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基于机器学习的利用早孕期母体特征和生物标志物预测子痫前期。

Machine-learning-based prediction of pre-eclampsia using first-trimester maternal characteristics and biomarkers.

机构信息

Department of Mathematics, Bar Ilan University, Ramat Gan, Israel.

Fetal Medicine Research Institute, King's College Hospital, London, UK.

出版信息

Ultrasound Obstet Gynecol. 2022 Dec;60(6):739-745. doi: 10.1002/uog.26105.

DOI:10.1002/uog.26105
PMID:36454636
Abstract

OBJECTIVE

To evaluate the accuracy of predicting the risk of developing pre-eclampsia (PE) according to first-trimester maternal demographic characteristics, medical history and biomarkers using artificial-intelligence and machine-learning methods.

METHODS

The data were derived from prospective non-interventional screening for PE at 11-13 weeks' gestation at two maternity hospitals in the UK. The data were divided into three subsets. The first set, including 30 437 subjects, was used to develop the training process, the second set of 10 000 subjects was utilized to optimize the machine-learning hyperparameters and the third set of 20 352 subjects was coded and used for model validation. An artificial neural network was used to predict from the demographic characteristics and medical history the prior risk that was then combined with biomarker values to determine the risk of PE and preterm PE with delivery at < 37 weeks' gestation. An additional network was trained without including race as input. Biomarkers included uterine artery pulsatility index (UtA-PI), mean arterial blood pressure (MAP), placental growth factor (PlGF) and pregnancy-associated plasma protein-A. All markers were entered using raw values without conversion into standardized multiples of the median. The prediction accuracy was estimated using the area under the receiver-operating-characteristics curve (AUC). We further computed the detection rate at 10%, 20% and 40% false-positive rates (FPR). The impact of taking aspirin was also added. Shapley values were calculated to evaluate the contribution of each parameter to the prediction of risk. We used a non-parametric test to compare the expected AUC with the one obtained when we randomly scrambled the labels and kept the predictions. For the general prediction, we performed 10 000 permutations of the labels. When the AUC was higher than the one obtained in all 10 000 permutations, we reported a P-value of < 0.0001. For the race-specific analysis, we performed 1000 permutations. When the AUC was higher than the AUC in permutations, we reported a P-value of < 0.001.

RESULTS

The detection rate for preterm PE vs no PE, at a 10% FPR, was 53.3% when screening by maternal factors only, and the corresponding AUC was 0.816; these increased to 75.3% and 0.909, respectively, with the addition of biomarkers into the model. Information on race was important for the prediction accuracy; when race was not used to train the model, at a 10% FPR, the detection rate of preterm PE vs no PE decreased to 34.5-45.5% (for different races) when screening by maternal factors only and to 55.0-62.1% when biomarkers were added. The major predictors of PE were high MAP and UtA-PI, and low PlGF. The accuracy of prediction of all PE cases was lower than that for preterm PE. Aspirin use was recommended for cases who were at high risk of preterm PE. The AUC of all PE vs no PE was 0.770 when screening by maternal factors and 0.817 when the biomarkers were added; the respective detection rates, at a 10% FPR, were 41.3% and 52.9%.

CONCLUSIONS

Screening for PE using a non-linear machine-learning-based approach does not require a population-based normalization, and its performance is similar to that of logistic regression. Removing race information from the model reduces its prediction accuracy, especially for the non-white populations when only maternal factors are considered. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

摘要

目的

利用人工智能和机器学习方法,评估基于初产妇人口统计学特征、病史和生物标志物预测子痫前期(PE)风险的准确性。

方法

本研究的数据来源于英国两家产科医院在 11-13 孕周进行的前瞻性非干预性 PE 筛查。数据分为三组。第一组包括 30437 例受试者,用于开发训练过程;第二组 10000 例受试者用于优化机器学习超参数;第三组 20352 例受试者被编码并用于模型验证。使用人工神经网络根据人口统计学特征和病史预测既往风险,然后将该风险与生物标志物值结合,以确定 PE 和早产(<37 孕周)PE 的风险。另一个网络在训练时不包括种族作为输入。生物标志物包括子宫动脉搏动指数(UtA-PI)、平均动脉压(MAP)、胎盘生长因子(PlGF)和妊娠相关血浆蛋白-A。所有标志物均使用原始值输入,未经标准化中位数转换。使用受试者工作特征曲线下面积(AUC)估计预测准确性。我们进一步计算了在 10%、20%和 40%假阳性率(FPR)时的检出率。还添加了阿司匹林的影响。Shapley 值用于评估每个参数对风险预测的贡献。我们使用非参数检验来比较期望 AUC 与随机打乱标签并保留预测时获得的 AUC。对于一般预测,我们对标签进行了 10000 次随机排列。当 AUC 高于所有 10000 次随机排列时,我们报告 P<0.0001。对于种族特异性分析,我们进行了 1000 次随机排列。当 AUC 高于排列中的 AUC 时,我们报告 P<0.001。

结果

在 10%的 FPR 下,仅通过母体因素筛查时,早产 PE 的检出率为 53.3%,相应的 AUC 为 0.816;当将生物标志物纳入模型时,检出率分别提高至 75.3%和 0.909。种族信息对预测准确性很重要;当不使用种族信息来训练模型时,仅通过母体因素筛查时,早产 PE 的检出率在不同种族中下降至 34.5%-45.5%,当加入生物标志物时下降至 55.0%-62.1%。PE 的主要预测因素是高 MAP 和 UtA-PI,以及低 PlGF。所有 PE 病例的预测准确性均低于早产 PE。对于有早产 PE 高危的病例,推荐使用阿司匹林。仅通过母体因素筛查时,所有 PE 病例与无 PE 的 AUC 为 0.770,加入生物标志物后为 0.817;在 10%的 FPR 时,相应的检出率分别为 41.3%和 52.9%。

结论

利用基于非线性机器学习的方法筛查 PE 不需要基于人群的归一化,其性能与逻辑回归相似。从模型中删除种族信息会降低其预测准确性,尤其是在仅考虑母体因素时,对于非白人种族。© 2022 年国际妇产科超声学会。

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