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

2014 ◽  
Vol 171 (1) ◽  
pp. R13-R20 ◽  
Author(s):  
Peter Laurberg ◽  
Stine Linding Andersen
Keyword(s):  
High Risk ◽  
Birth Defects ◽  
Early Pregnancy ◽  
Time Windows ◽  
Antithyroid Drug ◽  
Antithyroid Drugs ◽  
Relative Safety ◽  
Time Period ◽  
Major Period ◽  
Number Of Publications

BackgroundAntithyroid drugs (ATDs) may have teratogenic effects when used in early pregnancy.ObjectiveTo review the association between the time period of ATD exposure in early pregnancy and the development of birth defects.MethodsWe 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.ResultsA 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.ConclusionBoth 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.

Maternal Thyroid Function, Use of Antithyroid Drugs in Early Pregnancy, and Birth Defects

2019 ◽  
Vol 104 (12) ◽  
pp. 6040-6048 ◽  
Author(s):  
Stine Linding Andersen ◽  
Louise Knøsgaard ◽  
Jørn Olsen ◽  
Peter Vestergaard ◽  
Stig Andersen
Keyword(s):  
Thyroid Function ◽  
Birth Defects ◽  
Early Pregnancy ◽  
Antithyroid Drug ◽  
Maternal Blood ◽  
Antithyroid Drugs ◽  
Birth Cohorts ◽  
Increased Risk ◽  
Maternal Thyroid

Abstract Context Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified. Objective To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy. Participants Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015. Main Outcome Measures Birth defects diagnosed before 2 years of age. Results In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8). Conclusions Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

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

2013 ◽  
Vol 98 (11) ◽  
pp. 4373-4381 ◽  
Author(s):  
Stine Linding Andersen ◽  
Jørn Olsen ◽  
Chun Sen Wu ◽  
Peter Laurberg
Keyword(s):  
Birth Defects ◽  
Early Pregnancy ◽  
Antithyroid Drugs ◽  
Nationwide Study

scholarly journals Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study

2017 ◽  
Vol 177 (4) ◽  
pp. 369-378 ◽  
Author(s):  
Stine Linding Andersen ◽  
Stefan Lönn ◽  
Peter Vestergaard ◽  
Ove Törring
Keyword(s):  
Birth Defects ◽  
Early Pregnancy ◽  
Cumulative Incidence ◽  
Heart Defects ◽  
Choanal Atresia ◽  
Antithyroid Drugs ◽  
Urinary System ◽  
Teratogenic Effects ◽  
Pregnancy And Birth ◽  
In Pregnancy

Objective Antithyroid drugs (ATDs) may have teratogenic effects, but more evidence is needed on the risk and types of birth defects after the use of methimazole (MMI) and propylthiouracil (PTU). This study aimed to evaluate the association between the use of ATDs in early pregnancy and birth defects. Design Swedish nationwide register-based cohort study. Methods The study included 684 340 children live-born in Sweden from 2006 to 2012. Exposure groups defined by maternal ATD use in early pregnancy were MMI (n = 162); PTU (n = 218); MMI and PTU (n = 66); ATD before or after, but not in pregnancy (n = 1551) and non-exposed (never ATD (n = 682 343)). Outcome was cumulative incidence of birth defects diagnosed before two years of age. Results The cumulative incidence of birth defects was not significantly different in children exposed to MMI (6.8%, P = 0.6) or PTU (6.4%, P = 0.4) vs non-exposed (8.0%). For subtypes of birth defects, MMI was associated with an increased incidence of septal heart defects (P = 0.02). PTU was associated with ear (P = 0.005) and obstructive urinary system malformations (P = 0.006). A case of choanal atresia was observed after exposure to both MMI and PTU. The incidence of birth defects in children born to mothers who received ATD before or after, but not in pregnancy, was 8.8% and not significantly different from non-exposed (P = 0.3), MMI exposed (P = 0.4) or PTU exposed (P = 0.2). Conclusions MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed.

Graves'-Basedow disease in pregnancy

2015 ◽  
Vol 54 (03) ◽  
pp. 106-111 ◽  
Author(s):  
S. L. Andersen ◽  
P. Laurberg
Keyword(s):  
Side Effects ◽  
Birth Defects ◽  
Thyroid Dysfunction ◽  
National Study ◽  
Antithyroid Drugs ◽  
Upper Limit ◽  
Special Concern ◽  
Maternal Thyroid ◽  
Toxic Reactions ◽  
Serum Tsh

SummaryThyroid hormones are essential development factors and maternal thyroid dysfunction may cause pregnancy complications and diseases in the fetus/child. In the present review we discuss new data on the incidence of Graves'-Basedow disease (GBD) in and around pregnancy, and how hyperthyroidism may affect the risk of spontaneous abortion and stillbirth.A special concern in pregnant women is the potential side effects from the use of antithyroid drugs (ATDs). One type of side effects is the allergic/toxic reactions to the drugs, which seem to be similar in and outside pregnancy, and another is that ATDs tend to over treat the fetus when the mother with GBD is made euthyroid. To avoid fetal hypothyroidism, the lowest possible ATD dose should be used to keep maternal thyroid function at the upper limit of normality with low serum TSH. Birth defects after the use of methimazole (MMI) (or its prodrug carbimazole) have been considered to be very rare, and no risk has previously been associated with the use of propylthiouracil (PTU). However, a recent Danish national study found that 1/30 of children exposed to MMI in early pregnancy had birth defects associated with this, and many defects were severe. PTU exposure was associated with defects in 1/40, and these defects were less severe. Proposals are given on how to reduce the risk of ATD associated birth defects.

Treatment of maternal hyperthyroidism with antithyroid agents and changes in thyrotrophin and thyroxine in the newborn

1981 ◽  
Vol 97 (2) ◽  
pp. 186-195 ◽  
Author(s):  
B.-A. Lamberg ◽  
E. Ikonen ◽  
K. Teramo ◽  
G. Wägar ◽  
K. Österlund ◽  
...  
Keyword(s):  
Laboratory Test ◽  
Cord Blood ◽  
Pregnant Women ◽  
Newborn Infants ◽  
Antithyroid Drug ◽  
Clinical Indication ◽  
Antithyroid Drugs ◽  
Serum Thyroxine ◽  
Antithyroid Agents ◽  
Serum Tsh

Abstract. Eleven pregnant women with concomitant hyperthyroidism were treated with antithyroid drugs. At monthly intervals serum thyroxine (T4) and triiodothyronine (T3) were measured with radioimmunoassay, the Sephadex uptake of radioactive triiodothyronine (T3U) determined and the free T4 and T3 indices calculated (FT4I, FT3I). TSH-binding inhibiting immunoglobulins (TBII) were determined by the radiomembrane assay. Serum TSH and T4 were measured at delivery from cord blood and/or from the newborn infants some days after birth. Serum TSH was significantly elevated in one infant. There was an inadequate post-partal rise in serum T4 concentration in this child and in another who showed only a marginal elevation of TSH. The mothers of these infants were given carbimazole in doses of 30 and 25 mg/day, respectively, at the time of delivery. No significant changes were seen in other infants, the daily doses being 20 mg of carbimazole or less. There was no clinical indication of hypo- or hyperthyroidism in any of the newborn. The TBII were positive in most patients and there was a trend of normalization during treatment. No relationship between the dose of antithyroid drug and the level of TBII could be seen. During treatment the dose was adjusted according to the FT3I values. This seems to be an adequate laboratory test for this purpose.

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