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Published in: Trials 1/2019

Open Access 01-12-2019 | Thyroiditis | Study protocol

Evaluation of the impact of levothyroxine treatment on the psychomotor developmental status of three-year-old children born to mothers with mild thyroid impairment; Tehran Thyroid and pregnancy study: study protocol for a randomized clinical trial

Authors: Sima Nazarpour, Fahimeh Ramezani Tehrani, Firoozeh Sajedi, Razieh Bidhendi Yarandi, Fereidoun Azizi

Published in: Trials | Issue 1/2019

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Abstract

Background

Despite the known adverse effects of maternal overt hypothyroidism on the neurocognitive development of children, there is uncertainty regarding the impact of gestational thyroid dysfunction or autoimmune thyroiditis on infant/child neurological development. This study aims to evaluate the impact of levothyroxine (LT4) treatment on the psychomotor developmental status of three-year-old children born to mothers with mild thyroid impairment (subclinical hypothyroidismwith/without autoimmune thyroiditis).

Methods/Design

This is a follow-up study of the Tehran Thyroid and Pregnancy Study, a randomized trial in which subclinical hypothyroid pregnant women were assigned to an intervention group (treated with levothyroxine) or a control group (received no treatment). The primary outcome for the purpose of the present study is the developmental status of the children, aged three years, in five domains (communication, gross motor, fine motor, problem-solving, and social–personal domains) using the Ages and Stages Questionnaire (ASQ).

Discussion

The study is designed to assess the developmental status of children born to mothers with mild thyroid impairment (subclinical hypothyroidism with/without autoimmune thyroiditis). This study is one of the limited studies available in this field and has the potential to facilitate much-needed information for related public health policies.

Trial registration

Iranian Registry of Clinical Trials, IRCT201709031484​9N5. Registered on 11 September 2017. Iranian Registry of Clinical Trials, IRCT201709041484​9N6. Registered on 14 October 2017.
Appendix
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Literature
1.
Ahmed OM, El-Gareib A, El-Bakry A, El-Tawab SA, Ahmed R. Thyroid hormones states and brain development interactions. Int J Dev Neurosci. 2008;26(2):147–209.CrossRef
2.
Morreale de Escobar G, Obregón MJ, Escobar del Rey F. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab. 2000;85(11):3975–87.PubMed
3.
Vulsma T, Gons M, de Vijlder J. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N Engl J Med. 1989;321:13–6.CrossRef
4.
Krassas G, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702–55.CrossRef
5.
Sajedi F, Vameghi R, Bandpei M, Alizad V, Hemmati Gorgani S, Shahshahani Pour S. Motor developmental delay in 7500 Iranian infants: prevalence and risk factors. Iran J Child Neurol. 2009;3(3):43–50.
6.
Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 Suppl):S1–47.CrossRef
7.
8.
Glinoer D, Riahi M, Grün J, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab. 1994;79(1):197–204.PubMed
9.
Glinoer D, Soto MF, Bourdoux P, Lejeune B, Delange F, Lemone M, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab. 1991;73(2):421–7.CrossRef
10.
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341(8):549–55.CrossRef
11.
Li Y, Shan Z, Teng W, Yu X, Li Y, Fan C, et al. Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months. Clin Endocrinol. 2010;72(6):825–9.CrossRef
12.
Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol. 1999;50(2):149–55.CrossRef
13.
Smit B, Kok J, Vulsma T, Briet J, Boer K, Wiersinga W. Neurologic development of the newborn and young child in relation to maternal thyroid function. Acta Paediatr. 2000;89(3):291–5.CrossRef
14.
Williams F, Watson J, Ogston S, Hume R, Willatts P, Visser T, Scottish Preterm Thyroid Group. Mild maternal thyroid dysfunction at delivery of infants born≤ 34 weeks and neurodevelopmental outcome at 5.5 years. J Clin Endocrinol Metab. 2012;97(6):1977–85.CrossRef
15.
Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, et al. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med. 2017;376(9):815–25.CrossRef
16.
Hershman JM. Levothyroxine therapy of subclinical hypothyroidism or hypothyroxinemia in pregnancy does not improve cognitive function in the offspring. Clin Thyroidology. 2017;29(4):132–5.CrossRef
17.
Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493–501.CrossRef
18.
Pop VJ, de Vries E, van Baar AL, Waelkens J, De Rooy H, Horsten M, et al. Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development? J Clin Endocrinol Metab. 1995;80(12):3561–6.CrossRef
19.
Williams FL, Watson J, Ogston SA, Visser TJ, Hume R, Willatts P. Maternal and umbilical cord levels of T4, FT4, TSH, TPOAb, and TgAb in term infants and neurodevelopmental outcome at 5.5 years. J Clin Endocrinol Metab. 2013;98(2):829–38.CrossRef
20.
Ghassabian A, Bongers-Schokking JJ, De Rijke YB, Van Mil N, Jaddoe VW, de Muinck Keizer-Schrama SM, et al. Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study. Thyroid. 2012;22(2):178–86.CrossRef
21.
Bath SC, Rayman MP. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(17):1640–1.CrossRef
22.
Hales C, Taylor PN, Channon S, Paradice R, McEwan K, Zhang L, et al. Controlled Antenatal Thyroid Screening II: effect of treating maternal sub-optimal thyroid function on child cognition. J Clin Endocrinol Metab. 2018;103(4):1583–91.
23.
Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Azizi F. Thyroid and Pregnancy in Tehran, Iran: Objectives and Study Protocol. Int J Endocrinol Metab. 2016;14(1):e33477.
24.
Nazarpour S, Tehrani FR, Simbar M, Tohidi M, Majd HA, Azizi F. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur J Endocrinol. 2017;176(2):253–65.CrossRef
25.
Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Minooee S, Rahmati M, et al. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. J Clin Endocrinol Metab. 2017;103(3):926–35.CrossRef
26.
Vameghi R, Sajedi F, Mojembari AK, Habiollahi A, Lornezhad HR, Delavar B. Cross-cultural adaptation, validation and standardization of Ages and Stages Questionnaire (ASQ) in Iranian children. Iran J Public Health. 2013;42(5):522.PubMedPubMedCentral
27.
Singh A, Yeh CJ, Blanchard SB. Ages and stages questionnaire: a global screening scale. Bol Med Hosp Infant Mex. 2017;74(1):5–12.PubMed
28.
Sajedi F, Vameghi R, Kraskian Mujembari A. Prevalence of undetected developmental delays in Iranian children. Child Care Health Dev. 2014;40(3):379–88.CrossRef
29.
Heo KH, Squires J, Yovanoff P. Cross-cultural adaptation of a pre-school screening instrument: comparison of Korean and US populations. J Intellect Disabil Res. 2008;52(3):195–206.CrossRef
30.
Otalvaro AMR, Grañana N, Gaeto N, Torres MÁ, Zamblera MN, Vasconez MA, et al. ASQ-3: Validation of the Ages and Stages Questionnaire for the detection of neurodevelopmental disorders in Argentine children. Arch Argent Pediatr. 2018;116(1):7–13.
31.
Saihong P. Use of screening instrument in Northeast Thai early childcare settings. Procedia Soc Behav Sci. 2010;7:97–105.CrossRef
32.
Sarmiento Campos JA, Squires J, Ponte J. Universal developmental screening: preliminary studies in Galicia, Spain. Early Child Dev Care. 2011;181(4):475–85.CrossRef
33.
Sajedi F, Vameghi R, Habibollahi A, Lornejad H, Delavar B. Standardization and validation of the ASQ developmental disorders screening tool in children of Tehran city. Tehran Univ Med Sci. 2012;70(7):436–46.
34.
Soleymani F, Vameghi R, Dadkhah A. High risk infants referred to health-care centers in North and East of Tehran and risk factors of motor developmental delay. Hakim Res J. 2009;12(2):11–18.
35.
Chan A-W, Tetzlaff JM, Altman DG, Dickersin K, Moher D. SPIRIT 2013: new guidance for content of clinical trial protocols. Lancet. 2013;381(9861):91–2.CrossRef
36.
Benhadi N, Wiersinga W, Reitsma J, Vrijkotte T, Bonsel G. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol. 2009;160(6):985–91.CrossRef
37.
Chen L-M, Du W-J, Dai J, Zhang Q, Si G-X, Yang H, 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(10):e109364.CrossRef
38.
Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012;119(2):315–20.CrossRef
39.
Behrooz HG, Tohidi M, Mehrabi Y, Behrooz EG, Tehranidoost M, Azizi F. Subclinical hypothyroidism in pregnancy: intellectual development of offspring. Thyroid. 2011;21(10):1143–7.CrossRef
40.
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. Obstet Gynecol Surv. 2000;55(1):3.CrossRef
41.
Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3(2):76–94.CrossRef
42.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081–125.CrossRef
43.
Hales C, Channon S, Taylor PN, Draman MS, Muller I, Lazarus J, et al. The second wave of the Controlled Antenatal Thyroid Screening (CATS II) study: the cognitive assessment protocol. BMC Endocr Disord. 2014;14(1):95.CrossRef
44.
45.
Group MTF-USC. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG. 2007;114(3):289–99.
46.
Yu LM, Hey E, Doyle LW, Farrell B, Spark P, Altman DG, et al. Evaluation of the Ages and Stages Questionnaires in identifying children with neurosensory disability in the Magpie Trial follow-up study. Acta Paediatr. 2007;96(12):1803–8.CrossRef
47.
Elbers J, Macnab A. The Ages and Stages Questionnaires: feasibility of use as a screening tool for children in Canada. Can J Rural Med. 2008;13(1):9.PubMed
48.
Klamer A, Lando A, Pinborg A, Greisen G. Ages and Stages Questionnaire used to measure cognitive deficit in children born extremely preterm. Acta Paediatrica. 2005;94(9):1327–9.CrossRef
49.
Squires J, Katzev A, Jenkins F. Early screening for developmental delays: Use of parent-completed questionnaires in Oregon’s Healthy Start Program. Early Child Dev Care. 2002;172(3):275–82.CrossRef
50.
Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014;72(4):267–84.CrossRef
Metadata
Title
Evaluation of the impact of levothyroxine treatment on the psychomotor developmental status of three-year-old children born to mothers with mild thyroid impairment; Tehran Thyroid and pregnancy study: study protocol for a randomized clinical trial
Authors
Sima Nazarpour
Fahimeh Ramezani Tehrani
Firoozeh Sajedi
Razieh Bidhendi Yarandi
Fereidoun Azizi
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-3130-5

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