Table 1.

Arguments regarding the ethical aspect of growth hormone treatment in children with Down syndrome.

Study	Arguments
	Safety of GH treatment	Necessity for GH treatment	Agreement, justice, and autonomy
Binder ND., 1992 (10)	Previous study of GH treatment was completed in a small group without any significant short-term side effects.	Missing a clear statement on the benefits of treatment for DS patients with GH. Raised questions on: what were the benefits to being taller for these patients?, and do benefits outweigh inconvenience or discomfort of the treatment?	Questions whether the researchers believe that it is obligatory to treat DS children with GH? Is the treatment required even if it is against the wishes of the parents?
Underwood LE., 1992 (11)	Authors fail to express concern about leukemia in GH-treated children with DS. Especially important as DS patients have a predisposition to leukemia.	Recommendation for studies to assess child’s biologic and psychologic need for GH, the potential benefits to the child, and the potential physical and psychological risks of treatment. Should question belief that “taller is more desirable”. Implied that head circumference provides special benefit to patient but did not show that increased head size related to improved intellectual performance. Parents might be misled and pursue therapy for the wrong reasons.	Physicians and parents should be wary before controlled studies are completed. Informed consent is difficult because many of these children are limited in their ability to understand issues involved with GH treatment.
Allen D., 1992 (12)	Analysis of potential risks of treatment should include development of leukemia in a population already at increased risk.	Goal of GH therapy is not tall stature, but rather improved quality of life resulting from having achieved height within the normal range. Evidence needed that short stature is a disability for a particular individual. Concern of psychologic effects of repeated injections, especially for children not understanding purpose of treatment. Disability related to height and likelihood of therapeutic benefit should guide therapy.	Assertion that GH responsiveness justifies treatment with GH is oversimplified, and specific diagnosis should not be an automatic indication for GH therapy.
Lantos JD., 2000 (13)		Relationship between GH and growth in DS patients has been established, but is height increase only of value because of perception of others? DS children may not experience enhanced sense of well-being by attempting to fit an externally defined ideal. The more GH treatment can be shown to produce benefits other than height, the more justifiable its use will be.
Allen DB, Frasier SD, Foley TP, Pescovitz OH., 1993 (14)	Although recombinant human GH appears to be safe, analysis of the risks of GH therapy in children with DS must include the possible development of leukemia, and risks not foreseen at present.	Neither short-term nor long-term therapeutic trials of GH therapy have demonstrated improvement in psychologic, intellectual, or social development of children with DS. There is no evidence that an increase in head circumference with GH treatment can be equated with improved intellectual performance by children with DS. Prospective placebo-controlled studies are needed to determine efficacy of GH in improving growth and functional capacity. Evidence that short stature is a disability for a particular individual should also be required. Does short stature per se impair increasingly improved outlook for socialization and employment?	Therapy should be based on child’s disability in relation to height and benefit, and not simply on diagnosis.
Castells S, Wisniewski KE., 1994 (15)	Each child receiving GH is routinely assessed with complete blood cell count and chemistry profile and monitored for: hypothyroidism, slipped capital femoral epiphysis, hyperglycemia, leukemia, and pseudotumor cerebri.	Researchers recognize that all children receiving GH should be in controlled studies to obtain information on effects on growth, head size, facial characteristics, and functional capacity, with special attention to intellectual or social development.	In all cases, parents are well informed of the known risks and benefits of GH treatment, diagnostic procedures are discussed, and a consent form is signed.
Duffey DL., 1994 (16)	Research in England reported that cancer patients receiving human GH treatment experienced 50% less recurrence of tumours than the children who were not receiving GH (Ogilvy-Stuart, 1992)	As inclusion in the normal classroom and realisation of potential growth for children with DS, benefits of normal height and growth and appearance become just as important for children with DS as for any other child. If ignored, risk layering handicaps on top of handicaps and depriving children with DS any chance of living a healthy and happy life as contributing members of society.	Treatment from child should not be withheld simply on basis of presence of disability (Child Abuse Amendments of 1984). It is ethically, morally, and legally right that every child with DS or disability receives same treatment as any other child, without bias or judgment.
Kodish E, Cuttler L., 1996 (17)	Risk of acute leukemia is elevated in all children with DS, and for this, the leukemogenic potential of GH therapy should be considered when balancing the risks and benefits.	There are data to suggest that psychosocial morbidity is associated with short stature in other groups of children but cannot be directly extrapolated to DS. GH may make children with DS stronger and taller, but these outcomes are not likely to decrease their morbidity or mortality. Children with DS are affected by many factors that contribute to morbidity (multifactorial etiologic contributors). The extent to which a child may perceive psychologic or functional morbidity and feel and appreciate benefit of treatment must be considered separately for each case. Measures are needed that assess functional benefit or functional outcomes of treatment; quantitative measures lack practical relevance, unless accompanied by an understanding of their functional impact. Major arguments for: accelerated growth velocity, increased height, and possibly improved muscle strength.	Pediatricians needs to respect and consider experiences of parents and their wishes regarding decisions about GH therapy. This does not relieve physicians of their obligation to the children under their care. Pediatricians should carefully discuss potential risks and benefits of GH therapy with parents of children with DS.
“Little bigger, little better” Lancet Article, 1994 (18)	Do not know about possible side-effects, for example: leukemia, effects on the CNS and skeleton, glucose tolerance, pubertal maturation, and final adult height.	Arguments in favor of therapy include a perceived need for extra height to help DS children feel “normal” in an uncaring world and a suggestion of improvement in general wellbeing. Trials show that at 2 years all 16 enrolled patients with GH therapy were above the 95 percentile for DS children. At 3 years there was no drop in growth velocity.