Thirty-five studies (2,251 children) were included in the review; two randomised controlled trials, 16 prospective cohort studies, 12 retrospective cohort studies, two pharmacokinetic studies and three studies where study design was not stated.
The pooled incidence rates for efficacy for primary prophylaxis in children at risk of venous thromboembolic events was 0.047 (95% CI 0.023 to 0.091; five studies) and treatment with low-molecular weight heparins for secondary prophylaxis was 0.052 (95% CI 0.037 to 0.073; ten studies). The incidence rate of a major bleeding event on low-molecular weight heparins treatment was significantly higher at 0.050 (95% CI 0.031 to 0.078; 15 studies).Moderate heterogeneity was observed for safety outcomes (Ι²=44%), but statistical heterogeneity for efficacy outcomes was not substantial (Ι²=12%).
The results of the meta-regression analyses showed there were no statistically significant effects on the efficacy results related to age at first venous thromboembolic events, publication year or study country. However, the country of study was shown to have an effect on bleeding events; countries in which twice daily low-molecular weight heparins treatment was administered with a peak target range of 0.5 and 1.0IU/mL anti-factor Xa levels showed significantly higher bleeding rates than countries in which low-molecular weight heparins was administered once daily.