P1.171: Systematic Analysis of biomarkers in Neonatal Venous Thromboembolism

Background: The incidence of venous thromboembolism (VTE) is rising in children, with neonates being at high risk. Understanding VTE incidence and risk factors can allow accurate risk stratification. We conducted a systematic review and meta-analysis to synthesize current data on neonatal VTE incidence and potential biomarkers.

Methods: 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/or 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. Cumulative incidence (95% confidence intervals [CI]) was calculated for the entire cohort and stratified by VTE screening and comorbidities (PROSPERO registration number: CRD42024518801).

Results: The search yielded 10,579 references, with 283 full-text articles retrieved. After screening, 91 studies involving 3,462,818 neonates were included (Table 1). Most studies focused on neonates admitted to general neonatal intensive care units (NICU) (58%), followed by those with cardiac disease (14%), prematurity/low birth weight (12%), or congenital anomaly (5%). Most studies (90%) were deemed to have a high risk of bias in at least one domain.

The cumulative incidence of VTE was 11.4% (95% CI: 7.0-16.9%) across 73 studies (3,284,829 neonates). VTE incidence was higher among studies that performed VTE screening compared to studies that did not (15.0% [95% CI: 4.1-25.8] vs 8.6% [95% CI: 0.80-18.0]). When stratified by comorbidities, VTE incidence was highest among neonates with cardiac disease and lowest among term/near-term infants.

Laboratory biomarkers were reported in seven studies. The relationship between platelet count (n=389) or elevated hematocrit or hemoglobin (n=294) and VTE was tested in three studies respectively, but no associations were found. In two studies of premature neonates, higher hemoglobin on day 3 of life (12.6 vs 11.4 g/dL, p=0.02) and polycythemia, defined as hematocrit >55% (Odds ratio: 3.66, 95% CI: 1.13-11.79, p=0.03), were statistically associated with VTE, though one prospective study found no such association. The potential predictive value of Factor V Leiden mutation, prothrombin gene mutation, and MTHFR polymorphisms were tested in three studies (n=85,463). Only one study indicated an increased VTE risk (3% vs 0%, p=0.02) in neonates with homozygous prothrombin gene mutation.

Conclusion: VTE is a frequent complication in neonates admitted to the NICU. While some biomarkers have been tested, discrepancies between different studies and the high risk of bias in the current literature hinder their widespread clinical use. Further prospective research is necessary to clarify these findings.