Abstract
Thyroid hormones are important regulators of fetal neurodevelopment. Among preterm infants, thyroid stimulating hormone (TSH) is highly variable. Understanding this variability will further improvements in screening for thyroid disorders in preterm infants. We examined 61 maternal and infant clinical and demographic factors for associations with neonatal TSH levels in 698 preterm neonates. TSH was measured as part of routine State-mandated newborn screening in Iowa. Of the maternal characteristics, nulliparous women (p=8×10–4), women with preeclampsia (p=2×10–3), and those with induced labor (p=3×10–3) had infants with higher TSH levels. TSH levels at the time of newborn screening were associated with respiratory distress syndrome (RDS) (p<0.0001) and sepsis (p=3×10–3). We replicated findings between parity and preeclampsia previously observed in primarily term infants. We also observed strong relationships between neonatal TSH and complications of prematurity including RDS and sepsis, which have implications for future studies examining this relationship both prenatally and longitudinally after birth.
Acknowledgments
We would like to express our thanks to all the participating families in our study. We would also like to express our gratitude to the coordinating medical and research staff at the University of Iowa Hospitals and Clinics in Iowa City, IA, USA; including a special thanks to research coordinators Laura Knosp and Susan Berends. We would also like to thank Franklin Delin, Dariush Shirazi, and Stanton Berberich from the State Hygienic Laboratory for their assistance in the acquisition of the newborn screening data.
Conflict of interest statement
Authors Disclosure Statement: No competing financial interests exist.
Financial Statement: This work was supported by the March of Dimes (1-FY05-126 and 6-FY08-260), National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01 HD-52953, R01 HD-57192, and R00 HD-065786). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the National Institutes of Health.
References
1. Medici M, de Rijke YB, Peeters RP, Visser W, de Muinck Keizer-Schrama SM, et al. Maternal early pregnancy and newborn thyroid hormone parameters: the generation R study. J Clin Endocrinol Metab 2012;97:646–52.10.1210/jc.2011-2398Search in Google Scholar PubMed
2. Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol 2012;119:315–20.10.1097/AOG.0b013e318240de6aSearch in Google Scholar PubMed
3. Schneuer FJ, Nassar N, Tasevski V, Morris JM, Roberts CL. Association and predictive accuracy of high TSH serum levels in first trimester and adverse pregnancy outcomes. J Clin Endocrinol Metab 2012;97:3115–22.10.1210/jc.2012-1193Search in Google Scholar PubMed
4. Ryckman KK, Berberich SL, Shchelochkov OA, Cook DE, Murray JC. Clinical and environmental influences on metabolic biomarkers collected for newborn screening. Clin Biochem 2013;46:133–8.10.1016/j.clinbiochem.2012.09.013Search in Google Scholar PubMed PubMed Central
5. Alul FY, Cook DE, Shchelochkov OA, Fleener LG, Berberich SL, et al. The heritability of metabolic profiles in newborn twins. Heredity (Edinb) 2013;110:253–8.10.1038/hdy.2012.75Search in Google Scholar PubMed PubMed Central
6. Tanaka K, Shimizu T, Hosaka A, Tokita A, Shiga S, et al. Serum free T4 and thyroid stimulating hormone levels in preterm infants and relationship between these levels and respiratory distress syndrome. Pediatr Int 2007;49:447–51.10.1111/j.1442-200X.2007.02390.xSearch in Google Scholar PubMed
7. Herbstman J, Apelberg BJ, Witter FR, Panny S, Goldman LR. Maternal, infant, and delivery factors associated with neonatal thyroid hormone status. Thyroid 2008;18:67–76.10.1089/thy.2007.0180Search in Google Scholar PubMed
8. Wilker RE, Fleischman AR, Saenger P, Pan C, Surks MI. Thyroid hormone levels in diabetic mothers and their neonates. Am J Perinatol 1984;1:259–62.10.1055/s-2007-1000015Search in Google Scholar PubMed
9. Ward LS, Kunii IS, de Barros Maciel RM. Thyroid stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers’ diseases. Sao Paulo Med J 2000;118:144–7.10.1590/S1516-31802000000500006Search in Google Scholar
10. Sullivan KM, May W, Nordenberg D, Houston R, Maberly GF. Use of thyroid stimulating hormone testing in newborns to identify iodine deficiency. J Nutr 1997;127:55–8.10.1093/jn/127.1.55Search in Google Scholar PubMed
11. Franklin R, O’Grady C, Carpenter L. Neonatal thyroid function: comparison between breast-fed and bottle-fed infants. J Pediatr 1985;106:124–6.10.1016/S0022-3476(85)80481-9Search in Google Scholar
12. Chan LY, Chiu PY, Lau TK. Cord blood thyroid-stimulating hormone level in high-risk pregnancies. Eur J Obstet Gynecol Reprod Biol 2003;108:142–5.10.1016/S0301-2115(02)00418-9Search in Google Scholar
13. Lao TT, Lee CP. Gestational diabetes mellitus and neonatal hyperthyrotropinemia. Gynecol Obstet Invest 2002;53:135–9.10.1159/000058363Search in Google Scholar
14. Hitchcock KR. Lung development and the pulmonary surfactant system: hormonal influences. Anat Rec 1980;198:13–34.10.1002/ar.1091980103Search in Google Scholar
15. Hitchcock KR. Hormones and the lung. I. Thyroid hormones and glucocorticoids in lung development. Anat Rec 1979;194:15–39.10.1002/ar.1091940103Search in Google Scholar
16. Wilson M, Hitchcock KR, Douglas WH, DeLellis RA. Hormones and the lung. II. Immunohistochemical localization of thyroid hormone binding in type II pulmonary epithelial cells clonally-derived from adult rat lung. Anat Rec 1979;195:611–9.10.1002/ar.1091950404Search in Google Scholar
17. 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;42:604–9.10.1203/00006450-199711000-00009Search in Google Scholar
18. Klein RZ, Carlton EL, Faix JD, Frank JE, Hermos RJ, et al. Thyroid function in very low birth weight infants. Clin Endocrinol (Oxf) 1997;47:411–7.10.1046/j.1365-2265.1997.2511064.xSearch in Google Scholar
19. Cuestas RA, Lindall A, Engel RR. Low thyroid hormones and respiratory-distress syndrome of the newborn. Studies on cord blood. N Engl J Med 1976;295:297–302.10.1056/NEJM197608052950601Search in Google Scholar
20. Cuestas RA, Engel RR. Thyroid function in preterm infants with respiratory distress syndrome. J Pediatr 1979;94:643–6.10.1016/S0022-3476(79)80042-6Search in Google Scholar
21. Steffen KM, Cooper ME, Shi M, Caprau D, Simhan HN, et al. Maternal and fetal variation in genes of cholesterol metabolism is associated with preterm delivery. J Perinatol 2007;27:672–80.10.1038/sj.jp.7211806Search in Google Scholar
22. Ehn NL, Cooper ME, Orr K, Shi M, Johnson MK, et al. Evaluation of fetal and maternal genetic variation in the progesterone receptor gene for contributions to preterm birth. Pediatr Res 2007;62:630–5.10.1203/PDR.0b013e3181567bfcSearch in Google Scholar
23. Simpson J, Williams FL, Delahunty C, van Toor H, Wu SY, et al. Serum thyroid hormones in preterm infants and relationships to indices of severity of intercurrent illness. J Clin Endocrinol Metab 2005;90:1271–9.10.1210/jc.2004-2091Search in Google Scholar
24. Ng SM, Wong SC, Paize F, Chakkarapani E, Newland P, et al. Multivariate analyses of factors that affect neonatal screening thyroid stimulating hormone. J Pediatr Endocrinol Metab 2011;24:727–32.Search in Google Scholar
25. Korada M, Pearce MS, Avis E, Turner S, Cheetham T. TSH levels in relation to gestation, birth weight and sex. Horm Res 2009;72:120–3.10.1159/000232165Search in Google Scholar
26. Dokumov SI, Milanov SC, Trepetshov SP. Thyroid-stimulating hormone in serum of mother and newborn at birth. J Obstet Gynaecol Br Commonw 1971;78:809–11.10.1111/j.1471-0528.1971.tb00343.xSearch in Google Scholar
27. Belet N, Imdat H, Yanik F, Kucukoduk S. Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency. J Pediatr Endocrinol Metab 2003;16:1131–5.10.1515/JPEM.2003.16.8.1131Search in Google Scholar
28. Narin N, Kurtoglu S, Basbug M, Caksen H, Kafali M, et al. Thyroid function tests in the newborn infants of preeclamptic women. J Pediatr Endocrinol Metab 1999;12:69–73.10.1515/JPEM.1999.12.1.69Search in Google Scholar
29. Faber J, Kirkegaard C, Rasmussen B, Westh H, Busch-Sorensen M, et al. Pituitary-thyroid axis in critical illness. J Clin Endocrinol Metab 1987;65:315–20.10.1210/jcem-65-2-315Search in Google Scholar
30. Mitchell IM, Pollock JC, Jamieson MP, Donaghey SF, Paton RD, et al. The effects of cardiopulmonary bypass on thyroid function in infants weighing less than five kilograms. J Thorac Cardiovasc Surg 1992;103:800–5.10.1016/S0022-5223(19)34965-7Search in Google Scholar
31. Murzi B, Iervasi G, Masini S, Moschetti R, Vanini V, et al. Thyroid hormones homeostasis in pediatric patients during and after cardiopulmonary bypass. Ann Thorac Surg 1995;59:481–5.10.1016/0003-4975(94)00879-CSearch in Google Scholar
32. Van den Berghe G, de Zegher F, Lauwers P. Dopamine suppresses pituitary function in infants and children. Crit Care Med 1994;22:1747–53.10.1097/00003246-199422110-00008Search in Google Scholar
33. Collaborative trial of prenatal thyrotropin-releasing hormone and corticosteroids for prevention of respiratory distress syndrome. Collaborative Santiago Surfactant Group. Am J Obstet Gynecol 1998;178:33–9.10.1016/S0002-9378(98)70622-2Search in Google Scholar
34. Fisch RO, Bilek MK, Miller LD, Engel RR. Physical and mental status at 4 years of age of survivors of the respiratory distress syndrome. Follow-up report from the collaborative study. J Pediatr 1975;86:497–503.10.1016/S0022-3476(75)80137-5Search in Google Scholar
35. Crump C, Winkleby MA, Sundquist J, Sundquist K. Preterm birth and risk of medically treated hypothyroidism in young adulthood. Clin Endocrinol (Oxf) 2011;75:255–60.10.1111/j.1365-2265.2011.04034.xSearch in Google Scholar PubMed PubMed Central
36. Yildizdas D, Onenli-Mungan N, Yapicioglu H, Topaloglu AK, Sertdemir Y, et al. Thyroid hormone levels and their relationship to survival in children with bacterial sepsis and septic shock. J Pediatr Endocrinol Metab 2004;17:1435–42.10.1515/JPEM.2004.17.10.1435Search in Google Scholar
37. den Brinker M, Joosten KF, Visser TJ, Hop WC, de Rijke YB, et al. Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins. J Clin Endocrinol Metab 2005;90:5613–20.10.1210/jc.2005-0888Search in Google Scholar PubMed
38. den Brinker M, Dumas B, Visser TJ, Hop WC, Hazelzet JA, et al. Thyroid function and outcome in children who survived meningococcal septic shock. Intensive Care Med 2005;31:970–6.10.1007/s00134-005-2671-8Search in Google Scholar PubMed
39. Das BK, Agarwal P, Agarwal JK, Mishra OP. Serum cortisol and thyroid hormone levels in neonates with sepsis. Indian J Pediatr 2002;69:663–5.10.1007/BF02722699Search in Google Scholar PubMed
40. Williams F, Hume R. The measurement, definition, aetiology and clinical consequences of neonatal transient hypothyroxinaemia. Ann Clin Biochem 2011;48:7–22.10.1258/acb.2010.010174Search in Google Scholar PubMed
©2014 by De Gruyter
