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Dahlgren and
Wikland report for the Swedish Study Group for growth hormone (GH)
treatment of short children born small for gestational age (SGA). The
final height (FH) achieved in 77 patients treated with exogenous GH
(33 µg/kg/day starting prior to puberty and continuing until
growth was less than 1 cm/year) was compared with data from GH
treatment trials. Data were compared with data from a group of 34
short untreated SGA children. All children were born SGA (−2
SDS from mean for gestational age) for weight, height, or both,
during the years 1973 to 1984. Only data from prepubertal children
were analyzed. Two groups were identified: those who received GH more
than 2 years before the onset of puberty (Group 1) and those who
received GH beginning less than 2 years from the start of puberty
(Group 2). A subset of 28 children were randomized to receive either
33 or 66 µg/kg/day during puberty. Children were excluded from
the analysis if they had chromosomal abnormalities, serious
malformations, chondrodysplasia, maternal history of alcohol or
substance abuse, or a condition requiring chronic medical treatment.
The projected FH was compared with height of the reference population
in Sweden and the gain in FH as the projected adult height in SDS
minus the achieved adult height in SDS. Maternal and paternal heights
were compared with reference values and mid-parental height (MPH) in
SDS. Arginine-insulin GH stimulation tests were performed in all but
2 children; 37% of patients failed to achieve maximal serum GH
stimulation values of 5.3 µg/L (cut-off for severe growth
hormone deficiency at the time of diagnosis).
The mean FH of
the entire group was –1.2 SDS, reaching the mean MPH of –1.2
SDS, and 86% of the children achieved a FH within their target height
(within 1 SDS from their MPH). In the untreated, comparison group,
only 52% achieved a FH within their target height (p<0.001).
Although the mean height gain for the entire group was 1.3 SDS +
0.8, those treated for more than 2 years prior to the onset of
puberty had a gain of 1.7 SDS + 0.7, while those treated less
than 2 years prior to the onset of puberty had a smaller gain of 0.9
SDS + 0.7. The growth responses were most pronounced among
those treated the longest prior to puberty. No differences were seen
in FH among the subset of children who received the higher doses of
GH during puberty (Figure).
The authors
discussed the importance of treating SGA children at as early an age
as possible and the effects of continuing that therapy until growth
is complete. They also noted that the therapy was well tolerated with
no drug-related adverse events. They emphasize that differences
between their study results and those of others may relate to the
long duration of GH treatment in their cohort. They concede that a
broad range of height gain was observed and that this suggests that
individualized dosing may be appropriate. They conclude that younger,
shorter, and lighter children at the start of GH treatment have
better growth responses, are taller at the onset of puberty, and
achieve a better FH.
Dahlgren
J, Wikland K on behalf of the Swedish Study Group for Growth Hormone
treatment. Final height in short children born small for gestational
age treated with growth hormone. Pediatr Res. 2005:57:216−222.
Editor’s
Comment: This is an interesting and potentially important study
of the long-term effects of GH therapy on FH in children born SGA.
Many pediatric endocrinologists are faced with the decision whether
or not to recommend GH therapy for young short children born SGA.
Parents often ask if there is any harm in delaying treatment until
the child is older, perhaps at an age when the benefits of daily
injections might be more understandable. This manuscript suggests
that delaying GH treatment in such children is not in their best
interest and that maximal benefits are associated with early
prepubertal therapy.
It would have
been interesting to know whether or not the children who had a GH
deficiency by stimulation testing (33%) grew better than those who
made sufficient amounts of GH. Since 50% of the comparison group
achieved FH at their MPH without any GH therapy, one wonders if the
difference in outcomes between the comparison group and the treated
group could be accounted for by the increased growth rates of treated
GH-deficient SGA children.
Finally, it
is important to note that although no adverse events related to GH
therapy were reported, the authors did not report which potential
side effects were screened for and what type of testing was performed
to assure that they did not occur. Specifically, it would be very
important to know how glucose intolerance and/or insulin resistance
was monitored in these children. This editor would caution pediatric
endocrinologists who opt for long-term GH therapy for short SGA
children to monitor them carefully and repeatedly for potential side
effects.
William L. Clarke, MD
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Current GGH - Vol. 24 No. 1
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