Hypothyroxinemia and weight velocity in preterm infants

Meira Zibitt; Brittany Ange; Zanna Wynter; Cynthia Mundy; Steve Herrmann; Brian K. Stansfield

doi:10.1515/jpem-2023-0496

Article

Hypothyroxinemia and weight velocity in preterm infants

Meira Zibitt , Brittany Ange , Zanna Wynter , Cynthia Mundy , Steve Herrmann and Brian K. Stansfield

Published/Copyright: January 29, 2024

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 3

Abstract

Objectives

Hypothyroxinemia of prematurity (HOP) is characterized by low free thyroxine (FT4) associated with low or normal thyroid stimulating hormone (TSH). The objective of this study is to define FT4 and TSH values in very preterm infants (<32 weeks postmenstrual age, PMA) and correlate hypothyroxinemia and levothyroxine treatment with growth velocity at 28 days and 36 weeks PMA.

Methods

Preterm neonates <32 weeks PMA admitted to the regional neonatal intensive care unit (NICU) at the Children’s Hospital of Georgia (USA) between January 2010 and July 2022 were routinely screened for hypothyroxinemia. FT4 and TSH values were obtained on 589 eligible neonates between day of life (DOL) 4 and 14. Growth velocity (g/kg/day) from DOL 14 to DOL 28 and 36-weeks PMA were calculated for each neonate and potential explanatory variables (PMA, sex, and race) were incorporated into multivariate regression models to identify associations between HOP and growth velocity.

Results

In 589 preterm infants, PMA at birth was strongly associated inversely with FT4 (R=0.5845) and modestly with TSH (R=0.2740). Both FT4 and gestational age, but not TSH or levothyroxine treatment, were associated with growth velocity at 28 days of life and at 36 weeks PMA.

Conclusions

We provide a large data set for identifying FT4 and TSH measurements and identify hypothyroxinemia of prematurity as a potential mediator of slow postnatal growth in very preterm infants.

Keywords: preterm; infant; thyroid; growth

Corresponding author: Brian K. Stansfield, MD, Department of Pediatrics, Medical College of Georgia, Augusta University, 1120 15th St, Augusta, GA 30912, USA, Phone: +706 721 5059, E-mail: BSTANSFIELD@augusta.edu

Research ethics: This retrospective, single-center cohort study was approved by the Institutional Review Board at Augusta University.
Informed consent: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. MZ, ZW, CM, and BKS designed the research. MZ and SH collected and organized the data. BA provided statistical analysis. MZ and BKS drafted the initial manuscript.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Ng, SM. Hypothyroxinemia of prematurity: cause, diagnosis and management. Expert Rev Endocrinol Metab 2008;3:453–62. https://doi.org/10.1586/17446651.3.4.453.Search in Google Scholar PubMed

2. Iijima, S. Current knowledge of transient hypothyroxinemia of prematurity: to treat or not to treat? J Matern Fetal Neonatal Med 2019;32:2591–7. https://doi.org/10.1080/14767058.2018.1441277.Search in Google Scholar PubMed

3. 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.Search in Google Scholar PubMed

4. Kaluarachchi, DC, Allen, DB, Eickhoff, JC, Dawe, SJ, Baker, MW. Thyroid-stimulating hormone reference ranges for preterm infants. Pediatrics 2019;144:e20190290. https://doi.org/10.1542/peds.2019-0290.Search in Google Scholar PubMed

5. Leviton, A, Paneth, N, Reuss, ML, Susser, M, Allred, EN, Dammann, O, et al.. Hypothyroxinemia of prematurity and the risk of cerebral white matter damage. J Pediatr 1999;134:706–11. https://doi.org/10.1016/s0022-3476(99)70285-4.Search in Google Scholar PubMed

6. Huang, CB, Chen, FS, Chung, MY. Transient hypothyroxinemia of prematurity is associated with abnormal cranial ultrasound and illness severity. Am J Perinatol 2002;19:139–47. https://doi.org/10.1055/s-2002-25308.Search in Google Scholar PubMed

7. Yilmaz, A, Ozer, Y, Kaya, N, Turan, H, Acar, HC, Ercan, O, et al.. The factors associated with transient hypothyroxinemia of prematurity. BMC Pediatr 2021;21:344. https://doi.org/10.1186/s12887-021-02826-6.Search in Google Scholar PubMed PubMed Central

8. Chiesa, AE, Tellechea, ML. Update on neonatal isolated hyperthyrotropinemia: a systematic review. Front Endocrinol 2021;12:643307. https://doi.org/10.3389/fendo.2021.643307.Search in Google Scholar PubMed PubMed Central

9. van Trotsenburg, P, Stoupa, A, Leger, J, Rohrer, T, Peters, C, Fugazzola, L, 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/10.1530/ey.18.3.8.Search in Google Scholar

10. Yoon, SA, Chang, YS, Yang, M, Ahn, SY, Sung, SI, Cho, HS, et al.. Effect of levothyroxine supplementation in extremely low birth weight infants with transient hypothyroxinemia of prematurity. Sci Rep 2022;12:9717. https://doi.org/10.1038/s41598-022-13927-2.Search in Google Scholar PubMed PubMed Central

11. Cormack, BE, Harding, JE, Miller, SP, Bloomfield, FH. The influence of early nutrition on brain growth and neurodevelopment in extremely preterm babies: a narrative review. Nutrients 2019;11:2029. https://doi.org/10.3390/nu11092029.Search in Google Scholar PubMed PubMed Central

12. Belfort, MB, Rifas-Shiman, SL, Sullivan, T, Collins, CT, McPhee, AJ, Ryan, P, et al.. Infant growth before and after term: effects on neurodevelopment in preterm infants. Pediatrics 2011;128:e899–906. https://doi.org/10.1542/peds.2011-0282.Search in Google Scholar PubMed PubMed Central

13. Cole, TJ, Green, PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992;11:1305–19. https://doi.org/10.1002/sim.4780111005.Search in Google Scholar PubMed

14. Fenton, TR, Chan, HT, Madhu, A, Griffin, IJ, Hoyos, A, Ziegler, EE, et al.. Preterm infant growth velocity calculations: a systematic review. Pediatrics 2017;139:e20162045. https://doi.org/10.1542/peds.2016-2045.Search in Google Scholar PubMed

15. Fenton, TR, Anderson, D, Groh-Wargo, S, Hoyos, A, Ehrenkranz, RA, Senterre, T. An attempt to standardize the calculation of growth velocity of preterm infants-evaluation of practical bedside methods. J Pediatr 2018;196:77–83. https://doi.org/10.1016/j.jpeds.2017.10.005.Search in Google Scholar PubMed

16. Grob, F. Approaching the diagnosis of thyroid disorders in preterm infants. Pediatr Res 2022;91:1021–2. https://doi.org/10.1038/s41390-022-01951-x.Search in Google Scholar PubMed

17. 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.Search in Google Scholar PubMed PubMed Central

18. Ziegler, GM, Slaughter, JL, Chaudhari, M, Singh, H, Sanchez, PJ, Bunch, DR. Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine. Pediatr Res 2022;91:1130–5. https://doi.org/10.1038/s41390-021-01838-3.Search in Google Scholar PubMed

19. Williams, FL, Simpson, J, Delahunty, C, Ogston, SA, Bongers-Schokking, JJ, Murphy, N, et al.. Developmental trends in cord and postpartum serum thyroid hormones in preterm infants. J Clin Endocrinol Metab 2004;89:5314–20. https://doi.org/10.1210/jc.2004-0869.Search in Google Scholar PubMed

20. Williams, FLR, Lindgren, A, Watson, J, Boelen, A, Cheetham, T. Thyroid function in preterm infants and neurodevelopment at 2 years. Arch Dis Child Fetal Neonatal Ed 2020;105:504–9. https://doi.org/10.1136/archdischild-2018-316742.Search in Google Scholar PubMed

21. 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.Search in Google Scholar PubMed PubMed Central

22. Ares, S, Quero, J, Diez, J, Morreale de Escobar, G. Neurodevelopment of preterm infants born at 28 to 36 weeks of gestational age: the role of hypothyroxinemia and long-term outcome at 4 years. J Pediatr Endocrinol Metab 2011;24:897–902. https://doi.org/10.1515/jpem.2011.166.Search in Google Scholar PubMed

23. Briet, 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.Search in Google Scholar PubMed

24. van Wassenaer-Leemhuis, A, Ares, S, Golombek, S, Kok, J, Paneth, N, Kase, J, 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.Search in Google Scholar PubMed PubMed Central

25. 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.Search in Google Scholar PubMed

26. Hollanders, JJ, Israels, J, van der Pal, SM, Verkerk, PH, Rotteveel, J, Finken, MJ, 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.Search in Google Scholar PubMed

27. Diggikar, S, Gurumoorthy, P, Trif, P, Mudura, D, Nagesh, NK, Galis, R, et al.. Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: a systematic review and meta-analysis. Front Pediatr 2023;11:1055813. https://doi.org/10.3389/fped.2023.1055813.Search in Google Scholar PubMed PubMed Central

28. Ahn, JH, Lee, KM, Kim, MJ, Park, HK, Kim, YJ, Ahn, SJ, et al.. Neurodevelopmental outcomes in very low birthweight infants with retinopathy of prematurity in a nationwide cohort study. Sci Rep 2022;12:5053. https://doi.org/10.1038/s41598-022-09053-8.Search in Google Scholar PubMed PubMed Central

29. Karmouta, R, Strawbridge, JC, Langston, S, Altendahl, M, Khitri, M, Chu, A, et al.. Neurodevelopmental outcomes in infants screened for retinopathy of prematurity. JAMA Ophthalmol 2023;141:1125–32. https://doi.org/10.1001/jamaophthalmol.2023.4787.Search in Google Scholar PubMed PubMed Central

30. Rovet, J, Simic, N. The role of transient hypothyroxinemia of prematurity in development of visual abilities. Semin Perinatol 2008;32:431–7. https://doi.org/10.1053/j.semperi.2008.09.009.Search in Google Scholar PubMed

31. Chen, YJ, Chu, WY, Pan, YW, Wang, CY, Chou, YY, Lin, CH, et al.. Postnatal serum total thyroxine level associated with short- and long-term anthropometric outcomes in very preterm infants. Nutrients 2022;14:2056. https://doi.org/10.3390/nu14102056.Search in Google Scholar PubMed PubMed Central

32. Ramel, SE, Demerath, EW, Gray, HL, Younge, N, Boys, C, Georgieff, MK. The relationship of poor linear growth velocity with neonatal illness and two-year neurodevelopment in preterm infants. Neonatology 2012;102:19–24. https://doi.org/10.1159/000336127.Search in Google Scholar PubMed

Received: 2023-11-08

Accepted: 2024-01-12

Published Online: 2024-01-29

Published in Print: 2024-03-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0496

Keywords for this article

preterm; infant; thyroid; growth