The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
THERAPY OF ENDOCRINE DISEASE: Antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk?
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Citations
Cites
Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., Negro, R., Nixon, A., Pearce, E. N., Soldin, O. P., Sullivan, S., et al. (2011) · Thyroid · doi:10.1089/thy.2011.0087 · Cited by 2,942
DeGroot, L. J., Abalovich, M., Alexander, E. K., Amino, N., Barbour, L. A., Cobin, R. H., Eastman, C. J., Lazarus, J. H., Luton, D., Mandel, S. J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2803 · Cited by 1,885
Bahn, R. S., Burch, H. B., Cooper, D. S., Garber, J. R., Greenlee, M. C., Klein, I., Laurberg, P., McDougall, I. R., Montori, V. M., Rivkees, S. A., et al. (2011) · Endocrine Practice · doi:10.4158/ep.17.3.456 · Cited by 1,098
Self-citationThe American Thyroid Association and American Association of Clinical Endocrinologists Taskforce on Hyperthyroidism and Other Causes of Thyrotoxicosis, Bahn, R. S., Burch, H. B., Cooper, D. S., Garber, J. R., Greenlee, M. C., Klein, I., Laurberg, P., McDougall, I. R., Montori, V. M., et al. (2011) · Thyroid · doi:10.1089/thy.2010.0417 · Cited by 898
Self-citationLaurberg, P., Wallin, G., Tallstedt, L., Abraham-Nordling, M., Lundell, G., & Tørring, O. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0450 · Cited by 428
Self-citationSubclinical Hyperthyroidism and Pregnancy Outcomes
Casey, B. M., Dashe, J. S., Wells, C. E., McIntire, D. D., Leveno, K. J., & Cunningham, F. G. (2006) · Obstetrics & Gynecology · doi:10.1097/01.aog.0000197991.64246.9a · Cited by 358
Cooper, D. S., & Laurberg, P. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70086-x · Cited by 310
Self-citationBirth Defects After Early Pregnancy Use of Antithyroid Drugs: A Danish Nationwide Study
Andersen, S. L., Olsen, J., Wu, C. S., & Laurberg, P. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2831 · Cited by 267
Self-citationMATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING
Momotani, N., Ito, K., Hamada, N., Ban, Y., NISHIKAWA, Y., & Mimura, T. (1984) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1984.tb00119.x · Cited by 238
Yoshihara, A., Noh, J., Yamaguchi, T., Ohye, H., Sato, S., Sekiya, K., Kosuga, Y., Suzuki, M., Matsumoto, M., Kunii, Y., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2860 · Cited by 231
Putting Propylthiouracil in Perspective
Cooper, D. S., & Rivkees, S. A. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0850 · Cited by 212
Adverse effects of prenatal methimazole exposure
Gianantonio, E. D., Schaefer, C., Mastroiacovo, P. P., Cournot, M. P., Benedicenti, F., Reuvers, M., Occupati, B., Robert, E., Bellemin, B., Addis, A., et al. (2001) · Teratology · doi:10.1002/tera.1072 · Cited by 204
Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study
Carlé, A., Pedersen, I. B., Knudsen, N., Perrild, H., Ovesen, L., Rasmussen, L. B., & Laurberg, P. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-1155 · Cited by 204
Self-citationLaurberg, P., Bournaud, C., Karmisholt, J., & Orgiazzi, J. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0663 · Cited by 178
Self-citationReview of Antithyroid Drug Use During Pregnancy and Report of a Case of Aplasia Cutis
Mandel, S. J., Brent, G. A., & Larsen, P. R. (1994) · Thyroid · doi:10.1089/thy.1994.4.129 · Cited by 150
Maternal methimazole and congenital defects in children
Milham, S., & Elledge, W. (1972) · Teratology · doi:10.1002/tera.1420050117 · Cited by 139
Remission of Graves’ disease during anti-thyroid drug therapy. Time to reconsider the mechanism?
Laurberg, P. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02295 · Cited by 139
Self-citationBarbero, P., Valdéz, R., Rodriguez, H. A., Tiscornia, C., Mansilla, E., Allons, A., Coll, S., & Liascovich, R. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32497 · Cited by 128
The preauricular sinus: A review of its aetiology, clinical presentation and management
Tan, T., Constantinides, H., & Mitchell, T. (2005) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2005.07.008 · Cited by 109
Carbimazole embryopathy: An emerging phenotype
Foulds, N. C., Walpole, I., Elmslie, F., & Mansour, S. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30418 · Cited by 108
Korelitz, J. J., McNally, D. L., Masters, M. N., Li, S. X., Xu, Y., & Rivkees, S. A. (2013) · Thyroid® · doi:10.1089/thy.2012.0488 · Cited by 91
Momotani, N., Hisaoka, T., Noh, J. Y., Ishikawa, N., & Ito, K. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.3.1517362 · Cited by 91
Goitre size and outcome of medical treatment of Graves' disease
Laurberg, P., Buchholtz, P. E., Iversen, E., Jensen, S. E., & Weeke, J. (1986) · European Journal of Endocrinology · doi:10.1530/acta.0.1110039 · Cited by 86
Self-citationTaylor, P. N., & Vaidya, B. (2012) · European Thyroid Journal · doi:10.1159/000342920 · Cited by 84
Chen, C., Xirasagar, S., Lin, C.-C., Wang, L., Kou, Y. R., & Lin, H.-C. (2011) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2011.03019.x · Cited by 81
Aplasia Cutis Congenita After Methimazole Exposure in Utero
Karg, E., Bereg, E., Gáspár, L., Katona, M., & Túri, S. (2004) · Pediatric Dermatology · doi:10.1111/j.0736-8046.2004.21417.x · Cited by 70
Association of preauricular sinuses and renal anomalies
Leung, A. K. C., & Robson, W. L. M. (1992) · Urology · doi:10.1016/0090-4295(92)90487-h · Cited by 60
Malformations following methimazole exposure in utero: An open issue
Ferraris, S., Valenzise, M., Lerone, M., Divizia, M. T., Rosaia, L., Blaid, D., Nemelka, O., Ferrero, G. B., & Silengo, M. (2003) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.10098 · Cited by 42
Iwayama, H., Hosono, H., Yamamoto, H., Oshiro, M., & Ueda, N. (2007) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20395 · Cited by 39
Two independent mutations in a family with neurofibromatosis type 1 (NF1)
Harder, A., Peters, H., Hoffmeyer, S., Buske, A., L�der, A., He�, D., Lehmann, R., N�rnberg, P., & Tinschert, S. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990305)83:1 · Cited by 34
Methimazole embryopathy: A contribution to defining the phenotype
Valdéz, R., Barbero, P., Liascovich, R., Rosa, L. F. D., Aguirre, M., & Alba, L. G. (2006) · Reproductive Toxicology · doi:10.1016/j.reprotox.2006.11.007 · Cited by 30
Seoud, M. A.-F., Nassar, A. H., Usta, I. M., Mansour, M., Salti, I., & Younes, K. (2003) · American Journal of Perinatology · doi:10.1055/s-2003-38320 · Cited by 29
Propylthiouracil Is Teratogenic in Murine Embryos
Benavides, V. C., Mallela, M. K., Booth, C. J., Wendler, C. C., & Rivkees, S. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035213 · Cited by 27
Carlé, A., Pedersen, I. B., Perrild, H., Ovesen, L., Jørgensen, T., & Laurberg, P. (2013) · Thyroid · doi:10.1089/thy.2013.0074 · Cited by 23
Self-citationKoenig, D., Spreux, A., Hiéronimus, S., Chichmanian, R. M., Bastiani, F., Fénichel, P., & Brucker-Davis, F. (2010) · Annales d Endocrinologie · doi:10.1016/j.ando.2010.07.001 · Cited by 23
Pharmacologic treatment of hyperthyroidism during pregnancy
Cassina, M., Donà, M., Gianantonio, E. D., & Clementi, M. (2012) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.23012 · Cited by 22
Guidelines for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum
Yi, K. H., Kim, K. W., Yim, C. H., Jung, E. D., Chung, J. H., Chung, H.-K., Hong, S., & Chung, J. H. (2014) · Journal of Korean Thyroid Association · doi:10.11106/jkta.2014.7.1.7 · Cited by 21
Embryonic exposure to propylthiouracil disrupts left‐right patterning in Xenopus embryos
van Veenendaal, N. R., Ulmer, B. M., Boskovski, M. T., Fang, X., Khokha, M. K., Wendler, C. C., Blum, M., & Rivkees, S. A. (2012) · The FASEB Journal · doi:10.1096/fj.12-218073 · Cited by 19
Gripp, K. W., Kuryan, R., Schnur, R. E., Kothawala, M., Davey, L., Antunes, M. J., Reichard, K. W., Schneider, A. S., & Hall, B. D. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33705 · Cited by 17
Aplasia Cutis Congenita Following in Utero Methimazole Exposure
Baid, S. K., & Merke, D. P. (2007) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2007.20.5.585 · Cited by 15
Choanal Atresia Associated With Tracheoesophageal Fistula: The Spectrum of Carbimazole Embryopathy
Douchement, D., Rakza, T., Holder, M., Bonne, N.-X., & Fayoux, P. (2011) · PEDIATRICS · doi:10.1542/peds.2010-0945 · Cited by 13
Kimura, M., Seki, T., Ozawa, H., Ishihara, T., Komatsu, M., Tajiri, S., Yanagi, H., Nishina, M., Noh, J. Y., Fukagawa, M., et al. (2012) · Endocrine Journal · doi:10.1507/endocrj.ej12-0212 · Cited by 12
Rodríguez-García, R. (1999) · PubMed · Cited by 9
Carbimazole embryopathy in a Chinese population: Case series and literature review
Ting, Y. H., Zhou, Y., & Lao, T. T.-H. (2013) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.23117 · Cited by 8
[Aplasia cutis as a teratogenic effect of methimazole].
Rubio, J. D.-D., Mj, B. M., Bonachera, M. D. C., & López Candel, E. (1999) · PubMed · Cited by 7
GRAVES (1834) · New England Journal of Medicine · doi:10.1056/nejm183407230102403 · Cited by 5
Research works printed but not linked: 5
- 2005, American journal of medical genetics. Part A, 132, 130
- D ez-Delgado Rubio, 1999, Anales espa oles de pediatr a, 51, 290
- Rodr guez-Garc a, 1999, Ginecolog a y obstetricia de M xico, 67, 587
- 2008, American journal of medical genetics. Part A, 146, 2390
- Momotani, 1992, Journal of Clinical Endocrinology & Metabolism, 75, 738, 10.1210/jc.75.3.738 · DOI
Cited by
Sorted by citations
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938
“The time window that will allow medication withdrawal or change in early pregnancy to prevent birth defects is narrow (468,469), probably confined to gestational week 5.”
BackgroundSelf-citationAlexander, E. K., Pearce, E. N., Brent, G. A., Brown, R. S., Chen, H., Dosiou, C., Grobman, W. A., Laurberg, P., Lazarus, J. H., Mandel, S. J., et al. (2017) · Thyroid® · doi:10.1089/thy.2016.0457 · Cited by 2,731
Self-citation2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism
Kahaly, G. J., Bartalena, L., Hegedüs, L., Leenhardt, L., Poppe, K. G., & Pearce, S. H. S. (2018) · European Thyroid Journal · doi:10.1159/000490384 · Cited by 1,025
Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis
Wiersinga, W. M., Poppe, K. G., & Effraimidis, G. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00005-0 · Cited by 254
Management of Graves Thyroidal and Extrathyroidal Disease: An Update
Kahaly, G. J. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa646 · Cited by 237
Metadata
- Authors
- Laurberg, P., & Andersen, S. L.
- Affiliations
- Aalborg University Hospital (DK)
- Corresponding author
- Laurberg, Peter
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07
- Volume
- 171
- Issue
- 1
- Pages
- R13-R20
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2078098699
- Cited by
- 115
- References
- 46
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 10 · 2022: 9 · 2021: 9 · 2020: 15 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 14 · 2015: 13 · 2014: 6
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- green
- vbn.aau.dk
- Licence
- other-oa
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (publishedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- antithyroid drugs, teratogenicity, congenital malformations, early pregnancy, methimazole, carbimazole, propylthiouracil, gestational age, hyperthyroidism in pregnancy, organogenesis, drug safety in pregnancy
- MeSH terms
- Congenital Abnormalities, Carbimazole, Endocrine System Diseases, Female, Humans, Male, Pregnancy, Pregnancy Complications, Propylthiouracil, Antithyroid Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
