Risk of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nationwide population-based study

Chen, Chi-Hung; Xirasagar, Sudha; Lin, Chia-Chin; Lh, Wang; Kou, Yu Ru; Lin, Horng Chyuan

doi:10.1111/j.1471-0528.2011.03019.x

Cited by 79 publications

(73 citation statements)

References 52 publications

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“…Overall, the defects were less severe than the MMI/CMZassociated defects (60), and they consisted of face and neck malformations (preauricular sinus and cysts), and urinary tract malformations (confined to boys). Some uncertainty has existed in this area of research, because some investigators found no association between ATD use in pregnancy and birth defects (61,62,63,64). As recently reviewed in detail (65), the cause for the negative findings likely resides with the methods used in the studies.…”

Section: Therapy Of Graves' Disease and The Risk Of Birth Defectsmentioning

confidence: 96%

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

Laurberg

Andersen

2016

European Journal of Endocrinology

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Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function.Thyroid hormones are essential developmental factors as first shown by Gudernatsch when he, in 1912, fed tadpoles thyroid tissue and observed metamorphosis (1). In mammals, thyroid hormones are especially of importance for brain development (2, 3), and even a few months with lack of thyroid hormones in infant life may lead to irreversible brain damage. This is the background for the universal screening for congenital hypothyroidism performed in many countries. However, thyroid hormones are also important for normal pregnancy, and maternal thyroid disease may severely increase the risk of pregnancy complications, including Invited author's profile Peter Laurberg was Clinical Professor of Internal Medicine and Endocrinology, Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. His research mainly focused on thyroid disease prevention, epidemiology, diagnosing and therapy, including studies on iodine and thyroid, and pregnancy and thyroid. He had special research interest on the risk from and optimal management of autoimmune hypo-and hyperthyroidism in pregnancy and post-partum, management of Graves' disease in general, and how the burden of thyroid disease can be minimized by adjusting the population's iodine intake. He has coauthored several international guidelines on thyroid disease management, including management of thyrotoxicosis, and thyroid disease in pregnancy. Peter Laurberg died June 20, 2016.

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Section: Therapy Of Graves' Disease and The Risk Of Birth Defectsmentioning

confidence: 96%

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

Laurberg

Andersen

2016

European Journal of Endocrinology

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“…3 Because PTU has (rarely) been associated with liver failure in pregnant women, 5, 57 current guidelines recommend switching to MMI after the first trimester. 5,26 Suggestion:…”

Section: Question 5: Do Maternal Atds Infl Uence the Newborn's Presenmentioning

confidence: 99%

“…[1][2][3][4] The prevalence of transient GD in infants born to these mothers is uncertain, varying from 1.5% to 2.5% [5][6][7] up to 20.0% in observational cohort studies. [7][8][9] The causative antibodies in GD, thyroid-stimulating hormone (TSH) receptor antibodies (TRAb), belong to the immunoglobulin G class and freely cross the placenta, particularly during the second half of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Management of Neonates Born to Mothers With Graves’ Disease

2016

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Neonates born to mothers with Graves’ disease are at risk for significant morbidity and mortality and need to be appropriately identified and managed. Because no consensus guidelines regarding the treatment of these newborns exist, we sought to generate a literature-based management algorithm. The suggestions include the following: (1) Base initial risk assessment on maternal thyroid stimulating hormone (TSH) receptor antibodies. If levels are negative, no specific neonatal follow-up is necessary; if unavailable or positive, regard the newborn as “at risk” for the development of hyperthyroidism. (2) Determine levels of TSH-receptor antibodies in cord blood, or as soon as possible thereafter, so that newborns with negative antibodies can be discharged from follow-up. (3) Measurement of cord TSH and fT4 levels is not indicated. (4) Perform fT4 and TSH levels at day 3 to 5 of life, repeat at day 10 to 14 of life and follow clinically until 2 to 3 months of life. (5) Use the same testing schedule in neonates born to mothers with treated or untreated Graves’ disease. (6) When warranted, use methimazole (MMI) as the treatment of choice; β-blockers can be added for sympathetic hyperactivity. In refractory cases, potassium iodide may be used in conjunction with MMI. The need for treatment of asymptomatic infants with biochemical hyperthyroidism is uncertain. (7) Assess the MMI-treated newborn on a weekly basis until stable, then every 1 to 2 weeks, with a decrease of MMI (and other medications) as tolerated. MMI treatment duration is most commonly 1 to 2 months. (8) Be cognizant that central or primary hypothyroidism can occur in these newborns.

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“…After this, more cases were published including, now also, more severe birth defects leading to the term methimazole/carbimazole embryopathy (7,8), as described in several reviews (9,15). Still, some studies have been negative (16,17), and until recently, the additional risk of birth defects after early pregnancy use of MMI/CMZ was considered to be very low (2,3). PTU was considered not to be teratogenic (2,3), even if some non-human studies were positive (18,19).…”

Section: Introductionmentioning

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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Risk of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nationwide population-based study

Cited by 79 publications

References 52 publications

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

Management of Neonates Born to Mothers With Graves’ Disease

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

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