This study, compared growth in children and adolescents with CP from a northern European (Germany) and a southern American country (Argentina) to both the WHO reference for TD children , and the US CP references from Brooks et al. .
Children with CP in both countries are shorter, lighter and smaller than their typically developed peers and these differences increase as their GMFCS level and age increase. Previous studies have also demonstrated that children with CP grow differently from their TD peers and that GMFCS level strongly influences their growth [9, 11, 13, 20]. Studies from German and Argentinian children with CP have also recently shown this difference [21, 22].
The second main finding is that between the two countries, children with CP differed significantly in height. German children with CP with GMFCS level I to III grow similarly to their TD peers, but those with GMFCS level IV and V are significantly shorter. In contrast, all the Argentinian children with CP were shorter than their TD peer, no matter the GMFCS level and their HAZ tended to decrease with age, twice as fast as for German children. Growth differences after pubertal age have been shown for healthy children in different countries and ethnicities [1, 23]. A large meta-analysis on fifty-three different healthy populations indicated that the mean height of preadolescent healthy children differs by 3 to 5 cm. At puberty, most non-European populations fall approximately 5 cm below the reference and northern European populations exceeding the reference by a similar amount . This finding may be explained proximally by population differences in the initiation and progression of puberty in TD children. In Argentina, children with TD show a two-year earlier sexual development, which leads to an earlier closure of the epiphyseal growth plate and explains a shorter final height in the general population when is compared to international references [24, 25]. Differences in the onset of puberty, which may also relate to the severity motor impairment, could partially explain differences in height between TD children and children with CP found in our study [10, 26]. The present study did not measure pubertal status or progression in children with CP, and further research would be needed to examine this possibility.
Our study demonstrates, for the first time, that the same ethnic differences that can be observed in children with TD can also been seen in children with CP. Differences in height between countries are multifactorial, but are likely to mostly relate to epigenetic, and environmental rather than genetic, factors. Secular trends in height are commonly seen within countries, related to changing socio-economic status, nutrition, and health, and these can serve as public health indicators for interactions between growth and environment [3, 4]. It has been demonstrated that social and psychological factors (such as socioeconomic status, parental education or emotional deprivation) are related to linear growth, and the effects of socio-economic crisis can increase low birthweight prevalence and can affect secular changes [27–29]. The effect of environmental factors may also explain differences in growth in children with CP from countries with difference socio-economic realities and healthcare systems, such as Germany and Argentina. Further research is needed to understand how environmental factors affect growth in children with CP.
It is puzzling that US CP charts tended to overestimate HAZ for children with CP in both countries, a similar finding to the earlier UK study . For context, it should be noted that height measurements used to develop the US CP charts were taken from medical records and were not validated, and the authors recommend that height curves should therefore be viewed with caution [7, 11]. Due to the difficulties in measure height in children with CP with severe motor compromise, it is possible that the differences in height could be related to the differences in measurement methods. Beyond the possible bias, differences were greater than 0 HAZ z-score for all GMFCS levels. It is also possible that this reflects the fact that the data used for the US charts was collected longer ago and that children with CP may grow better now than previously, due to improvements in neonatal nutrition. Future prospective multicenter studies with training measurement methods could help adjust this bias.
Besides the ethnic and sociodemographic differences, further influencing variables need to be considered for children with a chronic disease (such as CP). Compared to the US CP growth chart, children with non-oral feeding had higher BMIZ and a better fit to the charts. On the other hand, for WAZ there was a better fit for children with oral feeding, who presented lower z-score values than their peers with non-oral feeding. In the multivariate analysis, Argentinian children that were fed orally presented a significantly lower z-score than those with non-oral feeding. These findings suggest that some of the growth deficit in children with CP and GMFCS level V could be related to nutritional deficit, and when they are fed enterally, totally or partially, nutrition is more secure. This difference in growth according to the feeding modality have already been mentioned in other CP studies, showing differences between countries, and required the development of different growth charts according to feeding in the CP US Charts [11, 30].
Some limitations should be mentioned. Selection bias may exist when comparing different study populations. In Argentina, we were able to observe that the centers included had more children with GMFCS levels IV-V, whereas in the German study site patients showed a broader range of GMFCS Levels, and was predominately Level I. The prevalence of less compromised motor impairments seems to be increasing in European countries and Australia [31–33], with a similar distribution as that in our German sample. It is possible that in Argentina there is a bias due to the type of centers included, where motor disabilities were more severe. In the absence of a complete local register, it is difficult to establish if our sample distribution is representative of the Argentinian CP population. Another limitation is the possible information bias from a retrospective study. We tried to control this bias by including only patients with complete anthropometric measurements and chose their last visit if multiple measures were available. However, because of the difficulty of measuring height in children with CP, it is possible that children with more severe motor compromise were lost because measurements were not available. Due to the limitations of height measurement and the lack of relation between BMI and body fat mass [34, 35], the interpretation of BMI as an indicator of body composition should be considered with caution. To study nutritional assessment in detail, other anthropometric measures beyond weight, height and BMI are recommended  to assess nutritional status, such as segmental measures and skin fold. These measures were not available in all medical records.
The major strength of this study was the capacity to monitor growth in two well controlled settings. Another strength is the chance to compare children with CP form two difference settings, Argentina and Germany. Our analysis of growth possibly reflects environmental and health care differences that should be deeply studied in the field.