TY - JOUR
T1 - Improving the Dutch newborn screening for central congenital hypothyroidism by using 95% reference intervals for thyroxine-binding globulin
AU - Stroek, Kevin
AU - Heijboer, Annemieke C.
AU - van Veen-Sijne, Marja
AU - Bosch, Annet M.
AU - van der Ploeg, Catharina P. B.
AU - Zwaveling-Soonawala, Nitash
AU - de Jonge, Robert
AU - van Trotsenburg, A. S. Paul
AU - Boelen, Anita
N1 - Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Introduction: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/ TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. Materials and Methods: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical & Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. Results: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56-118 nmol/L), TSH (<2.6 mIU/L), TBG (116-271 nmol/L), and the T4/TBG ratio (>20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG de ficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). Discussion/Conclusion: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.
AB - Introduction: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/ TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. Materials and Methods: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical & Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. Results: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56-118 nmol/L), TSH (<2.6 mIU/L), TBG (116-271 nmol/L), and the T4/TBG ratio (>20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG de ficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). Discussion/Conclusion: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.
KW - Central congenital hypothyroidism
KW - Newborn screening
KW - Reference intervals
KW - Thyroxine
KW - Thyroxine-binding globulin
UR - http://www.scopus.com/inward/record.url?scp=85102557293&partnerID=8YFLogxK
U2 - https://doi.org/10.1159/000513516
DO - https://doi.org/10.1159/000513516
M3 - Article
C2 - 34178708
SN - 2235-0640
VL - 10
SP - 222
EP - 229
JO - European thyroid journal
JF - European thyroid journal
IS - 3
ER -