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Maternal hypothyroidism may be associated with CHD in offspring

Published online by Cambridge University Press:  02 October 2014

Michael J Grattan
Affiliation:
Division of Cardiology, Department of Paediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
Daina S Thomas
Affiliation:
Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
Lisa K. Hornberger
Affiliation:
Division of Cardiology, Department of Paediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
Robert M Hamilton
Affiliation:
Department of Paediatrics, Hospital for Sick Children, Canada and University of Toronto, Toronto, Ontario, Canada
William K Midodzi
Affiliation:
Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
Sunita Vohra*
Affiliation:
Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
*
Correspondence to: S. Vohra, MD, Edmonton General Hospital, 8B19-11111 Jasper Avenue, Edmonton, Alberta, Canada T5K 0L4. Tel: +780 342 8592; Fax: +780 342 8464; E-mail: [email protected]

Abstract

Objectives: This study tested whether mothers with maternal hypothyroidism have increased odds of CHD in their offspring, and examined the relationship between CHD, maternal thyroid function, and nausea and vomiting in pregnancy. Background: Maternal hypothyroidism increases the risk for foetal demise and prematurity and can have a negative impact on neurodevelopment. Prior studies have postulated a relationship between maternal thyroid function, CHD, and maternal nausea and vomiting in pregnancy. Methods: A cross-sectional case–control study was conducted over a 17-month period to obtain a history of maternal thyroid status and nausea and vomiting in pregnancy. Paediatric echocardiograms were evaluated for CHD by a blinded paediatric cardiologist. Logistic regression analysis was performed to examine the association between CHD and maternal hypothyroidism. Results: Of the 998 maternal–child pairs, 10% (98/998) of the mothers reported a history of prenatal hypothyroidism. The overall prevalence of CHD in the study sample was 63% (630/998). Mothers with a history of hypothyroidism were significantly more likely to have offspring with CHD compared with mothers without a history of hypothyroidism (72 versus 62%; p=0.04). The adjusted odds ratio (95% confidence interval) of CHD in offspring associated with reported maternal hypothyroidism was 1.68 (1.02–2.78). Conclusion: This study suggests that maternal hypothyroidism is a risk factor for the development of CHD. Further prospective investigations are necessary to confirm this association and delineate pathogenic mechanisms.

Type
Original Articles
Copyright
© Cambridge University Press 2014 

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References

1. Hoffman, JI, Kaplan, S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39: 18901900.CrossRefGoogle ScholarPubMed
2. Glinoer, D. Potential consequences of maternal hypothyroidism on the offspring: evidence and implications. Horm Res 2001; 55: 109114.Google ScholarPubMed
3. Lisowski, LA, Verheijen, PM, Copel, JA, et al. Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz 2010; 35: 1926.CrossRefGoogle ScholarPubMed
4. 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 postpartum. Thyroid 2011; 21: 10811125.CrossRefGoogle ScholarPubMed
5. Spence, D, Hornberger, L, Hamilton, R, Silverman, ED. Increased risk of complete congenital heart block in infants born to women with hypothyroidism and anti-Ro and/or anti-La antibodies. J Rheumatol 2006; 33: 167170.Google ScholarPubMed
6. Browne, ML, Rasmussen, SA, Hoyt, AT, et al. Maternal thyroid disease, thyroid medication use, and selected birth defects in the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol 2009; 85: 621628.CrossRefGoogle ScholarPubMed
7. Liu, S, Joseph, KS, Lisonkova, S, et al. Association between maternal chronic conditions and congenital heart defects: a population-based cohort study. Circulation 2013; 128: 583589.CrossRefGoogle ScholarPubMed
8. Robert, E, Vollset, SE, Botto, L, et al. Malformation surveillance and maternal drug exposure: the MADRE project. Int J Risk Saf Med 1994; 6: 75118.CrossRefGoogle ScholarPubMed
9. Wikner, BN, Sparre, LS, Stiller, CO, Kallen, B, Asker, C. Maternal use of thyroid hormones in pregnancy and neonatal outcome. Acta Obstet Gynecol Scand 2008; 87: 617627.CrossRefGoogle ScholarPubMed
10. Khoury, MJ, Becerra, JE, d’Almada, PJ. Maternal thyroid disease and risk of birth defects in offspring: a population-based case-control study. Paediatr Perinat Epidemiol 1989; 3: 402420.CrossRefGoogle ScholarPubMed
11. Boneva, RS, Moore, CA, Botto, L, Wong, LY, Erickson, JD. Nausea during pregnancy and congenital heart defects: a population-based case-control study. Am J Epidemiol 1999; 149: 717725.CrossRefGoogle ScholarPubMed
12. Goodwin, TM, Hershman, JM. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin Obstet Gynecol 1997; 40: 3244.CrossRefGoogle ScholarPubMed
13. Goodwin, TM, Montoro, M, Mestman, JH. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am J Obstet Gynecol 1992; 167: 648652.CrossRefGoogle ScholarPubMed
14. Goodwin, TM, Montoro, M, Mestman, JH, Pekary, AE, Hershman, JM. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab 1992; 75: 13331337.Google ScholarPubMed
15. Leylek, OA, Cetin, A, Toyaksi, M, Erselcan, T. Hyperthyroidism in hyperemesis gravidarum. Int J Gynaecol Obstet 1996; 55: 3337.CrossRefGoogle ScholarPubMed
16. Nader, S, Mastrobattista, J. Recurrent hyperthyroidism in consecutive pregnancies characterized by hyperemesis. Thyroid 1996; 6: 465466.CrossRefGoogle ScholarPubMed
17. Vohra, S, Koren, G. Hypothetical framework for a relationship between maternal thyroid function, nausea and vomiting of pregnancy, and congenital heart disease. Med Hypotheses 2001; 56: 392394.CrossRefGoogle ScholarPubMed
18. Clark, EB. Pathogenetic mechanisms of congenital cardiovascular malformations revisited. Semin Perinatol 1996; 20: 465472.CrossRefGoogle ScholarPubMed
19. Berkow, R, Merck Research Laboratories. The Merck Manual of Medical Information: Home Edition. Merck Research Laboratories, Whitehouse Station, New Jersey, 1997.Google Scholar
20. Bloch, W, Fleischmann, BK, Lorke, DE, et al. Nitric oxide synthase expression and role during cardiomyogenesis. Cardiovasc Res 1999; 43: 675684.CrossRefGoogle ScholarPubMed
21. Sinha, RA, Pathak, A, Mohan, V, Bandyopadhyay, S, Rastogi, L, Godbole, MM. Maternal thyroid hormone: a strong repressor of neuronal nitric oxide synthase in rat embryonic neocortex. Endocrinology 2008; 149: 43964401.CrossRefGoogle Scholar
22. Oceandy, D, Cartwright, EJ, Emerson, M, et al. Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b. Circulation 2007; 115: 483492.CrossRefGoogle ScholarPubMed
23. Lynch, JM, Chilibeck, K, Qui, Y, Michalak, M. Assembling pieces of the cardiac puzzle; calreticulin and calcium-dependent pathways in cardiac development, health, and disease. Trends Cardiovasc Med 2006; 16: 6569.CrossRefGoogle ScholarPubMed
24. Prins, D, Michalak, M. Endoplasmic reticulum proteins in cardiac development and dysfunction. Can J Physiol Pharmacol 2009; 87: 419425.CrossRefGoogle ScholarPubMed
25. Ridings, JE, Palmer, AK, Davidson, EJ, Baldwin, JA. Prenatal toxicity studies in rats and rabbits with the calcium channel blocker diproteverine. Reprod Toxicol 1996; 10: 4349.CrossRefGoogle ScholarPubMed
26. Scott, WJ Jr., Resnick, E, Hummler, H, Clozel, JP, Burgin, H. Cardiovascular alterations in rat fetuses exposed to calcium channel blockers. Reprod Toxicol 1997; 11: 207214.CrossRefGoogle ScholarPubMed
27. Reed, TD, Babu, GJ, Ji, Y, et al. The expression of SR calcium transport ATPase and the Na(+)/Ca(2+)exchanger are antithetically regulated during mouse cardiac development and in hypo/hyperthyroidism. J Mol Cell Cardiol 2000; 32: 453464.CrossRefGoogle Scholar
28. Blazer, S, Moreh-Waterman, Y, Miller-Lotan, R, Tamir, A, Hochberg, Z. Maternal hypothyroidism may affect fetal growth and neonatal thyroid function. Obstet Gynecol 2003; 102: 232241.Google ScholarPubMed
29. Maran, RR. Thyroid hormones: their role in testicular steroidogenesis. Arch Androl 2003; 49: 375388.CrossRefGoogle ScholarPubMed
30. Matsuo, SE, Ebina, KN, Kulcsar, MA, Friguglietti, CU, Kimura, ET. Activin betaB expression in rat experimental goiter and human thyroid tumors. Thyroid 2003; 13: 239247.CrossRefGoogle ScholarPubMed
31. Kosaki, R, Gebbia, M, Kosaki, K, et al. Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB. Am J Med Genet 1999; 82: 7076.3.0.CO;2-Y>CrossRefGoogle ScholarPubMed
32. Ticho, BS, Goldstein, AM, Van Praagh, R. Extracardiac anomalies in the heterotaxy syndromes with focus on anomalies of midline-associated structures. Am J Cardiol 2000; 85: 729734.CrossRefGoogle ScholarPubMed
33. Kokan-Moore, NP, Bolender, DL, Lough, J. Secretion of inhibin beta A by endoderm cultured from early embryonic chicken. Dev Biol 1991; 146: 242245.CrossRefGoogle ScholarPubMed
34. Smedts, HP, van Uitert, EM, Valkenburg, O, et al. A derangement of the maternal lipid profile is associated with an elevated risk of congenital heart disease in the offspring. Nutr Metab Cardiovasc Dis 2012; 22: 477485.CrossRefGoogle ScholarPubMed
35. Haddad, F, Jiang, W, Bodell, PW, Qin, AX, Baldwin, KM. Cardiac myosin heavy chain gene regulation by thyroid hormone involves altered histone modifications. Am J Physiol Heart Circ Physiol 2010; 299: H1968H1980.CrossRefGoogle ScholarPubMed
36. Pandya, K, Kohro, T, Mimura, I, et al. Distribution of histone3 lysine 4 trimethylation at T3-responsive loci in the heart during reversible changes in gene expression. Gene Expression 2012; 15: 183198.CrossRefGoogle ScholarPubMed
37. Bryant, HE, Visser, N, Love, EJ. Records, recall loss, and recall bias in pregnancy: a comparison of interview and medical records data of pregnant and postnatal women. Am J Pub Health 1989; 79: 7880.CrossRefGoogle ScholarPubMed
38. Roodpeyma, S, Kamali, Z, Afshar, F, Naraghi, S. Risk factors in congenital heart disease. Clin Pediatr 2002; 41: 653658.CrossRefGoogle ScholarPubMed