Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Graduate School of Public Health, St Luke's International University, Tokyo, Japan.
JAMA Netw Open. 2023 Oct 2;6(10):e2339347. doi: 10.1001/jamanetworkopen.2023.39347.
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.
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.
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.
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.
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).
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.
皮质类固醇和β2-肾上腺素能激动剂常用于治疗哮喘孕妇。然而，宫内暴露于这些药物对后代神经发育结局的影响仍不清楚。
研究宫内暴露于皮质类固醇和β2-肾上腺素能激动剂的时间与生命前 3 年后代神经发育里程碑之间的关系。
设计、设置和参与者：本队列研究从日本环境与儿童研究中获取数据，这是一项在日本 15 个地区中心合作进行的正在进行的出生队列研究。参与者是在 2011 年 1 月 1 日至 2014 年 3 月 31 日期间招募的母婴对子。数据于 2023 年 1 月至 2 月之间进行分析。
皮质类固醇和β2-肾上腺素能激动剂是本研究的关注点。皮质类固醇和β2-肾上腺素能激动剂暴露的时间包括早孕（第 0-12 周）、中晚期妊娠（第 12 周以后）和妊娠的两个阶段。
使用日本版年龄与阶段问卷 3 版评估后代的神经发育里程碑（沟通、大运动、精细运动、解决问题和个人-社会技能），在 6、12、18、24、30 和 36 个月时进行评估。
总共分析了 91460 对母婴对子。在母亲中，分娩时的平均（SD）年龄为 31.20（5.05）岁。在后代中，46596 名（50.9%）为男性，44864 名（49.1%）为女性，其中 66.4%的人有 39 至 41 周的胎龄。在早孕、中晚期和两个阶段的妊娠中，分别有 401 名（0.4%）、935 名（1.0%）和 568 名（0.6%）的后代暴露于皮质类固醇，而分别有 170 名（0.2%）、394 名（0.4%）和 184 名（0.2%）的后代暴露于β2-肾上腺素能激动剂。在早孕、中晚期和两个阶段的妊娠中暴露于皮质类固醇与所有 5 个神经发育里程碑均无关联。同样，在早孕期间β2-肾上腺素能激动剂的使用与所有 5 个神经发育里程碑也没有关联。在中晚期妊娠期间β2-肾上腺素能激动剂暴露与个人-社会技能延迟有关（调整后的优势比，1.48；95%CI，1.01-2.32；P=0.045）。
本研究结果发现，无论暴露时间如何，宫内皮质类固醇和β2-肾上腺素能激动剂暴露与后代神经发育结局均无关联。尽管研究存在局限性和低效力，但研究结果表明皮质类固醇和β2-肾上腺素能激动剂对患有哮喘的孕妇及其后代的神经发育是安全的。
