Skip to main content
Top
Published in: Orphanet Journal of Rare Diseases 1/2019

Open Access 01-12-2019 | Neonatal Screening | Research

Health services use among children diagnosed with medium-chain acyl-CoA dehydrogenase deficiency through newborn screening: a cohort study in Ontario, Canada

Authors: Maria D. Karaceper, Sara D. Khangura, Kumanan Wilson, Doug Coyle, Marni Brownell, Christine Davies, Linda Dodds, Annette Feigenbaum, Deshayne B. Fell, Scott D. Grosse, Astrid Guttmann, Steven Hawken, Robin Z. Hayeems, Jonathan B. Kronick, Anne-Marie Laberge, Julian Little, Aizeddin Mhanni, John J. Mitchell, Meranda Nakhla, Murray Potter, Chitra Prasad, Cheryl Rockman-Greenberg, Rebecca Sparkes, Sylvia Stockler, Keiko Ueda, Hilary Vallance, Brenda J. Wilson, Pranesh Chakraborty, Beth K. Potter, in collaboration with the Canadian Inherited Metabolic Diseases Research Network (CIMDRN)

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

Login to get access

Abstract

Background

We describe early health services utilization for children diagnosed with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency through newborn screening in Ontario, Canada, relative to a screen negative comparison cohort.

Methods

Eligible children were identified via newborn screening between April 1, 2006 and March 31, 2010. Age-stratified rates of physician encounters, emergency department (ED) visits and inpatient hospitalizations to March 31, 2012 were compared using incidence rate ratios (IRR) and incidence rate differences (IRD). We used negative binomial regression to adjust IRRs for sex, gestational age, birth weight, socioeconomic status and rural/urban residence.

Results

Throughout the first few years of life, children with MCAD deficiency (n = 40) experienced statistically significantly higher rates of physician encounters, ED visits, and hospital stays compared with the screen negative cohort. The highest rates of ED visits and hospitalizations in the MCAD deficiency cohort occurred from 6 months to 2 years of age (ED use: 2.1–2.5 visits per child per year; hospitalization: 0.5–0.6 visits per child per year), after which rates gradually declined.

Conclusions

This study confirms that young children with MCAD deficiency use health services more frequently than the general population throughout the first few years of life. Rates of service use in this population gradually diminish after 24 months of age.
Literature
1.
go back to reference Kennedy S, Potter BK, Wilson K, Fisher L, Geraghty M, Milburn J, et al. The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) by newborn screening Ontario. BMC Pediatr. 2010;10:82.CrossRef Kennedy S, Potter BK, Wilson K, Fisher L, Geraghty M, Milburn J, et al. The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) by newborn screening Ontario. BMC Pediatr. 2010;10:82.CrossRef
2.
go back to reference Oerton J, Khalid JM, Besley G, Dalton RN, Downing M, Green A, et al. Newborn screening for medium chain acyl-CoA dehydrogenase deficiency in England: prevalence, predictive value and test validity based on 1.5 million screened babies. J Med Screen. 2011;18:173–81.CrossRef Oerton J, Khalid JM, Besley G, Dalton RN, Downing M, Green A, et al. Newborn screening for medium chain acyl-CoA dehydrogenase deficiency in England: prevalence, predictive value and test validity based on 1.5 million screened babies. J Med Screen. 2011;18:173–81.CrossRef
3.
go back to reference Grosse SD, Khoury MJ, Greene CL, Crider KS, Pollitt RJ. The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: an update. Genet Med. 2006;8:205–12.CrossRef Grosse SD, Khoury MJ, Greene CL, Crider KS, Pollitt RJ. The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: an update. Genet Med. 2006;8:205–12.CrossRef
5.
go back to reference Bennett MJ. Pathophysiology of fatty acid oxidation disorders. J Inherit Metab Dis. 2010;33:533–7.CrossRef Bennett MJ. Pathophysiology of fatty acid oxidation disorders. J Inherit Metab Dis. 2010;33:533–7.CrossRef
6.
go back to reference Wilcken B. Fatty acid oxidation disorders: outcome and long-term prognosis. J Inherit Metab Dis. 2010;33:501–6.CrossRef Wilcken B. Fatty acid oxidation disorders: outcome and long-term prognosis. J Inherit Metab Dis. 2010;33:501–6.CrossRef
7.
go back to reference Wilcken B, Haas M, Joy P, Wiley V, Chaplin M, Black C, et al. Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet. 2007;369:37–42.CrossRef Wilcken B, Haas M, Joy P, Wiley V, Chaplin M, Black C, et al. Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet. 2007;369:37–42.CrossRef
8.
go back to reference Wilcken B, Haas M, Joy P, Wiley V, Bowling F, Carpenter K, et al. Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics. 2009;124:e241–8.CrossRef Wilcken B, Haas M, Joy P, Wiley V, Bowling F, Carpenter K, et al. Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics. 2009;124:e241–8.CrossRef
9.
go back to reference Prosser LA, Grosse SD, Kemper AR, Tarini BA, Perrin JM. Decision analysis, economic evaluation, and newborn screening: challenges and opportunities. Genet Med. 2012;14:703–12.CrossRef Prosser LA, Grosse SD, Kemper AR, Tarini BA, Perrin JM. Decision analysis, economic evaluation, and newborn screening: challenges and opportunities. Genet Med. 2012;14:703–12.CrossRef
10.
go back to reference Hamers FF, Rumeau-Pichon C. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France. BMC Pediatr. 2012;12:60.CrossRef Hamers FF, Rumeau-Pichon C. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France. BMC Pediatr. 2012;12:60.CrossRef
11.
go back to reference Ahrens-Nicklas RC, Pyle LC, Ficicioglu C. Morbidity and mortality among exclusively breastfed neonates with medium-chain acyl-CoA dehydrogenase deficiency. Genet Med. 2016;18:1315–9.CrossRef Ahrens-Nicklas RC, Pyle LC, Ficicioglu C. Morbidity and mortality among exclusively breastfed neonates with medium-chain acyl-CoA dehydrogenase deficiency. Genet Med. 2016;18:1315–9.CrossRef
12.
go back to reference van der Hilst CS, Derks TGJ, Reijngoud DJ, Smit GPA, TenVergert EM. Cost-effectiveness of neonatal screening for medium chain acyl-CoA dehydrogenase deficiency: the homogeneous oopulation of the Netherlands. J Pediatr. 2007;151:115–20.CrossRef van der Hilst CS, Derks TGJ, Reijngoud DJ, Smit GPA, TenVergert EM. Cost-effectiveness of neonatal screening for medium chain acyl-CoA dehydrogenase deficiency: the homogeneous oopulation of the Netherlands. J Pediatr. 2007;151:115–20.CrossRef
13.
go back to reference Prosser LA, Kong CY, Rusinak D, Waisbren SL. Projected costs, risks, and benefits of expanded newborn screening for MCADD. Pediatrics. 2010;125:e286–94.CrossRef Prosser LA, Kong CY, Rusinak D, Waisbren SL. Projected costs, risks, and benefits of expanded newborn screening for MCADD. Pediatrics. 2010;125:e286–94.CrossRef
14.
go back to reference Norman R, Haas M, Wilcken B. International perspectives on the cost-effectiveness of tandem mass spectrometry for rare metabolic conditions. Health Policy. 2009;89:252–60.CrossRef Norman R, Haas M, Wilcken B. International perspectives on the cost-effectiveness of tandem mass spectrometry for rare metabolic conditions. Health Policy. 2009;89:252–60.CrossRef
15.
go back to reference Feuchtbaum L, Cunningham G. Economic evaluation of tandem mass spectrometry screening in California. Pediatrics. 2006;117:S280–6.CrossRef Feuchtbaum L, Cunningham G. Economic evaluation of tandem mass spectrometry screening in California. Pediatrics. 2006;117:S280–6.CrossRef
16.
go back to reference Venditti LN, Venditti CP, Berry GT, Kaplan PB. Newborn screening by tandem mass spectrometry for medium-chain acyl-CoA dehydrogenase deficiency: a cost-effectiveness analysis. Pediatrics. 2003;112:1005–15.CrossRef Venditti LN, Venditti CP, Berry GT, Kaplan PB. Newborn screening by tandem mass spectrometry for medium-chain acyl-CoA dehydrogenase deficiency: a cost-effectiveness analysis. Pediatrics. 2003;112:1005–15.CrossRef
17.
go back to reference Grosse SD. Economic evaluations of newborn screening. In: Ungar WJ, editor. Economic evaluation in child health. New York: Oxford University Press; 2009. p. 113–32.CrossRef Grosse SD. Economic evaluations of newborn screening. In: Ungar WJ, editor. Economic evaluation in child health. New York: Oxford University Press; 2009. p. 113–32.CrossRef
18.
go back to reference Andresen BS, Dobrowolski SF, O’Reilly L, Muenzer J, McCandless SE, Frazier DM, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet. 2001;68:1408–18.CrossRef Andresen BS, Dobrowolski SF, O’Reilly L, Muenzer J, McCandless SE, Frazier DM, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet. 2001;68:1408–18.CrossRef
19.
go back to reference Maier EM, Liebl B, Roschinger W, Nennstiel-Ratzel U, Fingerhut R, Olgemoller B, et al. Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat. 2005;25:443–52.CrossRef Maier EM, Liebl B, Roschinger W, Nennstiel-Ratzel U, Fingerhut R, Olgemoller B, et al. Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat. 2005;25:443–52.CrossRef
20.
go back to reference Hsu H-W, Zytkovicz TH, Comeau AM, Strauss AW, Marsden D, Shih VE, et al. Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening. Pediatrics. 2008;121:1108–14.CrossRef Hsu H-W, Zytkovicz TH, Comeau AM, Strauss AW, Marsden D, Shih VE, et al. Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening. Pediatrics. 2008;121:1108–14.CrossRef
21.
go back to reference Gramer G, Haege G, Fang-Hoffmann J, Hoffmann GF, Bartram CR, Hinderhofer K, et al. Medium-chain acyl-CoA dehydrogenase deficiency: evaluation of genotype-phenotype correlation in patients detected by newborn screening. JIMD Rep. 2015;23:101–12.CrossRef Gramer G, Haege G, Fang-Hoffmann J, Hoffmann GF, Bartram CR, Hinderhofer K, et al. Medium-chain acyl-CoA dehydrogenase deficiency: evaluation of genotype-phenotype correlation in patients detected by newborn screening. JIMD Rep. 2015;23:101–12.CrossRef
22.
go back to reference Potter BK, Little J, Chakraborty P, Kronick JB, Evans J, Frei J, et al. Variability in the clinical management of fatty acid oxidation disorders: results of a survey of Canadian metabolic physicians. J Inherit Metab Dis. 2012;35:115–23.CrossRef Potter BK, Little J, Chakraborty P, Kronick JB, Evans J, Frei J, et al. Variability in the clinical management of fatty acid oxidation disorders: results of a survey of Canadian metabolic physicians. J Inherit Metab Dis. 2012;35:115–23.CrossRef
23.
24.
go back to reference Canadian Institute for Health Information (CIHI). National Ambulatory Care Reporting System Data Quality Documentation - Current-Year Information, 2011–2012. Toronto: CIHI; 2012. Canadian Institute for Health Information (CIHI). National Ambulatory Care Reporting System Data Quality Documentation - Current-Year Information, 2011–2012. Toronto: CIHI; 2012.
25.
go back to reference Canadian Institute for Health Information (CIHI). Data quality documentation, Discharge Abstract Database - Current-year information, 2011–2012. Toronto: CIHI; 2012. Canadian Institute for Health Information (CIHI). Data quality documentation, Discharge Abstract Database - Current-year information, 2011–2012. Toronto: CIHI; 2012.
26.
go back to reference Statistics Canada. 2006 Census Dictionary. Ottawa, Ontario; Statistics Canadsa, 2007. Statistics Canada. 2006 Census Dictionary. Ottawa, Ontario; Statistics Canadsa, 2007.
27.
go back to reference Wang C, Guttmann A, To T, Dick PT. Neighborhood income and health outcomes in infants: how do those with complex chronic conditions fare? Arch Pediatr Adolesc Med 2009;163:608–615. Wang C, Guttmann A, To T, Dick PT. Neighborhood income and health outcomes in infants: how do those with complex chronic conditions fare? Arch Pediatr Adolesc Med 2009;163:608–615.
28.
go back to reference Kralj B. Measuring rurality - RIO2008 BASIC: Methodology and results. Ottawa: Ontario Medical Association; 2010. Kralj B. Measuring rurality - RIO2008 BASIC: Methodology and results. Ottawa: Ontario Medical Association; 2010.
29.
go back to reference Ontario Ministry of Health and Long-term Care. (OMHLTC). Rural physician eligibility requirements. Toronto: OMHLTC; 2013. Ontario Ministry of Health and Long-term Care. (OMHLTC). Rural physician eligibility requirements. Toronto: OMHLTC; 2013.
30.
go back to reference Vuong QH. Likelihood ratio tests for model selection and non-nested hypotheses. Econometrica. 1989;57:307–33.CrossRef Vuong QH. Likelihood ratio tests for model selection and non-nested hypotheses. Econometrica. 1989;57:307–33.CrossRef
31.
go back to reference Bollen KA, Jackman RW. Regression diagnostics: an expository treatment of outliers and influential cases. Sociol Methods Res. 1985;13:510–42.CrossRef Bollen KA, Jackman RW. Regression diagnostics: an expository treatment of outliers and influential cases. Sociol Methods Res. 1985;13:510–42.CrossRef
32.
go back to reference Belsley D, Kuh E, Welsch RE. Regression Diagnostics: Identifying influential data and sources of collinearity. Hoboken: Wiley-Interscience; 2005. Belsley D, Kuh E, Welsch RE. Regression Diagnostics: Identifying influential data and sources of collinearity. Hoboken: Wiley-Interscience; 2005.
33.
go back to reference Hinton CF, Mai CT, Nabukera SK, Botto LD, Feuchtbaum L, Romitti PA, et al. Developing a public health-tracking system for follow-up of newborn screening metabolic conditions: a four-state pilot project structure and initial findings. Genet Med. 2014;16:484–90.CrossRef Hinton CF, Mai CT, Nabukera SK, Botto LD, Feuchtbaum L, Romitti PA, et al. Developing a public health-tracking system for follow-up of newborn screening metabolic conditions: a four-state pilot project structure and initial findings. Genet Med. 2014;16:484–90.CrossRef
34.
go back to reference Wang Y, Sango-Jordan M, Caggana M. Acute care utilization for inherited metabolic diseases among children identified through newborn screening in New York state. Genet Med. 2014;16:665–70.CrossRef Wang Y, Sango-Jordan M, Caggana M. Acute care utilization for inherited metabolic diseases among children identified through newborn screening in New York state. Genet Med. 2014;16:665–70.CrossRef
35.
go back to reference Haas M, Chaplin M, Joy P, Wiley V, Black C, Wilcken B. Healthcare use and costs of medium-chain acyl-CoA dehydrogenase deficiency in Australia: screening versus no screening. J Pediatr. 2007;151:121–6.CrossRef Haas M, Chaplin M, Joy P, Wiley V, Black C, Wilcken B. Healthcare use and costs of medium-chain acyl-CoA dehydrogenase deficiency in Australia: screening versus no screening. J Pediatr. 2007;151:121–6.CrossRef
36.
go back to reference Schatz UA, Ensenauer R. The clinical manifestation of MCAD deficiency: challenges towards adulthood in the screened population. J Inherit Metab Dis. 2010;33:513–20.CrossRef Schatz UA, Ensenauer R. The clinical manifestation of MCAD deficiency: challenges towards adulthood in the screened population. J Inherit Metab Dis. 2010;33:513–20.CrossRef
37.
go back to reference Lang TF. Adult presentations of medium-chain acyl-CoA dehydrogenase deficiency (MCADD). J Inherit Metab Dis. 2009;32:675–83.CrossRef Lang TF. Adult presentations of medium-chain acyl-CoA dehydrogenase deficiency (MCADD). J Inherit Metab Dis. 2009;32:675–83.CrossRef
38.
go back to reference Arnold GL, Saavedra-Matiz CA, Galvin-Parton PA, Erbe R, DeVincentis E, Kronn D, et al. Lack of genotype-phenotype correlations and outcome in MCAD deficiency diagnosed by newborn screening in New York state. Mol Genet Metab. 2010;99:263–8.CrossRef Arnold GL, Saavedra-Matiz CA, Galvin-Parton PA, Erbe R, DeVincentis E, Kronn D, et al. Lack of genotype-phenotype correlations and outcome in MCAD deficiency diagnosed by newborn screening in New York state. Mol Genet Metab. 2010;99:263–8.CrossRef
39.
go back to reference Berry SA, Leslie ND, Edick MJ, Hiner S, Justice K, Cameron C. Inborn errors of metabolism collaborative: large-scale collection of data on long-term follow-up for newborn-screened conditions. Genet Med. 2016;18:1276–81.CrossRef Berry SA, Leslie ND, Edick MJ, Hiner S, Justice K, Cameron C. Inborn errors of metabolism collaborative: large-scale collection of data on long-term follow-up for newborn-screened conditions. Genet Med. 2016;18:1276–81.CrossRef
40.
go back to reference Wasserstein MP. Long-term follow-up in newborn screening: the role of collaboration. Genet Med. (e-pub ahead of print). Wasserstein MP. Long-term follow-up in newborn screening: the role of collaboration. Genet Med. (e-pub ahead of print).
Metadata
Title
Health services use among children diagnosed with medium-chain acyl-CoA dehydrogenase deficiency through newborn screening: a cohort study in Ontario, Canada
Authors
Maria D. Karaceper
Sara D. Khangura
Kumanan Wilson
Doug Coyle
Marni Brownell
Christine Davies
Linda Dodds
Annette Feigenbaum
Deshayne B. Fell
Scott D. Grosse
Astrid Guttmann
Steven Hawken
Robin Z. Hayeems
Jonathan B. Kronick
Anne-Marie Laberge
Julian Little
Aizeddin Mhanni
John J. Mitchell
Meranda Nakhla
Murray Potter
Chitra Prasad
Cheryl Rockman-Greenberg
Rebecca Sparkes
Sylvia Stockler
Keiko Ueda
Hilary Vallance
Brenda J. Wilson
Pranesh Chakraborty
Beth K. Potter
in collaboration with the Canadian Inherited Metabolic Diseases Research Network (CIMDRN)
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-019-1001-0

Other articles of this Issue 1/2019

Orphanet Journal of Rare Diseases 1/2019 Go to the issue