Quality & Quantity

, Volume 52, Issue 3, pp 1423–1435 | Cite as

Does the iodized salt therapy of pregnant mothers increase the children IQ? Empirical evidence of a statistical study based on permutation tests

  • Massimiliano Giacalone
  • Agata Zirilli
  • Mariacarla Moleti
  • Angela Alibrandi
Article
First Online:
  • 75 Downloads

Abstract

The nutritional iodine deficiency disorders are still a major health problem in industrialized countries, but they are completely preventable by means of iodine prophylaxis. Iodine is essential for thyroid hormone (TH) synthesis and TH is required for normal brain development. Gestational iodine supplementation may improve infant cognitive development. In this study we aimed at evaluating the intelligence quotient of children born to mothers with different levels of iodine supplementation, with or without the administration of levothyroxine (LT4), prior to and during pregnancy. In particular we focused our attention on some mother–child pairs and we compared them according to iodized salt consumption and LT4 treatment. In this specific context, NPC test was applied to compare four groups of children, defined on the basis of maternal history related to iodized salt consumption and LT4 treatment. The results show that the deficit in functionality cognitive (in terms of intelligence quotient) is significantly higher in the children of mothers that does not make supplementation of iodized salt. This shows how a lack of iodine can hinder children in reaching their full intellectual potential. From a methodological point of view, our research showed the utility of the Non Parametric Combination test (NPC test) into analyze data concerning medical research.

Keywords

Neurocognitive development Iodine nutrition Thyroid status Comparative analysis Permutation test 
This is a preview of subscription content, log in to check access.

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare that there is no conflict of interest.

Human and animals rights

The study involved mother–child pairs.

Informed consent

All participants gave their informed consent (such as specified in subsection 2.2).

References

  1. Alibrandi, A., Zirilli, A.: A statistical evaluation on high seric levels of D-Dimer: a case control study to test the influences of ascites. In: Atti S.Co.2007 Conference, CLEUP, Padova, pp. 9–14 (2007)Google Scholar
  2. Arboretti Giancristofaro, R., Marozzi, M., Salmaso, L.: Repeated measures designs: a permutation approach for testing for active effects. Far East. J. Theor. Stat. 16(2), 303–325 (2005)Google Scholar
  3. Arboretti Giancristofaro, R., Pesarin, F., Salmaso, L., Solari, A.: Nonparametric procedure for testing for dropout rates on university courses with application to an Italian case study. In: Sawilowsky, S. (ed.) Real Data Analysis, pp. 355–385. Information Age Publishing, Charlotte (2007)Google Scholar
  4. Arboretti Giancristofaro, R., Brombin, C., Pellizzari, S., Salmaso, L., Mozzanega, B.: Nonparametric methods applied to nuchal translucency and fetal macrosomia. J Biostat 2, 19–36 (2008)Google Scholar
  5. Arboretti Giancristofaro, R., Bonnini, S., Salmaso, L.: Employment status and education/employment relationship of PhD graduates from the University of Ferrara. J. Appl. Stat. 36(12), 1329–1344 (2009). doi: 10.1080/02664760802638108 CrossRefGoogle Scholar
  6. Bath, S.C., Steer, C.D., Golding, J., Emmett, P., Rayman, M.P.: Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet 382(27), 331–337 (2013). doi: 10.1016/S0140-6736(13)60436-5 CrossRefGoogle Scholar
  7. Bonnini, S., Corani, L., Marozzi, M., Salmaso, L.: Nonparametric Hypothesis Testing: Rank and Permutation Methods with Applications in R. Wiley, Hoboken (2014). doi: 10.1002/9781118763490 CrossRefGoogle Scholar
  8. Bonnini, S., Salmaso, L., Solari, A.: Multivariate permutation tests for evaluating effectiveness of universities through the analysis of students dropouts. Stat. Appl. 3, 37–44 (2005)Google Scholar
  9. Bonnini, S., Corain, L., Munaò, F., Salmaso, L.: Neurocognitive effects in welders exposed to aluminium: an application of the NPC test and NPC ranking methods. Stat. Methods Appl. 15(2), 191–208 (2006)CrossRefGoogle Scholar
  10. Callegaro, A., Pesarin, F., Salmaso, L.: Test di permutazione per il confronto di curve di sopravvivenza. Statistica Applicata 15(2), 241–261 (2003)Google Scholar
  11. Corain, L., Salmaso, L.: Multivariate and multistrata nonparametric tests: the nonparametric combination method. J. Mod. Appl. Stat. Methods 3, 443–461 (2004)CrossRefGoogle Scholar
  12. De Escobar, G.M., Obregón, G., Escobar Del Rey, M.J.: Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J. Clin. Endocrinol. Metab. 85(11), 3975–3987 (2000)Google Scholar
  13. De Vivo, A., Mancuso, A., Giacobbe, A., Moleti, M., Maggio, Savasta L., De Dominici, R., Priolo, A.M., Vermiglio, F.: Thyroid function in women found to have early pregnancy loss. Thyroid 20(6), 633–637 (2010)CrossRefGoogle Scholar
  14. Di Castelnuovo, A., Mazzaro, D., Pesarin, F., Salmaso, L.: Test di permutazione multidimensionali in problemi d’inferenza isotonica: un’applicazione alla genetica. Statistica 60(4), 691–700 (2000)Google Scholar
  15. Feyrer, J., Politi, D., Weil, D.N.: The cognitive effects of micronutrient deficiency: evidence from salt iodization in the United States., National Bureau of Economic Research, w19233 (2013)Google Scholar
  16. Finos, L., Pesarin, F., Salmaso, L., Solari, A.: Nonparametric iterated procedure for testing genetic differentiation, Atti XLIII Riunione Scientifica SIS, CLEUP, Padova, 95–98 (2004)Google Scholar
  17. Giacalone, M., Zirilli, A., Alibrandi, A.: The use of Permutation Tests on Large-Sized Datasets. In: Proceedings of the 48th Scientific Meeting of the Italian Statistical Society, Università degli Studi di Salerno, Monica Pratesi and Cira Perna Editors, ISBN: 9788861970618 (2016)Google Scholar
  18. Gianetti, E., Russo, L., Orlandi, F., Chiovato, L., Giusti, M., Benvenga, S., Moleti, M., Vermiglio, F., Macchia, P.E., Vitale, M., Regalbuto, C., Centanni, M., Martino, E., Vitti, P., Tonacchera, M.: Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy. J. Endocrinol. Invest. 38(9), 977–985 (2015)CrossRefGoogle Scholar
  19. Glinoer, D., Delange, F.: The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny. Thyroid 10(10), 871–887 (2000)CrossRefGoogle Scholar
  20. Good, P.: Permutation Test, 2nd edn. Springer-Verlag, New York (2000)CrossRefGoogle Scholar
  21. Krassas, G.E., Poppe, K., Glinoer, D.: Thyroid function and human reproductive health. Endocr. Rev. 31(5), 702–755 (2010)CrossRefGoogle Scholar
  22. Liu, H., Momotani, N., Noh, J.Y., Ishikawa, N., Takebe, K., Ito, K.: Maternal hypothyroidism during early pregnancy and intellectual development of the progeny. Arch. Intern. Med. 154(7), 785–787 (1994)CrossRefGoogle Scholar
  23. Marozzi, M.: Combination of distribution-free tests for the general two-sample problem with application to the social sciences. Commun. Stat. Theory Methods 45, 6421–6435 (2016)CrossRefGoogle Scholar
  24. Methodologica Srl: NPC Test© 2.0 Statistical Software For Multivariate Permutation Tests. Methodologica srl (www.methodologica.it), Treviso, Italy (2001)
  25. Moleti, M., Lo Presti, V.P., Campolo, M.C., Mattina, F., Galletti, M., Mandolfino, M., Violi, M.A., Giorgianni, G., De Domenico, D., Trimarchi, F., Vermiglio, F.: Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency. J. Clin. Endocrinol. Metab. 93(7), 2616–2621 (2008)CrossRefGoogle Scholar
  26. Moleti, M., Vermiglio, F., Trimarchi, F.: Maternal isolated hypothyroxinemia: to treat or not to treat? J. Endocrinol. Invest. 32(9), 780–782 (2009a)CrossRefGoogle Scholar
  27. Moleti, M., Lo Presti, V.P., Mattina, F., Mancuso, A., De Vivo, A., Giorgianni, G., Di Bella, B., Trimarchi, F., Vermiglio, F.: Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus continuous monitoring of maternal thyroid status. Eur. J. Endocrinol. 160(4), 611–617 (2009b)CrossRefGoogle Scholar
  28. Moleti, M., Di Bella, B., Giorgianni, G., Mancuso, A., De Vivo, A., Alibrandi, A., Trimarchi, F., Vermiglio, F.: Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study. Clin. Endocrinol. Oxf. 74(6), 762–768 (2011)CrossRefGoogle Scholar
  29. Moleti, M., Trimarchi, F., Vermiglio, F.: Doubts and concerns about isolated maternal hypothyroxinemia. J. Thyroid Res. 2011, 463029 (2011b)CrossRefGoogle Scholar
  30. Moleti, M., Trimarchi, F., Vermiglio, F.: Thyroid physiology in pregnancy. Endocr. Pract. 20(6), 589–596 (2014)CrossRefGoogle Scholar
  31. Moleti, M., Trimarchi, F., Tortorella, G., Candia Longo, A., Giorgianni, G., Sturniolo, G., Alibrandi, A., Vermiglio, F.: Effects of maternal iodine nutrition and thyroid status on cognitive development in offspring: a pilot study. Thyroid 26(2), 296–305 (2016)CrossRefGoogle Scholar
  32. Momotani, N., Iwama, S., Momotani, K.: Neurodevelopment in children born to hypothyroid mothers restored to normal thyroxine (T4) concentration by late pregnancy in Japan: no apparent influence of maternal T4 deficiency. J. Clin. Endocrinol. Metab. 97(4), 1104–1108 (2012)CrossRefGoogle Scholar
  33. OSNAMI: Prevenzione dei disordini da carenza iodica e delle malattie dovute a eccessivo consumo di sale: due strategie compatibili. Istituto Superiore di Sanità, 28(1) (2014)Google Scholar
  34. Pesarin, F.: Permutation Testing of Multidimensional Hypotheses. CLEUP, Padova (1997)Google Scholar
  35. Pesarin, F.: Multivariate Permutation Tests with Applications in Biostatistics. Wiley, Chichester (2001)Google Scholar
  36. Pesarin, F., Salmaso, L.: Permutation Tests for Complex Data: Theory. Applications and Software. Wiley Series in Probability and Statistics. Wiley, Chichester (2010)CrossRefGoogle Scholar
  37. Roy, S.N.: On heuristic method of test construction and its use in multivariate analysis. Ann. Math. Stat. 24, 220–238 (1953)CrossRefGoogle Scholar
  38. Redman, K.F.: Iodine and cognition in young adults: a randomised, Placebo-Controlled Trial. Thesis submitted for the degree of Master of Science at the University of Otago, Dunedin, New Zealand (2011)Google Scholar
  39. Salmaso, L.: Permutation tests in screening two-level factorial experiments. Adv. Appl. Stat. 5(1), 91–110 (2005)Google Scholar
  40. Vermiglio, F., Lo Presti, V.P., Moleti, M., Sidoti, M., Tortorella, G., Scaffidi, G., Castagna, M.G., Mattina, F., Violi, M.A., Crisà, A., Artemisia, A., Trimarchi, F.: Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J. Clin. Endocrinol. Metab. 89(12), 6054–6060 (2004)CrossRefGoogle Scholar
  41. Wechsler, D.: WISC-III: Wechsler Intelligence Scale for Children. The Psychological Corporation, New York (1991)Google Scholar
  42. Williams, G.R.: Neurodevelopmental and neurophysiological actions of thyroid hormone. J. Neuroendocrinol. 20(6), 784–794 (2008)CrossRefGoogle Scholar
  43. Zimmermann, M.B.: Iodine deficiency. Endocr. Rev. 30(4), 376–408 (2009)CrossRefGoogle Scholar
  44. Zirilli, A., Alibrandi, A., Spadaro, A., Freni, M.A. Prognostic factors of survival in the cirrhosis of the liver: a statistical evaluation in a multivariate approach. In: Atti S.Co.2005 Conference, CLEUP, Padova, 173–178 (2005)Google Scholar
  45. Zirilli, A., Alibrandi, A.: A permutation approach to evaluate hyperhomocysteinemia in epileptic patients. In: Supplemento ai rendiconti del circolo matematico di Palermo. VII International Conference in “Stochastic Geometry, Convex Bodies, Empirical Measures and application to mechanics and Engineering train-transport”, 369–378 (2009)Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Department of Economics and StatisticsUniversity of Naples Federico IINaplesItaly
  2. 2.Department of Economics, Section of Statistical and Mathematical SciencesUniversity of MessinaMessinaItaly
  3. 3.Department of Clinical and Experimental Medicine, AOU Policlinico G. MartinoUniversity of MessinaMessinaItaly

Personalised recommendations