Cord Blood Treatment for Children With Cerebral Palsy

In this issue of Pediatrics, Finch-Edmondson and colleagues present a systematic review and meta-analysis regarding the treatment of cerebral palsy (CP) with umbilical cord blood (UCB).¹ This article is based on data from 498 participants reported in 11 studies. The results showed that children with CP treated with UCB made greater gains than controls as measured by the Gross Motor Function Measure (GMFM-66)² at 6 months and 12 months but not at 1 or 3 months. Furthermore, UCB treatment was effective only for children younger than 40–60 months and for children classified in levels I-III on the Gross Motor Function Classification System (GMFCS).³ 

This intervention appears to target disturbances to the developing brain associated with CP through mechanisms that are thought to involve “…anti-inflammatory and immune-modulating actions and help improve the local environment via paracrine signaling to promote endogenous repair following injury.”¹ The main outcome—changes in GMFM-66 scores—implies that the impact of UCB is happening at the level of “activity.” This is noteworthy because most evidence-based interventions for children with CP are primarily directed at the biomedical impairments thought to underly the condition, addressing what the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) framework for health refers to as “body structure and function” (BSF)⁴; however, there is credible evidence that even statistically significant changes in measures of BSF are not necessarily associated with changes in activity or participation.⁵ It is also important to recognize that the GMFM-66 assesses “capacity,” what people do in a standardized evaluation situation. In contemporary ICF thinking, we are increasingly interested in people’s everyday “performance” of activities and in understanding the personal and environmental factors that influence (enhance or interfere with) that performance.

The main finding of the meta-analysis is that mean GMFM-66 scores at 6 months and 12 months following UCB treatment were higher for children who received UCB treatment, with effect sizes of 1.36 at 6 months and 1.42 at 12 months (note that the effect size is calculated as the difference between the mean treatment group score and the mean control group score divided by the common SD). Thus, the effect sizes reported in this study represent what is conventionally considered a large treatment effect.⁶ By way of comparison, the effect size for evidence-based interventions for children with CP is often small or medium. Furthermore, the effect size at 6 and 12 months indicates that approximately 68% of children who received UCB treatment had GMFM-66 scores that were higher than the scores of all children in the control group.⁶ The percentage of nonoverlap of scores has important implications when sharing findings with families, whose primary interest is of course not group differences but whether an intervention will likely benefit their child. Presentation of the mean GMFM-66 scores and SDs at each end point would have enabled discussion of whether the mean differences are clinically meaningful.

Critical to shared decision-making with families is knowledge of the characteristics of the children most likely to benefit from a treatment or intervention. This is especially true for children with CP who, as a population, are very varied in their gross motor function and their potential for change, even when classified in the same GMFCS level.⁷ The effect size statistic indicates that among children who received UCB treatment, younger children (≤40–60 months) and those classified in GMFCS levels I-III (some ability to walk) had significantly higher GMFM-66 scores compared with children in the control group, whereas children older than 40–60 months and those in levels IV-V (requiring powered mobility or needing to be transported by others) did not. The gross motor function curves for children with CP⁷ indicate that children younger than 5 years classified in levels I-III demonstrate age-related increases in GMFM-66 scores. In our opinion, this is not sufficiently emphasized and has important implications for decision-making.

The finding that the effect size at 1 month and 3 months following UCB treatment was not significant has implications for anticipatory guidance regarding how we counsel parents about this potential intervention. The authors suggest that the presumed mechanisms of UCB are not immediate, and “subsequent clinical improvements likely rely on the principles of neuroplasticity, with neural pathways strengthened by physical therapy over weeks to months.”¹ This raises several important questions. How should families be counseled on expectations for their children’s motor function after UCB? Should children’s and families’ priorities and goals for activity and participation be modified based on the potential effects of UCB treatment? Should children receive additional therapies for 6–12 months following UCB treatment?

Based on the conclusions of this meta-analysis, there are clearly research opportunities to explore the potential impacts of (1) varied doses of UCB on (2) younger children with CP (those aged <5 years) and (3) in children in GMFCS levels I-III, for whom there appears to be greater potential for change. We would, of course, encourage all researchers to engage parents in identifying their children’s pre- and posttreatment functioning (as might be provided by the Pediatric Evaluation of Disability Inventory Computer Adaptive Test⁸ or the new Gross Motor Family Report⁹) and their goals for their children (and, wherever possible, the children’s self-reported hopes). We look forward to seeing such future work performed to better understand the true benefits of UCB treatment for children with CP.

BSF

body structure and function

CP

cerebral palsy

GMFCS

Gross Motor Function Classification System

GMFM

Gross Motor Function Measure

ICF

International Classification of Functioning, Disability, and Health

UCB

umbilical cord blood