Critical Concerns in Pediatrics

Educational Objectives

The goal of this program is to improve management of gender variance in children and jaundice in neonates. After hearing and assimilating this program, the clinician will be better able to:

1.   Identify gender variance in children.

2.   Describe stages of gender identity.

3.   Counsel parents of gender-variant children about transitioning and hormone therapy.

4.   Discuss causes of jaundice, such as hemolytic disorders and breastfeeding.

5.   Provide appropriate management of jaundice, such as phototherapy.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose. In her lecture, Dr. Hersh presents information that is related to the off-label or investigational use of a therapy, product, or device.

Recognizing and Helping the Gender-Variant Child

Eva S. Hersh, MD, Chief Medical Officer, Chase Brexton Health Services, Baltimore, MD

Gender variance: transsexuality; gender identity disorder (GID); 1 in 10,000 born with severe disconnection be­tween internally perceived sex and chromosomal sex; permanent condition; children know they are gender variant before they can talk; children almost always try to tell others (verbally or behaviorally); increasingly regarded as in­born condition; forcing change in those who present strongly at young age ineffective and creates harm

Transition: only successful way to manage severe gender variance; early social transition  —  allowing child to live in sex they feel themselves to be leads to happier childhood and normal development; hormone replacement treatment can be started at Tanner stage 2 (eg, beginning of breast development or testicle enlargement; typically at 10-12 yr of age in girls, 12-14 yr of age in boys); associated with improved ability to function socially and live normal life, compared to not being allowed to transition (ie, being forced to play unfitting role) until >18 yr of age; important to recognize gender variance in young children to avoid permanent psychologic damage, internal discomfort, bully­ing, and violence

Gender-variant behavior: spectrum; »10% of children say, “I wish I were a girl” or “I wish I were a boy” (normal in childhood; many children later homo- or bisexual; may be sign of later transsexuality); family must understand child can be happy and have, eg, successful relationship, children, and functional family life in adulthood; very young presentation suggests gender variance as inborn personality trait that may not be caused, prevented, or changed by parent’s actions or childhood experiences

Research: long-term (20 yr) research conducted at gender clinic in Toronto found pressure from rigid behavioral pro­grams that involve forbiddance of cross-gender play or dress can result in children becoming homosexual rather than transsexual adults; many researchers beginning to view gender variance as intersex condition of brain (ie, part of spectrum of intersexuality); varied presentations (eg, degree of severity, age of presentation) suggest gender vari­ance may be polygenic; prenatal hormonal influences (eg, androgen exposure) may play role

Prognosis: study from 1987  —  among children who had strong GID in childhood, »20% became transsexual adults, 70% homo- or bisexual adults, and 10% heterosexual adults; counseling important; emerging study  —  »50% of “fe­male-to-male” children and 20% of “male-to-female” children transitioned; 100% of children who continued as­serting feeling like other sex through adolescence transitioned

Significance of cross-gender behavior: consistent  —  when allowed, assertion of being other sex (eg, girl says, “I’m really a boy”) made year after year; persistent  —  assertions and behaviors continue despite discouragement; acute  —  associated with how severely child reacts when cross-gender behavior forbidden; persistent temper tan­trums and complete withdrawal indicate likelihood of child retaining transsexual identity; Diagnostic and Statisti­cal Manual of Mental Disorders (DSM) criteria include persistent cross-gender identification (eg, cross-dressing, persistent preference for cross-gender role in play, and preference for friends of other sex at young age)

Transsexuality: individual wants and plans to live entire life as sex other than biologic sex at birth; in GID, disorder causes severe disruption in ³1 realm (eg, family, work, social activity) of individual’s life; transsexuals experience distress only when transsexual behaviors forbidden (primarily pertains to reaction of family)

Stages of gender identity: infancy  —  first stages of gender recognition; at 6 mo of age, genetic girls focused longer on images of faces, while boys focused longer on images of trucks; gender-variant children can express preference for clothing and toys of other sex before being able to speak; ages 2 to 3 yr  —  children begin to learn about gender labeling; children learn they are supposed to want toys and clothes that match who they are, and base their behavior on other people who are the sex they feel themselves to be; ages 3 to 4 yr (gender stability)  —  children begin under­standing that, eg, “if you’re a boy, you’re always a boy”; children aware of differences between male and female genitals, but do not use them as primary marker of distinguishing sex; gender-variant child may start to withdraw; parents become aware when child refuses to give up cross-gender play; cross-dressing increases as child resists; gender-variant girls may, eg, insist on standing to urinate, refuse to wear girls’ bathing suits, or stuff socks into their underwear; gender-variant boys may, eg, refuse to wear boys’ underwear, sit down to urinate, or tuck genitals be­tween thighs; preschool age (gender permanency)  —  girls who prefer boys’ toys rejected or ignored by other girls; boys who choose girls’ toys often bullied by other boys; families become worried and “come down” on kids; ele­mentary school age  —  children start to see genitals as marker of distinguishing sex; once children realize that geni­talia determine gender label, they become less rigid about behavior; gender-variant boys often try to remove their genitals or talk about having them removed (should be addressed by physician); early puberty  —  second peak age at which families forced to come to terms with child’s transsexuality to avoid loss of hope and withdrawal; develop­ment of breasts and start of menses perceived as crises by transsexual girls; puberty  —  children either protest harder or try to accept and adapt to genetic sex (issues often reappear later); adulthood  —  peak times for transitioning, 1) young adulthood and 2) age 40 to 50 yr

Depression and withdrawal: child who continues to protest may develop depression and self-neglect; suicidal state­ments and gestures common, but child may not say why; children aware of social unacceptability of expressing their feelings; be aware that transsexuality and sexual identity factors in major depression in adolescents; homosex­uality (especially in boys) source of adolescent suicide; girls with GID may deny having periods or refuse to wear bras; social isolation common; adolescents may refuse to address gender variance until after high school (due to peer pressure), even if family understanding and accepting

Presentations of GID: small children  —  adults often express concern (eg, mother says, “he likes to dress in my clothes; it doesn’t bother me, but my husband gets really upset”); elementary school age  —  boy teased for, eg, bringing girls’ toy to school; parents concerned for child’s safety outside of home; many transsexual youths unfa­miliar with transsexuality and start out thinking they are homosexual; children may say, “I’m uncomfortable with myself; I don’t feel right in my body”; children often shamed and punished by peers and family; low self-esteem, shyness, and poor performance in school common

British study: found average age at which children knew they were different from others, 5 yr (many showed behav­ioral cues earlier); children reported feeling different at start of school or earlier, and learned importance of hiding differences; average age at which children able to speak about differences, 15 yr (most children have difficulty ver­balizing); only »30% of adults reported ever disclosing they were transsexual after start of elementary school (younger children willing to disclose, but by school age become aware that differences often unacceptable); those who disclosed (mostly in later teenage years) confided in sibling or friend they thought was gay; those who told parents after age 7 yr universally reported it as negative experience and wished they had not; 55% reported being bullied (eg, questioned about appearance or sex) by peers in elementary school (64% in secondary school); 20% re­ported being bullied by teachers or other school staff; 70% reported being bullied by other children’s parents

Counseling parents: child who asserts being other sex should not be ignored, although assertion does not signify transsexuality; encourage parents to say, eg, “that’s really interesting; can you tell me more about it?”; child who persistently asks to be allowed to live as other sex happier if allowed to; some children may not embrace either sex (work with child through adolescence); helpful to present gender variance as unusual but normal; parents should not feel at fault; acceptance by family members can increase likelihood of more positive outcomes (eg, finishing high school); no decisions about hormone therapy need to be made until puberty; no decisions about surgery need to be made until adulthood; children perceive their cross-gender behavior as normal (attempting to change behavior ineffective and leaves child feeling rejected); parents should not label, tease, or avoid child; consider individual therapy for parents or family therapy; parents should not favor other children; parent should not fail to protect child (eg, “he’ll see what’s going to happen to him if he goes out dressed like that”) or threaten abandonment; transsexual adolescents often leave home at young age due to abuse by family (can lead to homelessness, sex work, even death)

Helping transsexual children: promote child’s self-acceptance; demonstrate acceptance of child as they are; sit next to child; find cross-gender behaviors that can be praised (say, eg, “that’s a beautiful picture of a princess”); do not associate with people or family members who disparage or reject child; facilitate social transition if and when child chooses it; help child meet other transsexual children and adults; internet support

Jaundice in the Newborn

Theodore R. Thompson, MD, Professor of Pediatrics, University of Minnesota Medical School, and Associate Head of Community Affairs, Department of Pediatrics, University of Minnesota Medical Center, Minneapolis

Indirect hyperbilirubinemia (HBR): 1 g of hemoglobin (Hb) produces »34 mg of bilirubin (BR); red blood cells (RBCs) produce indirect (unconjugated) BR; indirect BR binds to albumin, conjugated in liver, then excreted into intestine; in infants, conjugated BR broken down to unconjugated BR again due to lack of bacteria and b-glucuron­idase; this unconjugated BR reabsorbed; BR production load enhanced in infants by higher RBC volume and short­ened RBC lifespan; uptake delayed; conjugation slower; enterohepatic circulation enhanced; occurs in exclusively breastfed infants; indirect BR  —  fat soluble; lipophilic; nontoxic when bound to albumin (when unbound, may cross blood-brain barrier and damage brain cells); total serum BR (TSB)  —  in neonates, primarily consists of indirect BR bound to albumin and small amount of free BR (toxic) plus minimal amount of direct BR (unless liver disease pres­ent); 1 g of albumin binds »8.5 mg BR

Neonatal HBR: often outpatient disorder due to early discharge of infants (<48 hr of age); TSB >20 mg/dL worri­some; TSB <20 mg/dL in full-term or late preterm healthy infants does not cause damage; TSB cutoff for physio­logic HBR  (now called developmental jaundice), 15 to 17 mg/dL; 10% to 20% of breastfed infants may have TSB >13 mg/dL; classification of HBR  —significant, ³17 mg/dL; severe, ³20 mg/dL; extreme, ³25 mg/dL; hazardous, ³30 mg/dL; prolonged (>3 wk) jaundice often related to breast milk jaundice

Risk factors for developmental HBR: some overlap with pathologic; lower gestational age; exclusive breastfeeding (especially in infants not feeding well, with loss of >10% of body weight); jaundice in first 24 hr pathologic; early hospital discharge; hemolytic disorders (eg, ABO incompatibility); previous sibling that required phototherapy; ex­tensive ecchymoses; cephalohematoma; subgaleal hematoma; east Asian ethnicity

ABO incompatibility: maternal blood type O, infant blood type A or B; O type mothers have IgG antibodies to A or B antigens that cross placenta and attach to RBCs (occurs in »33% of infants [20% develop significant HBR]; re­sults in positive direct Coombs or direct antiglobulin testing); in patients with significant ABO hemolytic disease, Coombs test may be negative (perhaps due to saturation of antibodies by antigens in tissues); common cause of jaundice in first 24 hr of life; uncommon cause for readmission, compared to breastfeeding (nonfeeding) jaundice; late anemia rare; pathologic because hemolysis may release toxins that may damage cells in brain

Breastfeeding vs breast milk jaundice: breastfeeding jaundice  —often occurs in first week; often due to poor feed­ing that causes dehydration and significant HBR; hospital admission required; may require phototherapy, feeding supplementation (ie, formula), and lactation consultation; breast milk jaundice  —  can occur in first week; persists for £3 mo; indirect BR 10 to 15 mg/dL; often occurs in vigorous healthy infants; stopping breastfeeding for 2 days reduces TSB by 50%; risk factors  —cesarean delivery; maternal illness; multiple gestations; oral cleft; signs of healthy breastfeeding  —  “latch on” well; 4 to 6 wet diapers/day; <10% loss of body weight; breastfeeding 8 to 12 times/day; 3 to 4 mustard-yellow stools/day

Risk factors for neurotoxicity: any illness; late preterm or premature birth; hemolytic disease; glucose-6-phosphate dehydrogenase (G6PD) deficiency; asphyxia; acidosis; sepsis; serum albumin <3 g/dL

Evaluation: visual assessment unreliable; if infant appears slightly jaundiced, obtain TSB or transcutaneous BR (TcBR) level; when to evaluate for pathologic jaundice  —  first 24 hr; BR elevated on nomography; BR rapidly ris­ing; unexplained elevated BR; concern about need for exchange transfusion; jaundice in infants >3 wk of age; check TSB (high direct BR suggestive of liver damage [further work-up required]); check blood type and Rh (if mother blood type O, save cord blood to test infant’s blood type); consider Hb, complete blood cell count, reticulo­cyte count, and peripheral smear; consider G6PD deficiency (if persistent or patient in high-risk group [eg, east Asian or black ethnicity]) and viral or bacterial infection; if HBR prolonged, check thyroid function; TcBR  —instantaneous; measures color of skin; more accurate when used on chest, but forehead commonly used; average of 3 to 4 values; good correlation with TSB (may be 2-3 mg/dL below TSB); useful in preterm infants and infants <30 wk; not reliable if infant under phototherapy; obtain TSB before starting treatment; TcBR helpful for predischarge screening

Management of healthy late preterm infant with HBR: hospitalization; intensive phototherapy; frequent breast­feeding with formula supplementation; frequent monitoring of TSB; consider obtaining cultures and checking C-reactive protein; direct Coombs test (if positive, give intravenous immunoglobulin over 2 hr; repeat 1-3 times); ex­change transfusion if no change in BR; in ABO incompatibility, bring TSB to »20 mg/dL

Phototherapy: changes BR into easily excreted water-soluble isomers; more effective when distance between lights and infant smaller; BR should drop 30% to 40% within 4 to 12 hr;  maximize exposure of skin areas (cover eyes and genitals); increase fluid intake with more frequent breastfeeding; continue until TSB 12 to 14 mg/dL; rebound may occur, particularly in preterm infants or those with hemolysis

Acknowledgments

Dr. Hersh spoke in Annapolis, MD, on June 24, 2010, at Solutions Through Interactive Learning, presented by the Maryland Academy of Family Physicians (visit www.mdafp.org/conferences/). Dr. Thompson was recorded in Minneapolis, MN, at Family Medicine Update 2010: Lifelong Learning, Key Topics for the Primary Provider, presented May 12-14, 2010, by the University of Minnesota Medical School (www.cmecourses.umn.edu). The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

For a list of meeting sponsors and upcoming meetings we’re recording, go to www.audiodigest.org/upcomingmeetings.

Suggested Reading

Ahlfors CE: Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr. 2010 Apr;22(2):129-33; Cohen RS et al: Understanding neonatal jaundice: a perspective on causation. Pediatr Neonatol. 2010 Jun;51(3):143-8; Cohen-Kettenis PT et al: The treatment of adolescent transsexuals: changing insights. J Sex Med. 2008 Aug;5(8):1892-7; de Vries AL et al: Comparing adult and adolescent transsexuals: An MMPI-2 and MMPI-A study. Psychiatry Res. 2010 Aug 27. [Epub ahead of print]; de Vries AL et al:  Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med. 2010 Jul 14. [Epub ahead of print]; Fouzas S et al: Transcutaneous bilirubin levels for the first 120 postnatal hours in healthy neonates. Pediatrics. 2010 Jan;125(1):e52-7; Hansen TW: Management of jaundice in newborn nurseries: measuring, predicting and avoiding the sequelae. Acta Paediatr. 2009 Dec;98(12):1866-8; Knafo A, Spinath FM: Genetic and environmental influences on girls' and boys' gender-typed and gender-neutral values. Dev Psychol. 2010 Dec 13. [Epub ahead of print]; Maisels MJ et al: Hyperbilirubinemia in the newborn infant > or =35 weeks' gestation: an update with clarifications. Pediatrics. 2009 Oct; 124(4):1193-8; Malone SM: A new approach to neonatal hyperbilirubinemia. J AHIMA. 2009 Mar;80(3):68-71; Martin GI: Safer management of newborn jaun­dice. J Perinatol. 2009 Feb;29 Suppl 1:S1; Möller B et al: Gender identity disorder in children and adolescents. Curr Probl Pediatr Adolesc Health Care. 2009 May-Jun;39(5):117-43; Shechner T: Gender identity disorder: a literature review from a develop­mental perspective. Isr J Psychiatry Relat Sci. 2010;47(2):132-8; Wennberg RP et al: Intervention guidelines for neonatal hyperbili­rubinemia: an evidence based quagmire. Curr Pharm Des. 2009;15(25):2939-45; Zhao Y et al: Suicidal ideation and attempt among adolescents reporting "unsure" sexual identity or heterosexual identity plus same-sex attraction or behavior: forgotten groups? J Am Acad Child Adolesc Psychiatry. 2010 Feb;49(2):104-13; Zucker KJ: The DSM diagnostic criteria for gender identity disorder in children. Arch Sex Behav. 2010 Apr;39(2):477-98.