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Usefulness of angiogenic factors in prenatal counseling of late-onset fetal growth-restricted and small-for-gestational-age gestations: a prospective observational study

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objectives

To create a predictive model including biomarkers and evaluate its ability to predict adverse perinatal outcomes in late-onset small fetuses, ultimately helping to provide individualized counseling at the time of diagnosis.

Methods

This was a prospective observational study, including singleton pregnancies with an estimated fetal weight (EFW) below the 10th percentile, at a gestational age between 32 + 0 and 36 + 6 weeks of gestation (WG). Variables recorded at diagnosis to predict adverse pregnancy outcomes were: soluble fms-like tyrosine-kinase-1 to placental growth factor ratio (sFlt-1/PlGF), fetal Doppler (umbilical artery and middle cerebral artery), uterine artery pulsatility index (UtAPI), EFW percentile, gestational age, and the presence of maternal risk factors for placental insufficiency. Logistic regression models were developed for the prediction of three co-primary outcomes: composite adverse perinatal outcomes (APO), and the need for elective delivery before 35 or 37 WG.

Results

Sixty (52.2%) fetal growth restricted (FGR) and 55 (47.8%) small for gestational age (SGA) were enrolled. Thirteen (11.3%) women needed elective delivery before 35 WG and 27 (23.5%) women before 37 WG. At least one APO occurred in 43 (37.4%) pregnancies. The best marker in univariate analyses was the sFlt-1/PlGF ratio [AUC = 0.932 (95% CI, 0.864–0.999)]. The multivariate model including sFlt-1/PlGF showed a better predictive performance for APO than the multivariate model without sFlt-1/PlGF (P < 0.024).

Conclusions

sFlt-1/PlGF is a good predictor of APO at the time of late-onset FGR/SGA diagnosis. Our predictive models may be useful to provide early individualized prenatal counseling in this group of women. Further studies are needed to validate these preliminary findings in a larger cohort.

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Abbreviations

FGR:

Fetal growth restriction

SGA:

Small for gestational age

sFlt-1:

Fms-like tyrosine kinase-1

PlGF:

Placental growth factor

GA:

Gestational age

EFW:

Estimated fetal weight

CTG:

Cardiotocography

UtA:

Uterine artery

PI:

Pulsatility index

UA:

Umbilical artery

AUC:

Area under the curve

APO:

Adverse perinatal outcome

CPR:

Cerebro-placental ratio

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Acknowledgements

We thank all the physicians who facilitated the recruitment of individuals at Hospital Universitari Vall d’Hebron; the participants who agreed to take part in the study and, finally, Mar Jiménez Quesada for editing the manuscript in English language.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Author notes

  1. Ivan Hurtado, Erika Bonacina, Nerea Maiz and Elena Carreras contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics, Maternal Fetal Medicine Unit, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Passeig de La Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Ivan Hurtado, Erika Bonacina, Pablo Garcia-Manau, Berta Serrano, Mireia Armengol-Alsina, Manel Mendoza, Nerea Maiz & Elena Carreras

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  1. Ivan Hurtado
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by IH, EB, PG-M, BS and MA-A. Data analysis was performed by NM and MM. The first draft of the manuscript was written by IH, EB and MM. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Manel Mendoza.

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Conflict of interest

Manel Mendoza has received lecture fees by Roche diagnostics. The other authors report no conflicts of interest. Roche Diagnostics had no influence on the study design, data collection, or analysis and interpretation of results. The other authors have no relevant financial or non-financial interests to disclose.

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Hurtado, I., Bonacina, E., Garcia-Manau, P. et al. Usefulness of angiogenic factors in prenatal counseling of late-onset fetal growth-restricted and small-for-gestational-age gestations: a prospective observational study. Arch Gynecol Obstet 308, 1485–1495 (2023). https://doi.org/10.1007/s00404-022-06833-5

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