Background: Critically ill infants are susceptible to thrombosis due to several risk factors. The aim of this study was to identify risk factors associated with venous and arterial thrombosis in neonates admitted to the neonatal intensive care unit (NICU) and to identify differences in risk factors for venous versus arterial thrombosis. Methods: We conducted a case-control study at 31 level IV NICUs using the Children's Hospital Neonatal Database between Jan 1, 2010, and Dec 13, 2016, in the USA. Cases were identified on the basis of having an outcome of venous or arterial thrombosis. Controls were matched by gestational age, presence of a central access device (CAD), hospital, and admission year. Four controls per case (1:4) were randomly selected. Bivariable and multivariable regression analyses were performed to examine the associations between potential risk factors and venous or arterial thrombosis. CAD-related risk factors were analysed in the subset of neonates with a CAD. Findings: We identified 118 952 new admissions to 31 NICUs. The overall thrombosis incidence was 15·5 per 1000 NICU admissions (95% CI 14·8–16·2). After exclusion of patients with a length of hospitalisation longer than 3 days or heart disease, the study included 1326 thrombosis cases (1022 with venous thrombosis and 362 with arterial thrombosis; 58 patients had both types of thrombosis and are included within both of these numbers) and 5304 randomly selected controls. Venous thrombosis was independently associated with bloodstream infection (odds ratio 2·07, 95% CI 1·72–2·49; p<0·0001), maternal diabetes (1·62, 1·30–2·03; p<0·0001), abdominal or gastrointestinal surgery (1·36, 1·17–1·58; p<0·0001), thrombocytopenia (2·44, 2·02–2·94; p<0·0001), prolonged mechanical ventilation (1·27, 1·10–1·46; p=0·0014), and age 7 days or older at admission (1·49, 1·28–1·74; p<0·0001). Arterial thrombosis was independently associated with maternal hypertension (1·42, 1·05–1·91; p=0·030), thrombocytopenia (2·20, 1·59–3·06; p<0·0001), prolonged mechanical ventilation (1·58, 1·24–2·01; p=0·0002), age 7 days or older at admission (1·35, 1·05–1·74; p=0·0018), and small for gestational age (1·56, 1·13–2·16; p=0·0003). In the CAD subset analysis, CAD duration of 21 days or longer (venous thrombosis: 1·52, 1·15–2·01, p=0·0034; arterial thrombosis: 1·98, 1·25–3·14, p=0·035) and CAD in both the upper and lower body (venous thrombosis: 2·43, 1·92–3·08, p<0·0001; arterial thrombosis: 1·58, 1·02–2·45, p=0·040) were associated with higher odds of thrombosis. Interpretation: Identification of thrombosis-associated risk factors will be useful in developing a risk prediction model to prevent thrombosis and in improving outcomes. The study results add to the knowledge of the differences in risk factors for venous versus arterial thrombosis in neonates and to the understanding of the associations of CAD characteristics with neonatal thrombosis. Funding: Bristol-Myers Squibb–Pfizer Alliance.
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