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DOI: 10.1542/peds.2004-1721O 2004

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  • 1. A Newborn Infant With a Disorder of Sexual Differentiation Martin T. Stein, David E. Sandberg, Tom Mazur, Erica Eugster and Jorge Daaboul Pediatrics 2004;114;1473-1477 DOI: 10.1542/peds.2004-1721O The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.pediatrics.org/cgi/content/full/114/5/S2/1473 PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2004 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from www.pediatrics.org by on October 21, 2010
  • 2. A Newborn Infant With a Disorder of Sexual Differentiation* CASE about the complexity of gender identity and gender Following an uncomplicated 38-weeks pregnancy, role, bioethical considerations, and the influence of a normal labor, and delivery with Apgar scores 8 and patient-advocacy groups. These recent consider- 9 at 1 and 5 minutes, respectively, a newborn was ations are of interest to developmental-behavioral delivered with a birth weight of 6 pounds 5 ounces. pediatricians in that they focus on critical aspects of The physical examination was unremarkable except subsequent developmental outcomes. for complete absence of the penis. The scrotum ap- Dr David Sandberg and Dr Tom Mazur are pedi- peared normal with bilateral palpable gonads of nor- atric psychologists who specialize in the care of chil- mal size. A voiding cystourethrogram demonstrated dren and adolescents with endocrine disorders. They a normal bladder without uretero-vesical reflux; the are members of a comprehensive clinical manage- contrast study revealed that urine partially emptied ment team in pediatric endocrinology at the Chil- into the rectum and colon. The urethral meatus was dren’s Hospital of Buffalo, New York, and the De- positioned at the anterior anal verge. Karyotype was partments of Psychiatry and Pediatrics, University at 46,XY. This is the third child for this couple. They Buffalo School of Medicine and Biomedical Sciences. have a 4-year-old boy and a 6-year-old girl. Drs Sandberg and Mazur are involved in clinical To which sex should this infant be assigned? Ac- research on the psychological adaptation of individ- companying decisions concern disclosure of infor- uals with a variety of endocrine-related conditions mation to patient and family (what should be dis- and their families. Dr Erica Eugster is a Clinical closed about the condition and its treatment and Associate Professor of Pediatrics in the Section of when?); surgery to have the genitalia match the sex Pediatric Endocrinology at the Riley Hospital for assignment, or alternatively, female genital anatomy Children in Indianapolis, Indiana. Dr Jorge Daaboul (what should be done and when?); psychological is an Assistant Professor of Pediatrics in the Division support of the patient and family (who should pro- of Pediatric Endocrinology at the University of Flor- vide it, and what model of care should be followed?); ida (Gainesville), College of Medicine. Dr Daaboul and involvement of other family members and has studied ethical issues that impact the early deci- friends (should they be told, and if so, what should sion-making in children with intersex conditions. they be told and when?). Martin T. Stein, MD Professor of Pediatrics INDEX TERMS. ambiguous genitalia, sex differentiation, intersex, bio- University of California medical ethics, penile agenesis. Children’s Hospital San Diego San Diego, California Dr Martin T. Stein This Challenging Case is a rare condition that will Drs David E. Sandberg and Tom Mazur not be encountered by most pediatricians. However, Don’t be fooled—this rare case has more to teach it represents a dramatic example of other more com- than you might think! The infant is born with the mon conditions discovered in the newborn period extremely rare condition of penile agenesis (also associated with ambiguous genitalia. Primary care known as aphallia). Mortality is high because of as- pediatricians are often the first to recognize the struc- sociated urinary and gastrointestinal tract problems; tural abnormalities in the external genitalia and the however, complex forms of these associations are first to speak to the parents about the condition. A absent in this particular infant. Although rare, the knowledge of genetic and endocrinologic principles case illustrates common challenges in the clinical that modulate fetal sex differentiation is essential but care of patients with disorders of sexual differentia- insufficient to provide comprehensive information to tion (“intersex”), in whom there is discordance the parents. The influence of fetal sex hormones on among sex chromosomes, gonads, sex hormones, gender identity and the incorporation of principles of and phenotypic sex (internal reproductive structure patient rights and patient autonomy are additional and external genital appearance).1 These conditions areas of knowledge required to guide therapeutic include true hermaphroditism (in which both ovar- decision-making. ian and testicular tissue are present in the same or A variety of new concepts about newborns with opposite gonads); 46,XX individuals with congenital intersex conditions have surfaced in the medical and adrenal hyperplasia, particularly those born with bioethical literature. They reflect recent knowledge marked or complete masculinization of the external genitalia; 46,XY individuals with partial androgen insensitivity; 46,XY individuals with 5- -reductase * Originally published in J Dev Behav Pediatr. 2003;24:115–119. doi:10.1542/peds.2004-1721O deficiency; 46,XY individuals with a very small but PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad- normally formed penis (micropenis) or malformed emy of Pediatrics and Lippincott Williams & Wilkins. penis (microphallus); and 46,XY individuals with PEDIATRICS Vol. 114 No. 5 November 2004 1473 Downloaded from www.pediatrics.org by on October 21, 2010
  • 3. cloacal exstrophy. The prevalence rate for these con- line occupational and recreational interests and a ditions combined may be as high as 1 of 3000.2 bisexual orientation. Until the mid-1950s, medical management of indi- A second challenge to the “optimal gender” policy viduals with intersex conditions was guided by the comes from intersex individuals themselves, who are belief that an individual’s “true sex” could be re- angry about their treatment.10 They object to the fact vealed through examination of internal anatomy. It that they were either not informed or misinformed was assumed that a person’s identification as male or about their condition, they are still unable to obtain female would naturally conform to “true sex.” Based accurate information about their condition and treat- on reports suggesting that this assumption was in- ment, and they feel stigmatized and shamed by the correct, guidelines were changed, and sex-assign- secrecy surrounding their condition and its manage- ment decisions were based on the principle of “op- ment. Many also attribute poor sexual function to timal gender,” which considered multiple aspects of damaging genital surgery and repeated and insensi- outcome, most prominently potential for complete tive genital examinations, both of which were per- sexual functioning.3 This approach, which stood formed without their consent. largely uncontested until recently, is predicated on 2 Finally, social constructionists have challenged the assumptions4: (a) “gender identity” (ie, identification entire enterprise of medical management of intersex of self as either girl/woman or boy/man) is not cases by arguing that medical practices are rooted in firmly established at birth but rather is the outcome history, language, politics, and culture and therefore of rearing sex; and (b) stable gender identity and are not universal scientific facts.10 Thus, the “correc- positive psychological adaptation require that geni- tion” of an intersexed infant’s genitals is less a med- tal appearance match assigned sex, which often calls ical emergency than it is the adoption of medical for reconstructive genital surgery. It is essential to technology to support a cultural imperative to view distinguish between gender identity and other as- the sexes as dichotomous. Supporters of this point of pects of gender-related behavior, which may be in- view contend that such beliefs result in unnecessary fluenced by prenatal hormones. This includes “gen- and damaging surgery. der role,” which refers to behaviors that differ in How should a decision regarding sex assignment frequency or level between males and females in this be reached in the present case? Until recently, most culture and time (such as toy play or maternal inter- children with aphallia would receive a female sex est), and “sexual orientation,” which refers to sexual assignment. Accordingly, the testicles would be re- arousal to individuals of the same sex (homosexual), moved and genital surgery performed to create the opposite sex (heterosexual), or both sexes (bisexual). outward appearance of female genitalia, that is, labia The clinical approach to disorders of sexual differ- and clitoris. Surgical construction of a vagina might entiation (“optimal gender policy”) has recently been be performed at this time or be postponed until criticized from several perspectives. First, the notion of gender “neutrality” at birth has been challenged as adolescence. A feminizing puberty (development of a result of a widely publicized case.5 The individual breasts and feminine body) would be achieved in this case has a 46,XY karyotype and was born with through the administration of estrogen therapy be- normally formed male genitalia. After a circumcision ginning in the early teenage years. It has been accident at the age of 7 months left him without a thought that this approach would maximize the in- penis, the child’s gender was reassigned but not until dividual’s psychological adaptation, including gen- 17 months, and the child was subsequently reared as der identity, body image, and sexual function. Con- a girl. This individual (referred to as “John/Joan”) versely, delaying or avoiding surgical construction of has been studied extensively as an adult.6 He reports female external genitalia would potentially jeopar- having been uncomfortable as a girl (“gender dys- dize the formation of an unambiguous gender iden- phoric”) and, starting at age 14 years, began to live as tity because of the incongruence between gender a male. He received a mastectomy and began testos- rearing and genital appearance. An alternative deci- terone replacement therapy in adolescence followed sion might be to rear this infant as a male (consistent shortly after by phallic reconstruction. At age 25, he with his gonadal sex) because prenatal testosterone married and adopted the woman’s children. The has presumably “organized” the brain, foreclosing gender dysphoria and ultimate sex reassignment of identification as a female. Phalloplasty might then be this individual is believed by some to have been considered, although the challenges of this option predictable from experimental studies in animals in are daunting and it has only rarely been attempted. which exposure to androgens during sensitive peri- The option of not attempting to provide the child ods of early brain development is associated with with a phallic structure would potentially jeopardize male-typical brain and behavioral development.7 Al- stable gender-identity formation. though animal experimental research has shown a Given the dearth of systematic information on relation between prenatal androgen exposure and long-term outcome in individuals with aphallia and sex-dimorphic behavior, such studies have not exam- other forms of intersexuality, how should this clini- ined “gender identity” per se.8 The impact of the cal problem be resolved? How are the parents to be John/Joan case for clinical practice is also tempered involved in the decision? What information do they by the report of another child with a traumatic need to make informed decisions on behalf of their amputation of the penis with considerably different child? Rare as this case is, it has much to teach us. outcome.9 As an adult, the individual maintains a Questions emerge regardless of whether the infant is female gender identity, although she exhibits mascu- assigned a gender and reared as a boy or as a girl. 1474 A NEWBORN INFANT WITH A DISORDER OF SEXUAL DIFFERENTIATION Downloaded from www.pediatrics.org by on October 21, 2010
  • 4. (We acknowledge Dr Sheri Berenbaum’s construc- sex-of-rearing have also been reported in a small tive comments on a draft of this commentary.) number of individuals.4 A few sensationalized cases of extreme gender David E. Sandberg, PhD dysphoria and patient groups advocating a morato- Pediatric Psychiatry and Psychology rium on early genital surgery have encouraged the Children’s Hospital of Buffalo medical community to recognize the critical need for Tom Mazur, PsyD long-term outcome data on intersex populations. Pediatric Endocrinology However, the few existing studies of the claims made Children’s Hospital of Buffalo by intersex support groups have been limited by Buffalo, New York small sample size and selection bias.5 Therefore, we find ourselves currently in a situation with far more REFERENCES questions than answers. How, then, should we begin 1. Grumbach M, Conte FA. Disorders of sex differentiation. In: Wilson JD, to address this Challenging Case? Foster D, eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, Once the medical diagnosis has been established, PA: WB Saunders; 1998:1303–1425 parents of an infant with intersex should be given a 2. Melton L. New perspectives on the management of intersex. Lancet. 2001;357:2110 comprehensive and explicit explanation of normal 3. Money J. Sex Errors of the Body and Related Syndromes. Baltimore, MD: and abnormal sexual differentiation. Considering the Paul H. Brookes Publishing Co; 1994 paucity of scientifically validated outcome data in 4. Zucker K. Intersexuality and gender identity differentiation. Annu Rev the management of intersex, all available informa- Sex Res. 1999;10:1– 69 5. Colapinto J. As Nature Made Him. New York, NY: HarperCollins tion should be shared, including that which has been Publishers; 2000 highly publicized and is arguably biased. A consis- 6. Diamond M, Sigmundson HK. Sex reassignment at birth. Long-term tent source of dissatisfaction among adult intersexu- review and clinical implications. Arch Pediatr Adolesc Med. 1997;151: als, even among those for whom the psychosexual 298 –304 outcome appears favorable, has been the lack of dis- 7. Goy RW, McEwen BS. Sexual Differentiation of the Brain. Cambridge, MA: MIT Press; 1980 closure by medical professionals (and often parents) 8. Collaer MA, Hines M. Human behavioral sex differences: a role for regarding their diagnosis and treatment. The per- gonadal hormones during early development? Psychol Bull. 1995;118: ceived secrecy can be experienced as shame. The 55–107 ideal time at which to establish a culture of full 9. Bradley SJ, Oliver GD, Chernick AB, Zucker KJ. Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months, and a psycho- disclosure is in the initial discussions with parents. sexual follow-up in young adulthood. Pediatrics. 1998;102(1). Available At that time, information should be provided about at: www.pediatrics.org/cgi/content/full/102/1/e9 the diagnosis and options regarding sex assignment 10. Kessler SJ. Lessons From the Intersexed. New Brunswick, NJ: Rutgers and surgery. Surgical options for this Challenging University Press; 1998 Case include the technically difficult phalloplasty6 or the easier vaginoplasty.7,8 Each procedure is associ- Dr Erica Eugster ated with short- and long-term complications. All This case represents one of the most difficult situ- options should be considered in the case of the infant ations faced by parents and health care professionals with aphallia. If the child is reared male, there is the involved in the care of infants born with an intersex potential for endogenous steroidogenesis and fertil- condition. Unlike many other conditions that result ity, whereas if the child is reared female, hypogonad- in undervirilization of a genetic male, the 46,XY in- ism and infertility are guaranteed. fant with isolated aphallia was presumably exposed A third option promoted by patient-advocacy to normal levels of male testosterone during intra- groups would be to rear the child as either a boy or uterine life. A major concern revolves around the as a girl but defer gonadectomy and genital surgery effect of prenatal androgen exposure on “masculin- until the child can independently provide informed ization” of the brain and ultimate gender identity. consent.9 However, early gonadectomy should be What can we learn from the literature regarding considered in cases of a female sex assignment in sex assignment and outcomes in similar cases? Con- light of the postnatal rise of testicular testosterone genital absence of the penis is extremely rare, with that may further masculinize sex-dimorphic regions fewer than 100 cases reported. Although female sex of the brain. Gender-validating surgery has long reassignment and early bilateral orchiectomy histor- been considered crucial to the development of un- ically have been considered the standard of care for complicated gender identity. However, a widely these patients, follow-up studies focus primarily on publicized case report of a boy with traumatic am- success of surgical procedures rather than psycho- putation of the penis reared as a girl after feminizing sexual development and function.1 In the few case genital surgery10 and the example of physically nor- reports of aphallia in which a male gender was as- mal transsexuals who request sex reassignment illus- signed,2 limited information is available regarding trate that genital appearance consistent with rearing psychological adaptation and long-term satisfaction. gender is not a guarantee against the development of Another strategy is to attempt to extrapolate from gender dysphoria later in life. similar populations of 46,XY patients with appar- In light of contemporary controversy, few would ently normal early prenatal testicular function, such hazard the assertion that there is an absolute “right” as those with micropenis or traumatic penile loss. or “wrong” answer regarding optimal sex assign- Although there are reports of normal male gender ment in this case. Nonetheless, honesty and empathy identity and fulfilling heterosexual activity in such go far in establishing an atmosphere of trust within patients,3 female gender role and satisfaction with which the parents may become full participants in SUPPLEMENT 1475 Downloaded from www.pediatrics.org by on October 21, 2010
  • 5. the decision-making process. This goal can be facili- tween the assigned gender and the physical appear- tated by the inclusion of a mental health professional ance of the child. To assure gender-appropriate par- in the clinical care team. Necessary qualifications of enting, parents were often not fully informed of the such a team member would be knowledge regarding child’s condition, because it was felt that if the par- the process of physical sexual differentiation and its ents had any doubts about the child’s gender, they disorders, psychosexual development, and the po- might send the child mixed signals, resulting in an tential contributions of the social environment and insecure gender identity.1 With small modifications, biology to individual variability. In addition, this this management strategy remained in place until the team member would have more general knowledge mid-1990s and is still accepted in many centers in the and experience in caring for children with congenital United States and around the world.2,3 health problems and their immediate and extended In the mid-1990s, social scientists, a number of families. This behavioral specialist can provide psy- intersex activists, and some physicians called for a choeducational counseling at the time of diagnosis to revision of this management strategy. The debate support the objective of fully informed consent for focused on management strategy continues to this medical management including surgical decisions. date. It has led physicians to be more open and share The mental health specialist would be available to more information with patients about their condition parents and the child to provide ongoing support to and about the consequences of medical and/or sur- address inevitable concerns regarding the correct- gical therapy. However, the focus of management ness of the sex-assignment decision and to provide has remained fixed on determining which medical the parents with the skills to deliver developmentally and/or surgical interventions will yield an optimal appropriate education to the child regarding his/her outcome for each intersex condition. The general condition and treatment. Although not yet sup- feeling is that the current debate on intersex will be ported by controlled studies, such a comprehensive resolved when the appropriate outcome studies are clinical care model holds the promise of enhanced done and that, when these data are generated, phy- quality of life for the affected individual and his/her sicians will, in effect, be able to use an algorithm to family. determine a child’s sex-of-rearing and the appropri- Erica Eugster, MD ate medical and surgical interventions that the child Clinical Associate Professor of Pediatrics will require to make her/him a well-adjusted indi- Riley Hospital for Children vidual with a secure gender identity and adequate Indianapolis, Indiana sexual function. Although I believe that studies are important and REFERENCES necessary to establish the efficacy of the various 1. Hendren WH. The genetic male with absent penis and urethrorectal medical, surgical, and psychological interventions communication: experience with 5 patients. J Urol. 1997;157:1469 –1474 that are used in the management of the child with 2. Ciftci AO, Senocak ME, Buyukpamukcu N. Male gender assignment in penile agenesis: a case report and review of the literature. J Pediatr Surg. intersex, I believe that the data will yield results that 1995;30:1358 –1360 confirm an enormous variability in how individuals 3. Reilly JM, Woodhouse CRJ. Small penis and the male sexual role. J Urol. with identical intersex conditions develop psycho- 1989;142:569 –572 logically. Even the limited studies available (eg, be- 4. Wisniewski AB, Migeon CJ, Gearhart JP, et al. Congenital micropenis: long-term medical, surgical and psychosexual follow-up of individuals havioral characteristics of girls with congenital adre- raised male or female. Horm Res. 2001;56:3–11 nal hyperplasia4) point to widely divergent 5. Dayner J, Witchel SF, Lee PA. Assessing care of intersex patients: initial outcomes. There are conditions such as complete survey results [abstract]. Pediatr Res. 2002;51(pt 2):119A androgen-insensitivity syndrome for which out- 6. Ochoa B. Trauma of the external genitalia in children: amputation of the penis and emasculation. J Urol. 1998;160:1116 –1119 comes are almost universally predictable. But for 7. Creatsas G, Deligeoroglou E, Makrakis E, Kontoravdis A, Papadimi- most intersex conditions, the psychological outcome triou L. Creation of a neovagina following Williams vaginoplasty and will be so variable that, for each specific case, the the Creatsas modification in 111 patients with Mayer-Rokitansky- outcome will be unpredictable. Kuster-Hauser syndrome. Fertil Steril. 2001;76:1036 –1040 8. Krege S, Walz KH, Hauffa BP, Korner I, Rubben H. Long-term fol- Therefore, the current medical model with its fo- low-up of female patients with congenital adrenal hyperplasia from cus on diagnosis and medical-surgical treatment 21-hydroxylase deficiency, with special emphasis on the results of vag- does not assure the best possible outcome for chil- inoplasty. BJU Int. 2000;86:253–258 dren with intersex conditions. The appropriate care 9. Diamond M, Sigmundson HK. Management of intersexuality. Guide- lines for dealing with persons with ambiguous genitalia. Arch Pediatr model is one in which the focus is shifted away from Adolesc Med. 1997;151:1046 –1050 the precise medical diagnosis and toward the par- 10. Colapinto J. As Nature Made Him. New York, NY: HarperCollins ents’ conception of what their child has, what they Publishers; 2000 believe their child’s gender to be, and how they see their child’s future in the context of their family and Dr Jorge J. Daaboul of society. Each set of parents, with their unique This case serves as a model for the current debate sociocultural beliefs and backgrounds, would then on the management of the child with “ambiguous make all decisions regarding the care of their child. genitalia” or, to use the term that has acquired wide These decisions will be unique to each family and currency in the last 5 years, intersex. In the 1950s, a will reflect each family’s unique perspective on the management strategy for children with intersex was incredibly complex issues of sex and gender. This formulated that included early sex assignment with task should be facilitated by health care professionals early surgical correction to assure consonance be- expert in the field of family counseling and child 1476 A NEWBORN INFANT WITH A DISORDER OF SEXUAL DIFFERENTIATION Downloaded from www.pediatrics.org by on October 21, 2010
  • 6. development who are, in addition, familiar with in- commentaries that accompany this case emphasize tersex conditions.5 contemporary social and ethical issues that have not To apply this reasoning to the Challenging Case, always been considered in the early medical deci- there is no “right” medical-surgical procedure for the sion-making process. In addition, cultural differ- infant with aphallia. Rather, after informing the fam- ences with regard to the acceptance of intersex con- ily of what is known and not known about the out- ditions may not conform to those of Western society comes of this condition, the caregiver should explore and should be taken into consideration.1 with the family members their feelings about what The contemporary dialogue on an approach to the they believe is best for their child and respect their child with an intersex condition is a credit to our decision. colleagues in pediatric endocrinology who have re- In summary, it is my opinion that when all the sponded to recent scientific discoveries (both biolog- outcome data on intersex are collected and analyzed, ical and psychological) and the concerns of patients we will discover that there will be no one answer or and their families. Dr Robert Blizzard, in a recent management protocol per intersex condition but commentary in Pediatrics, wrote: “There exists a se- rather many answers, each unique to a given family. ries of conundrums regarding gender assignment, gender identity, gender role, and sexual preference Jorge Daaboul, MD that need solving before we can be comfortable in Assistant Professor of Pediatrics providing reasonable answers to the questions posed Division of Pediatric Endocrinology Department of Pediatrics by parents of intersexed patients and those of the University of Florida, College of Medicine patients themselves.”2(p620) Gainesville, Florida This is an area in which a developmental-behav- ioral pediatrician can contribute in significant ways. REFERENCES With an emphasis on the interactions between bio- 1. Money J. Sex Errors of the Body and Related Syndromes. Baltimore, MD: Paul logical and psychosocial aspects of child develop- Brookes Publishing Co; 1994 ment, the issues raised by the birth of a child with an 2. Lifshitz F. Pediatric Endocrinology. New York, NY: Marcel Dekker, Inc; 1996:296 intersex condition are particularly suitable to the 3. Sperling M. Pediatric Endocrinology. Philadelphia, PA: W. B. Saunders Co; clinical perspectives of a developmental-behavioral 1996:449 – 450 pediatrician. The commentaries invite an interdisci- 4. Meyer-Bahlburg HF. Gender and sexuality in classic congenital adrenal plinary approach that should be seen as an opportu- hyperplasia. Endocrinol Metab Clin North Am. 2001;30:155–171 5. Daaboul J, Frader J. Ethics and the management of the patient with nity for participation. intersex: a middle way. J Pediatr Endocrinol Metab. 2001;14:1575–1583 REFERENCES Martin T. Stein 1. Kuhnle U, Krohl W. The impact of culture on sex assignment and gender Children who are born with intersex conditions development in intersex patients. Perspect Biol Med. 2002;45:85–103 bring enormous challenges to the fields of develop- 2. Blizzard RM. Intersex issues: a series of continuing conundrums [com- mental endocrinology and child development. The mentary]. Pediatrics. 2002;110:616 – 621 SUPPLEMENT 1477 Downloaded from www.pediatrics.org by on October 21, 2010
  • 7. A Newborn Infant With a Disorder of Sexual Differentiation Martin T. Stein, David E. Sandberg, Tom Mazur, Erica Eugster and Jorge Daaboul Pediatrics 2004;114;1473-1477 DOI: 10.1542/peds.2004-1721O Updated Information including high-resolution figures, can be found at: & Services http://www.pediatrics.org/cgi/content/full/114/5/S2/1473 References This article cites 16 articles, 3 of which you can access for free at: http://www.pediatrics.org/cgi/content/full/114/5/S2/1473#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Office Practice http://www.pediatrics.org/cgi/collection/office_practice Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.pediatrics.org/misc/Permissions.shtml Reprints Information about ordering reprints can be found online: http://www.pediatrics.org/misc/reprints.shtml Downloaded from www.pediatrics.org by on October 21, 2010