ObjectiveTo assess the added value of fetal fraction of cell‐free DNA in the maternal circulation in the prediction of adverse pregnancy outcomes.DesignRetrospective cohort study.SettingNationwide implementation study on non‐invasive prenatal testing (NIPT; TRIDENT‐2 study).PopulationPregnant women in the Netherlands opting for NIPT between June 2018 and June 2019.MethodsTwo logistic regression prediction models were constructed for each adverse pregnancy outcome. The first model (base model) included prognostic clinical parameters that were selected from existing first‐trimester prediction models for adverse pregnancy outcomes. The second model (fetal fraction model) included fetal fraction as a predictor on top of the prognostic clinical parameters included in the base model. The added prognostic value of fetal fraction was assessed by comparing the base and fetal fraction models in terms of goodness of fit and predictive performance.Main Outcome MeasuresLikelihood ratio test (LRT), area under the curve (AUC) and Integrated Discrimination Improvement (IDI) index.ResultsThe study cohort consisted of 56 110 pregnancies. The incidence of adverse pregnancy outcomes was 5.7% for hypertensive disorders of pregnancy (HDP; n = 3207), 10.2% for birthweight < p10 (n = 5726), 3.2% for birthweight < p2.3 (n = 1796), 3.4% for spontaneous preterm birth (sPTB; n = 1891), 3.4% for diabetes (n = 1902) and 1.3% for congenital anomalies (n = 741). Adding fetal fraction to the base model improved model fit for HDP, birthweight < p10, birthweight < p2.3, all sPTB, and diabetes, but not for congenital anomalies (LRT p < 0.05). For HDP, the AUC improved from 0.67 to 0.68 by adding fetal fraction to the base model (p = 0.14) with an IDI of 0.0018 (p < 0.0001). For birthweight < p10, the AUC improved from 0.65 to 0.66 (p < 0.0001) with an IDI of 0.0023 (p < 0.0001). For birthweight < p2.3, the AUC improved from 0.67 to 0.69 (p < 0.0001) with an IDI of 0.0011 (p < 0.0001). For all sPTB, the AUC was similar for both models (AUC 0.63, p = 0.021) with an IDI of 0.00028 (p = 0.0023). For diabetes, the AUC was similar (AUC 0.72, p = 0.35) with an IDI of 0.00055 (p = 0.00015).ConclusionsFetal fraction has statistically significant but limited prognostic value in the prediction of adverse pregnancy outcomes in addition to known prognostic clinical parameters.

中文翻译：

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胎儿游离 DNA 分数在不良妊娠结局预测中的作用：一项全国范围的回顾性队列研究


目的评估母体循环中胎儿游离DNA分数在预测不良妊娠结局中的附加价值。设计回顾性队列研究。设置全国范围内实施无创产前检测研究（NIPT；TRIDENT-2研究）。人群孕妇荷兰在 2018 年 6 月至 2019 年 6 月期间选择进行 NIPT。方法针对每种不良妊娠结局构建了两个逻辑回归预测模型。第一个模型（基础模型）包括从现有的妊娠早期不良妊娠结局预测模型中选择的预后临床参数。第二个模型（胎儿分数模型）包括胎儿分数作为基本模型中包含的预后临床参数之上的预测因子。通过比较基础模型和胎儿分数模型的拟合优度和预测性能，评估胎儿分数的附加预后价值。主要结果指标似然比检验 (LRT)、曲线下面积 (AUC) 和综合判别改进 (IDI)结果 该研究队列由 56 110 名孕妇组成。妊娠期高血压疾病 (HDP；n = 3207) 的不良妊娠结局发生率为 5.7%，出生体重 < p10 的不良妊娠结局发生率为 10.2% (n = 5726)，出生体重 < p2.3 的不良妊娠结局发生率为 3.2% (n = 1796)，自发性早产 (sPTB；n = 1891) 为 3.4%，糖尿病 (n = 1902) 为 3.4%，先天性异常 (n = 741) 为 1.3%。在基础模型中添加胎儿分数改进了模型对 HDP、出生体重 < p10、出生体重 < p2.3、所有 sPTB 和糖尿病的拟合，但不适用于先天性异常 (LRT p < 0.05)。对于 HDP，通过将胎儿分数添加到基础模型中 (p = 0.14)，AUC 从 0.67 提高到 0.68，IDI 为 0.0018 (p < 0.0001)。 对于出生体重 < p10，AUC 从 0.65 提高到 0.66 (p < 0.0001)，IDI 为 0.0023 (p < 0.0001)。对于出生体重 < p2.3，AUC 从 0.67 提高到 0.69 (p < 0.0001)，IDI 为 0.0011 (p < 0.0001)。对于所有 sPTB，两种模型的 AUC 相似（AUC 0.63，p = 0.021），IDI 为 0.00028（p = 0.0023）。对于糖尿病，AUC 相似（AUC 0.72，p = 0.35），IDI 为 0.00055（p = 0.00015）。 结论 除已知的预后临床参数外，胎儿分数在预测不良妊娠结局方面具有统计学显着性但预后价值有限。