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  • Systematic Review
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Perinatal arterial ischemic stroke (PAIS) and neonatal cerebral sinovenous thrombosis (CSVT) in the preterm neonate: a systematic review

Pediatric Research (2026)Cite this article

Abstract

Perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) cause significant neurological morbidity, including cerebral palsy, in preterm infants. Compared to term infants, the epidemiology, risk factors, and outcomes of PAIS and CSVT in preterm infants are less well understood. This systematic review aimed to summarize the literature on incidence, risk factors, clinical presentation, neuroimaging, and neurodevelopmental outcomes of PAIS and CSVT in infants born before 37 weeks’ gestation. A comprehensive search of PubMed, Embase, and Web of Science for studies from 2004 to 2025 identified 14 eligible studies including 132 infants with PAIS and 57 with CSVT. Incidence rates were higher in infants of lower gestational age. Identified PAIS risk factors included twin-to-twin transfusion syndrome, fetal heart rate abnormalities, and hypoglycemia. Perforator artery strokes were most common, while CSVT frequently involved the transverse sinus. Many risk factors overlapped with term infants but preterm infants showed more prematurity-related complications, longer ventilation, and postoperative states. Neurodevelopmental outcomes were poor, with high rates of impairment and mortality, especially in CSVT. The review highlights urgent needs for larger, controlled studies to improve prevention, early diagnosis, and management in this vulnerable population.

Impact

  • This review systematically summarizes incidence, risk factors, neuroimaging patterns, treatment, and outcomes of perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) specifically in preterm infants—a group often excluded from previous studies.

  • The findings reveal that preterm infants with PAIS and CSVT have unique and overlapping risk factors (such as twin-to-twin transfusion syndrome and hypoglycemia), often present asymptomatically, and are at high risk for poor neurodevelopmental outcomes and mortality.

  • The review highlights urgent knowledge gaps, especially regarding the safety and effectiveness of anticoagulation therapy in preterm CSVT, and stresses the need for larger studies and targeted strategies to improve recognition, management, and long-term outcomes for this vulnerable group.

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Fig. 1
Fig. 2: Overview of reported risk factors and vascular distribution in studies on PAIS included in the systematic review.
Fig. 3: Overview of reported risk factors and vascular distribution in studies on CSVT included in the systematic review.

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Funding

This study received funding from the Cerebral Palsy Alliance (Australia) and the Phelps Foundation (the Netherlands). They did not take part in designing this study.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, Willem Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands

    Bregje O. van Oldenmark, Andrea van Steenis, Enrico Lopriore, Linda S. de Vries & Sylke J. Steggerda

  2. Department of Neonatology, University Medical Center Utrecht Brain Center and Wilhelmina Children’s Hospital, Utrecht University, Utrecht, The Netherlands

    Niek E. van der Aa

  3. Ludwig-Maximilians University Munich, Munich, Germany

    Anna-Lisa Oechsle

  4. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany

    Mark Dzietko

  5. Department of Pediatrics Curaçao Medical Center, Willemstad, Curaçao

    Ginette M. Ecury-Goosen

Authors
  1. Bregje O. van Oldenmark
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  2. Andrea van Steenis
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Contributions

Bregje O. van Oldenmark designed the search strategy, conducted the literature search, assessed articles for quality, drafted the manuscript, and created the illustrations. Drs. Andrea van Steenis critically reviewed, provided feedback and revised the manuscript. Dr. Niek E. van der Aa critically reviewed, provided feedback and revised the manuscript. Dr. Anna-Lisa Oechsle shared data, critically reviewed, provided feedback and revised the manuscript. Prof. Dr. Mark Dzietko critically reviewed, provided feedback and revised the manuscript. Dr. Ginette Ecury-Goossen shared data, critically reviewed, provided feedback and revised the manuscript. Prof. Dr. Enrico Lopriore critically reviewed, provided feedback and revised the manuscript. Prof. Dr. Linda S. de Vries searched for additional relevant literature, and critically reviewed and revised the manuscript. Dr. Sylke J. Steggerda conducted the literature search, assessed articles for quality and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Bregje O. van Oldenmark.

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van Oldenmark, B.O., van Steenis, A., van der Aa, N.E. et al. Perinatal arterial ischemic stroke (PAIS) and neonatal cerebral sinovenous thrombosis (CSVT) in the preterm neonate: a systematic review. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-04800-3

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