The Association of Aplasia Cutis Congenita with Therapy of Maternal Thyroid Disease

Abstract

Aplasia cutis congenita, the localized absence of skin at birth, usually is an isolated scalp defect. We examined an infant with aplasia cutis congenita associated with maternal Grave's disease and the use of methimazole during pregnancy. This association was reported twice before. It has certain implications with respect to therapy of pregnant hyperthyroid women.

Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy

“…Both the available antithyroid drugs (MMI and PTU) share similar placental cross-kinetics [6] and risks of producing fetal and neonatal hypothyroidism [7], but since Milham and Elledge described an increased incidence of scalp defects in neonates born to mothers treated with MMI during pregnancy [8], 30 cases of scalp defects in children born to mothers treated with MMI during pregnancy have been reported [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], either isolated or associated with other congenital malformations (imperforate anus, choanal atresia, esophageal atresia, hypoplastic nipple, facial anomalies and psychological delay). Moreover, in 1992, an increased incidence of aplasia cutis was described in some Spanish regions where MMI was illegally used as a fattening agent in animal food [18].…”

“…Later, scalp defects associated with other malformations such as imperforate anus, choanal atresia, esophageal atresia, hypoplastic nipple, facial anomalies and psychological delay were described, giving the picture of the so-called "methimazole embryopathy", for which diagnostic criteria were proposed [25]. Most of these descriptions pertained to case reports which, while being important for highlighting possible adverse effects, suffer from the weakness of being anecdotal evidence [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Later on, eight epidemiological studies were conducted to verify the existence of a methimazole embryopathy [2,[28][29][30][31][32][33], but, as assessed by a recent review of the literature [34], most of them do not take into account crucial factors such as maternal thyroid function, ATD dose and exposure time during pregnancy or do not include controls, so that a definitive answer is still lacking.…”

“…Since then, 30 cases of isolated aplasia cutis have been described in children born to MMI-treated women [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Later, scalp defects associated with other malformations such as imperforate anus, choanal atresia, esophageal atresia, hypoplastic nipple, facial anomalies and psychological delay were described, giving the picture of the so-called "methimazole embryopathy", for which diagnostic criteria were proposed [25].…”

Neonatal thyroid disorders

“…67 Carbimazole is rapidly converted in the liver into methimazole, 69 which is the preparation available in the United States. The latter has been linked to the development of cutis aplasia in the offspring of mothers treated with thionamides in pregnancy, [70][71][72] although several large series studies have not confirmed this observation. 66 68 Of greater concern is that the fetus of a mother on thionamides may be rendered hypothyroid; however, there is no evidence of adverse effects, particularly intellectual and growth defects in children exposed to antithyroid drugs in utero compared with both siblings who were not exposed or age matched controls.…”

Hyperthyroidism in Pregnancy: Diagnosis and Treatment

“…There is a tendency to a slight increase in volume of distribution and slowed rate of elimination with long-term use of the medication (23). In general, PTU has been the drug of choice in pregnant women due to the possible link of MMI use to the development of aplasia cutis congenita in the offspring of treated mothers (25)(26)(27)(28)(29)(30). Although larger studies failed to confirm this observation, apparently there have been no reports of cases of aplasia cutis congenita in offspring of mothers treated with PTU (25).…”