ATDs in 1st trimester link to higher birth defect risk

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Taking anti-thyroid drugs (ATDs) during the first trimester of pregnancy is associated with an increased risk for birth defects, particularly for women receiving prescriptions for methimazole (MMI) or both MMI and propylthiouracil (PTU).

Researchers from Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea, conducted a nationwide cohort study to examine the association between maternal prescriptions for ATDs and congenital malformations in live births. The study included a cohort of 2,886,970 pregnancies linked to live-born infants in 2,210,253 women between 2008 and 2010.

Of those, 12,891 pregnancies were exposed to ATDs during the first trimester. The data showed that prenatal exposure to MMI and PTU during the first trimester resulted in relative increases in the risk for congenital malformations of 31% and 16%, respectively.

The increased risk for malformations associated with MMI remained among those who switched to PTU several months before their pregnancy or during the first trimester. The researchers conclude that ATD exposure during the first trimester of pregnancy is associated with significantly increased risk for congenital malformations.

These findings confirm the importance of minimizing MMI use in the first trimester and suggest that the current recommendation of switching from MMI to PTU after pregnancy detection should be reconsidered.

Abstract
Background: Untreated or insufficiently treated Graves disease in pregnancy may pose risks to both mother and fetus. Antithyroid drugs (ATDs) are the treatment mainstay, but the potential teratogenic effect of these drugs has prompted clinicians to question the safe management of this vulnerable population.
Objective: To examine the association between maternal prescriptions for ATDs and congenital malformations in live births.
Design: Nationwide cohort study.
Setting: Korean National Health Insurance database.
Participants: A cohort of 2 886 970 completed pregnancies linked to live-born infants in 2 210 253 women between 2008 and 2014.
Intervention: Maternal prescriptions for ATDs in the first trimester.
Measurements: The risk for overall and organ-specific congenital malformations in offspring, with logistic regression models used to control for potential confounders.
Results: 12 891 pregnancies (0.45%) were exposed to ATDs during the first trimester. The prevalence of malformations in exposed offspring was 7.27%, compared with 5.94% in offspring of women who were not prescribed ATDs during pregnancy (P < 0.001) (adjusted odds ratio, 1.19 [95% CI, 1.12 to 1.28]). Absolute increases in the prevalence of congenital malformations per 1000 live births were 8.81 cases (CI, 3.92 to 13.70 cases) for propylthiouracil alone, 17.05 cases (CI, 1.94 to 32.15 cases) for methimazole (MMI) alone, and 16.53 cases (CI, 4.73 to 28.32 cases) for propylthiouracil and MMI, compared with pregnancies without ATD prescriptions. In the MMI group, a high cumulative dose (>495 mg) during the first trimester was associated with an increased risk for malformations compared with a low dose (1 to 126 mg) (adjusted odds ratio, 1.87 [CI, 1.06 to 3.30]).
Limitation: The study used a prescription claims database to assess ATD exposure.
Conclusion: Exposure to ATDs during the first trimester was associated with increased risk for congenital malformations, particularly for pregnancies in which women received prescriptions for MMI or both ATDs.

Authors
Gi Hyeon Seo, Tae Hyuk Kim, Jae Hoon Chung

American College of Physicians material
Annals of Internal Medicine abstract


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