Evaluating the Value of Quadruple Thyroid Screening in the Diagnosis of Hypothyroidism among Premature Neonates in Tehran in 2019-2020

Document Type : Original Article


1 Neonatal Health Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2. Department of Pediatrics, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran

2 Neonatal Health Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Computer Engineering, Kashan branch, Islamic Azad University, Kashan, Iran


Background: Neonate screening is a preventative measure that can contribute to early diagnosis of treatable diseases. Hypothyroidism in neonates is among the common preventable factors leading to intellectual disability. This study aims to describe the prevalence and experience with four-step screening to diagnose congenital hypothyroidism.
Methods: The statistical population of this cross-sectional study included 392 preterm neonates (gestational ages less than 36 weeks and 6 days) in 2018-2019 from the health centers covered by Shahid Beheshti University of Medical Sciences (Tehran, Iran) who had been referred for screening. Neonates were screened in the first 3-6 days after birth and then on days 14, 42, and 72. In neonates with TSH serum levels of 10 mU/L, TSH-T4 was measured. Next, the physician decided on the medication based on the results.
Results: At the primary screening of the neonates average TSH level was 2.08 ± 2.4 mU/L. Thirty-three neonates (8.4%) indicated disrupted screening results. The secondary screening of 388 neonates (98.97%) revealed an average TSH serum level of 1.9 ± 1.96 mU/L, and 19 (5.9%) indicated TSH serum levels higher than 5 (mU/L). The third screening test was performed on 382 (97.44%) of the neonates. The average TSH level was 1.3 ± 2.4 mU/L, 340 (85.96%) indicated normal levels, and 42 (11.47%) had unfavorable results. Finally, the fourth screening test was performed on 373 (95.15%) neonates. The mean TSH level was 2.21 ± 1.9 mU/L, which revealed 24 (6.12%) unfavorable test results. The percentage of hypothyroidism in neonates was 5.6% (23 cases).  In this study, the prevalence of hypothyroidism was 4.33% (17 cases) in girls and 1.53% (6 cases) in boys.   
Conclusion: The results of this study revealed the high incidence rate of congenital hypothyroidism among preterm neonates. Therefore, preventing congenital hypothyroidism misdiagnosis requires a series of screening tests. Also, findings indicated that the results of screening tests for preterm neonates with prolonged GAs and higher birth weights are more accurate and reliable.


  1. Ordookhani A, Mirmiran PA, Pourafkari M, Neshandar-Asl E, Fotouhi F, Hedayati M, Azizi F. Permanent and transient neonatal hypothyroidism in Tehran. Iran J Endocrinol Metab. 2004;6(1):5-11.
  2. Wassner AJ. Congenital Hypothyroidism. Clin Perinatol. 2018;45(1):1-18.
  3. Karamizadeh Z, Saneifard H, Amirhakimi G, Karamifar H, Alavi M. Evaluation of congenital hypothyroidism in fars province, Iran. Iran J Pediatr. 2012;22(1):107-12.
  4. Sharifi N, Khazaeian S, Pakzad R, Fathnezhad Kazemi A, Chehreh H. Investigating the Prevalence of Preterm Birth in Iranian Population: A Systematic Review and Meta-Analysis. J Caring Sci. 2017;
  5. Vigone MC, Caiulo S, Di Frenna M, Ghirardello S, Corbetta C, Mosca F, et al. Evolution of thyroid function in preterm infants detected by screening for congenital hypothyroidism. J Pediatr. 2014;
  6. Ordooei M, Mottaghipisheh H, Fallah R, Rabiee A. Cognitive outcomes for congenital hypothyroid and healthy children: a comparative study. Iran J Child Neurol. 2014;8(4):28-32.
  7. Patyra K, Makkonen K, Haanpää M, Karppinen S, Viikari L, Toppari J, et al. Screening for Mutations in Isolated Central Hypothyroidism Reveals a Novel Mutation in Insulin Receptor Substrate 4. Front Endocrinol. 2021;12:658137.
  8. Siami R, Kosarian M, Valaei N, Hatami H, Mirzajani MR. Neonatal screening for congenital hypothy-roidism and increase transient TSH, Mazandaran, 2006-2010. Research in Medicine. 2014;37(4):244-52.
  9. Yoon S, Chang YS, Ahn SY, In Sung S, Park WS. Initial and delayed thyroid-stimulating hormone elevation in extremely low-birth-weight infants. BMC Pediatr. 2019;19(1):1-9.
  10. Afjeh SA, Sabzehei MK, Fallahi M, Esmaili F. Outcome of very low birth weight infants over 3 years report from an Iranian center. Iran J Pediatr. 2013;23(5):579-87.
  11. Hashemipour M, Hovsepian S, Ansari A, Keikha M, Khalighinejad P, Niknam N. Screening of congenital hypothyroidism in preterm, low birth weight and very low birth weight neonates: a systematic review. Pediatr Neonatol. 2018;59(1):3-14.
  12. Tfayli H, Charafeddine L, Tamim H, Saade J, Daher RT, Yunis K. Higher incidence rates of hypothyroidism and late TSH rise in preterm very-low-birth-weight infants at a tertiary care center. Horm Res Paediatr. 2018;89(4):224-32.
  13. Zdraveska N, Kocova M. Thyroid function and dysfunction in preterm infants-Challenges in evaluation, diagnosis and therapy. Clin Endocrinol. 2021;95(4):556-70.
  14. Belfort MB, Pearce EN, Braverman LE, He X, Brown RS. Low iodine content in the diets of hospitalized preterm infants. J Clin Endocrinol Metab. 2012;97(4):E632-6.
  15. Kaluarachchi DC, Allen DB, Eickhoff JC, Dawe SJ, Baker MW. Increased congenital hypothyroidism detection in preterm infants with serial newborn screening. J Pediatr. 2019;207:220-5.
  16. Srinivasan R, Harigopal S, Turner S, Cheetham T. Permanent and transient congenital hypothyroidism in preterm infants. Acta Paediatr. 2012;101(4):
  17. Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010;5(1):1-22.