title: Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy.
abstract: OBJECTIVE
  Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy.
  
  
  METHODS
  A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed.
  
  
  RESULTS
  The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy".
  
  
  CONCLUSIONS
  While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy.
authors.affiliation: Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Paradisa 2, Cisanello, 56124, Pisa, Italy, elena.gianetti@hotmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Gianetti
authors.forename: L
authors.initials: L
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Orlandi
authors.forename: L
authors.initials: L
authors.lastname: Chiovato
authors.forename: M
authors.initials: M
authors.lastname: Giusti
authors.forename: S
authors.initials: S
authors.lastname: Benvenga
authors.forename: M
authors.initials: M
authors.lastname: Moleti
authors.forename: F
authors.initials: F
authors.lastname: Vermiglio
authors.forename: P E
authors.initials: PE
authors.lastname: Macchia
authors.forename: M
authors.initials: M
authors.lastname: Vitale
authors.forename: C
authors.initials: C
authors.lastname: Regalbuto
authors.forename: M
authors.initials: M
authors.lastname: Centanni
authors.forename: E
authors.initials: E
authors.lastname: Martino
authors.forename: P
authors.initials: P
authors.lastname: Vitti
authors.forename: M
authors.initials: M
authors.lastname: Tonacchera
mesh_terms: D000328:Adult; D013956:Antithyroid Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006111:Graves Disease / Q000188:drug therapy; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy*; D007231:Infant, Newborn; D008713:Methimazole / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil
references.citation: Can Med Assoc J. 1984 May 15;130(10):1264
references.pmid: 6722686
references.citation: Fertil Steril. 1996 Mar;65(3):503-9
references.pmid: 8774277
references.citation: J Endocrinol Invest. 2014 Nov;37(11):1041-8
references.pmid: 25185644
references.citation: J Thyroid Res. 2013;2013:878467
references.pmid: 23762777
references.citation: Obstet Gynecol. 1975 Sep;46(3):282-6
references.pmid: 51489
references.citation: J Clin Endocrinol Metab. 2002 Feb;87(2):947-9
references.pmid: 11836348
references.citation: Pediatr Dermatol. 1986 Sep;3(4):327-30
references.pmid: 3774652
references.citation: J Obstet Gynaecol Can. 2012 Nov;34(11):1077-1086
references.pmid: 23231846
references.citation: J Thyroid Res. 2011;2011:235130
references.pmid: 21922050
references.citation: Teratology. 1985 Oct;32(2):321
references.pmid: 4049289
references.citation: Eur J Endocrinol. 2011 Jun;164(6):871-6
references.pmid: 21389085
references.citation: J Clin Endocrinol Metab. 1997 Nov;82(11):3633-6
references.pmid: 9360518
references.citation: Obstet Gynecol. 1988 Jun;71(6 Pt 2):996-7
references.pmid: 2453822
references.citation: J Clin Endocrinol Metab. 1997 Sep;82(9):3099-102
references.pmid: 9284751
references.citation: Am J Med Genet A. 2008 Sep 15;146A(18):2390-5
references.pmid: 18698631
references.citation: Birth Defects Res A Clin Mol Teratol. 2007 Oct;79(10):680-4
references.pmid: 17803201
references.citation: J Gynecol Obstet Biol Reprod (Paris). 1991;20(4):575-6
references.pmid: 1885895
references.citation: J Perinat Med. 2011 Nov;39(6):743-4
references.pmid: 21809898
references.citation: J Endocrinol Invest. 2011 Mar;34(3):225-31
references.pmid: 21427528
references.citation: Pediatr Dermatol. 2011 Nov-Dec;28(6):743-5
references.pmid: 21995270
references.citation: Am J Med Genet A. 2011 Mar;155A(3):526-33
references.pmid: 21344626
references.citation: An Esp Pediatr. 1999 Sep;51(3):290-2
references.pmid: 10575754
references.citation: Clin Endocrinol (Oxf). 1984 Jun;20(6):695-700
references.pmid: 6467634
references.citation: Br Med Bull. 2011;97:137-48
references.pmid: 21186204
references.citation: Pediatr Dermatol. 2004 Jul-Aug;21(4):491-4
references.pmid: 15283799
references.citation: Eur J Obstet Gynecol Reprod Biol. 1994 May 18;54(3):159-63
references.pmid: 7523202
references.citation: J Clin Endocrinol Metab. 1998 Jan;83(1):40-6
references.pmid: 9435414
references.citation: J Clin Endocrinol Metab. 2012 Jul;97(7):2396-403
references.pmid: 22547422
references.citation: Br J Dermatol. 1995 Dec;133(6):994-6
references.pmid: 8547058
references.citation: Lancet. 1992 Mar 21;339(8795):742-3
references.pmid: 1347607
references.citation: J Clin Endocrinol Metab. 2009 Jun;94(6):1881-2
references.pmid: 19401361
references.citation: J Clin Endocrinol Metab. 2013 Nov;98(11):4373-81
references.pmid: 24151287
references.citation: Thyroid. 1999 Jul;9(7):727-33
references.pmid: 10447021
references.citation: J Clin Endocrinol Metab. 2012 Aug;97(8):2543-65
references.pmid: 22869843
references.citation: Thyroid. 2011 Oct;21(10):1081-125
references.pmid: 21787128
references.citation: Thyroid. 1994 Spring;4(1):129-33
references.pmid: 7519913
references.citation: J Pediatr Endocrinol Metab. 2007 May;20(5):585-6
references.pmid: 17642418
references.citation: Ann Intern Med. 1987 Jan;106(1):60-1
references.pmid: 3789581
references.citation: Am J Med Genet A. 2005 Jan 15;132A(2):130-5
references.pmid: 15578620
references.citation: Teratology. 2001 Nov;64(5):262-6
references.pmid: 11745832
references.citation: J Clin Endocrinol Metab. 2010 Nov;95(11):E337-41
references.pmid: 20668039