Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis

Abstract

ObjectiveThe aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations.MethodsA meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case–control studies, prospective cohort studies, and retrospective cohort studies.ResultsTwelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI)/carbimazole (CMZ) only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004). No differences were observed between propylthiouracil (PTU) exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24). Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001).ConclusionFor pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure.

Teratogen update: Antithyroid medications

“…Epidemiological studies presented mixed results of no increased risk of congenital anomalies with MMI/CMZ exposure in some studies (Andersen et al, 2017;Chen et al, 2011;Di Gianantonio et al, 2001;Gianetti et al, 2015;Korelitz et al, 2013;Lo et al, 2015; compared to increased risk in other studies (Andersen et al, 2013;Seo et al, 2018;Yoshihara et al, 2012). Metaanalyses have demonstrated increased risks of anomalies with exposure to MMI/CMZ (Li, Liu, Ma, & Zhou, 2015;Li, Zheng, et al, 2015;Song, Lin, Chen, Zhang, & Feng, 2017).…”

Thyrotoxicosis: Diagnosis and Management

“…For example, in a young woman who desires future pregnancy, RAI and surgery are favored because of the increased incidence of congenital malformations seen with ATDs during pregnancy. 31,56 However, ATDs are favored in patients with a high likelihood of remission or with severe GO. Thyroidectomy is preferred when there are symptoms of compression from large goiters, suspicious nodules, or moderate to severe and active orbitopathy in patients who cannot tolerate ATDs.…”

“…However, if hyperthyroidism develops or persists during pregnancy, PTU is preferred during the first trimester because of the increased risk of serious birth defects associated with methimazole and carbimazole (odds ratio, 1.9 for methimazole/carbimazole vs PTU). 31 The risk for teratogenicity declines after week 10 of pregnancy, and thus PTU therapy is usually converted to methimazole because of the increased risk of hepatotoxicity from PTU. Given the risk of dysthyroidism associated with these therapeutic changes and the known teratogenicity of PTU itself, 58 these changes are still a matter of debate.…”

Hyperthyroid Fetal Goiter: A Case Report

“…In the first quarter: Propylthiouracil can be used as low as possible during the first trimester of pregnancy [2,5]. In the 2nd and / or 3rd trimester, due to the undesirable liver effects of the PTU, it is preferable, if possible, to relieve the PTU with Carbimazole beyond the 1st trimester [4][5]14]. If PTU is maintained, use the lowest possible dosage.…”