- Author
-
K. Stroek
- Title
- Optimization of established and assessment of novel newborn screening strategies in the Netherlands
- Supervisors
-
A. Boelen
A.M. Bosch - Co-supervisors
-
R. de Jonge
A.C. Heijboer - Award date
- 28 May 2021
- Number of pages
- 180
- ISBN
- 9789464232325
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Newborn screening (NBS) is an important method for prevention of long-term health consequences or premature death in newborns with inherited disorders. A challenge in NBS is to find a balance between disease detection and false-positive referrals by choosing appropriate screening markers and cut-off values (COVs). In our studies, we performed systematic reviews and prospective and retrospective studies to collect Dutch NBS data for evaluation and optimization of NBS strategies.
We proposed to perform the new GALK deficiency NBS with total galactose as a primary marker with a COV of ≥ 2500 µmol/L blood, to ensure detection of GALK deficiency patients and minimize false-positive referrals. Furthermore, for maple syrup urine disease NBS (positive predictive value (PPV) 3.3%), we recommend a strategy with the current leucine and valine COVs of ≥ 340 µmol/L blood as a first-tier test and the leucine/phenylalanine ratio with a COV of ≥ 5.0 as a second-tier to improve the PPV to 19%. In congenital hypothyroidism NBS (PPV 21%), 55% of false-positive referrals were caused by the thyroxine/thyroxine-binding globulin (TBG) ratio. To prevent false-positives due to (partial) TBG deficiency, we recommended against referral when TBG concentrations were above 105 nmol/L blood. Alternatively, we showed that random forest models have the potential to improve the PPV to 26%. In NBS for congenital adrenal hyperplasia, we recommended the addition of the 21-deoxycortisol second-tier test to all inconclusive first heel puncture results in order to reduce false-positives by 67% and remove the need for a second heel puncture. - Persistent Identifier
- https://hdl.handle.net/11245.1/66510804-80f7-4453-8af7-988f3b348019
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction and thesis outline
Chapter 2: Recommendations for newborn screening for galactokinase deficiency: A systematic review and evaluation of Dutch newborn screening data
Chapter 3: Evaluation of eleven years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature: Strategies for optimization
Chapter 4: Critical evaluation of the newborn screening for congenital hypothyroidism in the Netherlands
Chapter 5: Improving the Dutch newborn screening for central congenital hypothyroidism by using 95% reference intervals for thyroxine-binding globulin
Chapter 6: Newborn screening for congenital hypothyroidism: Man versus machine
Chapter 7: Second-tier testing for 21-hydroxylase deficiency in the Netherlands: A newborn screening pilot study
Chapter 8: General discussion and future perspectives
Chapter 9: Summary
Nederlandse samenvatting
List of publications; Dankwoord; PhD portfolio; About the author
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.