血管生成因子与胎儿-母体多普勒超声管理足月胎儿生长受限（GRAFD）试验以避免围产期不良结局：一项多中心、开放标签、随机对照试验的方案
The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.
作者信息
Garcia-Manau Pablo, Mendoza Manel, Bonacina Erika, Martin-Alonso Raquel, Martin Lourdes, Palacios Ana, Sanchez Maria Luisa, Lesmes Cristina, Hurtado Ivan, Perez Esther, Tubau Albert, Ibañez Patricia, Alcoz Marina, Valiño Nuria, Moreno Elena, Borrero Carlota, Garcia Esperanza, Lopez-Quesada Eva, Diaz Sonia, Broullon Jose Roman, Teixidor Mireia, Chulilla Carolina, Gil Maria M, Lopez Monica, Candela-Hidalgo Amparo, Salinas-Amoros Andrea, Moreno Anna, Morra Francesca, Vaquerizo Oscar, Soriano Beatriz, Fabre Marta, Gomez-Valencia Elena, Cuiña Ana, Alayon Nicolas, Sainz Jose Antonio, Vives Angels, Esteve Esther, Ocaña Vanesa, López Miguel Ángel, Maroto Anna, Carreras Elena
机构信息
Maternal Fetal Medicine Unit, Department of Obstetrics, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.
Maternal Fetal Medicine Unit, Department of Obstetrics, Hospital Universitario de Torrejón, Madrid, Spain.
出版信息
JMIR Res Protoc. 2022 Oct 11;11(10):e37452. doi: 10.2196/37452.
BACKGROUND
Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term.
OBJECTIVE
The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes.
METHODS
This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs.
RESULTS
Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023.
CONCLUSIONS
The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37452.
背景
胎儿生长受限影响10%的妊娠。小胎儿出现不良结局的风险更高。使用估计胎儿体重和胎儿-母体多普勒超声对其进行管理，对不良结局具有较高的敏感性；然而，超过60%的胎儿在37至38周时被选择性分娩。另一方面，使用血管生成因子进行分类似乎假阳性率较低。在此，我们介绍一项血管生成因子与胎儿-母体多普勒超声管理足月胎儿生长受限（GRAFD）试验的方案，该试验比较使用血管生成因子和多普勒超声对足月小胎儿进行管理的效果。
目的
主要目的是证明基于血管生成因子的分类在检测有围产期不良结局风险的胎儿方面不劣于估计胎儿体重和多普勒超声。
方法
这是一项在西班牙20家医院进行的多中心、开放标签、随机对照试验。共招募1030例单胎妊娠，这些妊娠在孕36⁺⁰至37⁺⁶周⁺天时估计胎儿体重≤第10百分位数，并随机分配至对照组或干预组。对照组采用基于标准多普勒超声的管理方法。干预组中，可溶性fms样酪氨酸激酶与胎盘生长因子比值≥38的病例将被分类为胎儿生长受限；否则，将被分类为小于胎龄儿。在两组中，胎儿生长受限组将在≥37周时分娩，小于胎龄儿组将在≥40周时分娩。我们将通过计算相对风险、发病率之间的绝对差异及其95%置信区间来评估两组之间的差异。
结果
本研究于2020年9月28日开始招募。研究结果预计将于2023年初在同行评审期刊上发表，并在国际会议上公布。
结论
基于血管生成因子的方案可能会减少被分类为胎儿生长受限的妊娠数量，而不会使围产期结局恶化。此外，减少不必要的引产次数将降低成本以及可能的医源性并发症带来的风险。此外，引产次数减少将降低早期新生儿的比例，从而改善新生儿结局，并可能降低婴儿长期发病率。
试验注册
ClinicalTrials.gov NCT04502823；https://clinicaltrials.gov/ct2/show/NCT04502823。
国际注册报告识别码（IRRID）：DERR1-10.2196/37452。
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