Relationship of sociodemographic factors to presentation and natural history of provoked venous thromboembolism in u.s. children: A secondary analysis of the multinational kids-DOTT trial Free

Introduction Venous thromboembolism (VTE) affects 1 in 200 hospitalized children. In adults, lower socioeconomic status, Black race, and Hispanic ethnicity have been associated with increased rates of VTE recurrence. While the impact of socioeconomic factors on pediatric health overall is well documented, clinical trial-derived data in pediatric VTE are limited. Our objective with this study was to assess whether epidemiologic features of VTE vary by sociodemographic variables among children enrolled in the Kids-DOTT randomized controlled trial (RCT).

Methods We conducted a secondary analysis of the multinational Kids-DOTT parallel-cohort RCT (NCT00687882), which evaluated anticoagulation duration for acute provoked VTE in children. The trial enrolled 532 children 0-<21 years of age with a first provoked VTE from 2008-2021.

Our analysis included only United States (US) participants. We consolidated the eight Health Resources and Services Administration (HRSA)-defined regions into four: North (Great Lakes, Northern States), South (Southeast, Great Plains), East (New England, Mid Atlantic) and West (Mountain States, Western States).

Categorical variables were summarized using counts and percentages; continuous variables using medians with interquartile ranges. Chi-squared or Fisher's exact tests and Kruskal-Wallis were used for group comparisons, with a significant threshold of p-value of <0.05.

Results Among the 409 US participants, lower extremity deep vein thrombosis (LE DVT) was most common (44%), followed by upper extremity (UE) DVT (33%). Central venous catheters (45%) and infection (27%) were the leading provoking factors. Most participants (84%) were treated with low molecular weight heparin. Clinically relevant bleeding (primary safety outcome) and symptomatic recurrent VTE (primary efficacy outcome) occurred in six patients (2%) each. Post-thrombotic syndrome (PTS) was identified in 47% (88/189) of those with limb DVT assessed at two years.

Patient Characteristics by Race and Ethnicity Most participants were White (70%, n=291) and non-Hispanic (81%, n=330). No statistically significant differences in VTE characteristics or outcomes were observed across racial or ethnic groups.

Patient Characteristics by Sex Males and females had similar distributions of UE and LE DVTs and comparable PTS rates. No males experienced VTE secondary to a prothrombotic medication (i.e., systemic estrogen, glucocorticoids, and L-asparaginase) compared to 22 (11%) females (p<0.001).

Patient Characteristics by Age Group Children aged 30 days to <13 years comprised 60% (n=247) of the cohort. The proportion of neonates (63%) and children (47%) with LE DVTs was significantly (p<0.001) higher than that in adolescents (36%). Neonates had the highest incidence of cerebral sinus venous thrombosis (CSVT, 25%, p<0.001).Teens were more likely to have trauma or recent surgery in the preceding 30 days (25%) as compared to neonates (19%) and children (13%), p=0.001) and showed the highest PTS rates (62%, p=0.003).

Patient Characteristics by Geography CSVT was more frequent in the West, while the North had a higher proportion of LE DVT. Infection-provoked DVTs were more common in the East (44%) and West (33%) regions as compared to the South (18%) and North (19%, p <.001).

Discussion This analysis revealed few clinically meaningful differences in VTE characteristics or outcomes across sociodemographic factors (race, ethnicity, sex, and geography) among US children with provoked VTE in the Kids-DOTT trial. Our age based analysis showed significant differences with teenagers having a high occurrence of PTS, emphasizing the need to promptly treat and prevent VTE in this age group. Strengths include the trial's multicenter prospective design, systematic follow-up and standardized outcome assessment. Limitations include absence of broader social determinants of health (SDOH) beyond sociodemographics and the low event rates of bleeding and recurrence, which limited statistical power to detect subgroup differences. Integration of comprehensive, validated SDOH measures into future pediatric VTE care and research will be essential to better understand how social context influences presentation, treatment and outcomes.