Columbia Children's Hospital Research Articles

MyoActivation®, a Structured Assessment and Therapeutic Process for Adolescents With Myofascial Dysfunction and Chronic Low Back Pain: A Case Series.

Introduction Myofascial dysfunction is a significant, but often unrecognized, contributor to chronic low back pain (CLBP). myoActivationis an innovative method that utilizes a structured assessment and therapeutic process to recognize and manage myofascial dysfunction and pain. Since 2017, the British Columbia Children's Hospital Complex Pain Service has used myoActivation as a tool in the interdisciplinary care of adolescents with chronic pain. This case series explores the journey to discharge of patients in whom myoActivation was incorporated as part of their CLBP management. Methods We retrospectively reviewed clinical records of adolescents reporting CLBP who underwent myoActivation between August 2022 and January 2023 and had subsequently been discharged. Information obtained for analysis included preclinical information (medical/injury/pain history, previous investigations, diagnoses, therapies, and quality of life indicators); clinic recommendations, assessment findings, management strategies, and specifics of the myoActivation process; and reported changes at discharge (quality-of-life measures and medication use). Results Eight cases were reviewed: all female, with a median age (range) of 16.5 (15.7-19.5) years. Before admission, patients had experienced chronic pain for a median duration of 4.3 (1-8) years, had self-reported average pain intensity of 7.5 (4-9) on the 0-10 numeric pain scale, with poor quality-of-life impacts including sleep disturbance (8/8, 100%), school absence (8/8, 100%), and low mood (6/8, 75%). Patients attended three (2-5) myoActivation sessions over two (1-10) weeks. The overall duration of their interdisciplinary care was 12 (7-25) months. At discharge, there were improvements in pain (7/8, 88%), physical functioning (5/8, 63%), sleep (6/8, 75%), school attendance (5/8, 63%), and mood (4/6, 67%) and reduced prescription and over-the-counter medication use in most cases. Conclusion This case series suggests that myoActivation may be a useful clinical tool in the assessment and management of adolescents with myofascial dysfunction and CLBP. Prospective longitudinal research is required to establish evidence that confirms the clinical efficacy of myoActivation within interdisciplinary care.

Quality of Life Measured Using the BODY-Q After Adolescent Gynecomastia Surgery: A Cross-Sectional Analysis

Background: Patient-reported outcome measures (PROMs) are increasingly used to seek feedback from patients. Knowledge gaps exist regarding outcomes in adolescents postgynecomastia surgery. This study assesses adolescent patients’ quality of life postgynecomastia surgery using a PROM specific for body contouring procedures, and identifies patient and treatment factors associated with quality of life scores. Methods: Adolescent patients undergoing surgical treatment for Simon grades I, IIa, or IIb gynecomastia from May 2009 to November 2022 at British Columbia Children's Hospital were invited to complete the Body Contouring Questionnaire (BODY-Q) Satisfaction with Chest and Psychological Function scales. Raw scores were Rasch transformed (scale 0-100), averaged, and compared to normative scores. Body mass index (BMI), Simon grade, postoperative complication, and revision procedure information were collected from medical charts and analyzed for associations with BODY-Q scores. Results: Thirty-seven of 76 patients (48.7%) completed the BODY-Q. At the time of survey completion, the median age of participants was 23.3 years, and the median BMI was 26.5. The median time from surgery to survey completion was 7 years. Median scores on the Satisfaction with Chest and Psychological Function scales were 70 and 71, respectively, which were significantly higher than normative scores of unaffected males on the same scales ( P = .0004 and P = .0014, respectively). Undergoing a revision procedure was associated with significantly worse satisfaction with chest appearance ( P = .045). Conclusion: Patients who underwent gynecomastia surgery report better satisfaction with chest appearance and psychological function, as measured by the BODY-Q, compared to unaffected males of similar age and BMI. These results may play an important role in destigmatizing gynecomastia surgery for adolescents.

P125 MIG (CXCL9) and IL22 are key biomarkers that discriminates between paediatric IBD patients and non-IBD patients in a novel biomarker model

Abstract Background The current gold standard for diagnosis of Inflammatory bowel disease (IBD) is based on clinical and endoscopic evaluation as well as histologic and radiologic evaluation. However, endoscopic evaluation can be uncomfortable and carry some risks, especially in the paediatric population that requires general anesthesia in order to perform the procedure. Our aim was to investigate whether serum biomarkers can differentiate between paediatric patients with and without IBD. Secondary aims were to determine whether there are biomarkers that can differentiate between Crohn's disease (CD) and Ulcerative colitis (UC), and whether we can predict progression to biologic treatment within one year from diagnosis using these biomarkers. Methods Paediatric patients undergoing a first diagnostic colonoscopy at British Columbia Children's Hospital (BCCH) between December 2019 and June 2022 were invited to participate in the study. A 2 ml blood sample was taken from each participant at the time of colonoscopy. Demographic and clinical data were collected from each patient. Blood samples were analyzed using the LegendplexTM flow cytometry kits investigating 12 different inflammatory cytokines and chemokines associated with IBD. Eleven of them were found most significant in an initial analysis performed on 100 patients using 50 biomarkers, and CCL7 was added due to significance in previous studies. A prediction model was built via a supervised learning method to determine how well we can predict the different groups. Results Two hundred and forty-six paediatric patients participated in the study. Median age was 13.03 years, 92 were females (37.4%) and 155 (63.01%) were diagnosed with IBD, with 103 (66.45%) diagnosed with Crohn's disease. The AUROC using SPLS-DA classification was 0.805. MIG and Il22 were found to be the key biomarkers to discriminate between pediatric IBD patients and non-IBD patients. In a random forest analysis MIG, Il8 and Il22 were found most important for discrimination. On a univariate analysis MIG and Il18 were found statistically significant as a predictor of CD (p=0.016 for both). CXCL1 was predictive to progression to biologic treatment within one year of diagnosis (p=0.039). However, the prediction model did not predict well the subclasses nor progression to biologic treatment. Conclusion Using serum biomarkers can predict the diagnosis of Paediatric IBD. MIG and Il22 were found to be the key biomarkers in the prediction model.

The Calgary Kids’ Hand Rule: External Validation of a Prediction Model to Triage Pediatric Hand Fractures

Background: The Calgary Kids’ Hand Rule (CKHR) is a clinical prediction rule intended to guide referral decisions for pediatric hand fractures presenting to the emergency department, identifying “complex” fractures that require surgical referral and optimizing care through better matching of patients’ needs to provider expertise. The objective of this study was to externally validate the CKHR in two different tertiary pediatric hospitals in Canada. Methods: We partnered with British Columbia Children's Hospital (BCCH) and the Children's Hospital of Eastern Ontario (CHEO) to externally validate the CKHR using data from retrospective cohorts of pediatric hand fractures (via electronic medical record and x-ray review). Model performance was evaluated at each site using sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and the C-statistic. Results: A total of 954 hand fractures were included in the analysis (524 at BCCH and 430 at CHEO. At BCCH, the CKHR had a sensitivity of 91.1% (133 predicted complex out of 146 total complex fractures), specificity of 71.4% (269 predicted simple out of 377 total simple fractures), and C-statistic of .81, 95% CI [0.78-0.84]. At CHEO, the CKHR had a sensitivity of 98.3%, specificity of 30.2%, and C-statistic of .64, 95% CI [0.61-0.67]. Conclusion: The CKHR performed well at two different tertiary care centres with high sensitivity, supporting its ability to facilitate hand fracture triage in other populations without further modification. This work should be followed by rigorous implementation analysis to determine its impact on patient care.

Short duration of parenteral antibiotics in infants with urinary tract infections.

Current guidelines by the Canadian Paediatric Society on treating urinary tract infections (UTIs) exclude infants ≤ 60 days old. There is considerable practice variability in this age group, especially around the optimal duration of parenteral antibiotics. The study aimed to assess local practice patterns, and the safety of a short course (≤3 days) of parenteral antibiotics in young infants. In this retrospective cohort study, 95 infants (≤60 days) with confirmed UTIs were identified at British Columbia Children's Hospital. Patients receiving short (≤3 days) and long (>3 days) duration of parenteral antibiotics were compared. Outcomes of interest included urinary tract infection recurrence within 30 days, hospital length of stay (LOS), representation, and readmission. Twenty infants (21%) received a short course of parenteral antibiotics. These infants were older (median 47 days versus 28 days) and non-bacteremic. Urinary tract infection recurrence was identified in 8 patients (8%), of which 7 were treated with a long duration (P = 1.0). Patients treated with a short duration had a significantly shorter LOS, with a mean difference of 4.21 days [95% CI: 3.37 to 5.05] (P < 0.001). All five (5%) bacteremic patients were treated exclusively with parenteral antibiotics. In a Canadian setting, a short course of parenteral antibiotics is safe in young, non-bacteremic infants with UTIs. Despite substantial evidence, local practice patterns suggest a tendency towards prescription of long courses, providing an opportunity for quality improvement.

Management of Brachial Plexus Birth Injuries at British Columbia Children's Hospital.

A multidisciplinary team at BC Children's Hospital provides brachial plexus birth injury management for our provincial catchment area. Although compared with many centers we service a relatively small clinic population, we have the benefit of universal health care, province-wide reach, and accessible research infrastructure. In 2008, we created the Sup-ER protocol, which includes an orthosis that passively positions the neonatal shoulder into more idealized glenohumeral contact during early growth. We have since shown that our Sup-ER patients have better shoulder outcomes, require less brachial plexus surgery, and need fewer shoulder tendon transfers than those patients treated in our clinic prior to 2008. We have also found that the rate and degree of elbow flexion contractures are reduced compared with results reported in the literature.

Reduced Physical Activity During COVID-19 in Children With Congenital Heart Disease: A Longitudinal Analysis

BackgroundCoronavirus disease 2019 (COVID-19) was associated with a reduction in physical activity in children with congenital heart disease (CHD) in early 2020. Given the increased cardiovascular risk of this population, optimizing cardiovascular health behaviour is important. The aim of the study is to determine how the ongoing COVID-19 pandemic has impacted longitudinal physical activity measures in children with CHD.MethodsAs part of a prospective cohort study, children and adolescents aged 9-16 years old with moderate-to-complex CHD were recruited from British Columbia Children’s Hospital and partnership clinics across British Columbia and the Yukon territory. Daily step counts were measured continuously over 3 years (2018-2021) with Fitbit Charge 2. School status during the COVID-19 pandemic was assessed with parent- or self-report survey.ResultsA total of 102, 114, and 93 participants had valid Fitbit data during 2018, 2019, and 2020, respectively. There was a significant reduction in the annual mean step count for 2020 (8225 ± 4328 steps) compared with both 2018 (9416 ± 3770 steps) and 2019 (9533 ± 4114 steps) (P < 0.001). There was a loss of seasonal variation in physical activity, and reduced levels of physical activity persisted when most children resumed in-person schooling in September 2020.ConclusionsWe demonstrated a significant decrease in physical activity and loss of seasonal patterns in children with CHD during 2020. These findings represent a worsening of the cardiovascular risk profile in children with CHD, who are already at an increased risk of adverse cardiovascular outcomes. Mitigation strategies are needed to optimize the cardiovascular health status of children with CHD as the pandemic persists.

Assessing the Social Determinants of Health and Adverse Childhood Experiences in Patients Attending a Children's Hospital Cleft Palate-Craniofacial Program.

Objective This study aimed to describe the social determinants of health (SDoH) for patients receiving multidisciplinary team care in a Cleft Palate-Craniofacial program, develop responsive and consistent processes to include trauma-informed psychosocial histories, promote discussions about additional “non-medical” factors influencing health and surgical outcomes, and demonstrate that these activities are feasible in the context of multidisciplinary patient-provider interactions. Design Single-site, cross-sectional study using a questionnaire. Setting Participants were recruited from a provincial quaternary care Cleft Palate-Craniofacial program at British Columbia Children's Hospital in Vancouver, BC, Canada. Participants 290 families completed the questionnaire. Results 34% of families experience significant barriers to accessing primary health care, 51% struggle financially, and 11% scored four or more on the Adverse Childhood Experiences scale. Furthermore, 47% reported not having adequate social support in their lives, and 5% reported not feeling resilient at the time of the survey. Conclusion Patients with cleft and craniofacial anomalies have complex needs that extend beyond the surgical and medical care they receive. It is critical that all Cleft and Craniofacial teams incorporate social histories into their clinic workflow and be responsive to these additional needs. Discussions surrounding SDoH and adversity are welcomed by families; being involved in the care and decision-making plans is highly valued. Healthcare providers can and should ask about SDoH and advocate for universal access to responsive, site-based, social work support for their patients.

Night to night variability of pulse oximetry features in children at home and at the hospital

Objective. Investigation of the night-to-night (NtN) variability of pulse oximetry features in children with suspicion of Sleep Apnea. Approach. Following ethics approval and informed consent, 75 children referred to British Columbia Children's Hospital for overnight PSG were recorded on three consecutive nights, including one at the hospital simultaneously with polysomnography and 2 nights at home. During all three nights, a smartphone-based pulse oximeter sensor was used to record overnight pulse oximetry (SpO2 and photoplethysmogram). Features characterizing SpO2 dynamics and heart rate were derived. The NtN variability of these features over the three different nights was investigated using linear mixed models. Main results. Overall most pulse oximetry features (e.g. the oxygen desaturation index) showed no NtN variability. One of the exceptions is for the signal quality, which was significantly lower during at home measurements compared to measurements in the hospital. Significance. At home pulse oximetry screening shows an increasing predictive value to investigate obstructive sleep apnea (OSA) severity. Hospital recordings affect subjects normal sleep and OSA severity and recordings may vary between nights at home. Before establishing the role of home monitoring as a diagnostic test for OSA, we must first determine their NtN variability. Most pulse oximetry features showed no significant NtN variability and could therefore be used in future at-home testing to create a reliable and consistent OSA screening tool. A single night recording at home should be able to characterize pulse oximetry features in children.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PurposeTo describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib.MethodsWe report on six patients with NF‐1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively.ResultsSubjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4–28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life‐threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1–2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy.ConclusionTrametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF‐1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

An Interrupted Time-Series Analysis of Pediatric Emergency Department Visits During the Coronavirus Disease 2019 Pandemic.

The objective of this study was to estimate the impact of the coronavirus disease 2019 pandemic on pediatric emergency department (PED) visits after declaration of stay-at-home orders within British Columbia, Canada, and the change in cases by acuity and age for 6 months during the pandemic. Retrospective data on PED visits at British Columbia Children's Hospital were collected between December 1, 2019, and August 31, 2020, and for 2 previous years. An interrupted time-series analysis was performed to estimate the difference in daily visits after stay-at-home orders on March 17, 2020, as well as before and after. Further analysis was performed to estimate the drop and recovery of admission and visits by age and acuity. After adjustment for year and seasonality, we documented a drop in the expected number of daily visits of 83 (95% confidence interval [CI], 78-89) after stay-at-home orders. Thereafter, daily visits increased by 12.9 (95% CI, 11.3-14.4) every month. Probability of admission adjusted for seasonality and acuity increased 6.9% (95% CI, 4.9%-9.0%) after stay-at-home orders and decreased in the odds of -0.7% (95% CI, -1% to -0.4%) monthly thereafter. The coronavirus disease 2019 pandemic has had a dramatic and lasting impact on the number of PED visits, with contracted rates 6 months into the pandemic. Further increase in acuity-adjusted rate of admissions after stay at home orders suggests that individuals may be delaying arrival to the emergency department. Further assessment is needed to determine if patients are seeking care through other venues or not seeking care altogether.

Exploring Perceptions of Education for Central Venous Catheter Care at Home.

Pediatric oncology patients with an external central venous catheter (CVC) in situ can be discharged from the hospital. Caregivers are expected to learn how to care for the CVC prior to discharge while also dealing with their child's new cancer diagnosis. This study aimed to evaluate the perceptions of a CVC education program received by caregivers to identify opportunities for improvement. A qualitative study was conducted in 3 stages, using an evidence-based co-design approach, involving caregivers and one adolescent patient discharged from the British Columbia Children's Hospital Oncology/Hematology/BMT inpatient unit. Stage I involved semi-structured interviews to gain feedback on the existing CVC education program. In Stage II, educational resources were updated or developed and implemented. For Stage III, the revised CVC education program was evaluated through a focus group and semi-structured interviews. Interview transcripts were analyzed using QSR NVivo®. The original CVC education program was overall well received. Repeated instruction and support provided by nurses was reported to have increased confidence with performing CVC skills. Participants appreciated the multimodal approach to meet learning needs and expressed interest in additional visual aids. Inconsistencies in nurses’ practice and offers of “tips and tricks” were identified to be challenging for caregivers while learning a new skill. Videos depicting CVC care were developed to provide an additional visual tool, decreased inconsistencies in care, and support to caregivers at home. Caring for a CVC at home is challenging and overwhelming for caregivers. A standardized multimodal education program is required to support caregivers at home.

Prevalence and risk factors for cisplatin-induced hearing loss in children, adolescents, and young adults: a multi-institutional North American cohort study

Cisplatin is used to treat a wide range of childhood cancers and cisplatin-induced hearing loss (CIHL) is a common and debilitating toxicity. We aimed to address persistent knowledge gaps in CIHL by establishing benchmarks for the prevalence of and risk factors for CIHL. In this multi-institutional cohort study, children (age 0-14 years), adolescents, and young adults (age 15-39 years) diagnosed with a cisplatin-treated tumour from paediatric cancer centres, who had available cisplatin dosing information, and primary audiology data for central review from consortia located in Canada and the USA were eligible for inclusion. Audiology was centrally reviewed and CIHL graded using the consensus International Society of Pediatric Oncology (SIOP) Boston Ototoxicity Scale. We assessed the prevalence of moderate or severe CIHL (SIOP grade ≥2) at latest follow-up and end of therapy, in each demographic, diagnosis, and treatment group and their relative contributions to risk for CIHL. Secondary endpoints explored associations of cisplatin dose reductions and CIHL with survival. We also examined whether cisplatin dose reductions and CIHL were associated with survival outcomes. We included 1481 patients who received cisplatin. Of the 1414 (95·5%) participants who had audiometry at latest follow-up (mean 3·9 years [SD 4·2] since diagnosis), 620 (43·8%) patients developed moderate or severe CIHL. The highest prevalence of CIHL was seen in the youngest patients (aged <5 years; 360 [59·4%] of 606 patients) and those with a CNS tumour (221 [50·9%] of 434 patients), hepatoblastoma (110 [65·9%] of 167 patients), or neuroblastoma (154 [62·1%] of 248 patients). After accounting for cumulative cisplatin dose, higher fractionated doses were associated with risk for CIHL (for each 10mg/m2 increase per day, adjusted odds ratio [aOR] 1·15 [95% CI 1·07-1·25]; for each 50 mg/m2 increase per cycle aOR 2·16 [1·37-3·51]). Vincristine exposure was newly identified as a risk factor for CIHL (aOR 3·55 [2·19-5·84]). Dose reductions and moderate or severe CIHL were not significantly associated with survival differences. Using this large, multicentre cohort, benchmarks were established for the prevalence of CIHL in patients treated with cisplatin. Variations in cisplatin dosing confer additive risk for developing CIHL and warrant investigation as a potential approach to decrease the burden of therapy. US National Institutes of Health and National Institute on Deafness and Other Communication Disorders, US National Institutes of Health and National Cancer institute, St Baldrick's Foundation, Genome Canada, Genome British Columbia, Canadian Institutes of Health Research, the Canada Foundation for Innovation, University of British Columbia, British Columbia Children's Hospital Research Institute, British Columbia Provincial Health Services Authority, Health Canada, and C17 Research Network.

Role of transient elastography and APRI in the assessment of pediatric cystic fibrosis liver disease.

Diagnosis and monitoring of cystic fibrosis liver disease (CFLD) is challenging. Transient elastography (TE) is a rapid, non-invasive method for assessing liver fibrosis. Its role in detecting fibrosis in CFLD has only begun to be explored. The aspartate aminotransferase to platelet ratio index (APRI) has been validated as a predictor of hepatic fibrosis in other chronic liver diseases. The purpose of this study was to assess the utility of APRI and TE in identifying liver fibrosis in pediatric CF patients. Patients aged 2-18 years were recruited from the British Columbia Children's Hospital CF clinic. Patients were determined to have CFLD using standard criteria. Charts were reviewed, and each patient underwent TE. Of the 55 patients included in the study (50.9% male, mean age 11.6 y), 22 (40%) had CFLD. All mean liver enzymes were higher in the CFLD group, notably alanine transaminase (p = 0.031). Mean liver stiffness (LS) and APRI were also higher in the CFLD group (LS: 5.9 versus 4.5 kPa, p = 0.015; APRI: 0.40 versus 0.32, p = 0.119). Linear regression showed a mild positive association between the two (r 2 = 0.386). TE values were higher among CFLD patients and correlated with APRI values, suggesting that these tools may have clinical applications for identifying and following this population. Further research is needed on a larger scale to determine the relative value and clinical utility of TE and APRI among patients with CFLD.

Setting the baseline: a description of cannabis poisonings at a Canadian pediatric hospital prior to the legalization of recreational cannabis.

This study describes the events and circumstances preceding children aged 16 years or younger being treated for cannabis poisoining in the emergency department (ED) of a Canadian pediatric hospital. We extracted cannabis poisoning treated in the ED at British Columbia Children's Hospital (BCCH) between 1 January, 2016 and 31 December, 2018, from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) database. The poisonings were distinguished by the inadvertent or intentional ingestion of cannabis. We reviewed the hospital's electronic health information system and the patients' health records to obtain additional information on the context, including spatial and temporal characteristics. Of the 911 poisonings treated at BCCH, 114 were related to intentional cannabis use (12.5%). Fewer than 10 poisonings resulted from inadvertent ingestions by children and the median age for these was 3 years. All inadvertent ingestion occurred at home and involved cannabis belonging to the patient's family. The vast majority of poisonings resulted from the intentional use of cannabis only (28.9%) or cannabis use with other psychoactive substances (co-ingestions; 71.1%). The median patient age was 15 years. Most patients reported consuming cannabis through inhalation with peers. Cannabis and co-ingestion poisonings were more often reported on weekdays than weekends. The consumption of cannabis leading to poisoning more often occurred in private residences. Patients with cannabis poisoning more often sought medical treatment themselves or were helped by their family. The characteristics of cannabis poisonings among children are described for the three-year period prior to recreational cannabis legalization in Canada in order to set a baseline for future comparisons. Implications for improving injury prevention initiatives and policies are discussed.

Vitamin B-12 Biomarkers Reviewed: Holotranscobalamin Allows Identification of Vitamin B12 Deficiency in Children with Short-Bowel Syndrome

Abstract Objectives Serum total vitamin B12 (tB12) is the most commonly used biomarker to assess B12 status in healthy and patient populations but there is ambiguity as to its performance for early and reliable B12 deficiency diagnosis. Holotranscobalamin (holoTC) is the B12 form taken up by cells and may be a more sensitive B12 indicator. This descriptive, prospective study aimed to compare serum tB12 with serum holoTC concentration in their ability to detect functional B12 deficiency defined as elevated methylmalonic acid (MMA) concentration in a pediatric population at risk of B12 deficiency. Methods A total of 26 infants and children aged 3 mo-15 yrs with a history of ileal resection were recruited from the Children's Intestinal Rehabilitation Program at the British Columbia Children's Hospital, Canada. Between 1 to 7 samples per patient were collected over 2yrs, with complete biomarker data for 41 samples. Clinical, anthropometric and dietary data were also collected. Age-specific reference limits derived from a healthy pediatric reference sample were used as cut-offs to categorize B12 deficiency. Results Of the 41 samples, 29 (71%) had concordant biomarker results all indicating adequate B12 status. Elevated MMA (&amp;gt;398 nmol/L) was found in only 2 samples and those had holoTC concentration indicative of B12 deficiency (&amp;lt;40 pmol/L) but normal tB12 (&amp;gt;209 pmol/L). While holoTC exceeded tB12 in sensitivity for the detection of functional B12 deficiency, holoTC had reduced specificity, 75% compared to 85% for tB12, leading to a reduced positive predictive value (22%). Patients receiving total parenteral nutrition (TPN) had significantly higher tB12 but similar holoTC concentration compared to those not receiving TPN. Conclusions Overall, the results suggest that serum holoTC detects patients with elevated MMA indicative of B12 deficiency, who are not identified by tB12 concentration, in children with short bowel syndrome. It also suggests that the current cut-off for tB12 may be too low. These descriptive findings warrant further evaluation and validation of B12 biomarkers and related cutoffs for adequate, suboptimal and deficient B12 status. Funding Sources Healthy Starts Catalyst Grant from the British Columbia Children's Hospital Research Institute, Vancouver BC, Canada.

Nutritional Status in Breastfed 18-Month Old Toddlers: Cross-Sectional Findings

Abstract Objectives Adequate nutrition is critical for infant and toddler growth and development. Breastfeeding is recommended until 2 years of age or beyond, and breastmilk is an important source of energy and nutrients for many toddlers beyond 12 mo of age. The composition of breastmilk changes over time during the lactation period. It is not yet known how prolonged breastfeeding influences nutritional status in toddlers aged 12–24 mo. The objective of this research was to explore biomarker differences between breastfed and non-breastfed toddlers residing in Metro Vancouver, Canada. Methods We studied cross-sectional baseline data from 18 mo old toddlers enrolled in a partially randomized controlled trial. Toddlers were categorized as breastfed (currently receiving breastmilk as the primary milk source, i.e., ≥2 times/day) and non-/occasionally-breastfed. Results Sixty-five toddlers, with preliminary data available at the time of analysis, had an equal distribution of males and females, 68% were the first-born child, and 55%, 19%, and 26% were of European, Chinese or other ethnicity, respectively. Twenty-eight of the 18-mo old toddlers (43%) were still breastfed, with 93% (n = 26) receiving breastmilk as the primary source of milk. Plasma vitamin A was lower, and plasma betaine and docosahexaenoic acid (DHA) as a percentage of red blood cell fatty acids were significantly higher in breastfed toddlers compared to the other group (all P &amp;lt; 0.05; Mann-Whitney U test). There was a trend for lower plasma ferritin in breastfed toddlers (P &amp;lt; 0.1). Plasma lutein, vitamin D, and choline concentrations did not differ between groups. Conclusions These preliminary findings reflect possible differences in biomarker status between breastfed and non-/occasionally-breastfed toddlers. The analysis of total dietary intake and complementary feeding patterns is warranted to determine what types of food and beverages take the place of breastmilk in 18 mo old toddlers, and which dietary sources may explain the differing nutrient status. Funding Sources This study is supported by The University of British Columbia, and the British Columbia Children's Hospital Research Institute, Canada, and is funded by Société des Produits Nestlé S.A.

Plasma Choline Concentration Is Positively Correlated with Visual Acuity in 18-Month Old Toddlers: Preliminary Findings

Abstract Objectives Adequate dietary intake of key nutrients is critical for brain and eye development in the first 1000 days of life. In particular, docosahexaenoic acid (DHA) and lutein are known for their roles in the development of visual acuity during infancy and early childhood. Preliminary data suggest that choline may also play a role in visual acuity; however, little is known about choline's role in visual acuity during toddlerhood. We hypothesize thatbiomarkers for DHA, choline, and lutein status are positively correlated with visual acuity in toddler-aged children. Methods We studied cross-sectional baseline data from participants aged 18 months ± 2 weeks enrolled in a partially randomized controlled trial investigating associations between feeding patterns, nutrient biomarker status, and neurodevelopmental outcomes. Participants were recruited in Metro Vancouver, Canada. Visual acuity was measured using the Cardiff Acuity test with the logarithm of the minimum angle of resolution (LogMAR) as the measure of visual acuity. The child's confidence in test completion was rated using a 5-point Likert scale; test results with confidence scores below 3 were excluded from further analyses. Results Sixty-nine toddlers, with preliminary data available at the time of analysis, had an equal distribution of males and females, 68% were the first-born child, and 55%, 19%, and 26% were of European, Chinese or other ethnicity, respectively. Preliminary (unadjusted) findings showed a positive correlation between plasma choline and visual acuity (rho = 0.33, P &amp;lt; 0.05). No significant correlations were observed between visual acuity and DHA concentration (as a percentage of total fatty acids from red blood cells) nor between visual acuity and plasma lutein concentration. Conclusions Plasma choline may be positively associated with visual acuity at 18 months of age. These preliminary findings require confirmation in a larger sample size and testing of the causality of this relationship in a dose-dependency trial. Acknowledgment: We are grateful for Dr. Margaret Woodhouse's guidance in the methodology of the Cardiff Acuity test. Funding Sources This study is supported by The University of British Columbia, and the British Columbia Children's Hospital Research Institute and is funded by Société des Produits Nestlé S.A.

Blood DHA, Choline, and Lutein Concentrations and Their Correlation with Cognitive and Behavioral Outcomes in 18-Month Old Toddlers: Preliminary Findings

Abstract Objectives The objective of this study was to investigate associations between key nutrients identified as critical for central nervous system development and function, but which are limited in the diet of toddlers, and neurodevelopmental outcomes in toddler-aged children. We hypothesize that higher concentrations of key nutrients are associated with higher neurocognitive development scores. Methods Cross-sectional baseline data were drawn from 18-month old toddlers residing in Vancouver, Canada, who participated in a partially randomized controlled trial investigating associations between feeding patterns, nutrient biomarker status, and neurodevelopmental outcomes. Cognitive and behavioural outcomes considered for this analysis included: The Bayley Scale of Infant Development (3rd Ed; BSID-III); Child Behavior Checklist (CBCL); Early Childhood Behavior Questionnaire Very Short Form (ECBQ); and the MacArthur-Bates Communicative Development Inventories (Words &amp; Gestures and Words &amp; Sentences; MCDI-WG &amp; WS). Blood biomarkers of nutrients of interest included plasma concentration of ferritin, lutein, choline, vitamins A and D, and betaine, as well as docosahexaenoic acid (DHA) measured as a percentage of total fatty acids in red blood cells. Results Sixty-nine toddlers (34 boys, 35 girls) with preliminary data available had a mean gestational age at birth and birthweight of 39.5 weeks and 3.48 kg, respectively. Preliminary (unadjusted) findings show higher levels of DHA corresponded with lower scores of effortful control on the ECBQ (rho = –.35, P &amp;lt; .01) while higher levels of lutein were associated with higher scores on the MCDI-WG (rho = .33, P &amp;lt; .05). Conclusions These preliminary findings may reflect an important association between nutritional status and optimal brain function at 18-months of age, a period of life which is particularly sensitive to nutrient inadequacies. These findings require confirmation in a larger sample size and causality testing of the relationship in a dose-dependency trial. Funding Sources This study is supported by The University of British Columbia, and the British Columbia Children's Hospital Research Institute, Canada, and is funded by Société des Produits Nestlé S.A.

Clinical Impact and Cost Efficacy of Newborn Screening for Congenital Adrenal Hyperplasia

To evaluate the clinical impact of a congenital adrenal hyperplasia (CAH) newborn screening program and incremental costs relative to benefits in screened vs unscreened infants. We hypothesized that screening would lead to clinical benefits and would be cost effective. This was an ambispective cohort study at British Columbia Children's Hospital, including infants diagnosed with CAH from 1988-2008 and 2010-2018. Data were collected retrospectively (unscreened cohort) and prospectively (screened cohort). Outcome measures included hospitalization, medical transport, and resuscitation requirements. The economic analysis was performed using a public payer perspective. Forty unscreened and 17 screened infants were diagnosed with CAH (47% vs 53% male). Median days to positive screen was 6 and age at diagnosis was 5days (range, 0-30days) and 6days (range, 0-13days) in unscreened and screened populations, respectively. In unscreened newborns, 55% required transport to a tertiary care hospital, 85% required hospitalization, and 35% required a fluid bolus compared with 29%, 29%, and 12% in screened infants, respectively. The cost of care was $33 770 per case in unscreened vs $17 726 in screened newborns. In the screened cohort, the incremental cost-effectiveness ratio was $290 in the best case analysis and $4786 in the base case analysis, per hospital day avoided. Compared with unscreened newborns, those screened for CAH were less likely to require medical transport and had shorter hospital stays. Screening led to a decrease in hospitalization costs. Although screening did not result in cost savings, it was assessed to be cost effective considering the clinical benefits and incremental cost-effectiveness ratio.