Long term outcomes of infants born by mothers with thyroid dysfunction during pregnancy.

Main Article Content

Laura Lucaccioni
Monica Ficara
Valentina Cenciarelli
Alberto Berardi
Barbara Predieri
Lorenzo Iughetti https://orcid.org/0000-0003-0370-7872

Keywords

Thyroid; Pregnancy; Intra uterine growth restriction; Small for Gestational Age; Prematurity

Abstract

According to Barker’s hypothesis, sub-optimal conditions during gestation might affect the predisposition for diseases in adulthood. Alteration in endocrine functions during pregnancy, such us thyroid function or glucose metabolism, are not exempt. It is well known that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism during early pregnancy are associated with increased risk of gestational diabetes mellitus and both conditions influence pregnancy outcome and newborn development and metabolism at short and long terms.


Fetal production of thyroid hormones starts from the 12th week of gestational age. The transplacental passage of maternal thyroxine (T4) is therefore essential for the fetal neurological development, especially during the first half of pregnancy.  If this passage is interrupted, such as in premature birth, neonates are more susceptible to develop impaired thyroid function, because of physiological immaturity of their hypothalamic-pituitary-thyroid axis, acute illnesses and stressful events (sepsis, invasive procedures, drugs). The aim of this review is to investigate the short and long term effects of maternal dysthyroidisms on term and preterm newborns, with particular attention to the metabolic and thyroid consequences. Metabolic syndrome, higher body mass index and greater waist circumference, seem to be more prevalent in children of TPO-Ab-positive mothers. Maternal hypothyroidism may be associated with higher risk of gestational diabetes and adverse birth outcomes, such as preeclampsia, preterm delivery, fetal death and low birth weight offspring.  In adulthood, preterm (< 37 weeks of gestational age) or low birth weight (<2.500 g) newborns  seem to be more susceptible to develop gestational diabetes, preeclampsia, type 2 diabetes mellitus and behavioral alterations. 

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References

1. Barker DJ, Hales CN, Fall H, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia, 1993; 36:62-67
2. Cuestas E, Gaido MI, Capra RH. Transient neonatal hyperthyrotropinemia is a risk factor for developing persistent hyperthyrotropinemia in childhood with repercussion on developmental status. Eur J Endocrinol. 2015; 172: 483-90.
3. Calaciura F, Motta RM, Miscio G et al. Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia. J Clin Endocrinol Metab. 2002; 87: 3209-14.
4. D. Leonardi, N. Polizzotti, A. Carta et al., “ Longitudinal study of thyroid function in children with mild hyperthyrotropinemia at neonatal screening for congenital hypothyroidism,” J Clin Endocrinol Metab., vol. 93, no.7, pp. 2679-85, 2008.
5. Oren A, Wang MK, Brnjac L, Mahmud FH, Palmert MR. Mild neonatal hyperthyrotrophinaemia: 10-year experience suggests the condition is increasingly common but often transient, Clin Endocrinol. 2013; 79:832-837.
6. Päkkilä F, Männistö T, Surcel HM et al. Maternal thyroid dysfunction during pregnancy and thyroid function of her child in adolescence. J Clin Endocrinol Metab. 2013; 98:965-972.
7. Mandel SJ, Hermos RJ, Larson CA et al. Atypical hypothyroidism and the very low birthweight infant. Thyroid. 2000; 10: 693-695.
8. Skjoldebrand L, Brundin J, Carlstrom A, Petterson T. Thyroid associated components in serum during normal pregnancy. Acta Endocrinol. 1982; 100:504-511.
9. Stagnaro-Green A, Abalovich M, Alexander E et al. Guidelines of the American Thyroid Association for the Diagnosis and management of thyroid disease during pregnancy and post-partum. Thyroid. 2011; 21:1081-1125.
10. Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstet Gynecol. 1988; 72:108-112.
11. Allan WC, Haddow JE, Palomaki GE, Williams JR et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen.2000; 7: 127-130.
12. Su PY, Huang K, Hao JH et al. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J Clin Endocrinol Metab. 2011; 96:3234-3241.
13. World Health Organization. Laboratory diagnosis and monitoring of diabetes mellitus. Geneva: World Health Organization; 2002.
14. Schneider S, Bock C, Wetzel M, Maul H, Loerbroks A. The prevalence of gestational diabetes in advanced economies. J Perinat Med. 2012; 40:511-520.
15. Philips JC, Emonts P, Pintiaux A, Kirkpatrick C, Scheen AJ. Management of gestational diabetes. Rev Med Liege. 2013; 68: 489-496.
16. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009; 373:1773-1779.
17. Bitterman O, Bongiovanni M, Giuliani C et al. Anti-thyroperoxidase and anti-thyroglobulin antibodies in diabetic pregnancies. J Endocrinol Invest. 2014; 37:911-915.
18. Casey BM, Dashe JS, Spong CY et al. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol. 2007; 109:1129-1135.
19. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol. 2012; 119: 983-988.
20. Karakosta P, Alegakis D, Georgiou V et al. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab. 2012; 97:4464-4472.
21. Männistö T, Mendola P, Grewal J et al. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endocrinol Metab. 2013; 98: 2725-2733.
22. Agarwal MM, Dhatt GS, Punnose J, Bishawi B, Zayed R. Thyroid function abnormalities and antithyroid antibody prevalence in pregnant women at high risk for gestational diabetes mellitus. Gynecol Endocrinol. 2006; 22: 261-266.
23. Chen LM, Du WJ, Dai J et al. Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population. PLoS One. 2014; 9:e109364.
24. Plowden TC, Schisterman EF, Sjaarda LA et al. Thyroid-stimulating hormone, anti-thyroid antibodies, and pregnancy outcomes. Am J Obstet Gynecol. 2017;. 217: 697.e1-697.e7.
25. Cleary-Goldman J, Malone FD, Lambert-Messerlian G et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol. 2008; 112:85-92.
26. Yang Y, Li Q, Wang Q, Ma X. Thyroid antibodies and gestational diabetes mellitus: a meta-analysis. Fertil Steril. 2015; 104: 665-671.e3.
27. Toulis KA, Stagnaro-Green A, Negro R. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta-analysis. Endocr Pract. 2014; 20:703-14.
28. Glinoer D, Delange F. The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny. Thyroid. 2000; 10: 871-887.
29. Pop VJ, Kuijpens JL, van Baar AL et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol. 1999; 50:149-155.
30. Haddow JE, Palomaki GE, Allan WC et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999; 341: 549-55.
31. Klein I. Thyroid hormone and the cardiovascular system. Am J Med. 1990; 88:631-637.
32. Pickard MR, Leonard AJ, Ogilvie LM et al. Maternal hypothyroidism in the rat influences placental and liver glycogen stores: fetal growth retardation near term is unrelated to maternal and placental glucose metabolic compromise. J Endocrinol. 2003; 176: 247-255.
33. Rovelli R, Vigone MC, Giovanettoni C et al. Newborn of mothers affected by autoimmune thyroiditis: the importance of thyroid function monitoring in the first months of life. Ital J Pediatr. 2010;10:24.
34. Ordookhani A, Mirmiran P, Walfish, Azizi F. Transient neonatal hypothyroidism is associated with elevated serum anti-thyroglobulin antibody levels in newborns and their mothers. J Pediatr. 2007; 150:315-317.e2.
35. Ozdemir H, Akman L, Coskun S et al. Maternal thyroid dysfunction and neonatal thyroid problems. Int J Endocrinol. 2013; 2013:987843
36. Dussault JH, Fisher DA. Thyroid function in mothers of hypothyroid newborns. Obstet Gyneco. 1999; 93:15-20.
37. Banigé M, Estellat C, Biran V et al. Study of the Factors Leading to Fetal and Neonatal Dysthyroidism in Children of Patients With Graves Disease. J Endocr Soc. 2017; 1:751-761.
38. Mittag J, Lyons DJ, Sällström J et al. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions. J Clin Invest. 2013; 123:509-516.
39. Vujovic M, Nordström K, Gauthier K et al. Interference of a mutant thyroid hormone receptor alpha1 with hepatic glucose metabolism. Endocrinology. 2009; 150:2940-2947.
40. Rytter D, Andersen SL, Bech BH et al. Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age. Pediatr Res. 2016; 80:7-13.
41. Godoy GA, Korevaar TL, Peeters RP et al. Maternal thyroid hormones during pregnancy, childhood adiposity and cardiovascular risk factors: the Generation R Study. Clin Endocrinol.2014; 81:117-125.
42. Heikkinen AL, Päkkilä F, Hartikainen AL, Vääräsmäki M, Männistö T, Suvanto E. Maternal Thyroid Antibodies Associates With Cardiometabolic Risk Factors in Children at the Age of 16. J Clin Endocrinol Metab. 2017; 102: 4184-4190.
43. Gardosi J. New definition of small for gestational age based on fetal growth potential. Horm Res, 2006; Suppl 3:15-8.
44. Gluckman PD, Harding JE. The physiology and pathophysiology of intrauterine growth retardation. Horm Res; 1997; 48:11-16.
45. Malik GK, Kacker S, Misra PK, Agarwal CG, Sharma B. Neonatal hypothyroxinemia. Indian J Pediatr. 1988; 55: 967-971.
46. Rashmi A, Seth A, Sekhri T, Agarwal A. Effect of perinatal factors on cord blood thyroid stimulating hormone levels. J Pediatr Endocrinol Metab 2007; 20: 59-64.
47. Mahajan SD, Aalinkeel R, Singh S et al. Endocrine regulation in asymmetric intrauterine fetal growth retardation. J Matern Fetal Neonatal Med. 2006; 19: 615-623.
48. Nieto-Díaz A, Villar J, Matorras-Weinig R, Valenzuela-Ruìz P .Intrauterine growth retardation at term: association between anthropometric and endocrine parameters. Acta Obstet Gynecol Scand 1996;. 75:127-1231.
49. Jacobsen BB, Hummer L. Changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins during early infancy. Studies in healthy full term, small-for gestational age and preterm infants aged 7 to 240 days. Acta Paediatr Scand 1979; 68: 411-418.
50. Radetti G, Renzullo L, Gottardi E, D'Addato G, Messner H. Altered thyroid and adrenal function in children born at term and preterm, small for gestational age. J Clin Endocrinol Metab, 2004; 89:6320-6324.
51. Cianfarani S, Maiorana A, Geremia C et al. Blood glucose concentrations are reduced in children born small for gestational age (SGA), and thyroidstimulating hormone levels are increased in SGA with blunted postanatal catch-up growth. J Clin Endocrinol Metab. 2003; 88: 2699-2705.
52. Bagnoli F, Farmeschi L, Nappini S, Grosso S. Thyroid function in small for gestational age newborns: a review. J Clin Res Pediatr Endocrinol. 2013; 5: 2-7.
53. Ahmed Aand, Kilby MD. Intrauterine growth restriction: placental hypoxia and hyperoxia. Lancet. 1997: 350: 826-827.

54. Kilby MD, Verhaeg J, Gittoes N. et al. Circulating thyroid hormone concentrations and placental thyroid hormone receptor expression in normal human pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR). J Clin Endocrinol Metab. 1998; 83: 2964-2971.
55. Setia S, Sridhar MG, Koner BC et al. Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role? Clin Chim Acta. 2007; 376: 37-40.
56. Monaco HL. The transthyretin-retinol-binding protein complex. Biochim Biophys Acta 2000; 1482: 65-72.
57. Hillman NH, Kallapur SG, Jobe AH. Physiology of transition from intrauterine to extrauterine life. Clin Perinatol. 2012; 39:769-83.
58. Chung HR. Adrenal and thyroid function in the fetus and preterm infant. Korean J Pediatr. 2014; 57: 425-433.
59. 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; 90:5954-5963.
60. van Wassenaer AG, Kok JH. Hypothyroxinaemia and thyroid function after preterm birth. Semin Neonatol. 2004, 9:3-11.
61. Ogilvy-Stuart AL. Neonatal thyroid disorders. Arch Dis Child Fetal and Neonatal Ed. 2002; 87:165–171.
62. Morreale de Escobar G, Ares S. The hypothyroxinemia of prematurity. J Clin Endocrinol Metab. 1998; 83:713-716.
63. Delahunty C, Falconer S, Hume R et al. Levels of neonatal thyroid hormone in preterm infants and neurodevelopmental outcome at 5 1/2 years: millennium cohort study. J Clin Endocrinol Metab. 2010; 95:4898-4908.
64. Díllí D, Eras Z, Dilmen U, Sakrucu ED. Neurodevelopmental evaluation of very low birth weight infants with sepsis at 18 to 24 months corrected age. Indian Pediatr. 2013;. 50:327-30.
65. Mercado M, Yu VY, Francis I, Szymonowicz W, Gold H. Thyroid function in very preterm infants. Early Hum Dev.1988; 16:131-41.
66. Osborn DA, Hunt RW. Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2007; 24: CD005948, 2007.
67. 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; 102:3050-3055.
68. Cavarzere P, Camilot M, Popa FI et al. Congenital hypothyroidism with delayed TSH elevation in low-birth-weight infants: incidence, diagnosis and management. Eur J Endocrinol. 2016;. 175: 395-402.