Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia

Objectives: To assess the predictive performance of angiogenic factors and fetal Doppler, alone and in combination, for composite adverse perinatal outcome (CAPO) in early-onset small-for-gestational age (SGA) and fetal growth restriction (FGR), in cases both with and without pre-eclampsia (PE), in...

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Autores: Bonacina, Erika|||0000-0002-8042-8247, Armengol-Alsina, Mireia|||0000-0002-2087-5176, Casellas, A., Dalmau, M., Diaz, P., Roldan Alarcón, Eva|||0009-0003-8109-8985, Temprado Piqueras, Joaquin|||0009-0002-3898-0203, Duaso, M., Ampurdanes, Q., San Jose, M., Armengol, T., Lizarraga, Z, Maiz, N., Mendoza, Manel|||0000-0002-3030-3833
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:326993
Acceso en línea:https://ddd.uab.cat/record/326993
https://dx.doi.org/urn:doi:10.1002/uog.70188
Access Level:acceso abierto
Palabra clave:Angiogenic factors
Doppler
Fetal growth restriction
PlGF
sFlt-1
SGA
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oai_identifier_str oai:ddd.uab.cat:326993
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
title Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
spellingShingle Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
Bonacina, Erika|||0000-0002-8042-8247
Angiogenic factors
Doppler
Fetal growth restriction
PlGF
sFlt-1
SGA
title_short Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
title_full Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
title_fullStr Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
title_full_unstemmed Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
title_sort Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsia
dc.creator.none.fl_str_mv Bonacina, Erika|||0000-0002-8042-8247
Armengol-Alsina, Mireia|||0000-0002-2087-5176
Casellas, A.
Dalmau, M.
Diaz, P.
Roldan Alarcón, Eva|||0009-0003-8109-8985
Temprado Piqueras, Joaquin|||0009-0002-3898-0203
Duaso, M.
Ampurdanes, Q.
San Jose, M.
Armengol, T.
Lizarraga, Z
Maiz, N.
Mendoza, Manel|||0000-0002-3030-3833
author Bonacina, Erika|||0000-0002-8042-8247
author_facet Bonacina, Erika|||0000-0002-8042-8247
Armengol-Alsina, Mireia|||0000-0002-2087-5176
Casellas, A.
Dalmau, M.
Diaz, P.
Roldan Alarcón, Eva|||0009-0003-8109-8985
Temprado Piqueras, Joaquin|||0009-0002-3898-0203
Duaso, M.
Ampurdanes, Q.
San Jose, M.
Armengol, T.
Lizarraga, Z
Maiz, N.
Mendoza, Manel|||0000-0002-3030-3833
author_role author
author2 Armengol-Alsina, Mireia|||0000-0002-2087-5176
Casellas, A.
Dalmau, M.
Diaz, P.
Roldan Alarcón, Eva|||0009-0003-8109-8985
Temprado Piqueras, Joaquin|||0009-0002-3898-0203
Duaso, M.
Ampurdanes, Q.
San Jose, M.
Armengol, T.
Lizarraga, Z
Maiz, N.
Mendoza, Manel|||0000-0002-3030-3833
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiogenic factors
Doppler
Fetal growth restriction
PlGF
sFlt-1
SGA
topic Angiogenic factors
Doppler
Fetal growth restriction
PlGF
sFlt-1
SGA
description Objectives: To assess the predictive performance of angiogenic factors and fetal Doppler, alone and in combination, for composite adverse perinatal outcome (CAPO) in early-onset small-for-gestational age (SGA) and fetal growth restriction (FGR), in cases both with and without pre-eclampsia (PE), in order to evaluate the ability of these markers to predict adverse outcomes beyond their established association with PE and to better delineate the specific contribution of PE to their predictive value. Methods: This was a retrospective observational study conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between January 2016 and January 2022. The study population included singleton pregnancies with an estimated fetal weight < 10 percentile, diagnosed with fetal smallness between 20 + 0 and 31 + 6 weeks' gestation, with fetal Doppler ultrasound data and available angiogenic factor measurements obtained at diagnosis. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at initial assessment. CAPO was defined as the presence of at least one of the following: 5-min Apgar score < 7; umbilical cord arterial pH < 7.0; admission to the neonatal intensive care unit for > 48 h; stillbirth; neonatal death; respiratory distress syndrome; bronchopulmonary dysplasia; neonatal sepsis; necrotizing enterocolitis; Grade-III-IV retinopathy of prematurity; Grade-III-IV intraventricular hemorrhage; or periventricular leukomalacia. Predictive performance for CAPO and subsequent PE was assessed using receiver-operating-characteristics (ROC)-curve analysis and area under the ROC curve (AUC) comparisons for fetal Doppler and angiogenic factors, alone and combined, within logistic regression models. Sensitivity, false-positive rate, positive predictive value and negative predictive value were calculated. All analyses were stratified according to PE development at any time before delivery. Results: Overall, 469 women with an early-onset small fetus were included. PE was present at diagnosis in 74/469 (15.8%) cases and developed later in 83 (17.7%) cases. CAPO occurred in 46.5% of cases. In the overall cohort, PlGF combined with fetal Doppler findings showed the highest predictive performance for CAPO (AUC, 0.866 (95% CI, 0.833-0.899)), outperforming fetal Doppler alone. Notably, the performance of the combined model was not significantly different from PlGF alone (AUC, 0.862 (95% CI, 0.828-0.895); P = 0.621). These findings were consistent in pregnancies without PE, in which PlGF remained the best-performing single predictor of CAPO (AUC, 0.797 (95% CI, 0.740-0.854)). In pregnancies with PE at any time, the best-performing single predictor was the sFlt-1/PlGF ratio (AUC, 0.802 (95% CI, 0.728-0.876)). For the prediction of subsequent PE after enrolment, the sFlt-1/PlGF ratio alone (AUC, 0.861 (95% CI, 0.821-0.901)) and in combination with fetal Doppler (AUC, 0.862 (95% CI, 0.822-0.902)) achieved the highest predictive performance. Combining fetal Doppler findings with angiogenic factors reduced false-positive rates, but did not improve sensitivity. Conclusion: This study confirmed the robust predictive performance of PlGF and the sFlt-1/PlGF ratio for identifying CAPO and PE in early-onset SGA/FGR. The predictive value of PlGF and fetal Doppler remained consistent irrespective of PE status, while the sFlt-1/PlGF ratio showed reduced predictive accuracy in non-PE pregnancies, but still outperformed Doppler. These findings support the integration of angiogenic factors into the clinical assessment of early-onset SGA/FGR, for both cases with and those without PE. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
publishDate 2026
dc.date.none.fl_str_mv 2
2026-01-01
2026
2026-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/326993
https://dx.doi.org/urn:doi:10.1002/uog.70188
url https://ddd.uab.cat/record/326993
https://dx.doi.org/urn:doi:10.1002/uog.70188
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CM23/00017
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Angiogenic factors and fetal Doppler for predicting adverse pregnancy outcome in early-onset small fetuses with and without pre-eclampsiaBonacina, Erika|||0000-0002-8042-8247Armengol-Alsina, Mireia|||0000-0002-2087-5176Casellas, A.Dalmau, M.Diaz, P.Roldan Alarcón, Eva|||0009-0003-8109-8985Temprado Piqueras, Joaquin|||0009-0002-3898-0203Duaso, M.Ampurdanes, Q.San Jose, M.Armengol, T.Lizarraga, ZMaiz, N.Mendoza, Manel|||0000-0002-3030-3833Angiogenic factorsDopplerFetal growth restrictionPlGFsFlt-1SGAObjectives: To assess the predictive performance of angiogenic factors and fetal Doppler, alone and in combination, for composite adverse perinatal outcome (CAPO) in early-onset small-for-gestational age (SGA) and fetal growth restriction (FGR), in cases both with and without pre-eclampsia (PE), in order to evaluate the ability of these markers to predict adverse outcomes beyond their established association with PE and to better delineate the specific contribution of PE to their predictive value. Methods: This was a retrospective observational study conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between January 2016 and January 2022. The study population included singleton pregnancies with an estimated fetal weight < 10 percentile, diagnosed with fetal smallness between 20 + 0 and 31 + 6 weeks' gestation, with fetal Doppler ultrasound data and available angiogenic factor measurements obtained at diagnosis. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at initial assessment. CAPO was defined as the presence of at least one of the following: 5-min Apgar score < 7; umbilical cord arterial pH < 7.0; admission to the neonatal intensive care unit for > 48 h; stillbirth; neonatal death; respiratory distress syndrome; bronchopulmonary dysplasia; neonatal sepsis; necrotizing enterocolitis; Grade-III-IV retinopathy of prematurity; Grade-III-IV intraventricular hemorrhage; or periventricular leukomalacia. Predictive performance for CAPO and subsequent PE was assessed using receiver-operating-characteristics (ROC)-curve analysis and area under the ROC curve (AUC) comparisons for fetal Doppler and angiogenic factors, alone and combined, within logistic regression models. Sensitivity, false-positive rate, positive predictive value and negative predictive value were calculated. All analyses were stratified according to PE development at any time before delivery. Results: Overall, 469 women with an early-onset small fetus were included. PE was present at diagnosis in 74/469 (15.8%) cases and developed later in 83 (17.7%) cases. CAPO occurred in 46.5% of cases. In the overall cohort, PlGF combined with fetal Doppler findings showed the highest predictive performance for CAPO (AUC, 0.866 (95% CI, 0.833-0.899)), outperforming fetal Doppler alone. Notably, the performance of the combined model was not significantly different from PlGF alone (AUC, 0.862 (95% CI, 0.828-0.895); P = 0.621). These findings were consistent in pregnancies without PE, in which PlGF remained the best-performing single predictor of CAPO (AUC, 0.797 (95% CI, 0.740-0.854)). In pregnancies with PE at any time, the best-performing single predictor was the sFlt-1/PlGF ratio (AUC, 0.802 (95% CI, 0.728-0.876)). For the prediction of subsequent PE after enrolment, the sFlt-1/PlGF ratio alone (AUC, 0.861 (95% CI, 0.821-0.901)) and in combination with fetal Doppler (AUC, 0.862 (95% CI, 0.822-0.902)) achieved the highest predictive performance. Combining fetal Doppler findings with angiogenic factors reduced false-positive rates, but did not improve sensitivity. Conclusion: This study confirmed the robust predictive performance of PlGF and the sFlt-1/PlGF ratio for identifying CAPO and PE in early-onset SGA/FGR. The predictive value of PlGF and fetal Doppler remained consistent irrespective of PE status, while the sFlt-1/PlGF ratio showed reduced predictive accuracy in non-PE pregnancies, but still outperformed Doppler. These findings support the integration of angiogenic factors into the clinical assessment of early-onset SGA/FGR, for both cases with and those without PE. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. 22026-01-0120262026-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/326993https://dx.doi.org/urn:doi:10.1002/uog.70188reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 CM23/00017open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3269932026-06-06T12:50:31Z
score 15.812429

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