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Am J Perinatol
DOI: 10.1055/a-2661-4287
Original Article

Perinatal Outcomes in Pregnancies Immediately following Stillbirth: A Multicenter, Prospective, Observational Study

Authors

  • Martina Benuzzi 

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Riccardo Cuoghi Costantini

    2   Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Antonio Saddò

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Camilla Selleri

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Sara Verra

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Beatrice Melis

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Gloria Guariglia

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Laura Avagliano

    3   University of Milano, Milan, Italy

  • Caterina Serena

    4   Obstetrics and Gynecology Unit, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy

  • Federico Mecacci

    4   Obstetrics and Gynecology Unit, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy

  • Benedetta Baggio

    4   Obstetrics and Gynecology Unit, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy

  • Benedetta Gabbrielli

    4   Obstetrics and Gynecology Unit, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy

  • Stefania Fieni

    5   Obstetrics and Gynaecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy

  • Ariane J. O. Kiener

    5   Obstetrics and Gynaecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy

  • Caterina Pavan

    5   Obstetrics and Gynaecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy

  • Marinunzia Salluce

    5   Obstetrics and Gynaecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy

  • Sabrina Cozzolino

    6   Obstetrics Unit, IRCCS San Gerardo dei Tintori, Monza, Monza and Brianza, Italy

  • Anna Locatelli

    6   Obstetrics Unit, IRCCS San Gerardo dei Tintori, Monza, Monza and Brianza, Italy
    7   Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

  • Silvia Alongi

    6   Obstetrics Unit, IRCCS San Gerardo dei Tintori, Monza, Monza and Brianza, Italy
    7   Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

  • Paola Camponovo

    6   Obstetrics Unit, IRCCS San Gerardo dei Tintori, Monza, Monza and Brianza, Italy
    7   Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

  • Sara Lazzarin

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Isabella Neri

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Fabio Facchinetti

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Antonio La Marca

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

  • Francesca Monari

    1   Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

Funding None.
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Abstract

Objective

This study aimed to evaluate the outcomes of pregnancies immediately following stillbirth in relation to treatments prescribed.

Study Design

A prospective, observational study was conducted in patients with a history of stillbirth (≥22 weeks) between 2014 and 2022 across four Italian University Hospitals. Outcomes were stratified based on the cause of previous fetal death (classified according to ReCoDe classification) and treatment (low dose aspirin [LDA], low molecular weight heparin [LMWH], both, progesterone, or other drugs). The main outcome was adverse neonatal outcome, including perinatal death, stillbirth recurrence, intrauterine growth restriction, early preterm birth, Apgar < 7 at 5 minutes, and need for neonatal resuscitation. The secondary outcome was adverse maternal outcome, including postpartum hemorrhage, emergency cesarean delivery, and operative vaginal delivery.

Results

Among 308 subsequent pregnancies, 46 (14.94%) had an adverse neonatal outcome, including 4 stillbirths. A total of 76 pregnancies (24.68%) experienced adverse maternal outcome, and 19 pregnancies (6.17%) had both. In individuals with previous placental vascular disorders (PVDs), adverse neonatal outcomes were reduced by 75% when treated with LDA + LMWH (odds ratio [OR]: 0.25; 95% confidence interval [CI]: 0.06–1.03; p = 0.049). However, adverse maternal outcome was significantly higher in individuals who received LDA + LMWH without specific indications (OR: 3.07; 95% CI: 1.07–8.78; p = 0.036).

Conclusion

LDA and LMWH should be prescribed only for previous PVDs to improve adverse neonatal outcome and avoid unnecessary maternal risk.

Key Points

  • LDA + LMWH reduces neonatal risk after placental stillbirths.

  • Unnecessary LDA + LMWH increases maternal complications.

  • Prescribe LDA + LMWH only with placental indications.

Keywords

subsequent pregnancy - stillbirth - adverse neonatal outcome - adverse maternal outcome

Declaration of GenAI Use

During the writing process of this paper, the author(s) used ChatGPT-4 in order to improve readability and language of the work. The author(s) reviewed and edited the text and take(s) full responsibility for the content of the paper.




Publication History

Received: 16 May 2025

Accepted: 21 July 2025

Accepted Manuscript online:
22 July 2025

Article published online:
07 August 2025

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