目标:首先,描述胎龄小于胎龄儿(SGA)妊娠合并新生儿发病的胎盘受损的生物标志物的分布,第二,为了检查高可溶性fms样酪氨酸激酶-1(sFLT-1)/胎盘生长因子(PlGF)比率或低PlGF的生长相关新生儿发病率的预测性能,第三,比较高sFLT-1/PlGF比率或低PlGF与SGA竞争风险模型的性能。
方法:这是一项前瞻性观察性研究,对象是英格兰两家妇产医院妊娠36周时常规就诊的妇女。访视包括记录产妇的人口学特征和病史,进行超声扫描并测量血清PlGF和sFLT-1。主要结局是出生体重<第10百分位数或<第3百分位数的SGA新生儿在评估后4周内分娩,妊娠<42周。合并新生儿单元(NNU)入院≥48小时或主要新生儿发病率的复合。任一PlGF在筛查中的检出率<10百分位数,sFLT-1/PlGF比率>第90个百分位数,sFLT-1/PlGF比率>38和SGA的竞争风险模型,使用母体危险因素和EFW的z评分与子宫动脉搏动指数(UtA-PI)的MoM值的组合,估计PlGF和sFLT-1。使用McNemar检验比较不同筛查方法的检出率。
结果:在29,035名妇女的研究人群中,竞争风险模型提供的足月生长相关新生儿发病率预测优于低PlGF浓度或高sFlt-1/PlGF浓度比筛查。例如,SPR为13.1%,根据sFLT-1/PlGF比率>38的定义,使用母体风险因素和EFW的竞争风险模型预测SGA<10百分位数的77.5%(95%CI71.7-83.3)和SGA<3百分位数的89.2%(83.7-94.8),NNU在评估后4周内入院≥48小时;这些显着高于41.0%(39.7-9%)和47.8%(3通过应用sFLT-1/PlGF比率>38(p<0.0001,p<0.0001)实现。具有主要新生儿发病率的SGA各自的值为71.4%(56.5-86.4),90.0%(76.9-100),37.1%(21.1-53.2)和55.0%(33.2-76.8)(p=0.003,p=0.035)。在10.0%的SPR下,由PlGF比率<10百分位数定义,使用母体因素和EFW的竞争风险模型预测,在评估后4周内,NNU入院≥48小时后,SGA<10百分位数的71.5%(65.2-77.8)和SGA<3百分位数的84.3%(77.8-90.8);这些显著高于36.5%(29.8-43.2)和46.3%(37.4-55.2)的值,通过应用PlGF<10个百分位数(p<0.0001,p<0.0001)实现。具有主要新生儿发病率的SGA各自的值为68.5%(53.1-83.9),85.0%(69.4-100),37.1%(21.1-53.2)和55.0%(33.2-76.80)(p=0.003,p=0.021)。
结论:妊娠36周时,SGA竞争风险模型对生长相关新生儿发病率的预测,使用孕产妇危险因素和EFW,优于高sFlt-1/PlGF比率或低PlGF。本文受版权保护。保留所有权利。
First, to describe the distribution of biomarkers of impaired placentation in small-for-gestational-age (
SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt-1/PlGF ratio or low PlGF with that of the competing-risks model for
SGA in predicting growth-related neonatal morbidity.
This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks\' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt-1. The primary outcome was delivery within 4 weeks after assessment and at < 42 weeks\' gestation of a
SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt-1/PlGF ratio > 90th percentile, sFlt-1/PlGF ratio > 38 and the competing-risks model for SGA, using combinations of maternal risk factors and Z-scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt-1, were estimated. The detection rates by the different methods of screening were compared using McNemar\'s test.
In the study population of 29 035 women, prediction of growth-related neonatal morbidity at term provided by the competing-risks model was superior to that of screening by low PlGF concentration or a high sFlt-1/PlGF concentration ratio. For example, at a screen-positive rate (SPR) of 13.1%, as defined by the sFlt-1/PlGF ratio > 38, the competing-risks model using maternal risk factors and EFW predicted 77.5% (95% CI, 71.7-83.3%) of SGA < 10th percentile and 89.3% (95% CI, 83.7-94.8%) of
SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for
SGA with major neonatal morbidity were 71.4% (95% CI, 56.5-86.4%) and 90.0% (95% CI, 76.9-100%). These were significantly higher than the respective values of 41.0% (95% CI, 34.2-47.8%) (P < 0.0001), 48.8% (95% CI, 39.9-57.7%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.035) achieved by the application of the sFlt-1/PlGF ratio > 38. At a SPR of 10.0%, as defined by PlGF < 10th percentile, the competing-risks model using maternal factors and EFW predicted 71.5% (95% CI, 65.2-77.8%) of SGA < 10th percentile and 84.3% (95% CI, 77.8-90.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95% CI, 53.1-83.9%) and 85.0% (95% CI, 69.4-100%). These were significantly higher than the respective values of 36.5% (95% CI, 29.8-43.2%) (P < 0.0001), 46.3% (95% CI, 37.4-55.2%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.021) achieved by the application of PlGF < 10th percentile.
At 36 weeks\' gestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt-1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.