Cargando…

Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used to treat pain, fever and inflammatory conditions. Due to evidenced fetotoxicity, treatment with NSAID and metamizole should be avoided in the 3rd trimester of pregnancy. There is an ongoing debate on fetotoxic risk of 2nd...

Descripción completa

Detalles Bibliográficos
Autores principales: Dathe, Katarina, Frank, Johanna, Padberg, Stephanie, Hultzsch, Stefanie, Beck, Evelin, Schaefer, Christof
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413886/
https://www.ncbi.nlm.nih.gov/pubmed/36028798
http://dx.doi.org/10.1186/s12884-022-04986-4
_version_ 1784775860891418624
author Dathe, Katarina
Frank, Johanna
Padberg, Stephanie
Hultzsch, Stefanie
Beck, Evelin
Schaefer, Christof
author_facet Dathe, Katarina
Frank, Johanna
Padberg, Stephanie
Hultzsch, Stefanie
Beck, Evelin
Schaefer, Christof
author_sort Dathe, Katarina
collection PubMed
description BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used to treat pain, fever and inflammatory conditions. Due to evidenced fetotoxicity, treatment with NSAID and metamizole should be avoided in the 3rd trimester of pregnancy. There is an ongoing debate on fetotoxic risk of 2nd trimester use which is why we have conducted this study. METHODS: In this observational cohort study outcome of pregnancies with NSAID and/or metamizole exposure in the 2nd and/or 3rd trimester (study cohort n = 1092) was compared with pregnancies exposed to NSAID and/or metamizole in the 1st trimester only (comparison cohort, n = 1154). The WHO-UMC system was used to assess causality between study medication and study endpoints. Prenatal study endpoints were constriction of ductus arteriosus Botalli, oligohydramnios, late spontaneous abortion (SAB) or stillbirth. Postnatal study endpoints were patent ductus arteriosus (PDA), anomalies of the right heart ventricle, primary pulmonary hypertension (PPHT), and neonatal impairment of kidney function. RESULTS: Ductus arteriosus constriction was diagnosed in 5/1092 (0.5%) in the study cohort versus 0/1154 pregnancies in the comparison cohort. In one fetus, ductus arteriosus constriction and oligohydramnios occurred already in the late 2nd trimester after long-term NSAID exposure. Oligohydramnios was diagnosed in 41/1092 (3.8%) in the study cohort versus 29/1154 (2.5%) cases in the comparison cohort [RR, 1.5 (95% CI 0.9–2.4)]. Limited to 2nd trimester, oligohydramnios occurred in 8/904 (0.9%) versus 2/1154 (0.2%) pregnancies [RR, 5.1 (95% CI 1.1–24.0)]. At least in four of the 2nd trimester exposed pregnancies NSAID exposure lasted several weeks. Late SAB or stillbirth occurred in 14/1092 (1.3%) versus 17/1154 (1.5%). Postnatal cardiovascular or renal pathology did not differ between the cohorts. CONCLUSIONS: NSAID use in the 2nd trimester limited to a few days does not appear to pose a relevant risk. Use for longer periods in the advanced 2nd trimester, however, may cause oligohydramnios and ductus arteriosus constriction similar to effects observed after 3rd trimester use. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-022-04986-4.
format Online
Article
Text
id pubmed-9413886
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-94138862022-08-27 Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort Dathe, Katarina Frank, Johanna Padberg, Stephanie Hultzsch, Stefanie Beck, Evelin Schaefer, Christof BMC Pregnancy Childbirth Research BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used to treat pain, fever and inflammatory conditions. Due to evidenced fetotoxicity, treatment with NSAID and metamizole should be avoided in the 3rd trimester of pregnancy. There is an ongoing debate on fetotoxic risk of 2nd trimester use which is why we have conducted this study. METHODS: In this observational cohort study outcome of pregnancies with NSAID and/or metamizole exposure in the 2nd and/or 3rd trimester (study cohort n = 1092) was compared with pregnancies exposed to NSAID and/or metamizole in the 1st trimester only (comparison cohort, n = 1154). The WHO-UMC system was used to assess causality between study medication and study endpoints. Prenatal study endpoints were constriction of ductus arteriosus Botalli, oligohydramnios, late spontaneous abortion (SAB) or stillbirth. Postnatal study endpoints were patent ductus arteriosus (PDA), anomalies of the right heart ventricle, primary pulmonary hypertension (PPHT), and neonatal impairment of kidney function. RESULTS: Ductus arteriosus constriction was diagnosed in 5/1092 (0.5%) in the study cohort versus 0/1154 pregnancies in the comparison cohort. In one fetus, ductus arteriosus constriction and oligohydramnios occurred already in the late 2nd trimester after long-term NSAID exposure. Oligohydramnios was diagnosed in 41/1092 (3.8%) in the study cohort versus 29/1154 (2.5%) cases in the comparison cohort [RR, 1.5 (95% CI 0.9–2.4)]. Limited to 2nd trimester, oligohydramnios occurred in 8/904 (0.9%) versus 2/1154 (0.2%) pregnancies [RR, 5.1 (95% CI 1.1–24.0)]. At least in four of the 2nd trimester exposed pregnancies NSAID exposure lasted several weeks. Late SAB or stillbirth occurred in 14/1092 (1.3%) versus 17/1154 (1.5%). Postnatal cardiovascular or renal pathology did not differ between the cohorts. CONCLUSIONS: NSAID use in the 2nd trimester limited to a few days does not appear to pose a relevant risk. Use for longer periods in the advanced 2nd trimester, however, may cause oligohydramnios and ductus arteriosus constriction similar to effects observed after 3rd trimester use. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-022-04986-4. BioMed Central 2022-08-26 /pmc/articles/PMC9413886/ /pubmed/36028798 http://dx.doi.org/10.1186/s12884-022-04986-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Dathe, Katarina
Frank, Johanna
Padberg, Stephanie
Hultzsch, Stefanie
Beck, Evelin
Schaefer, Christof
Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
title Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
title_full Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
title_fullStr Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
title_full_unstemmed Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
title_short Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
title_sort fetal adverse effects following nsaid or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the german embryotox cohort
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413886/
https://www.ncbi.nlm.nih.gov/pubmed/36028798
http://dx.doi.org/10.1186/s12884-022-04986-4
work_keys_str_mv AT dathekatarina fetaladverseeffectsfollowingnsaidormetamizoleexposureinthe2ndand3rdtrimesteranevaluationofthegermanembryotoxcohort
AT frankjohanna fetaladverseeffectsfollowingnsaidormetamizoleexposureinthe2ndand3rdtrimesteranevaluationofthegermanembryotoxcohort
AT padbergstephanie fetaladverseeffectsfollowingnsaidormetamizoleexposureinthe2ndand3rdtrimesteranevaluationofthegermanembryotoxcohort
AT hultzschstefanie fetaladverseeffectsfollowingnsaidormetamizoleexposureinthe2ndand3rdtrimesteranevaluationofthegermanembryotoxcohort
AT beckevelin fetaladverseeffectsfollowingnsaidormetamizoleexposureinthe2ndand3rdtrimesteranevaluationofthegermanembryotoxcohort
AT schaeferchristof fetaladverseeffectsfollowingnsaidormetamizoleexposureinthe2ndand3rdtrimesteranevaluationofthegermanembryotoxcohort