Catheter-related risk factors for neonatal venous thrombo-embolism: A systematic review of the literature

Abstract BACKGROUND Neonates are at high-risk of venous thrombo-embolism (VTE); central venous catheter (CVC) are related to 90% of VTE in this population. Understanding how catheter-related risk factors impact the risk of VTE in neonates could help elaborate preventative strategies. AIMS To synthetize data pertaining to CVC-related risk factors for VTE in neonates. METHOD A literature search was performed for peer-reviewed randomized and non-randomized trials, retrospective and prospective cohort studies, case-control studies and case series of ≥ 10 patients (1990-2024). Studies were eligible if ≥ 90% of participants were neonates – defined as infants with corrected gestational age ≤ 44 weeks at time of VTE diagnosis – and if studies reported VTE incidence or risk factors, including symptomatic and clinically unsuspected events. Study screening and data extraction were performed independently by two investigators; risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool. We extracted data related to the association of any catheter-related characteristics and VTE, including but not limited to: type of CVC, size, number of lumens, insertion technique, location, and tip position. The review was registered on PROSPERO (CRD42024518801). RESULTS The search yielded 10,579 references, with 283 full-text articles retrieved. Of these, 12 studies (3,352,908 neonates) reported on the predictive impact of catheter-related risk factors for neonatal VTE. Among them, five (42%) were retrospective cohort studies, four (33%) prospective cohort studies, and three (25%) were case-control studies. Most studies focused on neonates admitted to general neonatal intensive care units (NICU) (67%), followed by those focusing on low-birth-weight infants (8%), or neonates with congenital anomaly (8%). VTE screening was performed at least once in 42% of studies. The presence of a CVC was evaluated in four studies, all of which demonstrated a significant association with VTE (ORs: 3.32 to 18.97). The impact of CVC type was not formally compared, but one study (Easterlin et al, 2022) found differing risk based on CVC type (Umbilical vein catheters: OR=2.32; peripherally-inserted central catheters: OR=6.93; tunnelled and untunnelled CVCs: OR=8.50). CVC insertion site was assessed in five studies; three found a significantly increased risk associated with femoral access compared to subclavian access or other sites (ORs: 1.08 to 8.1). CVC duration was investigated in three studies, two of which presented a statistically significant association between prolonged catheter use and increased VTE incidence (ORs: 1.54 and 11.1). Two studies evaluated the use of heparin to prevent catheter-related thrombosis in neonates: one showed a reduction in thrombosis, while the other was inconclusive. Despite the limited and conflicted evidence, heparin remains commonly used in clinical practice, supporting the need for stronger data to support its routine use. No study assessing the impact of insertion technique, inserting clinicians, and CVC size and number of lumens on neonatal VTE was retrieved. CONCLUSIONS CVC are a major risk factor for neonatal VTE. Given the high burden and important morbidity associated with neonatal VTE and the lack of clear, consistent conclusions across existing studies, this review highlights the need for high-quality prospective research to guide safer CVC use in this vulnerable population.