Kamphof H D, Marijnen M C, Damhuis S E, Wolf H, Gordijn S J, Ganzevoort W
Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Obstetrics and Gynecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Ultrasound Obstet Gynecol. 2025 Jul 11. doi: 10.1002/uog.29266.
To evaluate the predictive value of markers of placental insufficiency and fetal growth restriction for a composite adverse perinatal outcome (CAPO) in a small-for-gestational-age (SGA) population. We also aimed to identify profiles that discriminate fetuses as low or high risk for CAPO, and to evaluate the association of onset of labor and mode of birth with CAPO.
This was a preplanned post-hoc analysis of the DRIGITAT study, a Dutch multicenter cohort study of management strategy in 690 singleton SGA pregnancies at 32.0-36.9 weeks' gestation, between 2018 and 2022. We used data from 440 participants with available biomarker measurements, who were not randomized for immediate birth before 36 weeks' gestation on the basis of recurrent abnormal Doppler velocimetry. We defined CAPO as fetal death, adverse condition at birth, major neonatal morbidity and/or neonatal mortality. We analyzed the predictive value for CAPO of maternal body mass index (BMI), gestational age, estimated fetal weight (EFW) and soluble fms-like tyrosine kinase-1 to placental growth factor ratio (sFlt-1/PlGF ratio) at inclusion, development of pre-eclampsia, highest value of the umbilicocerebral ratio (UCR) and fetal growth velocity. We also used these variables to develop a prediction model for CAPO using forward stepwise logistic regression to emulate real-world clinical evaluation.
In this population of 440 singleton SGA pregnancies, maternal BMI at inclusion (P = 0.02), gestational age at inclusion (P ≤ 0.001), EFW at inclusion (P ≤ 0.001), sFlt-1/PlGF ratio at inclusion (P ≤ 0.001), development of pre-eclampsia (P ≤ 0.001), highest value of the UCR measured at any time during pregnancy (P ≤ 0.001) and fetal growth velocity (P ≤ 0.001) were all associated significantly with CAPO. When combined into a prediction model using logistic regression analysis, maternal BMI at inclusion, gestational age at inclusion, development of pre-eclampsia and fetal growth velocity did not add to the predictive value of the model, because of their correlation with other variables. The area under the receiver-operating-characteristics curve of the final prediction model, comprising EFW at inclusion, sFlt-1/PlGF ratio at inclusion and the highest UCR value at any time, was 0.75 (95% CI, 0.70-0.81). At false-positive rates of 5%, 10% and 25%, the sensitivities of the prediction model for CAPO were 35.6%, 44.2% and 63.5%, respectively. The median gestational age at birth and birth weight were lower in neonates that experienced CAPO compared with those that did not (37.0 weeks vs 38.3 weeks and 1.993 kg vs 2.518 kg, respectively). Vaginal birth occurred in 69.3% of our population. In the group that experienced CAPO, a higher number of (emergency) Cesarean sections were performed.
In a SGA population, maternal BMI, gestational age, EFW and sFlt-1/PlGF ratio at inclusion, highest UCR at any time, development of pre-eclampsia and fetal growth velocity were associated with CAPO. A model incorporating EFW at inclusion, sFlt-1/PlGF ratio at inclusion and highest UCR was most effective for the prediction of CAPO. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
评估胎盘功能不全和胎儿生长受限标志物对小于胎龄（SGA）人群围产期复合不良结局（CAPO）的预测价值。我们还旨在确定区分胎儿CAPO低风险或高风险的特征，并评估分娩发作和分娩方式与CAPO的关联。
这是对DRIGITAT研究的一项预先计划的事后分析，DRIGITAT研究是一项荷兰多中心队列研究，研究了2018年至2022年期间690例妊娠32.0 - 36.9周的单胎SGA妊娠的管理策略。我们使用了440名有可用生物标志物测量数据的参与者的数据，这些参与者未因反复异常多普勒血流速度在妊娠36周前被随机立即分娩。我们将CAPO定义为胎儿死亡、出生时不良状况、主要新生儿发病率和/或新生儿死亡率。我们分析了纳入时孕妇体重指数（BMI）、孕周、估计胎儿体重（EFW）和可溶性fms样酪氨酸激酶-1与胎盘生长因子比值（sFlt-1/PlGF比值）、子痫前期的发生、脐脑比值（UCR）的最高值和胎儿生长速度对CAPO的预测价值。我们还使用这些变量通过向前逐步逻辑回归开发了一个CAPO预测模型，以模拟现实世界的临床评估。
在这440例单胎SGA妊娠人群中，纳入时的孕妇BMI（P = 0.02）、纳入时的孕周（P≤0.001）、纳入时的EFW（P≤0.001）、纳入时的sFlt-1/PlGF比值（P≤0.001）、子痫前期的发生（P≤0.001）、妊娠期间任何时间测量的UCR最高值（P≤0.001）和胎儿生长速度（P≤0.001）均与CAPO显著相关。当使用逻辑回归分析将它们组合成一个预测模型时，纳入时的孕妇BMI、纳入时的孕周、子痫前期的发生和胎儿生长速度由于与其他变量的相关性，并未增加模型的预测价值。最终预测模型的受试者工作特征曲线下面积，包括纳入时的EFW、纳入时的sFlt-1/PlGF比值和任何时间的UCR最高值，为0.75（95%CI，0.70 - 0.81）。在假阳性率为5%、10%和25%时，CAPO预测模型的敏感性分别为35.6%、44.2%和63.5%。与未发生CAPO的新生儿相比，发生CAPO的新生儿出生时的孕周中位数和出生体重更低（分别为37.0周对38.3周和1.
