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  • Clinical Research Article
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Neonatal morbidity in early-onset fetal growth restriction with and without anticoagulant therapy

Pediatric Research (2025)Cite this article

Abstract

Background

The study aims to evaluate the effectiveness of low molecular weight heparin (LMWH) in reducing neonatal morbidity in pregnancies with early-onset fetal growth restriction (FGR).

Methods

A phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two university hospitals in Spain. Singleton pregnancies with early-onset placental FGR (20 + 0–31 + 6 weeks at diagnosis) were randomized to receive bemiparin (3500 IU/0.2 mL/day) or placebo from diagnosis to delivery. The primary neonatal outcome was morbidity up to hospital discharge, assessed using the Morbidity Assessment Index for Newborns (MAIN) score. Analyses followed an intention-to-treat approach.

Results

Fifty patients were randomized (25 per arm), with 49 included in the final analysis (23 LMWH, 26 placebo). Median gestational ages at inclusion were 28.7 weeks (LMWH) and 28.4 weeks (placebo). No significant differences were observed in MAIN scores between groups (171.5 vs. 290; p = 0.887; adjusted median difference 139.1 [95% CI −88.4 to 319.8]). NICU stay lengths were also similar (9 vs. 6.5 days; p = 0.738; adjusted median difference 1.08 [95% CI −0.74 to 13.4]).

Conclusion

Prophylactic LMWH started at diagnosis of early-onset FGR does not decrease neonatal morbidity or NICU stay duration.

Impact

  • Prophylactic LMWH started at the diagnosis of early-onset FGR does not decrease neonatal morbidity or NICU stay duration.

  • Its design is a randomized, triple-blind clinical trial, which provides high-quality evidence.

  • LMWH is often prescribed during pregnancy for various indications, and in the absence of effective alternatives, it is increasingly used empirically in such cases. Our findings do not support its use for reducing perinatal morbidity or NICU admission duration.

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Data availability

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices), will be shared with researchers who provide a methodologically sound proposal. Data will be shared, until a maximum of 15 years after study closure, to achieve aims in the approved proposal. Proposals should be directed to ffiguera@clinic.cat. To gain access, data requestors will need to sign a data access agreement.

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Funding

This work has been funded by the Plan Estatal de I+D+i (Government R&D&I Plan) and Instituto de Salud Carlos III- Subdirección General de Evaluación y Fomento de la Investigación Sanitaria (Carlos III Health Institute – General Subdirectorate for Assessment and Promotion of Research), projects PI16/00151 and PI16/595, and the European Regional Development Fund (FEDER).

Author information

Author notes

  1. These authors contributed equally: Francesc Figueras, Edurne Mazarico.

Authors and Affiliations

  1. Hospital Sant Joan de Déu, BCNatal, Barcelona, Spain

    Alba González, Maria Dolores Gomez-Roig, Judit Hidalgo & Edurne Mazarico

  2. BCNatal – Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Sant Joan de Déu and Hospital Clínic), University of Barcelona, Barcelona, Spain

    Alba González & Marta Camprubi

  3. Hospital Clínic de Barcelona, BCNatal, Barcelona, Spain

    Anna Peguero, Eva Meler, Narcís Masoller & Francesc Figueras

  4. Department of Neonatology, Hospital Sant Joan de Déu, Barcelona, Spain

    Marta Camprubi

  5. Cardiovascular Research Group, Sant Joan de Déu Research Institute, Barcelona, Spain

    Marta Camprubi

  6. Department of Pathology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

    Carlota Rovira

  7. Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain

    Maria Dolores Gomez-Roig & Edurne Mazarico

  8. Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS), RD21/0012/0003, Instituto de Salud Carlos III, Madrid, Spain

    Maria Dolores Gomez-Roig & Edurne Mazarico

  9. Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain

    Maria Dolores Gomez-Roig, Francesc Figueras & Edurne Mazarico

  10. Aragon Institute for Health Research (IIS Aragón), Obstetrics Department, Hospital Clínico Universitario Zaragoza, Zaragoza, Spain

    Daniel Oros & Patricia Ibáñez

  11. Group B46_20R Placental Pathophysiology and Fetal programming, Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain

    Daniel Oros & Jon Schoorlemmer

  12. Instituto Aragonés de Ciencias de la Salud (IACS) and ARAID Foundation, Zaragoza, Spain

    Daniel Oros & Jon Schoorlemmer

  13. Department of Hemotherapy Hemostasis, Hospital Clínic de Barcelona, Barcelona, Spain

    Dolores Tàssies

  14. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Francesc Figueras

Authors
  1. Alba González
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  2. Anna Peguero
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  3. Eva Meler
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  13. Francesc Figueras
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  14. Edurne Mazarico
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Contributions

Alba González, Anna Peguero, Eva Meler, Narcís Masoller, Daniel Oros, Judit Hidalgo and Patricia Ibáñez-Burillo were coordinators at their respective sites and collected the data. Marta Camprubí, Carlota Rovira, Maria Dolores Gómez Roig, Jon Schoorlemmer and Maria Dolors Tàssies and contributed data or analysis tools. Edurne Mazarico is the general coordinator and principal investigator of the project, conceived and designed the analysis and wrote the paper. Francesc Figueras was consultant and co-principal investigator of the study, conceived and designed the analysis and wrote the paper.

Corresponding author

Correspondence to Francesc Figueras.

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Competing interests

The authors declare no competing interests.

Ethics

All participants provided individual informed consent. The trial was approved by the Ethics Committee of each participant centre (AC-09-17).

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González, A., Peguero, A., Meler, E. et al. Neonatal morbidity in early-onset fetal growth restriction with and without anticoagulant therapy. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04347-9

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  • DOI: https://doi.org/10.1038/s41390-025-04347-9

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