Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth

Introduction: Severe Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculos...

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Main Authors: Chan, Bianca Su-Wan, Zhong, Youjia, Lim, James Soon Chuan, Poh, Sherry, Teh, Kai Liang, Soh, Jian Yi, Chong, Chia Yin, Thoon, Koh Cheng, Seng, Michaela, Tan, Ee Shien, Arkachaisri, Thaschawee, Liew, Woei Kang
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/161474
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-161474
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Severe Combined Immunodeficiency
Newborn Screening
spellingShingle Science::Medicine
Severe Combined Immunodeficiency
Newborn Screening
Chan, Bianca Su-Wan
Zhong, Youjia
Lim, James Soon Chuan
Poh, Sherry
Teh, Kai Liang
Soh, Jian Yi
Chong, Chia Yin
Thoon, Koh Cheng
Seng, Michaela
Tan, Ee Shien
Arkachaisri, Thaschawee
Liew, Woei Kang
Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth
description Introduction: Severe Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculosis-endemic regions. Early diagnosis of SCID through newborn screening followed by pre-emptive treatment with anti-mycobacterial therapy may be an alternative strategy to delaying routine BCG vaccination. We report the results of the first year of newborn SCID screening in Singapore while continuing routine BCG vaccination at birth. Method: Newborn screening using a T-cell receptor excision circle (TREC) assay was performed in dried blood spots received between 10 October 2019 to 9 October 2020 using the Enlite Neonatal TREC kit. Patients with low TREC had lymphocyte subset analysis and full blood count performed to determine the severity of lymphopenia and likelihood of SCID to guide further management. Results: Of the 35888 newborns screened in 1 year, no SCID cases were detected, while 13 cases of non-SCID T-cell lymphopenia (TCL) were picked up. Using a threshold for normal TREC to be >18 copies/mL, the retest rate was 0.1% and referral rate to immunologist was 0.04%. Initial low TREC correlated with low absolute lymphocyte counts (ALC), and subsequent normal ALC corresponded with increases in TREC, thus patients with normal first CD3+ T cell counts were considered to have transient idiopathic TCL instead of false positive results. 7/13 (54%) had secondary TCL (from sepsis, Trisomy 21 with hydrops and stoma losses or chylothorax, extreme prematurity, or partial DiGeorge Syndrome) and 6/13 (46%) had idiopathic TCL. No cases of SCID were diagnosed clinically in Singapore during this period and for 10 months after, indicating that no cases were missed by the screening program. 8/9 (89%) of term infants with abnormal TREC results received BCG vaccination within the first 6 days of life when TREC and ALC were low. No patients developed BCG complications after a median follow-up of 17 months. Conclusion: Newborn screening for SCID can be implemented while continuing routine BCG vaccination at birth. Patients with transient TCL and no underlying primary immunodeficiency are able to tolerate BCG vaccination.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Chan, Bianca Su-Wan
Zhong, Youjia
Lim, James Soon Chuan
Poh, Sherry
Teh, Kai Liang
Soh, Jian Yi
Chong, Chia Yin
Thoon, Koh Cheng
Seng, Michaela
Tan, Ee Shien
Arkachaisri, Thaschawee
Liew, Woei Kang
format Article
author Chan, Bianca Su-Wan
Zhong, Youjia
Lim, James Soon Chuan
Poh, Sherry
Teh, Kai Liang
Soh, Jian Yi
Chong, Chia Yin
Thoon, Koh Cheng
Seng, Michaela
Tan, Ee Shien
Arkachaisri, Thaschawee
Liew, Woei Kang
author_sort Chan, Bianca Su-Wan
title Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth
title_short Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth
title_full Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth
title_fullStr Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth
title_full_unstemmed Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth
title_sort implementation of universal newborn screening for severe combined immunodeficiency in singapore while continuing routine bacille-calmette-guerin vaccination given at birth
publishDate 2022
url https://hdl.handle.net/10356/161474
_version_ 1759855146127327232
spelling sg-ntu-dr.10356-1614742023-03-05T16:52:07Z Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth Chan, Bianca Su-Wan Zhong, Youjia Lim, James Soon Chuan Poh, Sherry Teh, Kai Liang Soh, Jian Yi Chong, Chia Yin Thoon, Koh Cheng Seng, Michaela Tan, Ee Shien Arkachaisri, Thaschawee Liew, Woei Kang Lee Kong Chian School of Medicine (LKCMedicine) KK Women’s and Children’s Hospital Duke-NUS Medical School Science::Medicine Severe Combined Immunodeficiency Newborn Screening Introduction: Severe Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculosis-endemic regions. Early diagnosis of SCID through newborn screening followed by pre-emptive treatment with anti-mycobacterial therapy may be an alternative strategy to delaying routine BCG vaccination. We report the results of the first year of newborn SCID screening in Singapore while continuing routine BCG vaccination at birth. Method: Newborn screening using a T-cell receptor excision circle (TREC) assay was performed in dried blood spots received between 10 October 2019 to 9 October 2020 using the Enlite Neonatal TREC kit. Patients with low TREC had lymphocyte subset analysis and full blood count performed to determine the severity of lymphopenia and likelihood of SCID to guide further management. Results: Of the 35888 newborns screened in 1 year, no SCID cases were detected, while 13 cases of non-SCID T-cell lymphopenia (TCL) were picked up. Using a threshold for normal TREC to be >18 copies/mL, the retest rate was 0.1% and referral rate to immunologist was 0.04%. Initial low TREC correlated with low absolute lymphocyte counts (ALC), and subsequent normal ALC corresponded with increases in TREC, thus patients with normal first CD3+ T cell counts were considered to have transient idiopathic TCL instead of false positive results. 7/13 (54%) had secondary TCL (from sepsis, Trisomy 21 with hydrops and stoma losses or chylothorax, extreme prematurity, or partial DiGeorge Syndrome) and 6/13 (46%) had idiopathic TCL. No cases of SCID were diagnosed clinically in Singapore during this period and for 10 months after, indicating that no cases were missed by the screening program. 8/9 (89%) of term infants with abnormal TREC results received BCG vaccination within the first 6 days of life when TREC and ALC were low. No patients developed BCG complications after a median follow-up of 17 months. Conclusion: Newborn screening for SCID can be implemented while continuing routine BCG vaccination at birth. Patients with transient TCL and no underlying primary immunodeficiency are able to tolerate BCG vaccination. Published version KK Women’s and Children’s Hospital, Division of Pediatric Medicine Subspecialties Education, Training and Research Funds were used for open access publication fees. 2022-09-05T06:03:12Z 2022-09-05T06:03:12Z 2022 Journal Article Chan, B. S., Zhong, Y., Lim, J. S. C., Poh, S., Teh, K. L., Soh, J. Y., Chong, C. Y., Thoon, K. C., Seng, M., Tan, E. S., Arkachaisri, T. & Liew, W. K. (2022). Implementation of universal newborn screening for severe combined immunodeficiency in Singapore while continuing routine Bacille-Calmette-Guerin vaccination given at birth. Frontiers in Immunology, 12, 794221-. https://dx.doi.org/10.3389/fimmu.2021.794221 1664-3224 https://hdl.handle.net/10356/161474 10.3389/fimmu.2021.794221 35046952 2-s2.0-85123088008 12 794221 en Frontiers in Immunology © 2021 Chan, Zhong, Lim, Poh, Teh, Soh, Chong, Thoon, Seng, Tan, Arkachaisri and Liew. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. application/pdf