Prematurity, other factors appear to increase risk for thrombosis in infants
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Infants who were born prematurely, had a low birth weight, experienced sepsis or underwent invasive procedures appeared to be at increased risk for thrombosis, according to study results published in Journal of Thrombosis and Haemostasis.
“Neonatal thrombosis, including arterial and venous thrombosis, can lead to significant morbidity and mortality in hospitalized infants,” Victoria Robinson, BA, researcher at Duke University Medical Center, and colleagues wrote. “Approximately 2% to 4% of infants with thrombosis die as a direct results of thrombosis, and mortality in infants with thrombosis is as high as 33%. ...Thrombosis in the neonatal population is increasing, and its incidence, risk factors and management are not well known.”
Robinson and colleagues conducted a retrospective cohort study to examine incidence and management of neonatal thrombosis among 1,158,755 infants (median gestational age, 36 weeks; 56% male; 53% white) admitted to a Pediatrix Medical Group-affiliated neonatal ICU between 1997 and 2015. They used the Pearson chi-squared test to compare categorical variables, Wilcoxon rank-sum tests to compare continuous variables and stepwise logistic regression to identify associated factors.
Incidence of thrombosis served as the primary outcome. Measures of morbidity and mortality — including death, length of stay and incidence of intraventricular hemorrhage after anticoagulation — among infants with vs. without thrombosis served as secondary outcomes.
Overall, 2,367 infants (0.2%) had thrombosis.
Results of a multivariable regression analysis showed factors associated with increased risk for thrombosis included prematurity (gestational age < 25 weeks vs. 37 weeks, OR = 2.5; 95% CI, 2.15-2.91), male sex (OR = 1.1; 95% CI, 1.01-1.2), congenital heart disease (OR = 2.4; 95% CI, 2.19-2.63), sepsis (OR = 1.45; 95% CI, 1.28-1.63), ventilator support (OR = 2.43; 95% CI, 2.14-2.75), vasopressor receipt (OR = 1.45; 95% CI, 1.31-1.61), history of central venous catheter (OR = 1.25; 95% CI, 1.13-1.38), invasive surgery (OR = 3.24; 95% CI, 2.91-3.6) and receipt of erythropoietin (OR = 1.44; 95% CI, 1.26-1.65).
Conversely, factors associated with decreased risk included Black race (OR = 0.82; 95% CI, 0.73-0.91) and Hispanic ethnicity (OR = 0.88; 95% CI, 0.79-0.98).
Although most infants (73%) with thrombosis did not receive anticoagulation, use was higher among infants with thrombosis compared with those without (27% vs. 0.2%; P < .001).
The percentage of infants with thrombosis who received pharmacologic therapy increased over time, from 22% of infants treated between 1997 and 2001, to 23% between 2002 and 2006, 29% between 2007 and 2011 and 30% between 2012 and 2015.
Median duration of treatment was 8 days (interquartile range, 1-23). The most common anticoagulant used was low-molecular-weight heparin (75%), followed by unfractionated heparin (37%), direct thrombin inhibitors (2%) and warfarin (1%). Of note, 10% of infants with thrombosis who underwent pharmacologic therapy received tissue plasminogen activator.
The majority of infants treated with anticoagulation plus tissue plasminogen activator received only one anticoagulant (78%), whereas 18% received two such therapies and 3% received three or more of these therapies.
Only 5% of infants with thrombosis who received anticoagulation and/or tissue plasminogen activator developed intraventricular hemorrhage, compared with 7% of infants without thrombosis treated with anticoagulation or tissue plasminogen activator.
Researchers additionally found that infants with thrombosis had higher mortality (11% vs. 2%; P < .001) and longer hospital stays (57 days vs. 10 days; P < .001).
The extremely large study population and low incidence of thrombosis could alter the statistical significance of identified risk factors and may be a study limitation, researchers acknowledged.
“Future studies could use a case-control design to identify a subpopulation of age-, race- and sex-matched controls for those infants with thrombosis, which would permit more robust and discriminative application of statistical tests to determine significance of associations,” they wrote. “However, for this initial study, the observed incidence and high variability in diagnosis and management of thrombosis remain key, important findings in this very large sample of the neonatal ICU population.”
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