ImportanceUptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking.ObjectiveTo determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age.Design, Setting, and ParticipantsThis prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely.ExposureIn utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed.Main Outcomes and MeasuresNeurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay.ResultsA total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks’ gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07).Conclusions and RelevanceResults of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.

中文翻译：

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子宫内接种孕产妇 COVID-19 疫苗和后代 12 个月和 18 个月时的神经发育

重要性 由于对未出生婴儿潜在风险的安全担忧，孕妇接种 COVID-19 疫苗受到阻碍。缺乏阐明在子宫内接种 COVID-19 疫苗的后代早期神经发育结果的数据。 目的确定在子宫内接种孕产妇 COVID-19 疫苗是否与年龄和阶段问卷第三版 (ASQ-3) 得分差异相关，年龄为 12 个月和 18 个月。设计、设置和参与者这项前瞻性队列研究，评估冠状病毒大流行期间怀孕的安全性 (ASPIRE)，招募了 2020 年 5 月至 2021 年 8 月期间的怀孕参与者；对这些怀孕的孩子的后续行动正在进行中。参与者（包括来自全美 50 个州的孕妇及其后代）在网上自行注册。研究活动是远程进行的。暴露将怀孕期间胎儿在子宫内接受母亲 COVID-19 疫苗接种的情况与未暴露的情况进行比较。主要结果和测量经过验证的 ASQ-3 的神经发育评分，由出生母亲在 12 个月和 18 个月时完成。5 个子领域（沟通、粗大运动、精细运动、解决问题、社交技能）中任何一个的分数低于既定界限，构成发育迟缓的异常筛查。结果总共 2487 名怀孕个体（平均 [SD] 年龄，33.3 [4.2] ] 年）在怀孕不到 10 周时入组并完成研究活动，分别对 2261 名和 1940 名 12 个月和 18 个月的婴儿进行了神经发育评估。在粗略分析中，1541 名暴露婴儿中的 471 名（30.6%）在 12 个月时筛查出发育迟缓异常，而 720 名未暴露婴儿中则有 203 名（28.2%；χ22= 1.32；磷= .25); 18 个月时的相应患病率分别为 1301 例中的 262 例 (20.1%) 和 639 例中的 148 例 (23.2%) (χ2= 2.35;磷=.13）。在调整母亲年龄、种族、民族、教育、收入、母亲抑郁和焦虑的多变量混合效应逻辑回归模型中，在任一时间点（12 个月：调整后的风险比）均未观察到异常 ASQ-3 筛查的风险存在差异。 [aRR]，1.14；95% CI，0.97-1.33；18 个月：aRR，0.88；95% CI，0.72-1.07)。对早产和婴儿性别的进一步调整不会影响结果（12个月：aRR，1.16；95% CI，0.98-1.36；18个月：aRR，0.87；95% CI，0.71-1.07）。结论和相关性该队列的结果研究表明，从婴儿神经发育到 18 个月大的角度来看，怀孕期间接种 COVID-19 疫苗是安全的。应进行更多的长期研究来证实这些发现，并以强有力的证据基础支持临床指导。