目的:子宫肌瘤是单克隆肿瘤,它们通常是遗传异常的,并且与假阳性全基因组无细胞DNA(cfDNA)筛查结果有关,尤其是大的时候。子宫肌瘤也可能通过影响胎儿分数或由于其遗传异常混淆cfDNA算法而增加cfDNA衰竭的风险。我们的目的是调查肌瘤和cfDNA非信息结果之间的可能关联。
方法:这是一项回顾性队列研究,对2013年至2020年期间接受cfDNA筛查胎儿染色体异常的妇女进行了研究,比较了妊娠24周前任何产科超声记录的子宫肌瘤与无子宫肌瘤的妊娠情况。单变量和多变量logistic回归模型用于研究肌瘤和cfDNA失败之间的关联。调整胎龄,产妇年龄,采血时的体重和身高,观念模式,多个妊娠和测试平台(染色体选择性或全基因组)。根据肌瘤数量和总肌瘤体积进行分层分析。使用线性回归评估子宫肌瘤对胎儿分数的影响,调整相同的协变量。
结果:在19818例接受cfDNA筛查的孕妇中,在2038年(10.28%)报告了肌瘤,在228例(1.15%)怀孕中首次尝试筛查时出现了cfDNA失败。无信息的结果发生在子宫肌瘤妊娠的1.96%和无子宫肌瘤妊娠的1.06%(调整后的比值比(aOR),2.40(95%CI,1.65-3.48))。第一次筛查尝试失败的风险随着肌瘤数量的增加而逐渐增加(aOR,患有四个或更多肌瘤的女性的5.05(95%CI,2.29-11.13)和总肌瘤体积,在子宫肌瘤体积为100.1-400毫升的女性中,风险增加超过5倍和14倍(aOR,5.52(95%CI,2.30-13.25))和>400mL(aOR,14.80(95%CI,4.50-48.69)),分别。尽管染色体选择性筛查比全基因组筛查更常见测试失败,肌瘤同样增加了两种筛查平台失败的风险。与没有子宫肌瘤的怀孕相比,子宫肌瘤患者的胎儿分数平均低0.61%(调整后的平均差,-0.61%(95%CI,-0.77%至-0.45%))。
结论:子宫肌瘤与胎儿分数降低和cfDNA筛查失败的风险增加相关。这种关联的强度随着肌瘤数量和体积的增加而增加。©2024作者(S)。由JohnWiley&SonsLtd代表国际妇产科超声学会出版的妇产科超声。
OBJECTIVE: Uterine fibroids are monoclonal tumors, which are often genetically abnormal and associated with false-positive genome-wide cell-free DNA (cfDNA) screening results, particularly when large. It is plausible that fibroids may also increase the risk of cfDNA failure by affecting fetal fraction or due to their genetic anomalies confounding cfDNA algorithms. We aimed to investigate a possible association between fibroids and cfDNA non-informative results.
METHODS: This was a retrospective cohort study of women undergoing cfDNA screening for fetal chromosomal abnormalities between 2013 and 2020, comparing pregnancies with vs without uterine fibroids recorded on any obstetric ultrasound before 24 weeks\' gestation. Univariable and multivariable logistic regression models were used to investigate the association between fibroids and cfDNA failure, adjusting for gestational age, maternal age, weight and height at blood sampling, mode of conception, multiple gestation and test platform (chromosome-selective or genome-wide). Analyses were stratified according to the number of fibroids and total fibroid volume. The impact of fibroids on fetal fraction was assessed using linear regression, adjusting for the same covariates.
RESULTS: Among 19 818 pregnancies undergoing cfDNA screening, fibroids were reported in 2038 (10.28%) and cfDNA failure at the first screening attempt occurred in 228 (1.15%) pregnancies. Non-informative results occurred in 1.96% of pregnancies with fibroids and 1.06% of pregnancies without fibroids (adjusted odds ratio (aOR), 2.40 (95% CI, 1.65-3.48)). The risk of failure in the first screening attempt increased progressively with the number of fibroids (aOR, 5.05 (95% CI, 2.29-11.13) in women with four or more fibroids) and total fibroid volume, with greater than a 5-fold and 14-fold increase in risk among women with fibroid volumes of 100.1-400 mL (aOR, 5.52 (95% CI, 2.30-13.25)) and > 400 mL (aOR, 14.80 (95% CI, 4.50-48.69)), respectively. Although test failure was more common with chromosome-selective than genome-wide screening, fibroids similarly increased the risk of failure of both screening platforms. Compared to pregnancies without fibroids, those with fibroids had a fetal fraction on average 0.61% lower (adjusted mean difference, -0.61% (95% CI, -0.77% to -0.45%)).
CONCLUSIONS: Uterine fibroids are associated with lower fetal fraction and an increased risk of cfDNA screening failure. The strength of this association increases with increasing fibroid number and volume. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.