Growth Attenuation Therapy in Children with Severe Physical and Cognitive Disabilities

Julia R. Donner, MD (’23)
Developmental and Behavioral Pediatrics Rotation

In the field of pediatric endocrinology, growth attenuation therapy (GAT) is not a new concept, however its application and the ethical implications thereof in children with profound cognitive and physical disability remains an evolving conversation among many pediatric disciplines. 

The discussion around this topic began with Ashley’s story. Her pediatric endocrinologist Dr. Gunther and Dr. Diekema, a pediatrician who specializes in bioethics, reported Ashley’s case in 2006, a landmark article providing information on growth attenuation therapy in a child with profound physical and cognitive disability.  

Ashley was born in 1997 in the Seattle area, the product of a normal birth without complications. At around 1-2 months of life, she displayed hypotonia, feeding difficulties choreoathetoid movements, and profound developmental delay. She was referred to neurology, genetics, and developmental pediatrics and eventually diagnosed with static encephalopathy with marked global developmental deficits. The underlying cause of these deficits was not elucidated at the time of diagnosis although she was later found to have a de novo non-mosaic single-nucleotide polymorphism in the GRIN1 gene. Developmentally, she remained at the stage of an infant. At age 6 she could not sit, ambulate, or use language, however she made vocalizations and smiled responsively. She was dependent on a G-tube for feeding. Significant improvement was deemed unlikely. In terms of her home context, Ashley was cared for by her two parents and had two healthy siblings. She was a loved and integral member of the family.

At 6 years and 7-months, she was initially referred to pediatric endocrinology for precocious puberty. At that time her parents reported one year of pubic hair development, a three-month history of breast bud growth, and accelerated linear growth over the past 6 months with length increasing from 50th to 75th percentile. Her parents feared that her increased growth would make it impossible for them to care for her in their home and discussed growth attenuation therapy. They were referred to the institutional ethics committee who deemed treatment for Ashley ethically appropriate. 

Ashely received 400 μg of transdermal estradiol daily. She also received elective hysterectomy and removal of breast buds, neither of which are essential tenants of GAT therapy. These surgical procedures remain highly controversial and represent a separate issue. She was followed up every 3 months and carefully monitored for growth, bone age, insulin-like growth factor I, estrogen and prolactin levels, and thrombotic factors. Her final adult height was 53 inches at a weight of 63 pounds which was an estimated reduction of her potential height and weight of 20 and 40% respectively. This treatment was colloquially referred to as the “Ashley treatment” afterwards and the case instigated international discussion, publicity, controversy, and media attention, the result of which being the argument that GAT is both medically feasible and ethically defensible on a case-by-case basis.  

Growth attenuation therapy has been used historically to reduce final adult size of girls with constitutional tall stature or patients with acromegaly, but this was the first time it was applied in the context of a child with profound cognitive and physical disability. It is known that estrogen causes maturation of the epiphysial plates and therefore, growth attenuation therapy utilizes high dose estrogen for rapid maturation and closure of the epiphyseal plates for growth arrest resulting in a reduced adult height. It can also involve non-treatment of precocious puberty as earlier exposure to sex steroids and puberty lead to attenuated final adult height. 

The goal of therapy for Ashley’s family and of those like hers is to prolong care time at home within the family and make this care more feasible to prevent transition to facilities. Lifting and transferring of children becomes more challenging the larger they grow and formation of bed sores and other side effects of being sedentary become a larger issue with increasing size. Growth attenuation could potentially prevent these effects and allow for better quality of life for these children as they age and are able to remain at home. 

An opposing argument from disability rights groups is that GAT is a violation of personal civil rights and goes against basic principle of do not harm. These groups also discuss the technologies available such as mechanical lifts and motorized vehicles which can mitigate the burdens of body mass, arguing that because of these devices there is no need to alter the body itself. 

In 2015, members of the Pediatric Endocrine Society were surveyed about their experiences with GAT. In this report, Pollock and colleagues (2015) reported that 99 of 284 respondents (35%) disclosed that they had been asked to prescribe GAT and 11% had prescribed GAT. Of these endocrinologists, 94% said requests came from patient’s family and 34 reported seeking ethics consultation. Oral estrogen was the most common sex hormone therapy used for GAT. It is evident that GAT will continue to be a topic of conversation within pediatric endocrinology and an ever-evolving conversation in the field. 

Currently, growth attenuation therapy for children with profound cognitive and physical disability is considered sufficiently safe and with a low risk profile, however it remains an experimental therapy given the lack of large-scale studies or trials. There are no clear clinical guidelines to direct clinicians how and under what circumstances to initiate a referral for GAT. The most recent committee meeting in 2010 amongst experts in many fields and families of children with profound disabilities came to a “moral compromise” which deemed GAT acceptable in some circumstances, but should be preempted with a structured decision-making process, meeting set eligibility criteria, and the involvement of an ethics committee. It may offer improved quality of life for non-ambulatory children with profound cognitive disability and their families; however, it remains a controversial topic and one that needs to be addressed on a case-by-case basis. An ethics consultation recommended and multidisciplinary care to make the best choice for each individual child. 

References:

  1. David B. Allen, Michael Kappy, Douglas Diekema, Norman Fost; Growth-Attenuation Therapy: Principles for Practice. Pediatrics June 2009; 123 (6): 1556–1561. 10.1542/peds.2008-2951
  2. Gunther DF, Diekema D. Attenuating growth in children with profound developmental disability: a new approach to an old dilemma. Arch Pediatr Adolesc Med. 2006; 160(10):1013–1017
  3. Pollock AJ, Fost N, Allen DB. Growth attenuation therapy: practice and perspectives of paediatric endocrinologists. Arch Dis Child. 2015;100(12):1185. doi:10.1136/archdischild-2015-309130
  4. Wilfond BS, Miller PS, Korfiatis C, Diekema DS, Dudzinski DM, Goering S; Seattle Growth Attenuation and Ethics Working Group. Navigating growth attenuation in children with profound disabilities. Children’s interests, family decision-making, and community concerns. Hastings Cent Rep. 2010 Nov-Dec;40(6):27-40. doi: 10.1002/j.1552-146x.2010.tb00075.x. PMID: 21155109.

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