Angiogenic factors versus fetomaternal Doppler for fetal growth restriction at term: an open-label, randomized controlled trial
Open accessAbstract
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 ).
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Cites
Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2008.08.010 · Cited by 51,384 · see citing works
CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
Schulz, K. F., Altman, D. G., Moher, D., & for the CONSORT Group (2010) · BMJ · doi:10.1136/bmj.c332 · Cited by 9,329 · see citing works
Circulating angiogenic factors and the risk of preeclampsia
Levine, R. J., Maynard, S. E., Qian, C., Lim, K.-H., England, L. J., Yu, K. F., Schisterman, E. F., Thadhani, R., Sachs, B. P., Epstein, F. H., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031884 · Cited by 3,720 · see citing works
CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials
Schulz, K. F., Altman, D. G., Moher, D., & for the CONSORT Group (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000251 · Cited by 2,296 · see citing works
Consensus definition of fetal growth restriction: a Delphi procedure: Consensus definition of FGR
Gordijn, S. J., Beune, I. M., Thilaganathan, B., Papageorghiou, A., Baschat, A. A., Baker, P. N., Silver, R. M., Wynia, K., & Ganzevoort, W. (2016) · Ultrasound in Obstetrics & Gynecology · doi:10.1002/uog.15884 · Cited by 1,638 · see citing works
Figueras, F., & Gratacós, E. (2014) · Fetal Diagnosis and Therapy · doi:10.1159/000357592 · Cited by 799 · see citing works
Boers, K. E., Vijgen, S. M. C., Bijlenga, D., van der Post, J., Bekedam, D. J., Kwee, A., van der Salm, P. C. M., van Pampus, M. G., Spaanderman, M. E. A., de Boer, K., et al. (2010) · BMJ · doi:10.1136/bmj.c7087 · Cited by 536 · see citing works
McCowan, L. M., Figueras, F., & Anderson, N. H. (2018) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.12.004 · Cited by 451 · see citing works
Adverse Neonatal Outcomes Associated With Early-Term Birth
Sengupta, S., Carrion, V., Shelton, J., Wynn, R. J., Ryan, R. M., Singhal, K. K., & Lakshminrusimha, S. (2013) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2013.2581 · Cited by 223 · see citing works
An integrated approach to fetal growth restriction
Figueras, F., & Gratacós, E. (2016) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2016.10.006 · Cited by 221 · see citing works
Savchev, S., Figueras, F., Cruz‐Martinez, R., Illa, M., Botet, F., & Gratacos, E. (2012) · Ultrasound in Obstetrics & Gynecology · doi:10.1002/uog.10150 · Cited by 160 · see citing works
Figueras, F., Savchev, S., Triunfo, S., Crovetto, F., & Gratacós, E. (2014) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.14714 · Cited by 152 · see citing works
Gaccioli, F., Sovio, U., Cook, E., Hund, M., Jones, D. S., & Smith, G. C. S. (2018) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(18)30129-9 · Cited by 141 · see citing works
Levy, D. P., Sheiner, E., Wainstock, T., Sergienko, R., Landau, D., & Walfisch, A. (2017) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.07.015 · Cited by 84 · see citing works
Triunfo, S., Lobmaier, S. M., Parra-Saavedra, M. A., Crovetto, F., Peguero, A., Nadal, A., Gratacós, E., & Figueras, F. (2014) · Placenta · doi:10.1016/j.placenta.2014.03.021 · Cited by 75 · see citing works
Lobmaier, S. M., Figueras, F., Mercade, I., Perelló, M. F., Peguero, A., Crovetto, F., Ortiz, J. U., Crispi, F., & Gratacós, E. (2013) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.13246 · Cited by 72 · see citing works
Cruz‐Martinez, R., Savchev, S., Cruz‐Lemini, M., Mendez, A., Gratacos, E., & Figueras, F. (2015) · Ultrasound in Obstetrics & Gynecology · doi:10.1002/uog.14706 · Cited by 70 · see citing works
Triunfo, S., Crispi, F., Gratacós, E., & Figueras, F. (2016) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.15979 · Cited by 70 · see citing works
Walfisch, A., Beharier, O., Wainstock, T., Sergienko, R., Landau, D., & Sheiner, E. (2016) · Pediatric Pulmonology · doi:10.1002/ppul.23529 · Cited by 44 · see citing works
Bond, D. M., Gordon, A., Hyett, J. A., de Vries, B. S., Carberry, A. E., & Morris, J. M. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009433.pub2 · Cited by 43 · see citing works
Mild Neonatal Acidemia is Associated with Neonatal Morbidity at Term
Bailey, E. J., Frolova, A. I., López, J. D., Raghuraman, N., Macones, G. A., & Cahill, A. G. (2020) · American Journal of Perinatology · doi:10.1055/s-0040-1708800 · Cited by 31 · see citing works
Kwiatkowski, S., Bednarek-Jędrzejek, M., Ksel, J., et al. (2018) · Pregnancy Hypertension · doi:10.1016/j.preghy.2018.08.448 · Cited by 29 · see citing works
Wright, A., von Dadelszen, P., Magee, L. A., et al. (2022) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.17296 · Cited by 26 · see citing works
Pagé, J., Blue, N. R., & Silver, R. M. (2021) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/j.ogc.2021.03.001 · Cited by 23 · see citing works
Marchi, L., Zwertbroek, E. F., Snelder, J., et al. (2016) · Prenatal Diagnosis · doi:10.1002/pd.4970 · Cited by 21 · see citing works
Hurtado, I., Bonacina, E., García‐Manau, P., Serrano, B., Armengol‐Alsina, M., Mendoza, M., Maíz, N., & Carreras, E. (2022) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-022-06833-5 · Cited by 17 · see citing works
Self-citationThe effect of sampling site on the variability of Umbilical artery PI
Bhide, A., Badade, A., & Khatal, K. (2019) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2018.12.026 · Cited by 11 · see citing works
Assessment of reproducibility and repeatability of cerebro-placental ratio
Bhide, A., Badade, A., & Khatal, K. (2019) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2018.12.027 · Cited by 11 · see citing works
García‐Manau, P., Mendoza, M., Bonacina, E., Martin-Alonso, R., Martín, L., Palacios, A., Sanchez, M. L., Heredia, C. L., Hurtado, I., Carbajo, E. P., et al. (2022) · JMIR Research Protocols · doi:10.2196/37452 · Cited by 9 · see citing works
Self-citation200: Mild neonatal acidemia is associated with neonatal morbidity at term
Bailey, E. J., Frolova, A., López, J. D., et al. (2018) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2018.11.221 · Cited by 3 · see citing works
How to determine if a treatment works for some people but not for others?
Middleton, L., & Sitch, A. J. (2020) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.15852 · Cited by 2 · see citing works
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“14 More recently, machine learning models integrating clinical and imaging data have shown promise, particularly those using multimodal frameworks.”
- Authors
- Garcia-Manau, P., Bonacina, E., Martin-Alonso, R., Martin, L., Palacios, A., Sanchez-Camps, M. L., Lesmes, C., Hurtado, I., Perez, E., Tubau, A., Ibañez, P., Alcoz, M., Valiño, N., Moreno, E., Borrero, C., Garcia, E., Lopez-Quesada, E., Diaz, S., Broullon, J. R., Teixidor, M., Chulilla, C., Ferrer-Costa, R., Gil, M. M., Lopez, M., Ramos-Forner, G. M., Blanco, J. E., Moreno, A., Lázaro-Rodríguez, M., Vaquerizo, O., Soriano, B., Fabre, M., Gomez-Valencia, E., Cuiña, A., Alayon, N., Sainz-Bueno, J. A., Vives, A., Esteve, E., Ocaña, V., López, M. Á., Maroto, A., Carreras, E., & Mendoza, M.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Universidad Francisco de Vitoria (ES)
- Universitat de Miguel Hernández d'Elx (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Universidad de Oviedo (ES)
- Hospital Son Llatzer (ES)
- Hospital Clínico Universitario Lozano Blesa (ES)
- Althaia (ES)
- Hospital General Universitario de Elche (ES)
- Hospital Universitario de Valme (ES)
- Hospital Universitario de Getafe (ES)
- Universitat de Girona (ES)
- Hospital Universitario Nuestra Señora de Candelaria (ES)
- Corporació Sanitària Parc Taulí (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Universidade da Coruña (ES)
- University Hospital Mútua de Terrassa (ES)
- Hospital Universitario Puerta del Mar (ES)
- Corresponding author
- Mendoza, Manel
- ORCID
- Garcia-Manau, Pablo
- Bonacina, Erika
- Martin-Alonso, Raquel
- Palacios, Ana
- Hurtado, Ivan
- Tubau, Albert
- Alcoz, Marina
- Moreno, Elena
- Borrero, Carlota
- Diaz, Sonia
- Teixidor, Mireia
- Chulilla, Carolina
- Gil, Maria M.
- Blanco, José Eliseo
- Soriano, Beatriz
- Fabre, Marta
- Gomez-Valencia, Elena
- Cuiña, Ana
- Ocaña, Vanesa
- López, Miguel Ángel
- Maroto, Anna
- Carreras, Elena
- Mendoza, Manel
- Venue
- Nature Medicine
- Published
- 2025-01-07
- Volume
- 31
- Issue
- 3
- Pages
- 1008-1015
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W4406150764
- Cited by
- 21
- References
- 31
- Citations by year
- 2026: 10 · 2025: 11
- FWCI
- 24.47
- Type
- journal article
- Language
- en
- Open access
- green
- ddd.uab.cat
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Keywords
- fetal growth restriction, small for gestational age, sFlt-1/PlGF ratio, angiogenic factors, estimated fetal weight, non-inferiority, neonatal acidosis, cesarean section, term pregnancy, fetal distress, perinatal outcomes
- MeSH terms
- Placenta Growth Factor, Adult, Female, Fetal Growth Retardation, Gestational Age, Humans, Infant, Newborn, Infant, Small for Gestational Age, Pregnancy, Ultrasonography, Prenatal, Ultrasonography, Doppler, Fetal Weight, Vascular Endothelial Growth Factor Receptor-1, Angiogenesis Inducing Agents
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