Factors Associated With Thromboembolism in Neonates: A Systematic Review and Meta-Analysis.

Importance: While venous thromboembolism (VTE) is increasingly recognized in neonates and prothrombotic risk factors are being identified, no risk assessment model currently exists to enable early identification of neonates at high risk of VTE. A thorough understanding of existing evidence is necessary to inform the development of a risk-assessment model. Objectives: To describe maternal, obstetrical, and neonatal risk factors associated with VTE in neonates. Data Sources: A literature search of Medline, Embase, CINAHL, and clinicaltrials.gov databases was performed on March 16, 2025, for peer-reviewed publications (1990-2025). Reference lists of included articles were screened to identify other potentially relevant publications. Study Selection: Peer-reviewed studies describing factors associated with venous thrombosis in neonates up to 44 weeks of corrected gestational age were included. A total of 282 reports were retrieved and assessed for eligibility. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines were used to guide data abstraction. Studies were screened independently by 4 trained investigators. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was the factors associated with venous thrombosis. Maternal and obstetrical and patient-related risk factors were considered; catheter-related risk factors are reported separately. Results are expressed using mean differences (MDs) or odds ratio (ORs) with 95% CIs. The degree of heterogeneity (ie, τ2) was estimated using the restricted maximum-likelihood model estimator. Risk of bias in included studies was assessed using the Risk of Bias in Non-randomised Studies of Interventions tool. Results: A total of 60 studies (3 366 507 neonates) were included; most were retrospective cohort studies (26 studies [43%]) or case-control studies (15 studies [25%]). The following risk factors were significantly associated with venous thrombosis: preeclampsia (OR, 2.66; 95% CI, 1.70-4.16; P < .001; τ2 = 0.00), low birth weight (OR, 2.05; 95% CI, 1.41-3.00; P < .001; τ2 = 0.00), cardiac disease (OR, 5.90; 95% CI, 1.16-30.05; P = .03; τ2 = 1.27), and infection (OR, 2.90; 95% CI, 1.88-4.48; P < .001; τ2 = 0.33). Several other factors were identified in multiple studies, but with inconsistent results, including maternal diabetes, gestational age and prematurity, asphyxia, mechanical ventilation, surgery, and elevated hemoglobin or hematocrit levels. Conclusions and Relevance: In this systematic review and meta-analysis, preeclampsia, low birth weight, cardiac disease, and infection were identified as risk factors of neonatal venous thrombosis. Heterogeneity between studies, lack of thrombosis outcome definition, and limited studies addressing common conditions and medications were identified, highlighting the need for further studies and risk stratification.