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Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero

IMPORTANCE: Corticosteroids and β2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear. OBJECTIVE: To investigate the association between timing of in utero exposure to...

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Autores principales: Nagata, Abir, Masumoto, Toshio, Nishigori, Hidekazu, Nakagawa, Takatoshi, Otani, Shinji, Kurozawa, Youichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599123/
https://www.ncbi.nlm.nih.gov/pubmed/37874567
http://dx.doi.org/10.1001/jamanetworkopen.2023.39347
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author Nagata, Abir
Masumoto, Toshio
Nishigori, Hidekazu
Nakagawa, Takatoshi
Otani, Shinji
Kurozawa, Youichi
author_facet Nagata, Abir
Masumoto, Toshio
Nishigori, Hidekazu
Nakagawa, Takatoshi
Otani, Shinji
Kurozawa, Youichi
author_sort Nagata, Abir
collection PubMed
description IMPORTANCE: Corticosteroids and β2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear. OBJECTIVE: To investigate the association between timing of in utero exposure to corticosteroids and β2-adrenergic agonists and offspring neurodevelopmental milestones during the first 3 years of life. DESIGN, SETTING, AND PARTICIPANTS: This cohort study obtained data from the Japan Environment and Children’s Study, an ongoing birth cohort study conducted in collaboration with 15 Regional Centers across Japan. Participants were mother-offspring pairs who were recruited between January 1, 2011, and March 31, 2014. Data were analyzed between January and February 2023. EXPOSURE: Corticosteroids and β2-adrenergic agonists were the exposure of interest. Timing of corticosteroid and β2-adrenergic agonist exposure included early pregnancy (weeks 0-12), mid- to late pregnancy (weeks >12), and both stages of pregnancy. MAIN OUTCOMES AND MEASURES: Offspring neurodevelopmental milestones (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition, at 6, 12, 18, 24, 30, and 36 months. RESULTS: In total, 91 460 mother-offspring pairs were analyzed. Among mothers, the mean (SD) age at delivery was 31.20 (5.05) years. Among offspring, 46 596 (50.9%) were males and 44 864 (49.1%) were females, of whom 66.4% had a gestational age of 39 to 41 weeks. During early, mid- to late, and both stages of pregnancy, 401 (0.4%), 935 (1.0%), and 568 (0.6%) offspring, respectively, were exposed to corticosteroids, whereas 170 (0.2%), 394 (0.4%), and 184 (0.2%), respectively, were exposed to β2-adrenergic agonists. No association of corticosteroid exposure during early, mid- to late, and both stages of pregnancy with all 5 neurodevelopmental milestones was found. Similarly, no association between β2-adrenergic agonist use during early pregnancy and all 5 neurodevelopmental milestones was observed. An association was found between β2-adrenergic agonist exposure during mid- to late pregnancy and delayed personal-social skills (adjusted odds ratio, 1.48; 95% CI, 1.01-2.32; P = .045). CONCLUSIONS AND RELEVANCE: Results of this study found no association between in utero corticosteroid and β2-adrenergic agonist exposure and offspring neurodevelopmental outcomes, regardless of the timing of exposure. Despite the limitations and low power of the study, the findings suggest that corticosteroids and β2-adrenergic agonists are safe for pregnant individuals with asthma and the neurodevelopment of their offspring.
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spelling pubmed-105991232023-10-26 Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero Nagata, Abir Masumoto, Toshio Nishigori, Hidekazu Nakagawa, Takatoshi Otani, Shinji Kurozawa, Youichi JAMA Netw Open Original Investigation IMPORTANCE: Corticosteroids and β2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear. OBJECTIVE: To investigate the association between timing of in utero exposure to corticosteroids and β2-adrenergic agonists and offspring neurodevelopmental milestones during the first 3 years of life. DESIGN, SETTING, AND PARTICIPANTS: This cohort study obtained data from the Japan Environment and Children’s Study, an ongoing birth cohort study conducted in collaboration with 15 Regional Centers across Japan. Participants were mother-offspring pairs who were recruited between January 1, 2011, and March 31, 2014. Data were analyzed between January and February 2023. EXPOSURE: Corticosteroids and β2-adrenergic agonists were the exposure of interest. Timing of corticosteroid and β2-adrenergic agonist exposure included early pregnancy (weeks 0-12), mid- to late pregnancy (weeks >12), and both stages of pregnancy. MAIN OUTCOMES AND MEASURES: Offspring neurodevelopmental milestones (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition, at 6, 12, 18, 24, 30, and 36 months. RESULTS: In total, 91 460 mother-offspring pairs were analyzed. Among mothers, the mean (SD) age at delivery was 31.20 (5.05) years. Among offspring, 46 596 (50.9%) were males and 44 864 (49.1%) were females, of whom 66.4% had a gestational age of 39 to 41 weeks. During early, mid- to late, and both stages of pregnancy, 401 (0.4%), 935 (1.0%), and 568 (0.6%) offspring, respectively, were exposed to corticosteroids, whereas 170 (0.2%), 394 (0.4%), and 184 (0.2%), respectively, were exposed to β2-adrenergic agonists. No association of corticosteroid exposure during early, mid- to late, and both stages of pregnancy with all 5 neurodevelopmental milestones was found. Similarly, no association between β2-adrenergic agonist use during early pregnancy and all 5 neurodevelopmental milestones was observed. An association was found between β2-adrenergic agonist exposure during mid- to late pregnancy and delayed personal-social skills (adjusted odds ratio, 1.48; 95% CI, 1.01-2.32; P = .045). CONCLUSIONS AND RELEVANCE: Results of this study found no association between in utero corticosteroid and β2-adrenergic agonist exposure and offspring neurodevelopmental outcomes, regardless of the timing of exposure. Despite the limitations and low power of the study, the findings suggest that corticosteroids and β2-adrenergic agonists are safe for pregnant individuals with asthma and the neurodevelopment of their offspring. American Medical Association 2023-10-24 /pmc/articles/PMC10599123/ /pubmed/37874567 http://dx.doi.org/10.1001/jamanetworkopen.2023.39347 Text en Copyright 2023 Nagata A et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Nagata, Abir
Masumoto, Toshio
Nishigori, Hidekazu
Nakagawa, Takatoshi
Otani, Shinji
Kurozawa, Youichi
Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero
title Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero
title_full Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero
title_fullStr Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero
title_full_unstemmed Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero
title_short Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero
title_sort neurodevelopmental outcomes among offspring exposed to corticosteroid and b2-adrenergic agonists in utero
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599123/
https://www.ncbi.nlm.nih.gov/pubmed/37874567
http://dx.doi.org/10.1001/jamanetworkopen.2023.39347
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