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Changes in the incidence and etiology of congenital hypothyroidism detected during 30 years of a screening program in central Serbia

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Abstract

Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in Central Serbia from 1983 to 2013. Newborn screening for CH was based on measuring neonatal thyroid-stimulating hormone (TSH) using a 30 mU/l cutoff (CO) until 12/1987 (P1), 15 mU/l until 12/1997 (P2), 10 mU/l until 12/2006 (P3), and 9 mU/l thereafter (P4). During the study period, there were 1,547,122 live births screened for CH. Primary CH was detected in 434 newborns, with incidence of 1:3728. With gradual lowering of the CO, the incidences of CH increased from 1:5943 in P1 to 1:1872 in P4 (p < 0.001). Incidence of CH with ectopic and enlarged gland doubled (p < 0.001), while prevalence of athyreosis remained relatively constant. The most prominent finding was the increase in the transient CH from none in P1 to 35 % of all CH patients in P4.

Conclusion: The overall incidence of CH in Central Serbia during study period nearly tripled, with a significant increase in almost all etiological categories, and was associated with lowering TSH cutoffs as well as other yet unidentified factors. Further studies are needed to identify other factors associated with increasing incidence of CH.

What is Known:

• Congenital hypothyroidism (CH) is the main cause of preventable mental retardation.

• Recent reports have indicated a progressive increase in the incidence of primary CH throughout the world, partially explained by lowering of the TSH cutoff values.

What is New:

• During the study period associated with lowering of the TSH cutoffs, the overall incidence of CH in Serbia tripled, including transient CH, ectopy, and dyshormonogenesis, while prevalence of athyreosis remained stable during 30 years.

• Significant increase in the incidence of both permanent and transient CH was observed, associated with lowering of TSH cutoffs as well as other yet unidentified factors.

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Abbreviations

CO:

Cutoff

CH:

Congenital hypothyroidism

IFMA:

Immunofluorometric assay

RIA:

Radioimmunoassay

T4:

Thyroxin

TSH:

Thyroid-stimulating hormone

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Acknowledgments

The authors acknowledge the neonatology and pediatric centers in Central Serbia that conveyed the clinical information to the Central Laboratory for Neonatal Screening, situated at the Institute for Mother and Child Health Care of Serbia in Belgrade. The authors thank B. Opancina, O. Spasojevic, and M. Trajkovic (Central Laboratory for Neonatal Screening) for their skillful technical contribution.

Author contributions

KM and DZ helped in the conception, study design, and article drafting. RV and TM contributed to the study design, acquisition, analysis, and interpretation of data. ST and JR contributed to the study design, data acquisition, and article revision. KM revising the article critically for important intellectual content. All authors reviewed and approved the final version of the manuscript.

Compliance with Ethical Standards

ᅟ

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the Hospital Ethics Committee and performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Endocrinology, Institute for Mother and Child Healthcare of Serbia “Dr Vukan Čupić”, Radoja Dakica 6, 11070, Belgrade, Serbia

    Katarina Mitrovic, Rade Vukovic, Tatjana Milenkovic, Sladjana Todorovic, Jovana Radivojcevic & Dragan Zdravkovic

  2. Medical Faculty, University of Belgrade, Belgrade, 11000, Serbia

    Dragan Zdravkovic

Authors
  1. Katarina Mitrovic
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  2. Rade Vukovic
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  3. Tatjana Milenkovic
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  4. Sladjana Todorovic
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  5. Jovana Radivojcevic
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  6. Dragan Zdravkovic
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Corresponding author

Correspondence to Katarina Mitrovic.

Additional information

Communicated by Beat Steinmann

Revisions received: 16 August 2015 / 27 August 2015

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Mitrovic, K., Vukovic, R., Milenkovic, T. et al. Changes in the incidence and etiology of congenital hypothyroidism detected during 30 years of a screening program in central Serbia. Eur J Pediatr 175, 253–259 (2016). https://doi.org/10.1007/s00431-015-2630-5

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  • DOI: https://doi.org/10.1007/s00431-015-2630-5

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