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Open Access 01-12-2023 | Research

Clinical indicators that influence a clinician’s decision to start L-thyroxine treatment in prematurity with transient hypothyroxinemia

Authors: Aslan Yilmaz, Yavuz Ozer, Nesrin Kaya, Aydilek Dagdeviren Cakir, Hazal Cansu Culpan, Yildiz Perk, Mehmet Vural, Olcay Evliyaoglu

Published in: Italian Journal of Pediatrics | Issue 1/2023

Abstract

Background

Transient hypothyroxinemia of prematurity (THOP) is defined as a low level of circulating thyroxine (T4), despite low or normal thyroid-stimulating hormone (TSH) levels. Aims: We aimed to evaluate the incidence of THOP, the clinical and laboratory findings of preterm infants with this condition and the levothyroxine (L-T4) treatment.

Methods

Preterm infants (n = 181) delivered at 24–34 weeks of gestation were evaluated by their thyroid function tests that were performed between the 10^th and 20^th days of postnatal life and interpreted according to the gestational age (GA) references. Clinical and laboratory characteristics of the patients with THOP and normal thyroid function tests were compared. Patients with THOP and treated with L-T4 were compared with the ones who were not regarding laboratory, and clinical characteristics.

Results

Incidence of hypothyroxinemia of prematurity was 45.8% (n = 83). Euthyroidism, primary hypothyroidism, and subclinical hypothyroidism were diagnosed in 47.5% (n = 86), 5% (n = 9) and 1.7% (n = 3) of the patients, respectively. Mean birth weight (BW) and GA were significantly lower in the hypothyroxinemia group than in the euthyroid group (p < 0.001). L-T4 was started in 43% (n = 36) of the patients with THOP. Treatment initiation rate was 44.4% (n = 16) in 24–27 wk, 41.6% (n = 15) in 28–30 wk, and 13.8% (n = 5) in 31–34 wk. As the GA increased, the incidence of THOP and the rate of treatment initiation decreased (p < 0.001). The lowest free thyroxine (FT4) cut-off value was 0.72 ng/dl in the treated group. In addition, incidences of vancomycin + amikacin, caffeine, dopamine treatments, RDS, IVH, BPD, central catheter, FFP transfusion, and ventilator support were higher in the treated group (P < 0.05).

Conclusion

This study revealed that prevalence of THOP increased as the GA and BW decreased. As the GA decreased, THOP patients requiring L-T4 treatment increased. Additionally, association with comorbid diseases increased the requirement of treatment.

Klein AH, Meltzer S, Kenny FM. Improved prognosis in congenital hypothyroidism treated before age three months. J Pediatr. 1972;81:912–5. https://doi.org/10.1016/s0022-3476(72)80542-0.CrossRefPubMed

Ford G, LaFranchi SH. Screening for congenital hypothyroidism: a worldwide view of strategies. Best Pract Res Clin Endocrinol Metab. 2014;28:175–87. https://doi.org/10.1016/j.beem.2013.05.008.CrossRefPubMed

Chung HR. Screening and management of thyroid dysfunction in preterm infants. Ann Pediatr Endocrinol Metab. 2019;24:15–21. https://doi.org/10.6065/apem.2019.24.1.15.CrossRefPubMedPubMedCentral

van Trotsenburg P, Stoupa A, Léger J, et al. Congenital Hypothyroidism: A 2020–2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021;31:387–419. https://doi.org/10.1089/thy.2020.0333.CrossRefPubMedPubMedCentral

Rose SR, Wassner AJ, Wintergerst KA, et al. Congenital Hypothyroidism: Screening and Management. Pediatrics. 2023;151(1):e2022060420. https://doi.org/10.1542/peds.2022-060420.CrossRefPubMed

LaFranchi SH. Thyroid Function in Preterm/Low Birth Weight Infants: Impact on Diagnosis and Management of Thyroid Dysfunction. Front Endocrinol (Lausanne). 2021;12:666207. https://doi.org/10.3389/fendo.2021.666207. Published 2021 Jun 15.CrossRefPubMed

Zung A, Bier Palmon R, Golan A, et al. Risk Factors for the Development of Delayed TSH Elevation in Neonatal Intensive Care Unit Newborns. J Clin Endocrinol Metab. 2017;102:3050–5. https://doi.org/10.1210/jc.2017-00701.CrossRefPubMed

Yoon SA, 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;19:347. https://doi.org/10.1186/s12887-019-1730-1. Published 2019 Oct 11.CrossRefPubMedPubMedCentral

Williams F, Hume R. The measurement, definition, aetiology and clinical consequences of neonatal transient hypothyroxinaemia. Ann Clin Biochem. 2011;48:7–22. https://doi.org/10.1258/acb.2010.010174.CrossRefPubMed

10.

Briët JM, van Wassenaer AG, Dekker FW, de Vijlder JJ, van Baar A, Kok JH. Neonatal thyroxine supplementation in very preterm children: developmental outcome evaluated at early school age. Pediatrics. 2001;107:712–8. https://doi.org/10.1542/peds.107.4.712.CrossRefPubMed

11.

van Wassenaer AG, Westera J, Houtzager BA, Kok JH. Ten-year follow-up of children born at <30 weeks’ gestational age supplemented with thyroxine in the neonatal period in a randomized, controlled trial. Pediatrics. 2005;116:e613–8. https://doi.org/10.1542/peds.2005-0876.CrossRefPubMed

12.

van Wassenaer-Leemhuis A, Ares S, Golombek S, et al. Thyroid hormone supplementation in preterm infants born before 28 weeks gestational age and neurodevelopmental outcome at age 36 months. Thyroid. 2014;24:1162–9. https://doi.org/10.1089/thy.2013.0618.CrossRefPubMedPubMedCentral

13.

Williams FL, Simpson J, Delahunty C, et al. Developmental trends in cord and postpartum serum thyroid hormones in preterm infants. J Clin Endocrinol Metab. 2004;89:5314–20. https://doi.org/10.1210/jc.2004-0869.CrossRefPubMed

14.

American Academy of Pediatrics, Rose SR, Section on Endocrinology and Committee on Genetics, American Thyroid Association, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117:2290–303. https://doi.org/10.1542/peds.2006-0915.CrossRef

15.

Klosinska M, Kaczynska A, Ben-Skowronek I. Congenital Hypothyroidism in Preterm Newborns - The Challenges of Diagnostics and Treatment: A Review. Front Endocrinol (Lausanne). 2022;13:860862. https://doi.org/10.3389/fendo.2022.860862. Published 2022 Mar 18.CrossRefPubMed

16.

Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9. https://doi.org/10.1164/ajrccm.163.7.2011060.CrossRefPubMed

17.

Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390:1770–80. https://doi.org/10.1016/S0140-6736(17)31002-4.CrossRefPubMed

18.

Hamrick SEG, Sallmon H, Rose AT, et al. Patent Ductus Arteriosus of the Preterm Infant. Pediatrics. 2020;146:e20201209. https://doi.org/10.1542/peds.2020-1209.CrossRefPubMed

19.

International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991–9. https://doi.org/10.1001/archopht.123.7.991.CrossRef

20.

Parodi A, Rossi A, Severino M, et al. Accuracy of ultrasound in assessing cerebellar haemorrhages in very low birthweight babies. Arch Dis Child Fetal Neonatal Ed. 2015;100(4):F289–92. https://doi.org/10.1136/archdischild-2014-307176.CrossRefPubMed

21.

Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7. https://doi.org/10.1097/00000658-197801000-00001

22.

Hollanders JJ, Israëls J, van der Pal SM, et al. No Association Between Transient Hypothyroxinemia of Prematurity and Neurodevelopmental Outcome in Young Adulthood. J Clin Endocrinol Metab. 2015;100:4648–53. https://doi.org/10.1210/jc.2015-3078.CrossRefPubMed

23.

Tan LO, Tan MG, Poon WB. Lack of association between hypothyroxinemia of prematurity and transient thyroid abnormalities with adverse long term neurodevelopmental outcome in very low birth weight infants. PLoS One. 2019;14:e0222018. https://doi.org/10.1371/journal.pone.0222018.CrossRefPubMedPubMedCentral

24.

Yilmaz A, Ozer Y, Kaya N, et al. The factors associated with transient hypothyroxinemia of prematurity. BMC Pediatr. 2021;21:344. https://doi.org/10.1186/s12887-021-02826-6.CrossRefPubMedPubMedCentral

25.

van Wassenaer AG, Kok JH, Dekker FW, de Vijlder JJ. Thyroid function in very preterm infants: influences of gestational age and disease. Pediatr Res. 1997;42:604–9. https://doi.org/10.1203/00006450-199711000-00009.CrossRefPubMed

26.

Williams FL, Ogston SA, van Toor H, Visser TJ, Hume R. Serum thyroid hormones in preterm infants: associations with postnatal illnesses and drug usage. J Clin Endocrinol Metab. 2005;90:5954–63. https://doi.org/10.1210/jc.2005-1049.CrossRefPubMed

27.

Forghani N, Aye T. Hypothyroxinemia and prematurity. NeoReviews. 2008;9(2):e66–71.CrossRef

28.

La Gamma EF, et al. Transient hypothyroxinemia of prematurity. Neoreviews. 2016;17(7):e394–402.CrossRef

29.

La Gamma EF, van Wassenaer AG, Ares S, et al. Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks’ gestation. Pediatrics. 2009;124:e258–68. https://doi.org/10.1542/peds.2008-2837.CrossRefPubMed

30.

Ng SM, Turner MA, Weindling AM. Neurodevelopmental Outcomes at 42 Months After Thyroxine Supplementation in Infants Below 28 Weeks’ Gestation: A Randomized Controlled Trial. Thyroid. 2020;30:948–54. https://doi.org/10.1089/thy.2019.0293.CrossRefPubMedPubMedCentral

31.

Suzumura H, Nitta A, Tsuboi Y, Watabe Y, Kuribayashi R, Arisaka O. Thyroxine for transient hypothyroxinemia and cerebral palsy in extremely preterm infants. Pediatr Int. 2011;53:463–7. https://doi.org/10.1111/j.1442-200X.2010.03287.x.CrossRefPubMed

32.

Nomura S, Ikegami H, Wada H, Tamai H, Funato M, Shintaku H. Role of levothyroxine supplementation in extremely low birth weight infants who have transient hypothyroidism without thyroid-stimulating hormone elevation. Osaka City Med J. 2014;60(1):29–37.PubMed

33.

van Wassenaer AG, Kok JH, de Vijlder JJ, et al. Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks’ gestation. N Engl J Med. 1997;336:21–6. https://doi.org/10.1056/NEJM199701023360104.CrossRefPubMed

34.

Chowdhry P, Scanlon JW, Auerbach R, Abbassi V. Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia. Pediatrics. 1984;73:301–5.CrossRefPubMed

35.

Uchiyama A, Kushima R, Watanabe T, Kusuda S. Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial. J Pediatr Endocrinol Metab. 2015;28:177–82. https://doi.org/10.1515/jpem-2014-0024.CrossRefPubMed

36.

Vanhole C, Aerssens P, Naulaers G, et al. L-thyroxine treatment of preterm newborns: clinical and endocrine effects. Pediatr Res. 1997;42:87–92. https://doi.org/10.1203/00006450-199707000-00014.CrossRefPubMed

37.

Osborn DA, Hunt RW. Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2007;2007:CD005948. https://doi.org/10.1002/14651858.CD005948.pub2.CrossRefPubMedPubMedCentral

38.

Dilli D, Eras Z, Andiran N, Dilmen U, Sakrucu ED. Neurodevelopmental evaluation of very low birth weight infants with transient hypothyroxinemia at corrected age of 18–24 months. Indian Pediatr. 2012;49:711–5. https://doi.org/10.1007/s13312-012-0162-x.CrossRefPubMed

39.

Berbel P, Navarro D, Ausó E, et al. Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity. Cereb Cortex. 2010;20:1462–75. https://doi.org/10.1093/cercor/bhp212.CrossRefPubMed

40.

Cuestas RA, Engel RR. Thyroid function in preterm infants with respiratory distress syndrome. J Pediatr. 1979;94:643–6. https://doi.org/10.1016/s0022-3476(79)80042-6.CrossRefPubMed

41.

Abbassi V, Merchant K, Abramson D. Postnatal triiodothyronine concentrations in healthy preterm infants and in infants with respiratory distress syndrome. Pediatr Res. 1977;11:802–4. https://doi.org/10.1203/00006450-197707000-00004.CrossRefPubMed

42.

Fisher DA. Thyroid function in premature infants The hypothyroxinemia of prematurity. Clin Perinatol. 1998;25:999–viii.CrossRefPubMed

43.

Kok JH, Briet JM, van Wassenaer AG. Postnatal thyroid hormone replacement in very preterm infants. Semin Perinatol. 2001;25:417–25. https://doi.org/10.1053/sper.2001.27550.CrossRefPubMed

Title: Clinical indicators that influence a clinician’s decision to start L-thyroxine treatment in prematurity with transient hypothyroxinemia
Authors: Aslan Yilmaz
Yavuz Ozer
Nesrin Kaya
Aydilek Dagdeviren Cakir
Hazal Cansu Culpan
Yildiz Perk
Mehmet Vural
Olcay Evliyaoglu
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: Italian Journal of Pediatrics / Issue 1/2023
Electronic ISSN: 1824-7288
DOI: https://doi.org/10.1186/s13052-023-01516-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical indicators that influence a clinician’s decision to start L-thyroxine treatment in prematurity with transient hypothyroxinemia

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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