Skip to main content
SpringerLink
Log in

Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment

  • Review Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Amiodarone, a benzofuranic derivative, iodine-rich drug, has been used in pregnancy for either maternal or fetal tachyarrhythmias. Amiodarone, its main metabolite (desethylamiodarone) and iodine are transferred, albeit incompletely, through the placenta, resulting in a relevant fetal exposure to the drug and iodine overload. Since the fetus acquires the capacity to escape from the acute Wolff-Chaikoff effect only late in gestation, the iodine overload may cause fetal/neonatal hypothyroidism and goiter. Among the reported 64 pregnancies in which amiodarone was given to the mother, 11 cases (17%) of hypothyroidism in the progeny (10 detected at birth, 1 in utero) were reported, 9 non-goitrous (82%) and 2 (18%) associated with goiter. Hypothyroidism was transient in all cases, and only 5 infants were treated short-term with thyroid hormones. Only 2 newborns had transient hyperthyroxinemia, associated with low serum TSH concentrations in one. Neurodevelopment assessment of the hypothyroid infants, when carried out, showed in some instances mild abnormalities, most often reminiscent of the Non-verbal Learning Disability Syndrome; however, these features were also reported in some amiodarone-exposed euthyroid infants, suggesting that there might be a direct neurotoxic effect of amiodarone during fetal life. Breast-feeding was associated with a substantial ingestion of amiodarone by the infant, but in the few cases followed it did not cause changes in the newborn’s thyroid function. In conclusion, amiodarone therapy during pregnancy may cause fetal/neonatal hypothyroidism and, less frequently, goiter. Thus, the use of amiodarone in pregnancy should be limited to maternal/fetal tachyarrhythmias which are resistant to other drugs or life-threatening. If amiodarone is used during gestation, a careful fetal/neonatal evaluation of thyroid function and morphology is warranted. It seems prudent to advise that fetal/ neonatal hypothyroidism be treated, as soon as the diagnosis is made, even in utero, to avoid neurodevelopment abnormalities, although the latter may occur independently of hypothyroidism. If breast-feeding is allowed, careful evaluation of the infant’s thyroid function and morphology is required because of the continuing exposure of the infant to the drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Roy D., Talajic M., Dorian P., Connolly S., Eisenberg M.J., Green M., Kus T., Lambert J., Dubuc M., Gagnè P., Nattel S., Thibault B. Amiodarone to prevent recurrence of atrial fibrillation. N. Engl. J. Med. 2000, 342: 913–920.

    CAS  PubMed  Google Scholar 

  2. Kudenchuk P.J., Cobb L.A., Copass M.K., Cummins R.O., Doherty A.M., Fahrenbruch C.E., Hallstrom A.P., Muray W.A., Olsufka M., Walsh T. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N. Engl. J. Med. 1999, 341: 871–878.

    CAS  PubMed  Google Scholar 

  3. Daoud E.G., Strickberger S.A., Man K.G., Goyal R., Deeb G.M., Bolling S.F., Pagani F.D., Bitar C., Meissner M.D., Morady F. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N. Engl. J. Med. 1997, 337: 1785–1791.

    CAS  PubMed  Google Scholar 

  4. Doval H.C., Nul D.R., Grancelli H.O., Perrone S.V., Bortman G.R., Curiel R. Randomized trial of low-dose amiodarone in severe congestive heart failure. Lancet 1994, 344: 493–498.

    CAS  PubMed  Google Scholar 

  5. Ceremuzynski L., Kleczar E., Krzeminska-Pakula M., Kuch J., Nartowicz E., Smielak-Korombel J., Diduszynski A., Maciejewicz J., Zaleska T., Lazarczyk-Kedzia E. Effect of amiodarone on mortality after myocardial infarction: a double-blind, placebo-controlled, pilot study. J. Am. Coll. Cardiol. 1992, 20: 1056–1062.

    CAS  PubMed  Google Scholar 

  6. Holt D.W., Tucker G.T., Jackson P.R., Storey G.C.A. Amiodarone pharmacokinetics. Am. Heart J. 1983, 106: 843–847.

    Google Scholar 

  7. Plomp T.A., van Rossum J.M., Robles de Medina E.O., van Lier T., Maes R.A.A. Pharmacokinetics and body distribution of amiodarone in man. Arzneimittelforschung/Drug Res. 1984, 34: 513–520.

    CAS  Google Scholar 

  8. Berger Y., Harris L. Pharmacokinetics. In: Harris L., Roncucci R. (Eds.), Amiodarone. Médicine et Sciences Internationales, Paris, 1986, p. 45.

    Google Scholar 

  9. Rao R.H., McReady V.R., Spathis G.S. Iodine kinetic studies during amiodarone treatment. J. Clin. Endocrinol. Metab. 1986, 62: 563–567.

    CAS  PubMed  Google Scholar 

  10. McKenna W.J., Harris L., Rowland E., Whitelaw A., Storey G., Holt D. Amiodarone therapy during pregnancy. Am. J. Cardiol. 1983, 51: 1231–1233.

    CAS  PubMed  Google Scholar 

  11. Robson D.J., Jeeva Raj M.V., Storey G.C.A., Holt D.W. Use of amiodarone during pregnancy. Postgrad. Med. J. 1985, 61: 75–77.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Wiersinga W.M. Amiodarone and the thyroid. In: Weetman A.P., Grossman A. (Eds.), Pharmacotherapeutics of the thyroid gland. Springer Verlag, Berlin, 1997, p. 225.

    Google Scholar 

  13. Lombardi A., Martino E., Braverman L.E. Amiodarone and the thyroid. Thyroid Today 1990, 13: 1–7.

    Google Scholar 

  14. Harjai K.J., Licata A.A. Effects of amiodarone on thyroid function. Ann. Intern. Med. 1997, 126: 63–73.

    CAS  PubMed  Google Scholar 

  15. Iudica-Souza C., Burch H.B. Amiodarone-induced thyroid dysfunction. Endocrinologist 1999, 9: 216–227.

    Google Scholar 

  16. Krenning E.P., Docter R., Bernard B., Visser T., Hennemann G. Decreased transport of thyroxine (T4), 3,3′,5-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (rT3) into rat hepatocytes in primary culture due to a decrease of cellular ATP content and various drugs. FEBS Lett. 1982, 140: 229–233.

    CAS  PubMed  Google Scholar 

  17. Franklyn J.A., Davis J.R., Gammage M.D., Littler W.A., Ramsden D.B., Sheppard M.C. Amiodarone and thyroid hormone function. Clin. Endocrinol. (Oxf.) 1985, 22: 257–264.

    CAS  Google Scholar 

  18. Safran M., Fang S.-L., Bambini G., Pinchera A., Martino E., Braverman L.E. Effects of amiodarone and desethylamiodarone on pituitary deiodinase activity and thyrotropin secretion in the rat. Am. J. Med. Sci. 1986, 29: 13–16.

    Google Scholar 

  19. Amico J.A., Richardson V., Alpert B., Klein I. Clinical and chemical assessment of thyroid function during therapy with amiodarone. Arch. Intern. Med. 1984, 144: 487–490.

    CAS  PubMed  Google Scholar 

  20. Burger A., Dinichert D., Nicod P., Jenny M., Lemarchand-Beraud T., Vallotton M.B. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. J. Clin. Invest. 1976, 58: 255–259.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Melmed S., Nademanee K., Reed A.W., Hendrickson J.A., Singh B.N., Hershman J.M. Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration. J. Clin. Endocrinol. Metab. 1981, 53: 997–1001.

    CAS  PubMed  Google Scholar 

  22. Martino E., Safran M., Aghini-Lombardi F., Rajatanavin R., Lenziardi M., Fay M., Pacchiarotti A., Aronin A., Macchia E., Haffajee C., Baschieri L., Pinchera A., Braverman L.E. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann. Intern. Med. 1984, 101: 28–34.

    CAS  PubMed  Google Scholar 

  23. Martino E., Aghini-Lombardi F., Mariotti S., Bartalena L., Braverman L.E., Pinchera A. Amiodarone: a common source of iodine-induced thyrotoxicosis. Horm. Res. 1987, 26: 158–171.

    CAS  PubMed  Google Scholar 

  24. Martino E., Aghini-Lombardi F., Mariotti S., Bartalena L., Lenziardi M., Ceccarelli C., Bambini G., Safran M., Braverman L.E., Pinchera A. Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases. Clin. Endocrinol. (Oxf.) 1987, 26: 227–237.

    CAS  Google Scholar 

  25. Bartalena L., Grasso L., Brogioni S., Aghini-Lombardi F., Braverman L.E., Martino E. Serum interleukin-6 in amiodarone-induced thyrotoxicosis. J. Clin. Endocrinol. Metab. 1994, 78: 423–427.

    CAS  PubMed  Google Scholar 

  26. Beddows S.A., Page S.R., Taylor A.H., McNerney R., Whitley G.S.J., Johnstone A.P., Nussey S.S. Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes. Biochem. Pharmacol. 1989, 38: 4397–4403.

    CAS  PubMed  Google Scholar 

  27. Chiovato L., Martino E., Tonacchera M., Santini F., Lapi P., Mammoli C., Braverman L.E., Pinchera A. Studies on the in vitro cytotoxic effect of amiodarone. Endocrinology 1994, 134: 2277–2282.

    CAS  PubMed  Google Scholar 

  28. Hariai K.J., Licata A.A. Amiodarone-induced hyperthyroidism: a case series and brief review of the literature. Pacing Clin. Electrophysiol. 1996, 19: 1548–1554.

    Google Scholar 

  29. Martino E., Aghini-Lombardi F., Bartalena L., Grasso L., Loviselli A., Velluzzi F., Pinchera A., Braverman L.E. Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease. Arch. Intern. Med. 1994, 154: 2722–2726.

    CAS  PubMed  Google Scholar 

  30. Wolff J., Chaikoff I.L., Goldberg R.C., Meier J.L. The temporary nature of the inhibition action of excess iodide on organic iodine synthesis in the normal thyroid. Endocrinology 1949, 45: 504–513.

    CAS  PubMed  Google Scholar 

  31. Burrow G.N., Fisher D.A., Larsen P.R. Maternal and fetal thyroid function. N. Engl. J. Med. 1994, 331: 1072–1078.

    CAS  PubMed  Google Scholar 

  32. Guadano-Ferraz A., Obregon M.J., St Germain D.L., Bernal J. The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain. Proc. Natl. Acad. Sci. USA 1997, 94: 10391–10396.

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Leonard J., Kaplan M.M., Visser T.J., Silva J.E., Larsen P.R. Cerebral cortex responds rapidly to thyroid hormones. Science 1981, 214: 571–573.

    CAS  PubMed  Google Scholar 

  34. Guadano-Ferraz A., Escamez M.J., Rausell E., Bernal J. Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems. J. Neurosci. 1999, 19: 3430–3039.

    CAS  PubMed  Google Scholar 

  35. Utiger R.D. Maternal hypothyroidism and fetal development. N. Engl. J. Med. 1999, 341: 601–602.

    CAS  PubMed  Google Scholar 

  36. Vulsma T., Gons M.H., de Vijlder J.J.M. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N. Engl. J. Med. 1989, 321: 13–16.

    CAS  PubMed  Google Scholar 

  37. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr. Rev. 1997, 18: 404–433.

    CAS  PubMed  Google Scholar 

  38. Mandel S.J., Larsen P.R., Seely E.W., Brent G.A. Increased need for thyroxine treatment during pregnancy in women with primary hypothyroidism. N. Engl. J. Med. 1990, 323: 91–96.

    CAS  PubMed  Google Scholar 

  39. Kaplan M.M. Monitoring thyroxine treatment during pregnancy. Thyroid 1992, 2: 147–152.

    CAS  PubMed  Google Scholar 

  40. Haddow J.E., Palomaki G.E., Allan W.C., Williams J.R., Knight G.J., Gagnon J., O’Heir C.E., Mitchell M.L., Hermos R.J., Waisbren S.E., Faix J.D., Klein R.Z. Maternal thyroid deficiency during pregnancy and subsequent neupsychological development of the Child. N. Engl. J. Med. 1999, 341: 549–555.

    CAS  PubMed  Google Scholar 

  41. Pop V.J., Kuijpens J.L., van Baar A.L., Verkerk G., van Son M.M., de Vijlder J.J., Vulsma T., Wiersinga W.M., Drexhage H.A., Vader H.L. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin. Endocrinol. (Oxf.) 1999, 50: 149–155.

    CAS  Google Scholar 

  42. Man E., Brown J.F., Serunian S.A. Maternal hypothyroxinemia: psychoneurological deficits of progeny. Ann. Clin. Lab. Sci. 1991, 21: 227–239.

    CAS  PubMed  Google Scholar 

  43. Morreale de Escobar G., Calvo G., Obregon M.J., Escobar del Rey F. Contribution of maternal thyroxine to fetal thyroxine pools in normal thyroids near term. Endocrinology 1990, 126: 2765–2772.

    CAS  PubMed  Google Scholar 

  44. Calvo R., Obregon M.J., Escobar del Rey F., Morreale de Escobar G. The rat placenta and the transfer of thyroid hormones from the mother to the fetus: effect of maternal thyroid status. Endocrinology 1992, 131: 357–362.

    CAS  PubMed  Google Scholar 

  45. Contemprè B., Jauniaux E., Calvo R., Jurkovic D., Cambell S., Morreale de Escobar G. Detection of thyroid hormones in human embryionic cavities during the third trimester of pregnancy. J. Clin. Endocrinol. Metab. 1993, 77: 1717–1722.

    Google Scholar 

  46. Porterfield S.P., Henderson C.E. The role of thyroid hormone in prenatal and neonatal neurological development. Current perspectives. Endocr. Rev. 1993, 14: 94–106.

    CAS  PubMed  Google Scholar 

  47. Oppenheimer J.H., Schwartz H.L. Molecular basis of thyroid hormone-dependent brain development. Endocr. Rev. 1997, 18: 462–475.

    CAS  PubMed  Google Scholar 

  48. Kriplan A., Buckshee K., Bhargava V.L., Takkar D., Ammini A.C. Maternal and perinatal outcome in thyrotoxicosis complicating pregnancy. Eur. J. Obstet. Gynecol. 1994, 54: 159–163.

    Google Scholar 

  49. Mestman J.H., Goodwin M., Montoro M.M. Thyroid disorders of pregnancy. Endocrinol. Metab. Clin. North Am. 1995, 14: 41–71.

    Google Scholar 

  50. McKenzie J.M., Zakarija M. Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH antibodies. Thyroid 1992, 2: 155–159.

    CAS  PubMed  Google Scholar 

  51. Hidaka Y., Tamaki H., Iwatana Y., Tada H., Mitsuda N., Amion N. Prediction of post-partum Graves’ thyrotoxicosis by measurement of thyroid stimulating in early pregnancy. Clin. Endocrinol. (Oxf.) 1994, 41: 15–20.

    CAS  Google Scholar 

  52. Fisher D.A. Neonatal thyroid disease in the offspring of women with autoimmune thyroid disease. Thyroid Today 1986, 9: 1–8.

    Google Scholar 

  53. Wenstrom K.D., Weiner C.P., Williamson R.A., Grant S.S. Prenatal diagnosis of fetal hyperthyroidism using funipuncture. Obstet. Gynecol. 1990, 76: 513–518.

    CAS  PubMed  Google Scholar 

  54. Fisher D.A., Klein A.H. Thyroid development and disorders of thyroid function in the newborns. N. Engl. J. Med. 1981, 304: 702–712.

    CAS  PubMed  Google Scholar 

  55. Roti E., Gnudi A., Braverman L.E. The placental transport, synthesis and metabolism of hormones and drugs which affect thyroid function. Endocr. Rev. 1983, 4: 131–149.

    CAS  PubMed  Google Scholar 

  56. Robuschi G., Montermini M., Alboni A., Borciani E., Cersosimo G., Negrotti L., Gnudi A., Safran M., Braverman L.E., Roti E. Cord blood iodothyronine and thyrotropin concentrations in newborns of mothers exposed to povidone iodine in the last trimester. J. Endocrinol. Invest. 1987, 10: 183–186.

    CAS  PubMed  Google Scholar 

  57. Novaes M. Jr., Biancalana M.M., Garcia S.A., Rassi I., Romaldini J.H. Elevation of cord blood TSH concentration in newborn infants of mothers exposed to acute povidone iodine during delivery. J. Endocrinol. Invest. 1994, 17: 805–808.

    CAS  Google Scholar 

  58. Becks G.P., Burrow G.N. Thyroid disease and pregnancy. Med. Clin. North Am. 1991, 75: 121–135.

    CAS  PubMed  Google Scholar 

  59. Smerdely P., Boyages S.C., Wu D., Leslie G., John E., Lim A., Waite K., Roberts V., Arnold J., Eastman C.J. Topical iodine-containing antiseptics and neonatal hypothyroidism in very low-birthweight infants. Lancet 1989, 2: 661–664.

    CAS  PubMed  Google Scholar 

  60. Barakat M., Carson D., Hetherton A.M., Smyth P., Leslie H. Hypothyroidism secondary to topical iodine treatment in infants with spina bifida. Acta Paediatr. 1994, 83: 741–743.

    CAS  PubMed  Google Scholar 

  61. Brown R.S., Bloomfield S., Bednarek F.J., Mitchell M.L., Braverman L.E. Routine skin cleansing with povidone-iodine is not a common cause of transient neonatal hypothyroidism in North America: a prospective, controlled study. Thyroid 1997, 7: 395–400.

    CAS  PubMed  Google Scholar 

  62. Momotani N., Hisaoka T., Noh J., Ishikawa N., Ito K. Effects of iodine on thyroid status of fetus versus mother in treatment of Graves’ disease complicated by pregnancy. J. Clin. Endocrinol. Metab. 1992, 75: 738–744.

    CAS  PubMed  Google Scholar 

  63. Roti E., Braverman L.E. Iodine-induced thyroid disease. In: Braverman L.E. (Ed.), Contemporary endocrinology: Diseases of the thyroid. Humana Press, Totowa, 1997, p. 369.

    Google Scholar 

  64. Arnoux P., Seyral P., Llurens M., Djiane P., Potier A., Unal D., Cano J.P., Serradimigni A., Rouault F. Amiodarone and digoxin for refractory fetal tachycardia. Am. J. Cardiol. 1987, 59: 168–169.

    Google Scholar 

  65. Gembruch U., Manz M., Bald R., Ruddel H., Redel D.A., Schlebusch H., Nitsch J., Hansmann M. Repeated intravascular treatment with amiodarone in a fetus with refractory supraventricular tachycardia and hydrops fetalis. Am. Heart J. 1989, 118: 1335–1338.

    CAS  PubMed  Google Scholar 

  66. Hijazi Z.M., Rosenfeld L.E., Copel J.A., Kleinman C.S. Amiodarone therapy of intractable atrial flutter in a premature hydropic neonate. Pediatr. Cardiol. 1992, 13: 227–229.

    CAS  PubMed  Google Scholar 

  67. Fulgencio J.P., Hamza J. Anaesthesia for cesarean section in a patient receiving high dose amiodarone for fetal supraventricular tachycardia. Anaesthesia 1994, 49: 406–408.

    CAS  PubMed  Google Scholar 

  68. De Catte L., De Wolf D., Smitz J., Bougatef A., De Schepper J., Foulon W. Fetal hypothyroidism as a complication of amiodarone treatment for persistent fetal supraventricular tachycardia. Prenat. Diagn. 1994, 14: 762–765.

    PubMed  Google Scholar 

  69. Mangione R., Guyon F., Vergnaud A., Jimenez M., Saura R., Horovitz J. Successful treatment of refractory supraventricular tachycardia by repeated intravascular injection of amiodarone in a fetus with hydrops. Eur. J. Obstet. Gynecol. Reprod. Biol. 1999, 86: 105–107.

    CAS  PubMed  Google Scholar 

  70. Lupoglazoff J.M., Denjoy I., Luton D., Magnier S., Azancot A. Prenatal diagnosis of a familial form of junctional ectopic tachycardia. Prenat. Diagn. 1999, 19: 767–770.

    CAS  PubMed  Google Scholar 

  71. Vicens-Calvet E., Potau N., Carreras E., Bellart J., Albisu M.A., Carrascosa A. Diagnosis and treatment in utero of goiter with hypothyroidism caused by iodide overload. J. Pediatr. 1998, 133: 1478.

    Google Scholar 

  72. Candelpergher G., Buchberger R., Suzzi G., Padrini R. Passaggio transplacentare dell’amiodarone: evidenza elettrocardiografica e documentazione farmacologica in un neonato. G. Ital. Cardiol. 1982, 12: 79–82.

    CAS  PubMed  Google Scholar 

  73. Haffajee C.I. In discussion: amiodarone pharmacokinetics. Am. Heart J. 1983, 106: 847.

    Google Scholar 

  74. Lloyd E.A., Mabin T.A. Amiodarone in the treatment of patients with refractory symptomatic ventricular and supraventricular arrhythmias. S.A. Mediese Tydskrif Deel. 1983, 63: 759–763.

    CAS  Google Scholar 

  75. Pitcher D., Leather H.M., Storey G.C.A., Holt D.W. Amiodarone in pregnancy. Lancet 1983, 1: 597–598.

    CAS  PubMed  Google Scholar 

  76. Rey E., Duperron L., Gautheir R., Lemsy M., Grignon A., Le Lorier J. Transplacental treatment of tachycardia-induced fetal heart failure with verapamil and amiodarone. Am. J. Obstet. Gynecol. 1985, 153: 311–312.

    CAS  PubMed  Google Scholar 

  77. Penn I.M., Barrett P.A., Pannikote V., Barnaby P.F., Campbell I.B., Lyons N.R. Amiodarone in pregnancy. Am. J. Cardiol. 1985, 56: 196–197.

    CAS  PubMed  Google Scholar 

  78. Robson D.J., Jeeva Raj M.V., Storey G.C.A., Holt D.W. Use of amiodarone during pregnancy. Postgrad. Med. J. 1985, 61: 75–77.

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Wladimiroff J.W., Steward P.A. Treatment of fetal cardiac arrhythmias. Br. J. Hosp. Med. 1985, 34: 134–140.

    CAS  PubMed  Google Scholar 

  80. Rey E., Bachrach L.K., Burrow G.N. Effects of amiodarone during pregnancy. Can. Med. Assoc. J. 1987, 136: 959–960.

    CAS  Google Scholar 

  81. Laurent M., Betremieux P., Biron Y., Lellelloco A. Neonatal hypothyroidism after treatment by amiodarone during pregnancy. Am. J. Cardiol. 1987, 60: 142.

    Google Scholar 

  82. de Wolf D., de Schepper J., Verhaaren H., Deneyer M., Smitz J., Sacre-Smits L. Congenital hypothyroid goiter and amiodarone. Acta Paediatr. Scand. 1988, 77: 616–618.

    PubMed  Google Scholar 

  83. Wellers S. In discussion: R.S.M. International Congress and Symposium Series, 1979, 16: 74.

    Google Scholar 

  84. Strunge P., Frandsen J., Andreasen F. Amiodarone during pregnancy. Eur. Heart J. 1988, 9: 106–109.

    CAS  PubMed  Google Scholar 

  85. Foster C.J., Love H.G. Amiodarone in pregnancy. Case report and review of the literature. Int. J. Cardiol. 1988, 20: 307–316.

    CAS  PubMed  Google Scholar 

  86. Widerhorn J., Bhandari A.K., Bughi S., Rahimtoola S.H., Elkayam U. Fetal and neonatal adverse effects profile of amiodarone treatment during pregnancy. Am. Heart J. 1991, 122: 1162–1166.

    CAS  PubMed  Google Scholar 

  87. Valensise H., Civitella C., Garzetti G.G., Romanini C. Amiodarone treatment in pregnancy for dilatative cardiomyopathy with ventricular malignant extrasystole and normal maternal and neonatal outcome. Prenat. Diagn. 1992, 12: 705–708.

    CAS  PubMed  Google Scholar 

  88. Plomp T.A., Vulsma T., de Vijlder J.J. Use of amiodarone during pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 1992, 43: 201–207.

    CAS  PubMed  Google Scholar 

  89. Matsumura L.K., Born D., Kunii I.S., Franco D.B., Maciel R.M.B. Outcome of thyroid function in newborns from mothers treated with amiodarone. Thyroid 1992, 2: 279–281.

    CAS  PubMed  Google Scholar 

  90. Darwiche A., Vanlieferinghen P., Lemery D., Paire M., Lusson J.R. Amiodarone and fetal supraventriculr tachycardia. Apropos of a case with neonatal hypothyroidism. Arch. Fr. Pediatr. 1992, 49: 729–731.

    CAS  PubMed  Google Scholar 

  91. Ovadia M., Brito M., Hoyer G.L., Markus F.I. Human experience with amiodarone in the embryonic period. Am. J. Cardiol. 1994, 73: 316–317.

    CAS  PubMed  Google Scholar 

  92. Magee L., Downar E., Sermer M., Boulton B.C., Allen L.C., Koren G. Pregnancy outcome after gestational exposure to amiodarone in Canada. Am. J. Obstet. Gynecol. 1995, 172: 1307–1311.

    CAS  PubMed  Google Scholar 

  93. Grosso S., Berardi R., Cioni M., Morgese G. Transient neonatal hypothyroidism after gestational exposure to amiodarone: a follow-up of two cases. J. Endocrinol. Invest. 1998, 21: 699–702.

    CAS  PubMed  Google Scholar 

  94. Schardein J. Chemically induced birth defects. Marcel Dekker, New York, 1985, pp. 174–175.

    Google Scholar 

  95. Hill D.A., Reasor M.J. Effects of amiodarone administration during pregnancy in Fischer 344 rats. Toxicology 1991, 65: 259–269.

    CAS  PubMed  Google Scholar 

  96. Weiner S., Scharf J.I., Bolognese R.J., Librizi R.J. Antenatal diagnosis and treatment of a fetal goitre. J. Reprod. Med. 1980, 24: 39–42.

    CAS  PubMed  Google Scholar 

  97. Kourides I.A., Berkowitz R.L., Pang S., Van Natta F.D., Barone C.M., Ginsberg-Fellner F. Antepartum diagnosis of goitrous hypothyroidism by fetal ultrasonography and amniotic fluid thyrotropin concentration. J. Clin. Endocrinol. Metab. 1984, 59: 1016–1018.

    CAS  PubMed  Google Scholar 

  98. Perelman A.H., Johnson R.L., Clemons R.D., Finsberg H.J., Clewell W.H., Trujillo L.L. Intrauterine diagnosis and treatment of fetal goitrous hypothyroidism. J. Clin. Endocrinol. Metab. 1990, 71: 618–621.

    CAS  PubMed  Google Scholar 

  99. Davidson K.M., Richards D.S., Schatz D.A., Fisher D.A. Successful in utero treatment of fetal goiter and hypothyroidism. N. Engl. J. Med. 1991, 342: 543–546.

    Google Scholar 

  100. Branawig J.H., Holzgreve W., Zimmer K.P., Schellong G. Successful in utero treatment of fetal goiter and hypothyroidism in a patient with complete organification defect. Horm. Res. 1991, 35: 44 (Abstract).

    Google Scholar 

  101. Abuhamad A.Z., Fisher D.A., Warsof S.L., Stonick R.N., Pyle P.G., Wu S.-Y., Evans A.T. Antenatal diagnosis and treatment of fetal goitrous hypothyroidism: case report and review of the literature. Obstet. Gynecol. 1995, 6: 368–371.

    CAS  Google Scholar 

  102. Momotani N., Hisaoka T., Noh J., Ishikawa N., Ito K. Effects of iodine on thyroid status of fetus versus mother in treatment of Graves’ disease complicated by pregnancy. J. Clin. Endocrinol. Metab. 1992, 75: 738–744.

    CAS  PubMed  Google Scholar 

  103. Thorpe-Beeston J.G., Nicolaides K.H., Snijders R.J., Felton C.V., McGregor A.M. Thyroid function in small for gestational age fetuses. Obstet. Gynecol. 1991, 77: 701–706.

    CAS  PubMed  Google Scholar 

  104. LaFranchi S. Congenital hypothyroidism: a newborn screening success story? Endocrinologist 1994, 4: 477–486.

    Google Scholar 

  105. New England Congenital Hypothyroidism Collaborative Elementary school performance of children with congenital hypothyroidism. J. Pediatr. 1990, 116: 27–32.

    Google Scholar 

  106. Illicki A., Larsson A. Psychological development at 7 years of age in children with congenital hypothyroidism: timing and dosage of initial treatment. Acta Paediatr. Scand. 1991, 80: 199–204.

    Google Scholar 

  107. Simons W.F., Fuggle P.W., Grant D.B., Smith I. Intellectual development at 10 years in early treated congenital hypothyroidism. Arch. Dis. Child. 1994, 71: 232–234.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Glorieux J., Dussault J., Van Vliet G. Intellectual development at age 12 years of children with congenital hypothyroidism diagnosed by neonatal screening. J. Pediatr. 1992, 121: 581–584.

    CAS  PubMed  Google Scholar 

  109. Kooistra L., Laone C., Vulsma T., Schellekens J.M.H., van der Meer J.J., Kalverboer A.F. Motor and cognitive development in children with congenital hypothyroidism: a long term evaluation of the effects of neonatal treatment. J. Pediatr. 1994, 124: 903–909.

    CAS  PubMed  Google Scholar 

  110. Rovet J.F., Ehrlich R.M. Long-term effects of L-thyroxine therapy for congenital hypothyroidism. J. Pediatr. 1995, 126: 380–386.

    CAS  PubMed  Google Scholar 

  111. Heyerdahl S. Treatment variables as predictors of intellectual outcome in children with congenital hypothyroidism. Eur. J. Pediatr. 1996, 155: 357–361.

    CAS  PubMed  Google Scholar 

  112. Fuggle P.W., Grant D.B., Smith I., Murphy G. Intelligence, motor skills and behaviour at 5 years in early-treated congenital hypothyroidism. Eur. J. Pediatr. 1991, 150: 570–574.

    CAS  PubMed  Google Scholar 

  113. Rovet J.F., Ehrlich R.M., Sorbara D.L. Neurodevelopment in infants and preschool children with congenital hypothyroidism: etiological and treatment factors affecting outcome. J. Pediatr. Psychol. 1992, 17: 187–213.

    CAS  PubMed  Google Scholar 

  114. Rovet J., Ehrlich R., Sorbara D. Intellectual outcome in children with fetal hypothyroidism. J. Pediatr. 1987, 110: 700–704.

    CAS  PubMed  Google Scholar 

  115. Simons W.F., Fuggle P.W., Grant D.B., Smith I. Educational progress, behaviour, and motor skills at 10 years in early treated congenital hypothyroidism. Arch. Dis. Child. 1997, 77: 219–222.

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Bargagna S., Dinetti D., Pinchera A., Marcheschi M., Montanelli L., Presciuttini S., Chiovato L. School attainments in children with congenital hypothyroidism detected by neonatal screening and treated early in life. Eur. J. Endocrinol. 1999, 140: 407–413.

    CAS  PubMed  Google Scholar 

  117. Bargagna D., Canepa G., Costagli C., Dinetti D., Marcheschi M., Millepiedi S., Montanelli L., Pinchera A., Chiovato L. Neuropsychological follow-up in early treated congenital hypothyroidism: a problem oriented approach. Thyroid 2000, 10: 243–249.

    CAS  PubMed  Google Scholar 

  118. Magee L.A., Nulman I., Rovet J.F., Koren G. Neurodevelopment after in utero amiodarone exposure. Neurotoxicol. Teratol. 1999, 21: 261–265.

    CAS  PubMed  Google Scholar 

  119. Harnadek M.C.S., Rourke B.P. Principal identifying features of the syndrome of nonverbal learning disabilities in children. J. Learn. Disabil. 1994, 27: 144–154.

    CAS  PubMed  Google Scholar 

  120. Rovet J. Congenital hypothyroidism. In: Rourke B.P. (Ed.), Syndrome of nonverbal learning disabilities: neurodevelopmental manifestations. Guilford Publications, New York, 1995, p. 255.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Insubria, Varese, Italy

    L. Bartalena

  2. Department of Endocrinology and Metabolism, University of Pisa, Ospedale di Cisanello, Via Paradisa 2, 56124, Pisa, Italy

    F. Bogazzi &  E. Martino

  3. Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston, USA

    L. E. Braverman

Authors
  1. L. Bartalena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Bogazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. E. Braverman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Martino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bartalena, L., Bogazzi, F., Braverman, L.E. et al. Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment. J Endocrinol Invest 24, 116–130 (2001). https://doi.org/10.1007/BF03343825

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343825

Key-words

Search

Navigation