Risk Factors for Contra-Lateral Secondary Anterior Cruciate Ligament Injury: A Systematic Review with Meta-Analysis

Background The risk of sustaining a contra-lateral anterior cruciate ligament (C-ACL) injury after primary unilateral ACL injury is high. C-ACL injury often contributes to a further decline in function and quality of life, including failure to return to sport. There is, however, very limited knowledge about which risk factors that contribute to C-ACL injury. Objective To systematically review instrinsic risk factors for sustaining a C-ACL injury. Methods A systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases (MEDLINE, CINAHL, EMBASE, Sport Discus) were searched from inception to January 2020. Inclusion criteria were prospective or retrospective studies investigating any intrinsic risk factor for future C-ACL injury. Meta-analysis was performed and expressed as odds ratios (OR) if two or more articles assessed the same risk factor. Results 44 moderate-to-high quality studies were eventually included in this review, whereof 35 studies were eligible for meta-analysis, including up to 59 000 individuals. We identified seven factors independently increasing the odds of sustaining a C-ACL injury (in order of highest to lowest OR): (1) returning to a high activity level (OR 3.26, 95% CI 2.10-5.06); (2) Body Mass Index < 25 (OR 2.73, 95% CI 1.73-4.36); (3) age <= 18 years (OR 2.42, 95% CI 1.51-3.88); (4) family history of ACL injury (OR 2.07, 95% CI 1.54-2.80); (5) primary ACL reconstruction performed <= 3 months post injury (OR 1.65, 95% CI: 1.32-2.06); (6) female sex (OR 1.35, 95% CI 1.14-1.61); and (7) concomitant meniscal injury (OR 1.21, 95% CI 1.03-1.42). The following two factors were associated with decreased odds of a subsequent C-ACL injury: 1) decreased intercondylar notch width/width of the distal femur ratio (OR 0.43, 95% CI 0.25-0.69) and 2) concomitant cartilage injury (OR 0.83, 95% CI 0.69-1.00). There were no associations between the odds of sustaining a C-ACL injury and smoking status, pre-injury activity level, playing soccer compared to other sports or timing of return to sport. No studies of neuromuscular function in relation to risk of C-ACL injury were eligible for meta-analysis according to our criteria. Conclusion This review provides evidence that demographic factors such as female sex, young age (<= 18 years) and family history of ACL injury, as well as early reconstruction and returning to a high activity level increase the risk of C-ACL injury. Given the lack of studies related to neuromuscular factors that may be modifiable by training, future studies are warranted that investigate the possible role of factors such as dynamic knee stability and alignment, muscle activation and/or strength and proprioception as well as sport-specific training prior to return-to-sport for C-ACL injuries. PROSPERO: CRD42020140129.