Birth Defects After Early Pregnancy Use of Antithyroid Drugs: A Danish Nationwide Study

Andersen, Stine Linding; Olsen, Jeppe; Wu, Chun Sen; Laurberg, Peter

doi:10.1210/jc.2013-2831

Cited by 243 publications

(234 citation statements)

References 35 publications

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“…In this study, the highest relative risk was seen for various types of abdominal wall defects (Fig. 3), followed by skin defects (aplasia cutis), digestive (oesophageal and other atresias), eye, urinary tract, respiratory (choanal atresia), and circulatory (ventricular septum) defects (57,58).…”

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

confidence: 53%

“…In recent years, large studies from Japan (55, 56) and Denmark (57,58) have shown that MMI/CMZ-associated birth defects are more common than anticipated, and may affect ~1/30 of children exposed to the drug in the weeks 6-10 of pregnancy. This is considerably below 10% of the effect of thalidomide, the prime drug example of teratogenicity (59), but still enough to raise serious concern.…”

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

confidence: 99%

“…If ATD has to be started/restarted in early pregnancy to treat overt hyperthyroidism, the drug of choice is PTU, because the risk of severe birth defects is lower than with the use of MMI/CMZ (57,60). An argument against the Reference was children born to mothers who never received ATD therapy.…”

Section: Pre-pregnancy Counsellingmentioning

confidence: 99%

“…In the methimazole group, 'musculoskeletal, others' were various types of abdominal wall defects, 'integumentary' included aplasia cutis, 'digestive' included esophageal atresia, 'respiratory' included choanal atresia and 'circulatory' was ventricular septal defect. Reproduced with permission from Andersen SL et al (57).…”

Section: Pre-pregnancy Counsellingmentioning

confidence: 99%

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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: 53%

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

confidence: 99%

Section: Pre-pregnancy Counsellingmentioning

confidence: 99%

Section: Pre-pregnancy Counsellingmentioning

confidence: 99%

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

Laurberg

Andersen

2016

European Journal of Endocrinology

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“…In such studies, the prevalence of disease depends on the biochemical definition of thyroid disease as well as the gestational week of sampling. Similarly for register-based studies (19,20,21), the prevalence of disease will depend on the criteria applied and the available registered information. We evaluated the prevalence of thyroid dysfunction in the DNBC by redeemed prescription of thyroid medication and observed that 0.2% of the women were treated for hyperthyroidism and 0.5% for hypothyroidism in the pregnancy.…”

Section: Prevalence Of Thyroid Disease In Pregnancymentioning

confidence: 99%

Maternal thyroid disease in the Danish National Birth Cohort: prevalence and risk factors

Andersen

Olsen

Laurberg

2016

European Journal of Endocrinology

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Objective: Thyroid disorders are common in women of reproductive age, but the exact burden of disease before, during and after a pregnancy is not clear. We describe the prevalence of thyroid disease in women enrolled in the Danish National Birth Cohort (DNBC) and investigate some of its risk factors. Design: Population-based study within the DNBC, which included 101 032 pregnancies (1997)(1998)(1999)(2000)(2001)(2002)(2003). Methods: We studied women enrolled in the DNBC who gave birth to a live-born child. Information on maternal thyroid disease (hyperthyroidism, hypothyroidism, benign goiter/nodules, thyroid cancer, and other) before, during and up to 5 years after the woman's first pregnancy in the cohort was obtained from self-report (telephone interview in median gestational week 17) and from nationwide registers on hospital diagnosis of thyroid disease/thyroid surgery (from 1977) and prescriptions of thyroid drugs (from 1995). Results: Of the 77 445 women studied, 3018 (3.9%) were identified with an onset of thyroid disease before (2.0%), during (0.1%) or in the 5-year period after the pregnancy (1.8%). During the pregnancy, 153 (0.2%) women received antithyroid drugs and 365 (0.5%) received thyroid hormone for hypothyroidism (83 after previous hyperthyroidism, 42 after previous surgery for benign goiter/nodules or thyroid cancer). Significant risk factors for maternal thyroid disease were age, parity, origin, iodine intake, smoking, alcohol, and BMI. Conclusions: Around 4% of Danish pregnant women had either a history of thyroid disease or thyroid disease during pregnancy or were diagnosed with thyroid disease for the first-time in the years following a pregnancy. The spectrum of thyroid disease was influenced by demographic and environmental factors.

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Management of Graves Disease

Burch

Cooper

2015

JAMA

280

222

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Management of Graves disease includes treatment with antithyroid drugs, RAI, or thyroidectomy. The optimal approach depends on patient preference and specific patient clinical features such as age, history of arrhythmia or ischemic heart disease, size of goiter, and severity of thyrotoxicosis. Physicians should be familiar with the advantages and disadvantages of each therapy to best counsel their patients.

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Birth Defects After Early Pregnancy Use of Antithyroid Drugs: A Danish Nationwide Study

Abstract: Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed. More studies are needed to corroborate results in regard to early pregnancy shift from MMI/CMZ to PTU. New ATD with fewer side effects should be developed.

Cited by 243 publications

References 35 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

Maternal thyroid disease in the Danish National Birth Cohort: prevalence and risk factors

Management of Graves Disease

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