Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study

<b>Background/Objectives</b>: Maternal use of medication during pregnancy may have teratogenic effects, as seen with drugs like thalidomide, valproate, and phenytoin. Despite rigorous testing, both new and established drugs still pose a risk of teratogenesis, particularly if the teratoge...

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Main Authors: Ulrik Lausten-Thomsen, Rasmus Huan Olsen, Michael Christiansen, Paula L. Hedley, Ida Marie Heerfordt, Jon Trærup Andersen, Christina Gade
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/6/917
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author Ulrik Lausten-Thomsen
Rasmus Huan Olsen
Michael Christiansen
Paula L. Hedley
Ida Marie Heerfordt
Jon Trærup Andersen
Christina Gade
author_facet Ulrik Lausten-Thomsen
Rasmus Huan Olsen
Michael Christiansen
Paula L. Hedley
Ida Marie Heerfordt
Jon Trærup Andersen
Christina Gade
author_sort Ulrik Lausten-Thomsen
collection DOAJ
description <b>Background/Objectives</b>: Maternal use of medication during pregnancy may have teratogenic effects, as seen with drugs like thalidomide, valproate, and phenytoin. Despite rigorous testing, both new and established drugs still pose a risk of teratogenesis, particularly if the teratogenic effects are probabilistic and not deterministic. Public health organizations maintain registers to centralize and evaluate adverse drug reactions (ADR). However, underreporting in these registries can obscure the signals of drug-related congenital malformations. This study aims to evaluate potential ADR-associated congenital malformations in Denmark over the past decade; <b>Methods</b>: An observational cross-sectional study was conducted using data from the national Danish Medicines Agency’s pharmacovigilance database, which includes all spontaneous ADR reports submitted to the Danish Medicines Agency from 1 July 2013 to 30 June 2023. Maternal antenatal drug use was identified, and reported ADRs were assessed for congenital malformations; <b>Results</b>: We identified reports of potential ADR-related congenital malformations in 75 children, with 92 diagnoses as classified by ICD-10. Eighty-five different drugs from 58 ATC codes were implicated. Only three diagnoses were reported in five or more children. The reports were generally sporadic, with no new signals detected; <b>Conclusions</b>: Public awareness is crucial when novel threats arise from medications, infections, or technologies, as these may pose risks to unborn children. Ongoing monitoring of potential ADR-related congenital malformations remains a critical component of public health. Given the potential underreporting, we encourage a low threshold for reporting ADRs based on suspicion alone, with final causality assessments made by health authorities.
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spelling doaj-art-607658450f7f4113b1cc331fb99c56632025-08-20T03:16:35ZengMDPI AGPharmaceuticals1424-82472025-06-0118691710.3390/ph18060917Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register StudyUlrik Lausten-Thomsen0Rasmus Huan Olsen1Michael Christiansen2Paula L. Hedley3Ida Marie Heerfordt4Jon Trærup Andersen5Christina Gade6Department of Neonatology, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Clinical Pharmacology, Copenhagen University Hospital—Bispebjerg and Frederiksberg, 2400 Copenhagen, DenmarkDepartment for Congenital Disorders, Statens Serum Institut, 2300 Copenhagen, DenmarkDepartment for Congenital Disorders, Statens Serum Institut, 2300 Copenhagen, DenmarkDepartment of Clinical Pharmacology, Copenhagen University Hospital—Bispebjerg and Frederiksberg, 2400 Copenhagen, DenmarkDepartment of Clinical Pharmacology, Copenhagen University Hospital—Bispebjerg and Frederiksberg, 2400 Copenhagen, DenmarkDepartment of Clinical Pharmacology, Copenhagen University Hospital—Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark<b>Background/Objectives</b>: Maternal use of medication during pregnancy may have teratogenic effects, as seen with drugs like thalidomide, valproate, and phenytoin. Despite rigorous testing, both new and established drugs still pose a risk of teratogenesis, particularly if the teratogenic effects are probabilistic and not deterministic. Public health organizations maintain registers to centralize and evaluate adverse drug reactions (ADR). However, underreporting in these registries can obscure the signals of drug-related congenital malformations. This study aims to evaluate potential ADR-associated congenital malformations in Denmark over the past decade; <b>Methods</b>: An observational cross-sectional study was conducted using data from the national Danish Medicines Agency’s pharmacovigilance database, which includes all spontaneous ADR reports submitted to the Danish Medicines Agency from 1 July 2013 to 30 June 2023. Maternal antenatal drug use was identified, and reported ADRs were assessed for congenital malformations; <b>Results</b>: We identified reports of potential ADR-related congenital malformations in 75 children, with 92 diagnoses as classified by ICD-10. Eighty-five different drugs from 58 ATC codes were implicated. Only three diagnoses were reported in five or more children. The reports were generally sporadic, with no new signals detected; <b>Conclusions</b>: Public awareness is crucial when novel threats arise from medications, infections, or technologies, as these may pose risks to unborn children. Ongoing monitoring of potential ADR-related congenital malformations remains a critical component of public health. Given the potential underreporting, we encourage a low threshold for reporting ADRs based on suspicion alone, with final causality assessments made by health authorities.https://www.mdpi.com/1424-8247/18/6/917adverse drug reaction reporting systemscongenital abnormalitiesdrug-related side effects and adverse reactionsinfantnewbornpharmacovigilance
spellingShingle Ulrik Lausten-Thomsen
Rasmus Huan Olsen
Michael Christiansen
Paula L. Hedley
Ida Marie Heerfordt
Jon Trærup Andersen
Christina Gade
Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study
Pharmaceuticals
adverse drug reaction reporting systems
congenital abnormalities
drug-related side effects and adverse reactions
infant
newborn
pharmacovigilance
title Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study
title_full Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study
title_fullStr Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study
title_full_unstemmed Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study
title_short Spontaneous Adverse Drug Reaction Reporting of Congenital Malformations: A Danish National Register Study
title_sort spontaneous adverse drug reaction reporting of congenital malformations a danish national register study
topic adverse drug reaction reporting systems
congenital abnormalities
drug-related side effects and adverse reactions
infant
newborn
pharmacovigilance
url https://www.mdpi.com/1424-8247/18/6/917
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