Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Obstetrics and Gynecology, Amsterdam Reproduction & Development Research Institute, de Boelelaan 1117, 1007 MB Amsterdam, Netherlands.
Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynecology, Amsterdam Reproduction & Development Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
Eur J Obstet Gynecol Reprod Biol. 2021 Dec;267:213-220. doi: 10.1016/j.ejogrb.2021.11.010. Epub 2021 Nov 11.
To evaluate the long-term effects of antenatal aspirin exposure on child health and neurodevelopmental outcome beyond the perinatal period.
PubMed, Embase.com, the Cochrane Library and Web of Science were systematically searched from inception through 5 November 2020. We performed a cited-reference search and ClinicalTrials.gov was searched on 20 October 2020 to identify trial results that were not reported elsewhere. We included randomized controlled trials reporting on health-related outcomes in children (aged > 28 days) exposed to aspirin versus placebo or no treatment during pregnancy. Studies with any dose or duration of aspirin use were included. We excluded studies evaluating other antiplatelet agents or non-steroidal inflammatory drugs. Two authors independently performed study selection, data extraction and quality assessment. Quality assessment was performed using the Cochrane RoB2 tool for the original randomized controlled trials and the QUIPS for the follow-up studies. Results are presented as relative risks (RR) with 95% confidence intervals (95%CI).
The search yielded 6,907 unique records. Two studies were included, containing 4,168 children at age 12 months and 5,153 children at 18 months. Children were exposed to aspirin 50-60 mg versus placebo or no treatment. At 12 months, post-neonatal mortality was lower after allocation to aspirin (0.2% versus 0.5%; RR 0.28, 95%CI 0.08-0.99) in a single study. At 18 months, fewer children were found to have (gross and fine) motor problems (RR 0.49, 95%CI 0.26-0.91) after antenatal aspirin exposure in one study. No differences were found in mortality rate; the proportion of children with a short stature or low weight; or respiratory, hearing or visual problems at 18 months. Both included studies had a high risk of bias.
The two included studies showed evidence of potential benefit of antenatal low-dose aspirin on mortality and neurodevelopment up to the age of 18 months. Our findings support the current application of low-dose aspirin in pregnant women at risk for preeclampsia and fetal growth restriction. However, further follow-up research of children who were exposed to low-dose aspirin during pregnancy is of utmost importance to exclude potential long-term harm.
评估产前阿司匹林暴露对围产期后儿童健康和神经发育结局的长期影响。
系统检索了 PubMed、Embase.com、Cochrane 图书馆和 Web of Science，检索时间从建库至 2020 年 11 月 5 日。我们进行了参考文献追溯检索，并于 2020 年 10 月 20 日检索了 ClinicalTrials.gov，以确定未在其他地方报告的试验结果。我们纳入了报道在怀孕期间接受阿司匹林与安慰剂或未治疗的儿童（>28 天龄）的健康相关结局的随机对照试验。纳入了任何剂量或持续时间使用阿司匹林的研究。我们排除了评估其他抗血小板药物或非甾体类抗炎药的研究。两名作者独立进行了研究选择、数据提取和质量评估。使用 Cochrane RoB2 工具评估原始随机对照试验的质量，使用 QUIPS 评估随访研究的质量。结果表示为相对风险（RR）及其 95%置信区间（95%CI）。
检索得到 6907 条独特记录。纳入了两项研究，共包含 4168 名 12 月龄儿童和 5153 名 18 月龄儿童。儿童接受 50-60mg 阿司匹林与安慰剂或未治疗。在一项研究中，在新生儿期后，分配至阿司匹林组的死亡率较低（0.2% vs 0.5%；RR 0.28，95%CI 0.08-0.99）。在一项研究中，在接受产前阿司匹林暴露后，18 月龄时较少儿童出现（粗大和精细）运动问题（RR 0.49，95%CI 0.26-0.91）。在 18 月龄时，两组的死亡率、身材矮小或体重不足的儿童比例，或呼吸、听力或视力问题的比例均无差异。纳入的两项研究均存在高偏倚风险。
两项纳入研究表明，产前低剂量阿司匹林可能对 18 月龄内的死亡率和神经发育有潜在益处。我们的研究结果支持目前对有子痫前期和胎儿生长受限风险的孕妇应用低剂量阿司匹林。但是，进一步对接受产前低剂量阿司匹林暴露的儿童进行随访研究非常重要，以排除潜在的长期危害。
