Introduction

Is it medically and ethically appropriate to shorten and sterilize a six-year old girl to make it easier for her parents to properly care for her now and in the future? This is the question that confronted Seattle's Children's Hospital when the parents of a six-year old girl named Ashley approached the Ethics Committee requesting approval for various procedures that would improve the quality of life of their daughter. Ashley, called the “pillow angel” by her parents, suffers from a developmental brain condition known as static encephalopathy. “She had a normal birth, but failed to develop, mentally and physically, for reasons doctors could not ascertain. . . The diagnosis means that her brain has been damaged and the addition of the term ‘static' means that her condition will not improve. She will remain for the rest of her life with the mind of a baby”₁. Her profound developmental disabilities and her inability to ambulate, provide numerous challenges for her parents and caregivers. If her growth could be permanently arrested while she was still small in stature, then according to her parents the benefits would give Ashley a better quality of life and allow her parents to continue to care for her at home. The Ethics Committee recommended the procedure to keep Ashley small. High-dose estrogen treatments over the last two years “both inhibited growth and rapidly advanced maturation of the epiphyseal growth plates, bringing about permanent attenuation in size after a relatively short period of treatment” ₂. Ashley's prospective height was reduced about 13 inches to 4 feet 5 inches. Ashley's parents argue that “this makes it more possible to include her in the typical family life and activities that provide her with needed comfort, closeness, security and love: meal time, car trips, touch, snuggles, etc.”₃. However, besides the high-dose estrogen treatment, physicians removed Ashley's uterus, to prevent potential discomfort from menstrual cramps and pregnancy in the event of rape, and removed her breast buds because of a family history of cancer and fibrocystic disease. Ashley also had an appendectomy for preventative reasons₄. This treatment has now been named the “Ashley Treatment.”

The debate surrounding this treatment contrasts those who argue that the Ashley Treatment is for “creating a 21^st century Frankenstein and for maiming a child for the sake of convenience” versus those who argue that this treatment is not only in the best interest of the child because it will provide a better quality of life but is also in the best interest of the parents and society as a whole₁. Those advocating for the rights of the disabled see this treatment as potentially leading to the violation of human rights for the disabled. What can at first glance appear beneficial can in the long-run lead to harmful results. Disability-rights advocates argue that Ashley was not suffering and that the treatment was untested₄. In an editorial regarding the Ashley Treatment in Archives of Pediatric & Adolescent Medicine, the authors question whether the Ashley Treatment is a “simple technical fix”₅. Determining whether this treatment is in the best interest of the child is both a medical and ethical issue because substantive questions have arisen about this procedure. Are there uses of medical technology that are inconsistent with respect for the human person? If the Ashley Treatment becomes widely accepted, could this lead to the use of more controversial procedures that might reduce the size or reproductive capacity of other vulnerable people? If this treatment becomes a part of standard medical practice, could it affect insurance coverage and rates?₆ These questions are important because other families are contemplating the same procedure for their children.

The purpose of this article is twofold: first, to examine the medical facts of Ashley's condition and to analyze the Ashley Treatment; and second, to give an ethical analysis of the Ashley Treatment.

Medical Analysis

Since infancy, Ashley has been suffering from a developmental brain condition diagnosed as “static encephalopathy with marked global developmental deficits”₂. Encephalopathy, literally meaning “brain damage,” can stem from a variety of causes such as head trauma, brain tumor, exposure to toxic chemicals, pressure within the cranium, lack of oxygen or nutrition, bleeding in the brain, premature birth, birth defect, complications in labor and delivery and travel through the birth canal₇,₈. Encephalopathy is generally characterized by an “altered mental state,” and specific symptoms include the loss of cognitive abilities, lapse in memory, problems with speech and hearing, loss of muscle control, learning and speech delays, tremors and seizures₇,₈. Encephalopathy generally is graded such that the symptoms can range from mild to severe, and each case is unique to the individual₈.

Moreover, the cause of Ashley's condition is presently unidentifiable, which is sadly the etiology for many encephalopaths₃. Ashley's brain stopped developing at around three months rendering her with the cognitive and mental abilities of an infant and her developmental progress is stagnant at that stage₂. The defect in Ashley's brain has removed her ability to control her muscles, eliminating her ability to engage in even simple intentional movements or muscle manipulations. Specifically, Ashley “cannot keep her head up, roll or change her sleeping position, hold a toy or sit up by herself, let alone walk or talk,” according to Ashley's parents₃. In addition, at nine years old, she lacks the capacity to express complex emotions or participate in complicated or even simple thought processes that would be expected from other children of her same age₃. However, Ashley does exhibit an awareness of her own environment, expressing elation over music, lights and sounds, and appears to be soothed by personal contact., especially that of her parents, younger siblings and grandparents₃.

Given Ashley's limited mental capacity and mobility, she is absolutely dependent on her caregivers in every way, including, changing her position, transportation, entertainment and feeding₃. Ashley is fed through a percutaneous endoscopic gastrostomy (PEG) tube that has been inserted into her stomach during a surgical gastrostomy₉. The tube allows Ashley to obtain nutritionally balanced liquid products without oral ingestion to ensure she receives the proper balance of fats, proteins, carbohydrates, vitamins and minerals₉. The risks associated with this method of nutrition include aspiration, pneumonia from food traveling up into the esophagus, nausea, vomiting, cramping, diarrhea, infection and constipation as a result of improper food consistency₉. As a result, the peg tube must be constantly monitored and kept clean to prevent any complications or aspirations₉.

In early 2004, at 6 years and 7 months old, Ashley exhibited signs of puberty including the growth of her breasts and observable pubic hair₂. Consequently, her parents began to seek surgical and medical options available to Ashley with respect to menstruation, breast development and changes in height and weight₂. Ashley's parents, along with the help of Dr. Douglass Gunther, Associate Professor of Pediatrics in Endocrinology at Seattle's Children's Hospital, designed the following course of action that has since been entitled the “Ashley Treatment”: high-dose estrogen therapy to limit height and weight, hysterectomy to remove the uterus and prevent menstruation, breast bud removal to halt breast development, and an appendectomy₃. While such drastic procedures have recently become a controversial topic for discussion especially within the medical and ethical communities, Ashley's parents maintain that all of the procedures were performed in Ashley's best interest, in the preservation of her dignity as an individual, and with the goal of improving her quality of life (i.e. reduced chances of skin sores due to her sedentary nature, bladder infections and pneumonia)₁₀. Dr. Douglass Diekema, a physician on the Seattle Children's Hospital Ethics Committee that evaluated Ashley's case, also alludes to the fact that with her smaller size she will be able to participate in more family events, receive more personal contact and affection and no longer would experience the trauma of menstruation for which Ashley would have little comprehension₁₁.

Initially, physicians implemented the use of high-dose estrogen therapy to slow and halt the growth of Ashley's bones, limiting her size₂. Ashley is prescribed 400 µg of transdermal estradiol daily, using up to six transdermal patches at one time₂,₁₀. This prescription is eleven times greater than the standard prescribed oral contraceptive dosage of 20-35 µg₁₂. Every three months, Ashley is monitored for growth, bone age, insulin-like growth factor I, estrogen and prolactin levels, and thrombotic factors₂. Presently, Ashley has a bone age of 15 years old and her growth plates are 99% closed₁₀.

Estrogen plays a key role in the growth, differentiation and function of many tissues within the body. In particular, research has proven that estrogen helps to regulate the fusion of the epiphyseal disks, or growth plates, in the long bones of the body₁₃. During development, endochondral growth stimulates bone formation at the epiphyseal disks of the long bones₁₄. This process involves cartilage formation followed by the migration of osteoblasts, bone forming cells, into the epiphyseal space, ultimately concluding in bone mineralization and ossification₁₄. As an individual ages, there is a gradual decline in the proliferation of chondrocytes (cartilage forming cells) which slows bone formation in these areas, ultimately leading to the fusion of the epiphyseal disks and the cessation of the growth process₁₄. However, with the introduction of exogenous estrogen, the rate of proliferation slows much faster, inducing the termination of endochondral growth much earlier than without the estrogen₁₃. Research reveals that estrogen appears to be involved indirectly in the premature fusion of the epiphyseal disks, such that it “exhausts the proliferative potential of the growth plate chondrocytes, consequently triggering earlier epiphyseal fusion”₁₃.

In addition, research has proven that estrogen induces the apoptosis of osteoclasts, cells responsible for bone resporption and bone remodeling₁₄,₁₅. Following the addition of estrogen, osteoclasts display identifiable signs of apopotosis, or programmed cell death, including chromatin condensation and altered nuclear morphology₁₅. Cells that are in the stages of apoptosis have a distinct morphology and have unique biochemical features, which are easily identifiable under a microcscope₁₅. During apoptosis the DNA with the nucleus of the cell is degraded by nuclear enzymes resulting in the appearance of multiple collections of chromatin around the edge of the nucleus₁₄. In addition, the cell volume decreases, proteolytic enzymes begin to degrade the vital organelles such as mitochondria, and finally the membrane begins to fall apart₁₄.

Moreover, estrogen also grossly affects osteoblasts, the bone cells directly responsible for bone formation₁₆. Researchers assert that after the introduction of estrogen, there is a decline in cell proliferation and a decrease in osteoblast number₁₆. Inactivating both osteoclasts and osteoblasts, prevents any form of bone remodeling and significantly decreases the rate of bone synthesis within the body. As a result of the high-dose estrogen therapy, Ashley will reach a final height of 4'6” and weight of approximately 70 pounds rather than an anticipated height of 5'6” and about 120 pounds₁₀. While Ashley has a normal life expectancy, most likely comparable to that of an individual with cerebral palsy, she will permenently live in the body of a 9-year-old girl₃.

The notion of growth attenuation through high-dose estrogen therapy was first implemented in the 1950s in an effort to reduce the height of taller adolescent females₁₇. In the 1960s and 1970s researchers began to examine the potential side effects of high-dose estrogen therapy on females' health₁₈. It was concluded that side effects such as nausea, headaches, weight gain, mild hypertension, benign breast disease and ovarian cysts were reported₁₈. In addition, such a significant dose of estrogen could also lead to two other major side effects: endometrial cancer and breast cancer. While Ashley's parents claim they chose the hysterectomy and breast bud excision for alternative reasons, the removal of these two organs relieves the high risk of cancer from the high-estrogen therapy. While it was formerly believed that estrogen had positive effects on cardiovascular function, recent studies indicate that there is no significant increase or decrease on the rate of cardiovascular disease₁₉. Further risks include venous thromoembolism, gallstones and/or cholescytectomy, complications with lipid metabolism and cholesterol, stroke and myocardial infarction, endometrial and breast cancer, uterine bleeding, hypercalcemia in patients with breast cancer, and visual abnormalities in the form of vascular thrombosis₂₀.

While Ashley will not develop endometrial or breast cancer, or suffer from uterine bleeding, the risk of venous thromboembolism, via deep vein thrombosis, is truly a significant risk for Ashley. Deep vein thrombosis is caused by the formation of blood clots in the deep veins and appears to cause mild inflammation in the vein₂₁. This mild inflammation increases the chance that the clot will disengage from the vein wall, travel through the blood stream, and form a blockage in a major artery leading to the heart or lung, known medically as a pulmonary embolism₂₀. Such a condition can be potentially fatal in a matter of hours and is virtually asymptomatic₂₁. About one half of individuals experiencing vein thrombosis have no symptoms₂₀. Individuals experiencing typical estrogen therapy are at a two fold greater risk for venous thromboembolism from 9 in 100,000 users to 18 in 100,000 or even as high as 34 in 10,000 users₁₂,₂₀. This risk for Ashley is even greater considering that she is receiving eleven times the normal dosage. Estrogen directly inhibits anticoagulants within the blood from preventing the formation of clots, affects the synthesis coagulation factors in the blood and causes blood thickening, which allows clotting factors to associate more frequently, enhancing clot formation₁₂,₂₂,₂₃. Moreover, Ashley's sedentary condition puts her at even greater risk for venous thromboembolism as she has no mobility or means of circulating blood by movement₂₁.

In addition, estrogen therapy also has been shown to affect lipid metabolism and cholesterol by decreasing HDL cholesterol and increasing LDL cholesterol₁₂. Within the body, there are two types of carrier proteins that transport cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL)₂₃. The HDL cholesterol, or “good” cholesterol, removes cholesterol from cells to the liver to be eliminated from the body, while LDL cholesterol, or “bad” cholesterol, directs cholesterol to be transported from the liver to cells within the body₂₃. LDL cholesterol is often oxidized within cells and eventually leads to the development of atherosclerosis and plaque formation₂₃.

Moreover, any increase in the amount of cholesterol within the systemic system ultimately leads to an increase in cholesterol in bile composition₁₂. Even small increases in the amount of bile can cause precipitation and the formation of gallstones within the gallbladder₁₂. With extended exposure, there is a two to four fold increase in gallbladder disease, possibly resulting in a cholesctectomy as an additional surgical procedure₂₀. One final notion to take into consideration is that these risks are based on a daily estrogen dose of 20-35 µg. In Ashley's case, the risks are magnified greatly as she receiving a daily estrogen dose of 400 µg.

The second component of the treatment process is a hysterectomy, which is the complete removal of the uterus₂₅. However, the ovaries were still kept in order to provide Ashley with natural hormones. By leaving the ovaries still within the body, Ashley will continue to experience the normal hormonal fluctuation, including estrogen and testosterone associated with menstruation until menopause without the associated shedding of uterine lining and bleeding₂₃. The ovaries produce estrogen, progesterone and female androgens₂₄. Estrogen is necessary for the maintenance of the female reproductive system and secondary sex characteristics₂₄. Non-reproductively, estrogen promotes fat deposition, increases bone density and stimulates the closure of the epiphyseal disk, or growth plates, at the ends of long bones₂₄. It has also been asserted that leaving the ovaries intact actually decreases the risk of ovarian cancer by almost 50%₂₃. The ligation of the fallopian tubes prevents foreign agents, such as talc found in feminine hygiene products, from compromising the sterile ovarian environment and inducing the development of cancer₂₃. The ovaries will continue to release one egg monthly, yet the egg will simply be absorbed by the body₂₅. However, it has been cited that the ovaries may not function properly post-operatively as a result of altered blood supply₂₆. Such a malfunction results in a decrease in the natural hormones production which are also responsible for imparting protection against osteoporosis and heart disease₂₆.

Each year in the United States, there are 600,000 hysterectomies performed, making this type of surgery second only to cesarean sections₂₃. A hysterectomy can be surgically performed in one of three ways: vaginally, abdominally or laproscopically₂₃. Ashley underwent an abdominal hysterectomy enabling the surgeon to view all of the pelvic organs and access the appendix₂,₂₃. An abdominal hysterectomy is performed through a 13 cm incision in the abdomen, either vertically or horizontally, and the 1-3 hour procedure standardly necessitates general anesthesia, 3-5 days of hospitalization and 4-8 weeks recovery time₂₅,₂₇. An abdominal hysterectomy is performed as follows:

1. An incision is made through fat, muscle, fascia and peritoneal layers of tissue.

2. Fallopian tubes and ligaments are cut inside.

3. Uterine blood vessels are cut and tied.

4. Uterus is removed through the incision25.

Typically, pain killers are prescribed to alleviate any discomfort after the surgery and strenuous exercise or movement should be avoided₂₇.

In 25 – 50% of abdominal hysterectomies, women experience at least one complication, which can include: post-operative bleeding (1 in 10 women), the formation of a blood-clot in the lungs, damage the ureter, bowel or bladder (1 in 300 women), infections of wound (1 in 20 women) and urinary tract, weight gain, abdominal or back pain, constipation, fatigue or frequent urination₂₇. Some women also suffer from psychological side-effects such as depression, anxiety, mood change and irritability₂₇. In addition, even if the ovaries are not removed during the procedure, there is a chance that the individual may experience symptoms of early menopause such as hot flashes and vaginal dryness₂₇. Lastly, hysterectomies have a rather low mortality rate of between one in 2000 and one in 5000 women die as a result of the procedure₂₇.

Extracting Ashley's uterus consequently prevents menstruation and the painful cramps and bleeding that are associated with the cycle. During menstruation many women experience back abdominal cramps, headaches and nausea which illicit extreme discomfort. For Ashley, such an experience could be terrifying especially with her limited capacity for understanding the changes that are occurring within her body₃. Her only source of communication of pain and discomfort is crying, which is non-specific and can be attributed to any number of reasons₃. In addition, her parents contend that the removal of her uterus prevents any possibly pregnancy if she were ever sexually abused and also the removes any chance of uterine cancer, uterine fibroid tumors, cervical cancer, endometriosis, or other complications₃,₂₈.

In the same operation, physicians also performed an appendectomy on Ashley to remove her appendix and prevent the possibility of appendicitis₃. Harvard medical specialists assert that the simultaneous appendectomy is a common procedure as it only takes a few extra minutes during the actual surgery₂₅. There are approximately 250,000 appendectomies performed each year and about 7% of people in Western nations experience appendicitis₂₉. This type of appendectomy is known as an appendectomy-en-passant, referring to the removal of a healthy appendix during a procedure of alternative intention₃₀. Commonly, individuals suffer from wound infection following the surgery and antibiotics are typically prescribed both pre and post-operatively to help eliminate the chance of infection by a gut organism₃₀. Likewise, abscesses may also form in the pelvis, abdomen, and less commonly, the liver₃₀. Ashley's parents contend that the appendectomy is a preventative measure because the symptoms of appendicitis including, abdominal pain in the lower right quadrant, nausea, vomiting, high fever, and tenderness, are non-specific with the potential to be attributed to any number of ailments₃,₂₉.

Lastly, the treatment includes the removal of Ashley's breast buds, almond shaped centers of tissue that induce breast development and contribute to lactation₃,₃₁. While the actual breast buds were surgically removed, the areolas were not₃. The areolas are largely comprised of small nodules, below which are the sebaceous glands and sweat glands₁₄. These glands secrete oils that lubricate the skin and prevent cracking and drying₁₂. In addition, there are many sensory nerve endings located within the nipple and areola₁₂.

The breast buds begin to form during the sixth week of fetal development and are the source of all further breast growth and development₃₁. From each breast buds stems a column of cells that becomes part of the sweat and milk duct system₁₄. Removal of these tissue areas would halt progression of breast development and the underlying tissues.

This component of the treatment has multiple functions: prevention of breast cancer and fibryotic cysts that run in Ashley's family, removal of the chance for Ashley to develop large breasts that could impart a significant amount of discomfort when she is lying down, and helps to mitigate her sexual appeal to possible predators₃. Researchers assert that a female with disabilities is twice as likely to be a target of sexual abuse than a female without disabilities, and the risk increases with the more caregivers, attendants or physicians who are involved in treatment and care₃₂. The fear of sexual or physical assault becomes especially prevalent with the possibility that Ashley may one day have to be placed in a long-term facility. The perpetrators of these crimes include strangers 28% of the time and service providers 7% of the time₃₂. An additional study conducted in 1991 by the University of Alberta's Sexual Abuse and Disability Project revealed that of the 93 disabled women who reported cases of abuse, 44% of the perpetrators were service providers₃₃. Researchers further claim that 90% - 99% of children with disabilities report being sexually abused by the age of 18, which is four times the rate of children without disabilities₃₃. The rates of abuse are even higher for institutionalized individuals and highest for persons with combined mental retardation and physical disability₃₃. While these statistics may appear significant, “Ashley would get pregnant only through sexual abuse, but surely action should be taken against the offenders rather than Ashley,” asserts Liao et al in a recent Hastings report₂₆. Is it appropriate to punish Ashley, as a possible victim, in this scenario? The public should be focusing on the perpetrators not the innocent victims.

While it is abundantly clear Ashley's parents love her dearly and are devoted to her care, it is obvious that there are also ramifications of the Ashley Treatment that offer significant benefits for the caregivers. Ashley's size will allow her to be moved easier so that she can participate in more family events and will also be easier to move in general. Her smaller stature and weight will prevent the development of bed sores and skin infections from her sedentary lifestyle, but will also reduce the attention required from her parents to treat those ailments. In addition, the hysterectomy relieves Ashley of the pain and emotional trauma of menstruation, but also removes her caregivers from attending to those needs each month. This is not to say that there are not benefits of the treatment that do enhance Ashley's quality of life, but it is important to recognize that they also have direct advantages for the caregivers as well.

For a 6 ^1/2 year old female with very limited cognitive function, the treatment components appear to be very serious and highly invasive. At such a young age, a hysterectomy and breast bud removal surgery could be considered even radical and traumatic. There are a number of very serious risks when implementing estrogen therapy, which are consequently elevated considering the high level of estrogen that Ashley is receiving on a daily basis, compounded significantly by her immobility and low cognitive function. One of the most serious side effects of the estrogen therapy is the risk of deep vein thrombosis (DVT) and pulmonary embolism. Pulmonary embolism has the potential to be a fatal condition if not diagnosed early. The risk for DVT is elevated due to the estrogen therapy, but further increased due to Ashley's sedentary condition; her blood is not circulating as efficiently. While there are observable benefits to the Ashley Treatment, they do not appear to outweigh the risks. Furthermore, none of the procedures are medically necessary for Ashley's survival. Thousands of disabled individuals, from those with cerebral palsy to multiple sclerosis, live each an every day without this extreme type of medical intervention. To further determine if the Ashley Treatment is appropriate, an ethical analysis will be done to determine if the benefits outweigh the burdens at the present time.

Ethical Analysis

The issue of the Ashley Treatment has raised serious interdisciplinary concerns. There has been a call for a public debate on this issue that would examine all aspects of this treatment including the medical and ethical implications. Since the revelation of the Ashley Treatment, the public debate has ranged from support of her parents to accusations that this is a form of eugenics and even a violation of the basic human rights of the disabled. To determine if the Ashley Treatment is ethical, the principles of respect for persons, beneficence, nonmaleficence and justice will be applied to this treatment and its consequences.

Respect for Persons

Beneficience

Justice

Conclusion

The Ashley Treatment is experimental, non-therapeutic, and controversial and has the potential to set a dangerous precedent for society. The Seattle Children's Ethics Committee weighed the benefits and burdens of this treatment and recommended that it would be in the best interest of Ashley. Proponents of the treatment argue that the process of decision-making “increases the likelihood that a decision will withstand scrutiny, reduces the likelihood that participants will later realize they left out some important consideration, and should reassure the public, including advocates for handicapped children, that the child's interest is the focus of the decision”₃₄. Unfortunately, most advocates for the disabled do not support the Ashley Treatment. The public reaction has been one of skepticism, and many within both the medical and ethical communities have serious concerns. Until more research is done on this treatment and there can be a thorough examination of its benefits and burdens versus the reasonable and accepted non-pharmacological remedies, the Ashley Treatment should not be given to other disabled children. When solutions exist that allow individuals with severe brain impairments to be cared for without interfering with their natural developmental patterns, then these solutions should always take priority. To permit this treatment, when there are so many unknown dangers would be medically irresponsible and ethically objectionable.