The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: A cohort study

Background - There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. Methods - The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. Results - We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. Conclusions - The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.This study was Funded through a Canadian Institutes of Health Research (CIHR) Emerging Team Grant (TR3-119195). Maria Karaceper received a graduate scholarship through a charitable donation to the Children’s Hospital of Eastern Ontario. This study was performed at the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC)

An examination of sex differences in associations between cord blood adipokines and childhood adiposity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154308/1/ijpo12587.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154308/2/ijpo12587_am.pd

Scoping review of patient- and family-oriented outcomes and measures for chronic pediatric disease.

Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatric diseases similar to IEM in etiology or manifestations and in complexity of management; (ii) reported patient- and/or family-oriented outcomes; and (iii) measured these outcomes using self-administered tools.We developed a comprehensive review protocol and implemented an electronic search strategy to identify relevant citations in Medline, EMBASE, DARE and Cochrane. Two reviewers applied pre-specified criteria to titles/abstracts using a liberal accelerated approach. Articles eligible for full-text review were screened by two independent reviewers with discrepancies resolved by consensus. One researcher abstracted data on study characteristics, patient- and family-oriented outcomes, and self-administered measures. Data were validated by a second researcher.4,118 citations were screened with 304 articles included. Across all included reports, the most-represented diseases were diabetes (35%), cerebral palsy (23%) and epilepsy (18%). We identified 43 unique patient- and family-oriented outcomes from among five emergent domains, with mental health outcomes appearing most frequently. The studies reported the use of 405 independent self-administered measures of these outcomes.Patient- and family-oriented research investigating chronic pediatric diseases emphasizes mental health and appears to be relatively well-developed in the diabetes literature. Future research can build on this foundation while identifying additional outcomes that are priorities for patients and families

Achieving the "triple aim" for inborn errors of metabolism: a review of challenges to outcomes research and presentation of a new practice-based evidence framework

Across all areas of health care, decision makers are in pursuit of what Berwick and colleagues have called the “triple aim”: improving patient experiences with care, improving health outcomes, and managing health system impacts. This is challenging in a rare disease context, as exemplified by inborn errors of metabolism. There is a need for evaluative outcomes research to support effective and appropriate care for inborn errors of metabolism. We suggest that such research should consider interventions at both the level of the health system (e.g., early detection through newborn screening, programs to provide access to treatments) and the level of individual patient care (e.g., orphan drugs, medical foods). We have developed a practice- based evidence framework to guide outcomes research for inborn errors of metabolism. Focusing on outcomes across the triple aim, this framework integrates three priority themes: tailoring care in the context of clinical heterogeneity; a shift from “urgent care” to “opportunity for improvement”; and the need to evaluate the comparative effectiveness of emerging and established therapies. Guided by the framework, a new Canadian research network has been established to generate knowledge that will inform the design and delivery of health services for patients with inborn errors of metabolism and other rare diseases.This work was supported by a CIHR Emerging Team Grant (“Emerging team in rare diseases: acheiving the ‘triple aim’ for inborn errors of metabolism,” B.K. Potter, P. Chakraborty, and colleagues, 2012– 2017, grant no. TR3–119195). Current investigators and collaborators in the Canadian Inherited Metabolic Diseases Research Network are: B.K. Potter, P. Chakraborty, J. Kronick, D. Coyle, K. Wilson, M. Brownell, R. Casey, A. Chan, S. Dyack, L. Dodds, A. Feigenbaum, D. Fell, M. Geraghty, C. Greenberg, S. Grosse, A. Guttmann, A. Khan, J. Little, B. Maranda, J. MacKenzie, A. Mhanni, F. Miller, G. Mitchell, J. Mitchell, M. Nakhla, M. Potter, C. Prasad, K. Siriwardena, K.N. Speechley, S. Stocker, L. Turner, H. Vallance, and B.J. Wilson. Members of our external advisory board are D. Bidulka, T. Caulfield, J.T.R. Clarke, C. Doiron, K. El Emam, J. Evans, A. Kemper, W. McCormack, and A. Stephenson Julian. J. Little is supported by a Canada Research Chair in Human Genome Epidemiology. K. Wilson is supported by a Canada Research Chair in Public Health Policy

The Epidemiology and Health System Impact of Medium-Chain Acyl-CoA Dehydrogenase Deficiency Among Affected Children and Those with False Positive Newborn Screening Results in Ontario, Canada

Objective: To describe the epidemiology and health system impact of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in Ontario. Methods: Following a review of methods to estimating robust health event rates for small populations, this study described health services use among infants diagnosed with MCADD or received a false positive newborn screening result for MCADD from April 2006 through March 2010. Each cohort was compared with screen negative infants by linking to databases encompassing physician visits, emergency department care, and hospitalizations. Results: Relative to comparison birth cohorts, children with MCADD (n=40) experienced significantly higher rates of all health service types, regardless of age at the time of visit; infants with false positive results for MCADD (n=43) experienced significantly higher rates of physician visits and hospitalizations in the first year of life only. Conclusion: This study makes an important contribution to the limited existing research describing the health system impact of rare diseases

Prevalence and Risk Factors of Metabolic-Associated Fatty Liver Disease in Children with Down Syndrome at a Tertiary Care Center

Background: The global rise of metabolic-associated fatty liver disease (MAFLD) in children is particularly concerning in high-risk groups such as those with Down Syndrome (DS), who have an elevated risk of obesity and insulin resistance. Despite increasing recognition of MAFLD in pediatric populations, data on its prevalence and risk factors among children with DS in Canada remain limited. Method: This retrospective study reviewed medical records of children with DS at the CHEO Down Syndrome Clinic (2013–2023). A diagnosis of MAFLD required evidence of hepatic steatosis on imaging, lab markers, or biopsy, along with the presence of metabolic risk features. Demographic, laboratory, and diagnostic data were analyzed. Results: Among 503 children with DS (231 females, 271 males; median age: 172 months), 54 (10.7%) had MAFLD. The MAFLD group was older (median age: 205 vs. 163 months, p = 0.0002) and had higher BMI (31.39 vs. 20.5, p < 0.0001). Most cases (47/54) were diagnosed via ultrasound, and 49/54 met MAFLD criteria due to excessive adiposity. Lab results showed a median ALT of 35 U/L, triglycerides of 4.4 mmol/L, and LDL cholesterol of 2.59 mmol/L. FibroScan in 13 children revealed a median transient elastography of 5.3 kPa. BMI was the strongest predictor of MAFLD (OR: 1.2, 95% CI: 1.1–1.2). Conclusions: The DS clinic-based prevalence of MAFLD underscores the need for proactive screening and early intervention. BMI was the strongest predictor, emphasizing targeted management strategies. Further research is needed to refine diagnostic approaches and improve outcomes

Health services use by children identified as heterozygous hemoglobinopathy mutation carriers via newborn screening

Abstract Background Newborn screening (NBS) for sickle cell disease incidentally identifies heterozygous carriers of hemoglobinopathy mutations. In Ontario, Canada, these carrier results are not routinely disclosed, presenting an opportunity to investigate the potential health implications of carrier status. We aimed to compare rates of health services use among children identified as carriers of hemoglobinopathy mutations and those who received negative NBS results. Methods Eligible children underwent NBS in Ontario from October 2006 to March 2010 and were identified as carriers or as screen-negative controls, matched to carriers 5:1 based on neighbourhood and timing of birth. We used health care administrative data to determine frequencies of inpatient hospitalizations, emergency department (ED) visits, and physician encounters through March 2012, using multivariable negative binomial regression to compare rates of service use in the two cohorts. We analyzed data from 4987 carriers and 24,935 controls. Results Adjusted incidence rate ratios (95% CI) for service use in carriers versus controls among children &lt; 1 year of age were: 1.11 (1.06–1.17) for ED visits; 0.97 (0.89–1.06) for inpatient hospitalization; and 1.02 (1.00–1.04) for physician encounters. Among children ≥1 year of age, adjusted rate ratios were: 1.03 (0.98–1.07) for ED visits; 1.14 (1.03–1.25) for inpatient hospitalization and 0.92 (0.90–0.94) for physician encounters. Conclusions While we identified statistically significant differences in health services use among carriers of hemoglobinopathy mutations relative to controls, effect sizes were small and directions of association inconsistent across age groups and health service types. Our findings are consistent with the assumption that carrier status is likely benign in early childhood. </jats:sec

Health services use by children identified as heterozygous hemoglobinopathy mutation carriers via newborn screening

Abstract Background Newborn screening (NBS) for sickle cell disease incidentally identifies heterozygous carriers of hemoglobinopathy mutations. In Ontario, Canada, these carrier results are not routinely disclosed, presenting an opportunity to investigate the potential health implications of carrier status. We aimed to compare rates of health services use among children identified as carriers of hemoglobinopathy mutations and those who received negative NBS results. Methods Eligible children underwent NBS in Ontario from October 2006 to March 2010 and were identified as carriers or as screen-negative controls, matched to carriers 5:1 based on neighbourhood and timing of birth. We used health care administrative data to determine frequencies of inpatient hospitalizations, emergency department (ED) visits, and physician encounters through March 2012, using multivariable negative binomial regression to compare rates of service use in the two cohorts. We analyzed data from 4987 carriers and 24,935 controls. Results Adjusted incidence rate ratios (95% CI) for service use in carriers versus controls among children < 1 year of age were: 1.11 (1.06–1.17) for ED visits; 0.97 (0.89–1.06) for inpatient hospitalization; and 1.02 (1.00–1.04) for physician encounters. Among children ≥1 year of age, adjusted rate ratios were: 1.03 (0.98–1.07) for ED visits; 1.14 (1.03–1.25) for inpatient hospitalization and 0.92 (0.90–0.94) for physician encounters. Conclusions While we identified statistically significant differences in health services use among carriers of hemoglobinopathy mutations relative to controls, effect sizes were small and directions of association inconsistent across age groups and health service types. Our findings are consistent with the assumption that carrier status is likely benign in early childhood