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- Title
Neurodevelopmental Outcomes Among Offspring Exposed to Corticosteroid and B2-Adrenergic Agonists In Utero.
- Authors
Nagata, Abir; Masumoto, Toshio; Nishigori, Hidekazu; Nakagawa, Takatoshi; Otani, Shinji; Kurozawa, Youichi
- Abstract
This cohort study examines the parent-assessed communication, gross motor, fine motor, problem-solving, and personal-social skills in children whose mothers used corticosteroids and β2-adrenergic agonists for asthma during pregnancy. Key Points: Question: Is the timing of in utero corticosteroid and β2-adrenergic agonist exposure associated with offspring neurodevelopmental outcomes during the first 3 years of life? Findings: In this cohort study of 91 460 mother-offspring pairs, no associations were found between corticosteroid and β2-adrenergic agonist exposure in early pregnancy, mid- to late pregnancy, or both stages of pregnancy and the development of communication, gross motor, fine motor, problem-solving, and personal-social skills in offspring, when compared with nonexposed offspring, during the first 3 years of life. Meaning: Findings of this study suggest that corticosteroids and β2-adrenergic agonists are safe for pregnant individuals with asthma and their offspring's neurodevelopment. 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.
- Subjects
JAPAN; DRUG therapy for asthma; SYMPATHOLYTIC agents; ADRENOCORTICAL hormones; CONFIDENCE intervals; TIME; PRENATAL exposure delayed effects; PREGNANCY outcomes; CHILD psychopathology; RESEARCH funding; DESCRIPTIVE statistics; QUESTIONNAIRES; ODDS ratio; SENSITIVITY &; specificity (Statistics); LOGISTIC regression analysis; DATA analysis software; LONGITUDINAL method; FETUS
- Publication
JAMA Network Open, 2023, Vol 6, Issue 10, pe2339347
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2023.39347