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

Date Published: July 3, 2017

Publisher: Public Library of Science

Author(s): Rongjing Song, Hepu Lin, Yue Chen, Xiuying Zhang, Wanyu Feng, Ranji Cui.

http://doi.org/10.1371/journal.pone.0180108

Abstract

The aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations.

A 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.

Twelve 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).

For 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.

Partial Text

The prevalence of hyperthyroidism during pregnancy is approximately 0.1–0.2% [1]. Graves’ disease is the most common cause of gestational hyperthyroidism. In addition, other types of thyroid disorders, such as toxic multinodular goiter or solitary autonomously functioning nodules, induce gestational hyperthyroidism. Hyperthyroidism during pregnancy should be carefully treated because it can result in adverse maternal and neonatal outcomes. A cohort study performed by Mannisto et al. found that gestational hyperthyroidism was associated with an increased risk of labor induction, preeclampsia, superimposed preeclampsia, threatened and observed preterm births, and neonatal intensive care unit admission [2]. Therefore, there is a strong need to control hyperthyroidism during pregnancy.

Our meta-analysis follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. The PRISMA flow diagram is shown in Fig 1 and the PRISMA checklist is shown in the S3 Table.

We divided our meta-analysis into two parts. The first part evaluated the outcomes of the 12 included studies. Exposure to MMI/CMZ during pregnancy significantly increased the risk of neonatal congenital malformations compared to “No ATD” groups and “Control” groups (the specific definition of “No ATD” and “Control” in each individual study are presented in Tables 2 and 3). These results were consistent with those of previous studies [5, 9]. The risk of neonatal congenital malformations appeared to be higher in groups exposed to PTU compared to “Control” groups. However, no difference was observed between groups exposed to PTU and “No ATD” groups, which was different from the conclusion described by Li et al. [5]. This result indicated that neonatal congenital malformations that occurred in groups exposed to PTU may have been due to the gestational hyperthyroidism disorders rather than the administration of PTU. Therefore, we speculated that hyperthyroid states during pregnancy were not only associated with pregnancy loss, reduced fetal growth, and thyroid storm [22], but also put the fetus at a high risk of birth defects, which may exceed that of PTU exposure.

In this updated meta-analysis, the risk of neonatal congenital malformations after exposure to different ATDs during pregnancy was determined. In summary, for pregnant women with hyperthyroidism, no differences were observed between PTU exposure and no ATD exposure; however, PTU exposure led to less neonatal congenital malformations than MMI/CMZ exposure. Therefore, PTU was recommended during pregnancy with respect to neonatal congenital malformations. More trials are needed to confirm this conclusion in the future.

 

Source:

http://doi.org/10.1371/journal.pone.0180108

 

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