Growth Delay

“Growth retardation is a cardinal characteristic of Down syndrome” (Annerén et al, 1990). It is not known what the underlying mechanism is responsible for the retardation of growth. DS children have normal levels of human growth hormone (hGH) and low levels of somatomedin C — also called insulin-like growth factor (IGF-1). IGF-1 is regulated by hGH postnatally, and it appears that in DS there is a delayed, possibly incomplete, transfer from foetal IGF-1 to the hGH regulated IGF-1 (Annerén et al, 1990). Growth is mainly restricted between the ages of 6 months (when hGH starts to regulate growth) and 3 years. Some, but not all, researchers have found that growth after this age is near to normal, just starting from a smaller stature (Annerén et al, 1993). Napolitano et al (1990) found that the level of IGF-1 rose after zinc supplementation, especially in children over 7. Zinc levels diminish with age in DS people, as with normal people, though this happens earlier in DS, so it is conceivable that the results were more pronounced with older children as they had a greater need for extra zinc.

The effect of zinc supplementation

Strangely, despite the well documented link between zinc deficiency and growth delay (Passwater and Cranton, 1983), this author found only one paper investigating the effects of zinc supplementation on growth in DS children. Napolitano et al studied 22 DS children whose growth velocity was calculated for the six months before the period of supplementation and during the six months of therapy. They were supplemented by os, and their rate of growth compared with special growth charts for DS children (Cronk et al, 1988). It was found that 15 of the subjects moved into a higher centile in their growth charts and, interestingly, that the children older than 7 years showed a greater differential in growth velocities before and during supplementation than the children aged 4-7 years. This particularly noteworthy when compared to the finding that suppressed growth occurs earlier. Unfortunately, no children under 3.8 years were included. The results for children under 4 years, and over 10 years (girls) or12 years (boys) were considered separately to avoid interference by first childhood and pubertal growth spurts.

This author considers that there could be huge potential for zinc therapy to minimise growth retardation. Zinc is essential for DNA and RNA polymerase and thus for cell proliferation; it is necessary for protein metabolism; and as it is essential for the functioning of hormone receptors (such as protein kinase C) zinc is possibly required for hGH and/or any of the hGH regulated growth factors to function efficiently. The results of Napolitano et al’s work are encouraging, but need to be repeated with measurements of the foetal variant form of IGF-1, and assays into numbers and activity of hGH binding sites in DS would be useful.  Further research using younger children would be extremely valuable in illuminating the role of zinc in hGH functioning, transfer to hGH regulated IGF-1, and growth delay. Napolitano et al suggest the possibility that thymus hormones may have a role in regulating the secretion of hGH in DS children. Considering the importance of the thymus and thymic factors already discussed, this link raises many more possibilities.