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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

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
› Author Affiliations
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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