Methimazole embryopathy: A contribution to defining the phenotype

Valdez, Rita; Barbero, Pablo; Liascovich, Rosa; Rosa, Laura F. De; Aguirre, Miguel; Alba, Liliana

doi:10.1016/j.reprotox.2006.11.007

Cited by 28 publications

(19 citation statements)

References 20 publications

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“…Notwithstanding we focused our study in patients with choanal atresia, other congenital defects (esophageal atresia, abdominal wall defects, developmental delay, and specific facial features) would be included into the hyperthyroidism -MMI embryopathy [Momotani et al, 1984;Greenberg, 1987;Ramirez et al, 1992;Johnsson et al, 1997;Wilson et al, 1998;Clementi et al, 1999;MartinDenavit et al, 2000;Karlsson et al, 2002;Ferraris et al, 2003;Guignon et al, 2003;Seoud et al, 2003;Foulds et al, 2005;Ozgen et al, 2006;Wolf et al, 2006;Valdez et al, 2007]. Some of these cases also could be interpreted according to the previous described hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Choanal atresia associated with maternal hyperthyroidism treated with methimazole: A case–control study

Barbero

Valdez

Rodríguez

et al. 2008

American J of Med Genetics Pt A

114

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Thyrotoxicosis affects 0.2% of pregnant women and antithyroid drugs are the treatment of choice during pregnancy. Several case reports have suggested a relationship between the prenatal use of methimazole (MMI) and choanal atresia in the offspring. However, two epidemiological studies did not find an increased teratogenic risk for MMI. This multicenter case-control study compared the frequency of maternal hyperthyroidism treated with MMI during pregnancy, in children with choanal atresia (cases) and a control group randomly selected (three matched controls according to maternal age for each case). Mothers of cases (N = 61) and controls (N = 183) were interviewed for socio-demographic questions, obstetrical and genetic history, and exposure during pregnancy to different agents; specifically detailed information regarding hyperthyroidism and MMI intake was obtained. Prenatal exposure to maternal hyperthyroidism treated with MMI was identified in 10/61 cases (16.4%) compared to 2/183 (1.1%) in the control group (OR = 17.75; CI95% = 3.49-121.40). Cases and controls did not differ in their parental degree of education, paternal occupation, twinning, maternal parity, and other exposures during pregnancy. Facial features in exposed cases showed some similarities. Our data suggest that prenatal exposure to maternal hyperthyroidism treated with MMI is associated with choanal atresia. In addition, based on our cases and a critical literature review, we propose that the mother's disease might be the causal factor and not the MMI treatment.

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Section: Discussionmentioning

confidence: 99%

Choanal atresia associated with maternal hyperthyroidism treated with methimazole: A case–control study

Barbero

Valdez

Rodríguez

et al. 2008

American J of Med Genetics Pt A

114

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“…In addition to our Danish Registry study (11) to be discussed below, a total of 91 reports were read in detail, and 24 cases with ATD-associated birth defects where shifts in ATD therapy (start/stop of therapy or shifts between MMI/CMZ and PTU) had occurred during gestational weeks 1-10 were identified in 16 of the 91 publications (7,8,10,23,24,25,26,27,28,29,30,31,32,33,34,35). Published gestational week (calculated from the 1st day of the last menstrual period) when start or stop of ATD treatment had occurred was retrieved from these publications.…”

Section: Shift Between Therapies In Early Pregnancymentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk?

Laurberg

Andersen

2014

European Journal of Endocrinology

105

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Background: Antithyroid drugs (ATDs) may have teratogenic effects when used in early pregnancy. Objective: To review the association between the time period of ATD exposure in early pregnancy and the development of birth defects. Methods: We identified publications on birth defects after early pregnancy exposure to the ATDs methimazole (MMI; and its prodrug carbimazole (CMZ)) and propylthiouracil (PTU). Cases of birth defects after ATD treatment had been initiated or terminated within the first 10 weeks of pregnancy were identified and studied in detail. Results: A total of 92 publications were read in detail. Two recent large controlled studies showed ATD-associated birth defects in 2-3% of exposed children, and MMI/CMZ-associated defects were often severe. Out of the total number of publications, 17 included cases of birth defects with early pregnancy stop/start of ATD treatment, and these cases suggested that the high risk was confined to gestational weeks 6-10, which is the major period of organogenesis. Thus, the cases reported suggest that the risk of birth defects could be minimized if pregnant women terminate ATD intake before gestational week 6. Conclusion: Both MMI and PTU use in early pregnancy may lead to birth defects in 2-3% of the exposed children. MMI-associated defects are often severe. Proposals are given on how to minimize the risk of birth defects in fertile women treated for hyperthyroidism with ATDs.

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“…Neurodevelopmental delay and sensorineural deafness have been recently described as a component of the phenotype of MMI embryopathy [64]. While in utero iatrogenic hypothyroidism could be regarded as the cause of cognitive impairment due to insufficient thyroid hormone levels, thyroid status at birth was normal in all reported cases.…”

Section: Human Studiesmentioning

confidence: 94%

Toxicological considerations for antithyroid drugs in children

Karras¹,

Tzotzas²,

Krassas

2011

Expert Opinion on Drug Metabolism & Toxicology

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The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

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Methimazole embryopathy: A contribution to defining the phenotype

Cited by 28 publications

References 20 publications

Choanal atresia associated with maternal hyperthyroidism treated with methimazole: A case–control study

Choanal atresia associated with maternal hyperthyroidism treated with methimazole: A case–control study

THERAPY OF ENDOCRINE DISEASE: Antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk?

Toxicological considerations for antithyroid drugs in children

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