Frequency of Thyroid Function Disorders among a Population of Very-Low-Birth-Weight Premature Infants

Document Type : Original Article


1 MD, Associate Professor of Neonatology, Division of Neonatology, Department of Pediatrics, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 MD, Professor of Pediatrics, Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Diseases, Isfahan University of Medical Sciences, Isfahan, Iran

3 MD, Assistant Professor of Neonatology, Division of Neonatology, Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran

4 MD, General Physician, Department of Health, Academic Member of Al Mahdi- Mehr Isfahan Higher Education Institution, Isfahan, Iran

5 MD, Assistant Professor , Department of Epidemiology and Biostatistics, School of Health, Endocrinology and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Thyroid function disorders, particularly congenital hypothyroidism (CHT), are important endocrine dysfunctions associated with permanent morbidities. CHT is more prevalent among preterm low-birth-weight neonates compared to term infants with normal weight.
Methods: This prospective cohort study was conducted on 126 very-low-birth-weight (VLBW) neonates referred to the neonatal intensive care units (NICUs) of two tertiary referral hospitals affiliated to Isfahan University of Medical Sciences in Isfahan, Iran during 2012-2014. On day five of birth and two, four, and six weeks after birth, blood samples were collected from the infants to determine thyroid function disorders, including transient hypothyroxinemia, neonatal hypothyroidism, transient primary neonatal hypothyroidism, and transient hyperthyrotropinemia.
Results: In total, 126 infants with mean gestational age of 30.5±2.29 weeks and mean birth weight of 1246.90±193.58 g were enrolled in this study. Thyroid-stimulating hormone (TSH) level of Conclusion: According to the results of this study, thyroid function disorders are relatively common in preterm VLBW neonates, and serum T4 level is correlated with gestational age in these infants. Therefore, thyroid function tests with a consistent protocol are required for premature infants. It is recommended that further research be performed on larger sample sizes to investigate the prevalence of thyroid function disorders in preterm infants.


1. Claque A, Thomas A. Neonatal biochemical screening for disease. Chin Chim Acta. 2002; 315(1):99-110.
2. Fanaroff AA, Fanaroff RJ, Martin RJ, Klaus MH, Avroy A. Neonatal-perinatal medicine: diseases of the fetus and infant. 10th ed. Missouri: Mosby; 2015.
3. Elahi S, Laeeq F, Syed Z, Rizvi SM, Hyder SW. Serum thyroxine and thyroid stimulating hormone levels in maternal circulation and cord blood at the time of delivery. Pak J Med Sci. 2005; 21(3):325-30.
4. Harris KB, Pass KA. Increase in congenital hypothyroidism in New York State and in the United States. Mol Genet Metab. 2007; 91(3):268–77.
 5. American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006; 117(6):2290-303.
 6. Dussault JH, Coulombe P, Laberge C, Letarte J, Guyda H, Khoury K. Preliminary report on a mass screening program for neonatal hypothyroidism. J Pediatr. 1975; 86(5):670-4.
7. Ordookhani A, Mirmiran P, Najafi R, Hedayati M, Azizi F. Congenital hypothyroidism in Iran. Indian J Pediatr. 2003; 70(8):625-8.
 8. Hashemipour M, Amini M, Iranpour R, Sadri GH, Javaheri N, Haghighi S, et al. Prevalence of congenital hypothyroidism in Isaac, Iran: results of a survey on 20000 neonates. Horm Res Pediatr. 2004; 62(2):79-83.
 9. Ordookhani A, Mirmiran P, Hedayati SM, Hedayati M, Azizi F. Screening for congenital hypothyroidism in Tehran and Damavand: an interim report on descriptive and etiologic findings, 1998–2001. Iran J Endocrinol Metab. 2002; 4(3):153–60.
10. Thorpe_Beeston JG, Nicolasides KH, Felton CV, Butler J, McGregor AM. Maturation of the secretion of thyroid hormone and thyroid stimulating hormone in fetus. N Engl J Med. 1991; 324(8):532-6.
11. Thorpe_Beeston JG, Nicolaides KH, McGregor AM. Fetal thyroid function. Thyroid. 1992; 2(3):207-17.
12. Fisher DA, Brown RS. Thyroid physiology in the perinatal period and during childhood. In: Braverman LE, Uritger RD, editors. Werner's and Ingbar's The Thyroid. Philadelphia: Lippincott Williams and Wilkins; 2000. P. 959.
 13. Williams FL, Simpson J, Delahunty C, Ogston S , Bongers-Schokking JJ, Murphy N, et al. Developmental trends in cord and postpartum serum thyroid hormones in preterm infants. J Clin Endocrinol Metab. 2004; 89(11):5314-20.
 14. Williams FL, Mires GJ, Barnett C, Ogston S, van Toor H, Visser TJ, et al. Transient hypothyroxinemia in preterm infants: the role of cord sera thyroid hormone levels adjusted for prenatal and intrapartum factors. J Clin Endocrinol Metab. 2005; 90(8):4599-606.
15. Klein AH, Oddie TH, Parslow M, Foley TP Jr, Fisher DA. Developmental changes in pituitary_thyroid function in the human fetus and newborn. Early Hum Dev. 1982; 6(4):321-30.
 16. Adams LM, Emery JR, Clark SJ, Carlton EI, Nelson JC. Reference ranges for newer thyroid function tests in premature infants. J Pediatr. 1995; 126(1):122-7.
 17. Murphy N, Hume R, Van Toor H, Mattews TG, Ogston SA, Wu SY, et al. The hypothalamic_ pituitary _thyroid axis in preterm infants; changes in the first 24 hours of postnatal life. J Clin Endocrinol Metab. 2004; 89(6):2824-31.
18. Delange F. Iodine requirements during pregnancy, lactation and the neonatal period and indicators of optimal iodine nutrition. Public Health Nutr 2007; 10(12A):1571-80.
19. Ares S, Escobar-Morreale HF, Quero J, Durán S, Presas MJ, Herruzo R, et al. Neonatal hypothyroxinemia :effects of iodine intake and premature birth. J Clin Endocrinol Metab. 1997; 82(6):1704-12.
20. Carrascosa A, Ruiz-Cuevas P, Potau N, Almar J, Salcedo S, Clemente M, et al. Thyroid function in seventy-five healthy preterm infants thirty to thirtyfive weeks of gestational age: a prospective and longitudinal study during the first year of life. Thyroid. 2004, 14(6):435-42.
21. Chung HR, Shin CH, Yang SW, Choi CW, Kim BI, Kim EK, et al. High incidence of thyroid dysfunction in preterm infants. J Korean Med Sci. 2009; 24(4):627-31.
22. Calaciura F, Motta RM, Miscio G, Fichera G, Leonardi D, Carta A, et al. Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrothropinemia. J Clin Endocrinol Metab. 2002; 87(7):3209-14.
 23. Fisher DA. Thyroid function and dysfunction in premature infants. Pediatr Endocrinol Rev. 2007; 4(4):317-28.
24. Van Wassenaer AG, Kok JH. Hypothyroxinaemia and thyroid function after preterm birth. Semin Neonatol. 2004; 9(1):3-11.
25. Osborn DA. Thyroid hormones for preventing neurodevelopmental impairment in preterm infant. Cochrane Database Syst Rev. 2011; 4:CD001070.
26. LaFranchi S, Kirkland JL, Garcia-Prats JA, Hoppin AG. Clinical features and detection of congenital hypothyroidism. Waltham, MA: UpToDate; 2009.
27. Kapil U, Jain V, Kabra M, Pandey R, Sareen N, Khenduja P. Prevalence of neonatal hypothyroidism in Kangra Valley, Himachal Pradesh. European journal of clinical nutrition. 2014;68(6):748-9.
 28. Mandel SJ, Hermos RJ, Larson CA, Prigozhin AB, Rojas DA, Mitchell ML. Atypical hypothyroidism and the very low birthweight infant. Thyroid. 2000; 10(8):693-5.
 29. Larson C, Hermos R, Delaney A, Daley D, Mitchell M. Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism. J Pediatr. 2003; 143(5):587-91.
 30. Rooman RP, Du Caju MV, De Beeck LO, Docx M, Van Reempts P, Van Acker KJ. Low thyroxinaemia occurs in the majority of very preterm newborns. Eur J Pediatr. 1996; 155(3):211-5. 31. Perlman JM. Neurobehavioral deficits in premature graduates of intensive care potential medical and neonatal environmental risk factors. Pediatrics. 2001; 108(6):1339-48.
32. Gressens P, Rogido M, Paindaveine B, Sola A. The impact of neonatal intensive care practices on the developing brain. J Pediatr. 2002; 140(6):646-53.
33. Lim G, Lee YK, Han HS. Early discontinuation of thyroxine therapy is possible in most very lowbirthweight infants with hypothyroidism detected by screening. Acta Paediatr. 2014; 103(3):e123-9.
34. Srinivasan R, Harigopal S, Turner S, Cheetham T. Permanent and transient congenital hypothyroidism in preterm infants. Acta Paediatr. 2012; 101(4):e179-82.
 35. Chee YY, Wong KY, Low L. Review of primary hypothyroidism in very low birthweight infants in a perinatal centre in Hong Kong. J Paediatr Child Health. 2011; 47(11):824-31.
36. Armanian A-M, Mohammadzadeh M, Soleimani R, Salehimehr N, Hasanzadeh A. The Duration of Hospitalization and Readmission Rate of Low Birth Weight Infants in a Tertiary Referral Hospital in Isfahan, Iran. Iranian Journal of Neonatology IJN. 2015;6(3):17-21.
 37. Saeidi R, Rahmani S, Saeidi M. Developmental Outcomes of Premature and Low Birth Weight Infants. Iranian Journal of Neonatology IJN. 2016;7(1):62-6.