Becking Ellis C, Bekker Mireille N, Henrichs Jens, Bax Caroline J, Sistermans Erik A, Henneman Lidewij, Scheffer Peter G, Schuit Ewoud
Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Midwifery Science, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands.
BJOG. 2025 Feb;132(3):318-325. doi: 10.1111/1471-0528.17978. Epub 2024 Oct 2.
To assess the added value of fetal fraction of cell-free DNA in the maternal circulation in the prediction of adverse pregnancy outcomes.
Retrospective cohort study.
Nationwide implementation study on non-invasive prenatal testing (NIPT; TRIDENT-2 study).
Pregnant women in the Netherlands opting for NIPT between June 2018 and June 2019.
Two 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.
Likelihood ratio test (LRT), area under the curve (AUC) and Integrated Discrimination Improvement (IDI) index.
The 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).
Fetal fraction has statistically significant but limited prognostic value in the prediction of adverse pregnancy outcomes in addition to known prognostic clinical parameters.
评估母体循环中游离DNA的胎儿分数在预测不良妊娠结局方面的附加价值。
回顾性队列研究。
全国范围内的非侵入性产前检测实施研究（NIPT；TRIDENT-2研究）。
2018年6月至2019年6月在荷兰选择进行NIPT的孕妇。
针对每种不良妊娠结局构建两个逻辑回归预测模型。第一个模型（基础模型）包括从现有的孕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）在基础模型所包含的预后临床参数之上，将胎儿分数作为一个预测因子。通过比较基础模型和胎儿分数模型在拟合优度和预测性能方面的表现，评估胎儿分数的附加预后价值。
似然比检验（LRT）、曲线下面积（AUC）和综合判别改善（IDI）指数。
研究队列包括56110例妊娠。不良妊娠结局的发生率分别为：妊娠高血压疾病（HDP；n = 3207）5.7%，出生体重<第10百分位数（n = 5726）10.2%，出生体重<第2.3百分位数（n = 1796）3.2%，自发性早产（sPTB；n = 1891）3.4%，糖尿病（n = 1902）3.4%，先天性异常（n = 741）1.3%。在基础模型中加入胎儿分数可改善HDP、出生体重<第10百分位数、出生体重<第2.3百分位数、所有sPTB和糖尿病的模型拟合，但对先天性异常无改善（LRT p < 0.05）。对于HDP，在基础模型中加入胎儿分数后，AUC从0.67提高到0.68（p = 0.14），IDI为0.0018（p < 0.0001）。对于出生体重<第10百分位数，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<第2.3百分位数，AUC从0.67提高到0.69（p < 0.0001），IDI为0.0011（p < 0.0001）。对于所有sPTB，两个模型的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 照0.72，p = 0.35），IDI为0.00055（p = 0.00015）。
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上显著但有限的预后价值。
