Thyroid Dysfunction in Pregnancy

Greenman, George W.; Gabrielson, Mary O.; Howard-Flanders, June; Wessel, Morris A.

doi:10.1056/nejm196208302670902

Cited by 100 publications

(8 citation statements)

References 18 publications

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“…Methimazole intake during pregnancy may be associated with increased fetal death, intrauterine growth retardation, and congenital malformations, including scalp defects, hypospadias, imperforate anus, aortic atresia, and choanal atresia with athelia [Greenman et al, 1962;Mujtaba and Burrow, 1975;Greenberg, 1987;Dorangeon et al, 1989;Khoury et al;19891. Nevertheless, methimazole is classified by the Food and Drug Administration with the drugs without clear teratogenic effects [Drug, 19901. On the other hand, thyrotoxicosis state during pregnancy has also been associated with a greater frequency of abortions and fetal deaths [Montoro and Mestman, 1981;Espinoza de 10s Monteros et al, 1986;Thomas and Reid, 1987;Houck et al, 19881, although it is not clear if the frequency of congenital malformations in these infants is greater than in the general population.…”

Section: Discussionmentioning

confidence: 99%

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

et al. 1992

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We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypothyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF.

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Section: Discussionmentioning

confidence: 99%

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

et al. 1992

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“…There have, however, been a small number of birth defects reported in association with prenatal PTU use since its introduction in 1947 [27], [28], [29], [30], [31].…”

Section: Introductionmentioning

confidence: 99%

Propylthiouracil Is Teratogenic in Murine Embryos

et al. 2012

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BackgroundHyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed.MethodsWe examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis.ResultsWhen dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss of malformed embryos. These data show that PTU exposure during embryogenesis is associated with delayed neural tube closure and cardiac abnormalities. In contrast, we did not observe structural or cardiac defects associated with MMI exposure except at the higher dose. We find that PTU exposure during embryogenesis is associated with fetal loss. These observations suggest that PTU has teratogenic potential.

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“…A study including 65 infants born to mothers with Grave ' s disease treated with either PTU or MMI again found no excess congenital anomalies (17) . No case of ACC has been observed after maternal PTU treatment so far, but associations with other congenital anomalies have been reported, including congenital hip dislocation (18) , undescended testes and muscular hypotony (19) , hypospadias and aortic atresia (7) , choanal atresia (20) , ventricular septum defect, pulmonary stenosis, patent ductus arteriosus (13) and syndactily after combined PTU and 131 I therapy (21) . A cause of effect remains questionable in these mostly frequent anomalies.…”

Section: Discussionmentioning

confidence: 99%

Aplasia cutis congenita in surviving co-twin after propylthiouracil exposure in utero

Löllgen

Calza

Schwitzgebel

et al. 2011

Journal of Pediatric Endocrinology and Metabolism

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Aim: Aplasia cutis congenita (ACC) has been observed after fetal exposure to the antithyroid drug methimazole (MMI), but not reported after propylthiouracil (PTU), the current antithyroid drug of choice during pregnancy. This occurrence has implications for patient information and causal research. Case report: We describe a surviving term co-twin to a mother with hyperthyroidism exposed to PTU from conception to 34 weeks of gestation presenting with ACC at birth. Discussion: The association between PTU exposure and ACC is clinically relevant and allows speculation on the etiology. A similar mechanism to the classical MMI-induced ACC is postulated, unless a vascular etiology suggested by a vanishing twin or maternal hyperthyroidism itself is causal. Coincidence of PTU exposure and ACC seems unlikely. Conclusion: ACC in a newborn after PTU exposure during pregnancy hitherto observed only after MMI strongly encourages further reports of similar cases that may remain clinically underdiagnosed or unreported. Such confi rmation could have signifi cant implications for maternal treatment of hyperthyroidism, common in women of childbearing age.

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Thyroid Dysfunction in Pregnancy

Cited by 100 publications

References 18 publications

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

Propylthiouracil Is Teratogenic in Murine Embryos

Aplasia cutis congenita in surviving co-twin after propylthiouracil exposure in utero

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