Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates

Journal of Perinatology volume 28, pages 270–274 (2008)Cite this article

Abstract

Objective:

Newborn screening laboratories vary in the values that are used to define congenital hypothyroidism. Defining congenital hypothyroidism is particularly complex in premature neonates because prematurely born infants often have a low free thyroxine value and low or normal TSH value, termed as transient hypothyroxinemia of prematurity. In a multicenter (n=11 sites) trial, we randomly allocated premature neonates with a gestational age of 23 to 29 and 6/7 weeks to one of two parenteral nutrition approaches. The primary objective of our trial was to measure the effect of two distinct strategies of parenteral nutrition on neonatal growth and blood amino acids. A protocol defined secondary aim of our clinical trial was the evaluation of the influence of gestational age, time and the degree of amino-acid supplementation on total thyroxine levels. We hypothesized that an increase of amino-acid supplementation would be associated with the normalization of serum amino acids and that this would improve thyroxine synthesis.

Study Design:

Premature neonates (23 to 29 and 6/7 weeks) were randomly allocated to one of two approaches to intravenous amino-acid administration. In one group, amino-acid supplementation started at 1.0 g kg−1 per day and advanced by 0.5 g kg−1 per day to a maximum of 2.5 g kg−1 per day (2.5 group). The other group received amino acids at 1.5 g kg−1 per day and advanced by 1.0 g kg−1 per day to a maximum of 3.5 g kg−1 per day (3.5 group). Filter paper blood spots were obtained on the day of randomization, and on days 7 and 28 of age to monitor laboratory values.

Result:

Enrollment included 122 neonates, 64 in the 3.5 group and 58 in the 2.5 group. There were no differences in demographics or baseline characteristics between the two treatment groups. There were no significant differences in thyroid levels at baseline, on days 7 and 28 between the two treatment groups. Growth was similar in both groups. It was noted that thyroxine levels changed over time and that the changes with time were greatest in the most preterm neonates.

Conclusion:

The degree of amino-acid supplementation does not influence thyroxine levels and both time from birth and gestational age do influence thyroxine levels.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Kempers MJE, Lanting CI, van Heijst AFJ, van Trotsenburg ASP, Wiedijk BM, de Vijlder JJM et al. Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin, and thyroxine-binding globulin measurement: potentials and pitfalls. J Clin Endocrinol Metab 2006; 91: 3370–3376.

    Article  CAS  Google Scholar 

  2. Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 2006; 117: 2290–2303.

    Article  Google Scholar 

  3. Martin JA, Kochanek KD, Strobino DM, Guyer B, MacDorman MF . Annual summary of vital statistics—2003. Pediatrics 2005; 115: 619–634.

    Article  Google Scholar 

  4. Biswas S, Buffery J, Enoch H, Bland M, Markiewicz M, Walters D . Pulmonary effects of triiodothyronine (T(3)) and hydrocortisone (HC) supplementation in preterm infants less than 30 weeks gestation: results of the THORN trial-thyroid hormone replacement in neonates. Pediatr Res 2003; 53: 48–56.

    CAS  PubMed  Google Scholar 

  5. Biswas S, Buffery J, Enoch H, Bland JM, Walters D, Markiewicz M . A longitudinal assessment of thyroid hormone concentrations in preterm infants younger than 30 weeks' gestation during the first 2 weeks of life and their relationship to outcome. Pediatrics 2002; 109: 222–227.

    Article  Google Scholar 

  6. Van Wassenaer AG, Kok JH, Briet JM, Pijning AM, de Vijlder JJ . Thyroid function in very preterm newborns: possible implications. Thyroid 1999; 9: 85–91.

    Article  CAS  Google Scholar 

  7. Vaidya B, Anthony S, Bilous M, Shields B, Drury J, Hutchison S et al. Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding? J Clin Endocrinol Metab 2007; 92: 203–207.

    Article  CAS  Google Scholar 

  8. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005; 105: 239–245.

    Article  Google Scholar 

  9. Ballard PL, Hovey ML, Gonzales LK . Thyroid hormone stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung. J Clin Invest 1984; 74: 898–905.

    Article  CAS  Google Scholar 

  10. Gonzales LW, Ballard PL, Ertsey R, Williams MC . Glucocorticoids and thyroid hormones stimulate biochemical and morphological differentiation of human fetal lung in organ culture. J Clin Endocrinol Metab 1986; 62: 678–691.

    Article  CAS  Google Scholar 

  11. Ballard PL, Benson BJ, Brehier A, Carter JP, Kriz BM, Jorgensen EC . Transplacental stimulation of lung development in the fetal rabbit by 3,5-dimethyl-3′-isopropyl-L-thyronine. J Clin Invest 1980; 65: 1407–1417.

    Article  CAS  Google Scholar 

  12. Clark RH, Chace DH, Spitzer AR, The Pediatrix Amino-Acid Study Group. Effects of two different doses of amino acid supplementation on growth and blood amino acids in premature neonates admitted to the NICU: a randomized controlled trial. Pediatrics 2007; 120 (6): 1286–1296.

    Article  Google Scholar 

  13. Chace DH, Kalas TA, Naylor EW . Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem 2003; 49: 1797–1817.

    Article  CAS  Google Scholar 

  14. Degroot LJ, Niepomniszcze H . Biosynthesis of thyroid hormone: basic and clinical aspects. Metabolism 1977; 26: 665–718.

    Article  CAS  Google Scholar 

  15. Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 2006; 117: 2290–2303.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Pediatrix-Obstetrix Center for Research and Education and Pediatrix Analytical, Sunrise, FL, USA

    A S Kelleher, R H Clark, M Steinbach, D H Chace & A R Spitzer

Authors
  1. A S Kelleher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R H Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Steinbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D H Chace
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A R Spitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the Pediatrix Amino-Acid Study Group

Corresponding author

Correspondence to R H Clark.

Additional information

Conflict of interest

All authors are employees of Pediatrix Medical Group, which owns Pediatrix Screening, a company that offers newborn screening for inborn errors of metabolism and hearing loss.

Study registration number—ClinicalTrials.gov Identifier: NCT00120926.

Pediatrix Amino-Acid Study Group.

Principal Investigators: Debra Bender, ARNP—Swedish Medical Center (WA); Barbara Carr, MD—St Luke's Hospital (MO); Carlos Flores, MD—Tucson Medical Center (AZ); Jose Gierbolini, MD—Stormont-Vail Regional Health Center (KS); David W Green, MD—Presbyterian Hospital of Dallas (TX); Joseph Harlan, MD—McLeod Regional Medical Center (SC); Michael Kamitsuka, MD—Swedish Medical Center (WA); Sridhar Kaushik, MD—Pinnacle Health—Harrisburg Hospital (PA); Amy S. Kelleher, BS—Pediatrix Medical Group (FL); Jose Perez, MD—Arnold Palmer Medical Center (FL); Meera Sankar, MD—Good Samaritan Medical Center (CA); Bindya Singh, MD—Good Samaritan Medical Center (CA); Margaret Steinbach, NNP—Pediatrix Medical Group (FL); Robert White—Memorial Hospital of South Bend (IN); Henry H Wooldridge, MD—East Tennessee Children's Hospital (TN).

Contributors: East Tennessee Children's Hospital (TN)— P Kathine Fulton RNC, NNP; Good Samaritan Medical Center (CA)—Chrissy Weng RN; McLeod Regional Medical Center (SC)—Evelyn Fulmore, Pharm D; Memorial Hospital of South Bend (IN)—Delores Troyer NNP; Pinnacle Health—Harrisburg Hospital (PA)—Penny Barcavage NNP; Presbyterian Hospital of Dallas (TX)—Renuka K Reddy MD; Stormont-Vail Regional Health Center (KS)—Renee Hunt RNC, NNP; Tucson Medical Center (AZ)—Colleen Bakewell NNP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kelleher, A., Clark, R., Steinbach, M. et al. The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates. J Perinatol 28, 270–274 (2008). https://doi.org/10.1038/jp.2008.5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2008.5

Keywords

This article is cited by

Search

Advanced search

Quick links