Risk factors for thrombo-embolism in neonates: A systematic review of the literature and call to action
Bibliographic record
Abstract
Abstract BACKGROUND: While venous thrombo-embolism (VTE) is increasingly recognized in neonates and prothrombotic risk factors are increasing being identified, no risk prediction 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. We aimed to describe maternal, obstetrical, and neonatal risk factors associated with VTE in neonates 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 up to 28 days and with corrected gestational age ≤44 weeks at time of VTE diagnosis, and if studies reported VTE risk factors, including symptomatic and/or clinically unsuspected events. The review was registered on PROSPERO (CRD42024518801). Catheter-related risk factors are reported separately. 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. Risk factors described in ≥3 studies were considered. Random effect meta-analysis was performed in the absence of substantial methodological or clinical heterogeneity; results are expressed using mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was estimated using restricted maximum-likelihood model and expressed using I2. RESULTS: The search yielded 10,579 references, with 283 full-text articles retrieved. Of these, 58 studies (3,450,114 neonates) reporting on the predictive impact of maternal, obstetrical, and neonatal risk factors for VTE were included. Most studies were retrospective (n=25, 43%) or case-control (n=15, 26%) studies; 20 (34%) studies were published within the last 5 years. While VTE definition often did not differentiate symptomatic and clinically unsuspected VTE, 28 (50%) of studies performed at least one surveillance imaging for VTE screening. Most studies (n=48, 86%) had serious risk of bias in at least one domain, typically risk of confounding. Maternal/obstetrical risk factors: Pre-eclampsia and maternal diabetes were predictive of neonatal thrombosis in 2 of 4 (3,102,008 neonates) and 2 of 3 studies (3,106,857 neonates), respectively, while cesarean section was not predictive of thrombosis in 4 studies (40,925 neonates). Demographic variables: Among neonates hospitalised to the NICU, low birthweight was associated with VTE (OR: 2.05, 95% CI: 1.41-3.00, p<0.001, I2=0%, 4 studies). Conversely, gestational age (MD: -0.45, 95%CI: -1.71-0.82, p=0.49, I2=76%, 5 studies) and sex were not significantly associated with VTE (male vs. female, OR: 1.17, 95% CI: 0.94-1.45, p=0.15, I2=24%, 17 studies). Neonatal risk factors: Cardiac disease (OR: 5.90, 95% CI: 1.16-30.03, p=0.03, I2=62%, 3 studies) and infection (OR: 3.16, 95% CI: 1.87-5.33, p<0.001, I2=90%, 7 studies) were significantly associated with VTE. Asphyxia (OR: 5.88, 95% CI: 0.85-40.72, p=0.07, I2=94%, 4 studies), mechanical ventilation (OR: 2.00, 95% CI: 0.52-7.60, p=0.31, I2=99%, 4 studies), and surgery (OR: 3.05, 95% CI: 0.88-10.51, p=0.08, I2=95%, 4 studies) were more frequent in neonates with VTE, albeit not reaching statistical significance. The effect of respiratory distress syndrome, necrotizing enterocolitis, and cholestasis on VTE development was reported in fewer than three studies and was not analyzed. Medication and blood products: Overall, eight studies (202,480 neonates) investigated the impact of postnatal medication (total parental nutrition, steroids, recombinant factor VIIa) or blood product administration in neonates (any, fresh frozen plasma, activated 4-factor prothrombin complex concentrates, antithrombin concentrates) on the risk of VTE; with no intervention examined in more than one study. CONCLUSION: Several risk factors for VTE have been reported in the literature, including pre-eclampsia, maternal diabetes, low birthweight, infection, and cardiac disease. However, important discrepancies between studies and limited data regarding the impact of common conditions and medications persist. Comprehensive prospective research is urgently needed to enable accurate risk prediction and improve VTE prevention in neonates.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.045 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.009 |
| Bibliometrics | 0.009 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".