMP-like populations harboring unique mutation signatures. GMP-like cells might represent a cellular reservoir for clonal evolution.

Reanalysing genomic data by normalized coverage values uncovers CNVs in bone marrow failure gene panels.

Inherited bone marrow failure syndromes (IBMFSs) are genetically heterogeneous disorders with cytopenia. Many IBMFSs also feature physical malformations and an increased risk of cancer. Point mutations can be identified in about half of patients. Copy number variation (CNVs) have been reported; however, the frequency and spectrum of CNVs are unknown. Unfortunately, current genome-wide methods have major limitations since they may miss small CNVs or may have low sensitivity due to low read depths. Herein, we aimed to determine whether reanalysis of NGS panel data by normalized coverage value could identify CNVs and characterize them. To address this aim, DNA from IBMFS patients was analyzed by a NGS panel assay of known IBMFS genes. After analysis for point mutations, heterozygous and homozygous CNVs were searched by normalized read coverage ratios and specific thresholds. Of the 258 tested patients, 91 were found to have pathogenic point variants. NGS sample data from 165 patients without pathogenic point mutations were re-analyzed for CNVs; 10 patients were found to have deletions. Diamond Blackfan anemia genes most commonly exhibited heterozygous deletions, and included RPS19, RPL11, and RPL5. A diagnosis of GATA2-related disorder was made in a patient with myelodysplastic syndrome who was found to have a heterozygous GATA2 deletion. Importantly, homozygous FANCA deletion were detected in a patient who could not be previously assigned a specific syndromic diagnosis. Lastly, we identified compound heterozygousity for deletions and pathogenic point variants in RBM8A and PARN genes. All deletions were validated by orthogonal methods. We conclude that careful analysis of normalized coverage values can detect CNVs in NGS panels and should be considered as a standard practice prior to do further investigations.

Access to Hematopoietic Stem Cell Transplantation among Pediatric Patients with Acute Lymphoblastic Leukemia: A Population-Based Analysis.

Access to hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) primarily depends on disease-related factors but may be influenced by social and economic determinants. We included all children aged < 15 years with newly diagnosed ALL in Canada between 2001 and 2018 using the Cancer in Young People in Canada national registry. We examined factors potentially associated with the likelihood of receiving HSCT using univariate and multivariable logistic regression models. A total of 3992 patients with newly diagnosed ALL were included. Three hundred twenty-five (8.1%) received an HSCT and formed the transplant cohort. In multivariable analysis factors independently associated with an increased odds of receiving HSCT were male sex (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.05 to 1.93), initial WBC ≥ 50,000 × 109/L (OR, 1.58; 95% CI, 1.09 to 2.28), mixed phenotype acute leukemia relative to B-precursor ALL (OR, 34.32; 95% CI, 16.64 to 70.79), T cell relative to B-precursor ALL (OR, 1.77; 95% CI, 1.07 to 2.91), unfavorable relative to standard cytogenetics (OR, 3.96; 95% CI, 2.56 to 6.12), and relapse before HSCT (OR, 32.77; 95%, 23.89 to 44.96). No association was found between race, neighborhood income quintile or region at diagnosis, and receipt of HSCT. Diagnosis at an HSCT treating center (OR, 1.51; 95% CI, 1.09 to 2.09) and residential distance from the ALL treating center (OR, 1.84 for ≥300 km compared with <100 km; 95% CI, 1.17 to 2.91) were associated with higher odds of receiving HSCT. In a publically funded healthcare system, children with ALL had equitable access to HSCT, which was largely governed by biologic disease-related factors. Patients diagnosed at an HSCT performing center and patients who live farthest away from their treatment center had higher odds of receiving HSCT, although the effect was small, possibly suggesting preferential referral to HSCT for some patients.

A feasibility study examining the impact of yoga on psychosocial health and symptoms in pediatric outpatients receiving chemotherapy.

PURPOSE: Pediatric cancer patients experience symptoms that negatively impact quality of life; yoga may be an effective intervention. The primary objective was to determine the feasibility of a 10-week, weekly individualized yoga intervention for children and adolescents receiving outpatient cancer therapy primarily delivered remotely using Skype. Secondary objectives were to describe depression, anxiety, anger, fatigue, quality of life, and symptoms at 5 and 10 weeks after enrollment. METHODS: We included English-speaking patients aged 10 to 18 years receiving outpatient chemotherapy for cancer. Weekly individualized yoga sessions were offered for 10 weeks. Weeks 1, 5, and 10 were in-hospital while the remaining sessions were delivered remotely using Skype. Twice weekly, homework was assigned between each session. The primary outcome was feasibility, defined as 80% of participants completing at least 60% of planned in-hospital or remote yoga sessions. RESULTS: Between March and November 2017, 10 patients were enrolled. Two patients discontinued the study after one and two sessions. Only six participants achieved at least 60% of planned yoga sessions and thus, the study did not meet the a priori defined feasibility threshold. Among all participants, only one homework session was performed. CONCLUSIONS: A 10-week individualized in-person and remotely conducted yoga intervention was not feasible in children receiving cancer treatments because of failure to achieve the desired frequency of yoga sessions in a sufficient number of participants. Future research should identify approaches to improve compliance with remote yoga sessions and home practice. TRIAL REGISTRATION: NCT03318068.

Qualitative development of the sinus control test: a survey evaluating sinus symptom control.

BACKGROUND: Ideal management of chronic rhinosinusitis (CRS) requires ongoing monitoring of disease and its control. Existing control instruments are limited in their correlation to patient reported outcomes, the need for endoscopy, or lack of validation from a multidisciplinary group. The goal of this study was to develop a patient-based Sinus Control Test (SCT) for determining CRS control. METHODS: A systematic literature review and focus groups consisting of 20 patients and 11 medical experts in CRS from various medical specialties were used to generate items. A draft 13-item questionnaire was administered to 50 patients with CRS in a prospective fashion. Patients were evaluated using the 22-item Sino-Nasal Outcome Test (SNOT-22) instrument, Lund-Mackay computed tomography (CT) score, and Lund-Kennedy endoscopy score. A rhinologist blinded to the questionnaire results also provided an overall control of the disease for each patient. A regression model was generated to identify which subset of items showed the greatest discriminate ability in relation to specialist's and patient's global rating of disease control. RESULTS: Four questions were included in the final questionnaire (p < 0.05), each with a scale of 0 to 4, with an overall total score ranging from 0 to 16. Optimal classification resulted in patients with a score from 1 to 3 (well controlled), 4 to 11 (partially controlled), and 12 to 16 (uncontrolled). SCT scores correctly classified control levels 72% of the time when compared to physician's assessment. CONCLUSION: The SCT is a simple, patient generated questionnaire that can measure the control of CRS without requirement of endoscopy or CT evaluation.

Cost-Effectiveness Analysis Comparing Pre-diagnosis Autism Spectrum Disorder (ASD)-Targeted Intervention with Ontario's Autism Intervention Program.

Novel management strategies for autism spectrum disorder (ASD) propose providing interventions before diagnosis. We performed a cost-effectiveness analysis comparing the costs and dependency-free life years (DFLYs) generated by pre-diagnosis intensive Early Start Denver Model (ESDM-I); pre-diagnosis parent-delivered ESDM (ESDM-PD); and the Ontario Status Quo (SQ). The analyses took government and societal perspectives to age 65. We assigned probabilities of Independent, Semi-dependent or Dependent living based on projected IQ. Costs per person (in Canadian dollars) were ascribed to each living setting. From a government perspective, the ESDM-PD produced an additional 0.17 DFLYs for $8600 less than SQ. From a societal perspective, the ESDM-I produced an additional 0.53 DFLYs for $45,000 less than SQ. Pre-diagnosis interventions targeting ASD symptoms warrant further investigation.

Sarcopenia in children with acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia experience musculoskeletal morbidity during therapy. We examined the patterns of change in skeletal muscle mass (SMM) and the relationship between change in SMM and the burden of illness as reflected in days of hospitalization. Ninety-one children had dual energy x-ray absorptiometry (DXA scans) during treatment, yielding the sum of lean tissue mass in all 4 limbs; the appendicular lean mass. SMM was derived from appendicular lean mass. The number of inpatient days was recorded. DXA scans at 5 time points showed a profile of change in SMM characterized by a drop in the mean Z score from -0.18 at diagnosis to -1.08 after 6 months of therapy, with a partial recovery 12 to 24 months after diagnosis. Levels of serum creatinine, a surrogate measure of SMM, were mainly unchanged. The extent of the drop in SMM during early therapy was associated with the duration of hospitalization (r=0.31, P<0.05). Children with acute lymphoblastic leukemia experience a notable reduction in SMM early in treatment, with incomplete recovery. The degree of loss is associated with the burden of illness. These findings provide a target for a therapeutic intervention and a measure to determine its efficacy.

Predictors of bony morbidity in children with acute lymphoblastic leukemia.

BACKGROUND: To evaluate the relationship between lumbar spine (LS) bone mineral density (BMD) and patient-, disease-, and therapy-related variables, and to define the risk-factors for fractures in children receiving therapy on Dana-Farber Cancer Institute acute lymphoblastic leukemia (ALL) protocols. METHODS: Children (≤18 years) diagnosed with ALL during the period 1995-2006, who are in first clinical remission, were included (n = 124). Dual-energy X-ray absorptiometry provided LS-BMD at diagnosis (n = 46) and during continuation therapy. LS-BMD was expressed as Z scores based on local population norms. Regression analyses evaluated the risk of osteopenia (Z-score -1.01 to -1.99, osteoporosis (Z-score -2.00 or less) and fractures. RESULTS: At diagnosis, 14 0f 46 (30%) patients had osteopenia and 5 (11%) had osteoporosis; whereas, during continuation therapy, 47 of 124 (39.5%) patients had osteopenia, and 10 (8%) had osteoporosis. LS-BMD at diagnosis had a positive linear relationship with LS-BMD during continuation therapy (Pearson correlation coefficient 0.619, P < 0.0001). Multivariable analyses identified age ≥10 years and LS-BMD at diagnosis as independent predictors of LS-BMD during continuation therapy. Twenty-three (18.5%) patients developed fractures. Dexamethasone therapy (OR 3.4, 95% CI 1.31, 7.52, P = 0.01) and lower LS-BMD during the continuation therapy (OR 1.8, 95% CI 1.2, 2.8, P = 0.01) were independent predictors of fracture. CONCLUSIONS: Older age and lower LS-BMD at diagnosis are predictors of lower LS-BMD during continuation therapy. Dexamethasone and lower LS-BMD during continuation therapy are associated with fractures. Using these variables it is feasible to develop a predictor model to define the risk of bony morbidity in children receiving ALL therapy.

Should prevention of chronic kidney disease start before pregnancy?

OBJECTIVE: The objective was to evaluate whether there is a role for the prevention of future chronic kidney disease (CKD) in children by improving maternal health at conception, this review addresses: the risk of childhood obesity in the development of CKD, trends in childhood obesity and body composition in children with renal diseases, trends in pre-pregnancy BMI and its association with neonatal outcome, and the effect of pre-pregnancy body mass index (BMI) on blood pressure and body composition in the offspring. INCREASED BMI AND HYPERTENSION AS RISK FACTORS FOR CKD: It is now well established that the presence of hypertension increases the risk of CKD. Increased BMI can also increase the risk of the development of CKD indirectly, through an increase in the prevalence of hypertension, and, possibly, through a direct effect independent of hypertension. TRENDS IN CHILDHOOD OBESITY IN GENERAL, AND SPECIFICALLY AMONG CHILDREN WITH RENAL DISEASES: An unprecedented epidemic of childhood obesity has been witnessed since the 1970s. An estimated 35% of children in North America are reported to be overweight. Children with CKD have even higher BMIs. TRENDS IN PRE-PREGNANCY BMI AND ITS ASSOCIATION WITH NEONATAL OUTCOME: The average BMI of mothers delivering in a single hospital in London, Ontario, rose from 24.3 kg/m2 in 1995 to 25.1 kg/m2 in 2004, whereas the average age of conception of the first child remained unchanged at 28 years. High pre-pregnancy BMIs increased the proportion of large-for-gestational-age newborns, a high proportion of congenital anomalies including renal abnormalities, and the need for Cesarean sections. EFFECT OF PRE-PREGNANCY BMI ON BLOOD PRESSURE AND BODY COMPOSITION IN THE OFFSPRING: Among 1,915 children (mean age 8.3 +/- 5.2 years), studied at the Children's Hospital, London Health Science Centre, BMI z-score correlated significantly with systolic (Spearman r = 0.214, P < 0.0001), and diastolic blood pressure z-scores (Spearman r = 0.143, P < 0.0001). The pre-pregnancy BMI correlated with both BMI z-score (Spearman r = 0.144, P < 0.0001) and blood pressure z-score (Spearman r = 0.13, P = 0.0005) in the children. The birth weight also correlated significantly with a higher BMI z-score (Spearman r = 0.134, P < 0.0001). CONCLUSION: There are increasing trends in childhood obesity and pre-pregnancy maternal BMI. Higher pre-pregnancy BMI increases the risk for increased BMI z-score and blood pressure z-score in children. Since elevated BMI and blood pressure clearly are known risk factors of future CKD, targeting healthier weights prior to conception is likely to reduce the CKD burden in children.