Garcia-Manau Pablo, Bonacina Erika, Martin-Alonso Raquel, Martin Lourdes, Palacios Ana, Sanchez-Camps 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, Ferrer-Costa Roser, Gil Maria M, Lopez Monica, Ramos-Forner Gemma M, Blanco José Eliseo, Moreno Anna, Lázaro-Rodríguez Marta, Vaquerizo Oscar, Soriano Beatriz, Fabre Marta, Gomez-Valencia Elena, Cuiña Ana, Alayon Nicolas, Sainz-Bueno Jose Antonio, Vives Angels, Esteve Esther, Ocaña Vanesa, López Miguel Ángel, Maroto Anna, Carreras Elena, Mendoza Manel
Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Department of Obstetrics, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Nat Med. 2025 Mar;31(3):1008-1015. doi: 10.1038/s41591-024-03421-9. Epub 2025 Jan 7.
Small fetuses, with estimated fetal weight (EFW) below the tenth percentile, are classified as fetal growth restriction (FGR) or small for gestational age (SGA) based on prenatal ultrasound. FGR fetuses have a greater risk of stillbirth and perinatal complications and may benefit from serial ultrasound scans to guide early delivery. Abnormal serum angiogenic factors, such as the soluble fms-like tyrosine kinase-1 (sFlt-1):placental growth factor (PlGF) ratio, have shown potential to more accurately distinguish FGR from SGA, with fewer false positives. This randomized controlled trial compared a management protocol based on the sFlt-1:PlGF with EFW and Doppler ultrasound in avoiding adverse perinatal outcomes in small fetuses after 36 weeks of gestation. A total of 1,088 pregnant women with singleton pregnancies were randomized to either the Doppler-based (control) or the sFlt-1:PlGF-based (intervention) protocol. The primary outcome, neonatal acidosis or Cesarean delivery as a result of abnormal cardiotocography, was assessed in 1,013 participants. The incidence was 10.5% in the intervention group and 10.0% in the control group (absolute difference, 0.53 (-3.21 to 4.26)), with the upper limit of the confidence interval <8.5%, confirming noninferiority. Thus, the sFlt-1:PlGF was noninferior to EFW and Doppler ultrasound in avoiding neonatal acidosis or Cesarean delivery owing to nonreassuring fetal status in small fetuses after 36 weeks (ClinicalTrials.gov registration: NCT04502823 ).
估计胎儿体重（EFW）低于第十百分位数的小胎儿，根据产前超声被分类为胎儿生长受限（FGR）或小于胎龄儿（SGA）。FGR胎儿死产和围产期并发症的风险更高，可能受益于系列超声扫描以指导早期分娩。异常的血清血管生成因子，如可溶性fms样酪氨酸激酶-1（sFlt-1）与胎盘生长因子（PlGF）的比值，已显示出更准确地区分FGR与SGA的潜力，假阳性更少。这项随机对照试验比较了基于sFlt-1:PlGF与EFW及多普勒超声的管理方案，以避免妊娠36周后小胎儿出现不良围产期结局。共有1088名单胎妊娠孕妇被随机分为基于多普勒的（对照组）或基于sFlt-1:PlGF的（干预组）方案。在1013名参与者中评估了主要结局，即因胎心监护异常导致的新生儿酸中毒或剖宫产。干预组的发生率为10.5%，对照组为10.0%（绝对差异为0.53（-3.21至4.26）），置信区间上限<8.5%，证实了非劣效性。因此，在避免36周后小胎儿因胎儿状况不佳导致的新生儿酸中毒或剖宫产方面，sFlt-1:PlGF不劣于EFW和多普勒超声（ClinicalTrials.gov注册号：NCT04502823）。
