Fetal Medicine Research Institute, King's College Hospital, London, UK.
Fetal Medicine Unit, Medway Maritime Hospital, Gillingham, UK; Institute of Medical Sciences, Canterbury Christ Church University, Chatham, UK.
Am J Obstet Gynecol. 2019 May;220(5):486.e1-486.e11. doi: 10.1016/j.ajog.2019.01.227. Epub 2019 Jan 29.
Small for gestational age (SGA) neonates are at increased risk for perinatal mortality and morbidity; however, the risks can be substantially reduced if the condition is identified prenatally, because in such cases close monitoring and appropriate timing of delivery and prompt neonatal care can be undertaken. The traditional approach of identifying pregnancies with SGA fetuses is maternal abdominal palpation and serial measurements of symphysial-fundal height, but the detection rate of this approach is less than 30%. A higher performance of screening for SGA is achieved by sonographic fetal biometry during the third trimester; screening at 30-34 weeks' gestation identifies about 80% of SGA neonates delivering preterm but only 50% of those delivering at term, at a screen-positive rate of 10%. There is some evidence that routine ultrasound examination at 36 weeks' gestation is more effective than that at 32 weeks in predicting birth of SGA neonates.
To investigate the potential value of maternal characteristics and medical history, sonographically estimated fetal weight (EFW) and biomarkers of impaired placentation at 35- 36 weeks' gestation in the prediction of delivery of SGA neonates.
A dataset of 19,209 singleton pregnancies undergoing screening at 35-36 weeks' gestation was divided into a training set and a validation set. The training dataset was used to develop models from multivariable logistic regression analysis to determine whether the addition of uterine artery pulsatility index (UtA-PI), umbilical artery PI (UA-PI), fetal middle cerebral artery PI (MCA-PI), maternal serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT) would improve the performance of maternal factors and EFW in the prediction of delivery of SGA neonates. The models were then tested in the validation dataset to assess performance of screening.
First, in the training dataset, in the SGA group, compared to those with birthweight in ≥10th percentile, the median multiple of the median (MoM) values of PlGF and MCA-PI were reduced, whereas UtA-PI, UA-PI, and sFLT were increased. Second, multivariable regression analysis demonstrated that in the prediction of SGA in <10th percentile there were significant contributions from maternal factors, EFW Z-score, UtA-PI MoM, MCA-PI MoM, and PlGF MoM. Third, in the validation dataset, prediction of 90% of SGA neonates delivering within 2 weeks of assessment was achieved by a screen-positive rate of 67% (95% confidence interval [CI], 64-70%) in screening by maternal factors, 23% (95% CI, 20-26%) by maternal factors, and EFW and 21% (95% CI, 19-24%) by the addition of biomarkers. Fourth, prediction of 90% of SGA neonates delivering at any stage after assessment was achieved by a screen-positive rate of 66% (95% CI, 65-67%) in screening by maternal factors, 32% (95% CI, 31-33%) by maternal factors and EFW and 30% (95% CI, 29-31%) by the addition of biomarkers.
The addition of biomarkers of impaired placentation only marginally improves the predictive performance for delivery of SGA neonates achieved by maternal factors and fetal biometry at 35-36 weeks' gestation.
小于胎龄儿(SGA)新生儿围产期死亡率和发病率较高;然而,如果在产前识别出这种情况,风险可以大大降低,因为在这种情况下,可以进行密切监测,并适时分娩和及时新生儿护理。传统的识别 SGA 胎儿的方法是通过腹部触诊和耻骨联合上子宫底高度的连续测量,但这种方法的检测率不到 30%。通过在妊娠晚期进行超声胎儿生物测量,筛查 SGA 的性能更高;在 30-34 周的妊娠时筛查,可识别出约 80%的早产 SGA 新生儿,但只能识别出 50%的足月 SGA 新生儿,筛查阳性率为 10%。有证据表明,在 36 周时进行常规超声检查比在 32 周时更能有效预测 SGA 新生儿的分娩。
研究母亲特征和病史、超声估计胎儿体重(EFW)和胎盘功能障碍的生物标志物在预测 35-36 周妊娠 SGA 新生儿分娩中的潜在价值。
对 19209 例接受 35-36 周筛查的单胎妊娠患者的数据集进行了分析,分为训练集和验证集。在训练数据集中,使用多变量逻辑回归分析来确定是否可以通过添加子宫动脉搏动指数(UtA-PI)、脐动脉 PI(UA-PI)、胎儿大脑中动脉 PI(MCA-PI)、母体血清胎盘生长因子(PlGF)和可溶性 fms 样酪氨酸激酶-1(sFLT)来提高母亲因素和 EFW 在预测 SGA 新生儿分娩中的表现。然后在验证数据集中对这些模型进行测试,以评估筛查的性能。
首先,在训练数据集中,与出生体重在第 10 百分位数以上的组相比,PlGF 和 MCA-PI 的中位数倍数(MoM)值在 SGA 组中降低,而 UtA-PI、UA-PI 和 sFLT 增加。其次,多变量回归分析表明,在预测<第 10 百分位数的 SGA 时,母亲因素、EFW Z 分数、UtA-PI MoM、MCA-PI MoM 和 PlGF MoM 对 SGA 的预测有显著贡献。第三,在验证数据集中,通过母亲因素的筛查阳性率为 67%(95%置信区间[CI],64-70%),通过母亲因素和 EFW 的筛查阳性率为 23%(95% CI,20-26%),通过添加生物标志物的筛查阳性率为 21%(95% CI,19-24%),可实现 90%的 SGA 新生儿在 2 周内分娩的预测。第四,通过母亲因素的筛查阳性率为 66%(95% CI,65-67%),通过母亲因素和 EFW 的筛查阳性率为 32%(95% CI,31-33%),通过添加生物标志物的筛查阳性率为 30%(95% CI,29-31%),可实现 90%的 SGA 新生儿在评估后任何阶段分娩的预测。
在 35-36 周时,通过母亲因素和胎儿生物测量对 SGA 新生儿分娩的预测性能,添加胎盘功能障碍的生物标志物仅略有改善。