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Abnormal Results of Newborn Screening for SCID After Azathioprine Exposure In Utero: Benefit of TPMT Genotyping in Both Mother and Child

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All data generated or analyzed during this study are included in this published article and its supplementary information.

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  1. 1.

    Thomas C, et al. A severe neonatal lymphopenia associated with administration of azathioprine to the mother in a context of Crohn’s disease. J Crohn’s Colitis. 2017;12(2):258–61.

    Article  Google Scholar 

  2. 2.

    Kuo CY, et al. Profound T-cell lymphopenia associated with prenatal exposure to purine antagonists detected by TREC newborn screening. J Allergy Clin Immunol Pract. 2017;5(1):198–200.

    Article  Google Scholar 

  3. 3.

    Barbaro M, et al. Newborn screening for severe primary immunodeficiency diseases in Sweden-a 2-year pilot TREC and KREC screening study. J Clin Immunol. 2017;37(1):51–60.

    CAS  Article  Google Scholar 

  4. 4.

    Amatuni GS, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010–2017. Pediatrics. 2019;143(2):e20182300.

  5. 5.

    Thomas C, et al. Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results. Clin Immunol. 2019;202:33–9.

    CAS  Article  Google Scholar 

  6. 6.

    Giżewska M, et al. Newborn screening for SCID and other severe primary immunodeficiency in the Polish-German transborder area: experience from the first 14 months of collaboration. Front Immunol. 2020;11:1948–1948.

    Article  Google Scholar 

  7. 7.

    Gearry RB, Barclay ML. Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. J Gastroenterol Hepatol. 2005;20(8):1149–57.

    CAS  Article  Google Scholar 

  8. 8.

    Akbari M, et al. systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012;19(1):15–22.

    Article  Google Scholar 

  9. 9.

    Colombel JF, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000;118(6):1025–30.

    CAS  Article  Google Scholar 

  10. 10.

    Relling MV, et al. Clinical pharmacogenetics implementation consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther. 2019;105(5):1095–105.

    CAS  Article  Google Scholar 

  11. 11.

    Baron U, et al. Epigenetic immune cell counting in human blood samples for immunodiagnostics. Sci Transl Med. 2018; 10(452).

  12. 12.

    van der Woude CJ, et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohn’s Colitis. 2015;9(2):107–24.

    Article  Google Scholar 

  13. 13.

    Blom M, et al. parents’ perspectives and societal acceptance of implementation of newborn screening for SCID in the Netherlands. J Clin Immunol. 2021;41(1):99–108.

    Article  Google Scholar 

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The authors would like to thank all those involved in the SONNET-study for their contribution to the study. A special thanks to all parents of the cases and dr. S.M.H. Timmermans for their participation and support.


The Netherlands Organisation for Health Research and Development ZonMw financed the SONNET-study (project 543002002).

Author information




MB, MvdB, and DB designed the study; IP and JS performed flow cytometric and genetic analyses; DB, RB, and JvM did the clinical evaluations of the patients; MB, IP, JS, and DB analyzed the data; DB coordinated the project; MB and DB wrote the paper; all authors contributed to and approved the final version of the manuscript.

Corresponding author

Correspondence to Dagmar Berghuis.

Ethics declarations

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval for the SONNET-study was granted by the Medical Ethics Committee of the Erasmus MC, University Medical Center, Rotterdam (MEC-2017–1146).

Consent to Participate

In order to participate in newborn screening for SCID (SONNET-study), parents have to express verbal consent when the heel prick is performed (opt-out consent).

Consent for Publication

Parents of cases have provided consent for the publication of the data in this case report.

Conflict of Interest

The authors declare no competing interests.

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Blom, M., Pico-Knijnenburg, I., van Montfrans, J.M. et al. Abnormal Results of Newborn Screening for SCID After Azathioprine Exposure In Utero: Benefit of TPMT Genotyping in Both Mother and Child. J Clin Immunol (2021).

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