1. Screen newborns for inborn errors of metabolism and other treatable disorders.

2. Use simple tools to determine the developmental quotients of infants and children.

3. Identify red flags for delayed development in infants and children.

4. Educate parents of children with anxiety disorders about how to use behavioral interventions and positive reinforcement to manage anxiety.

5. Discuss the role of selective serotonin reuptake inhibitors in the management of anxiety disorders in children.

Expanded Newborn Screening
Kirk A. Aleck, MD, Professor of Clinical Pediatrics, University of Arizona College of Medicine, Phoenix

Rationale for newborn screening: available treatment affects course of disease; disorder potentially life-threatening; timely diagnosis difficult without screening test; opportunity for genetic counseling

History: first systematic screening of newborns (for phenylketonuria [PKU]) began in 1960s; screening tests for other disorders added over time; national recommendations for newborn screening exist, but practices vary by state

Phenylketonuria: incidence—1 in 15,000 births; phenylalanine level \>20 mg/dL in classic PKU and 6 to 20 mg/dL in hyperphenylalanemia; effects—mental retardation; seizures; behaviors similar to those of autistic children; treatment—restriction of dietary phenylalanine highly effective; lifetime dietary compliance required

Maple syrup urine disease: incidence—1 in 225,000; effects—classic form severe and results in deterioration within first week of life; severe neurologic damage and death may occur if treatment delayed; treatment— restriction of dietary branched-chain amino acids (leucine, isoleucine, and valine) effective if initiated early; gastric feeding (with restricted diet) has replaced hemodialysis as primary management approach

Homocystinuria: incidence—1 in 100,000; effects—learning problems and ectopia lentis evident by 4 to 5 yr of age; patients may have Marfanoid habitus; treatment—lifelong dietary restriction; compliance problems may occur because of subtle symptoms; elevated levels of homocysteine may increase risk for arteriosclerosis

Biotinidase deficiency: incidence—1 in 60,000; effects—defective recycling of biotin; as biotin reserves decrease, deficiency causes alopecia, eczema, and developmental delays; treatment—biotin supplementation (10 mg/day; required throughout lifetime) effective

Galactosemia: incidence—1 in 40,000; effects—defective metabolism of galactose (lactose is major source); jaundice, poor feeding, and lethargy appear within 1 to 2 wk of birth; children may become septic (with, eg, Escherichia coli); urine may contain reducing substances; treatment—restriction of dietary lactose helps, but not 100% effective; speech and language delays and premature ovarian failure (in girls) often occur, despite therapy

Congenital hypothyroidism: incidence—1 in 4000; most common screenable disorder among newborns; effects— thyroid gland fails to develop or function properly, resulting in cretinism (mental retardation; constipation; characteristic physical features); treatment—supplementation with thyroid hormone

Congenital adrenal hyperplasia: incidence—1 in 10,000; effect—inability to synthesize glucocorticoids and mineralocorticoids results in severe salt-wasting and hyperkalemia in boys and may result in ambiguous genitalia in girls; treatment—supplementation with glucocorticoids and mineralocorticoids; milder forms—later presentation includes hirsutism and reproductive problems; screening allows diagnosis before symptoms emerge

Hemoglobinopathies: sickle cell anemia occurs in 1 in 625 blacks; early identification important for initiating penicillin prophylaxis

Screening panel: obtaining 5 drops of blood from heel stick allows screening for many disorders; mass spectrometry—technique allows screening for other disorders (eg, fatty acid oxidation disorders); blood sample processed and components extracted; mass spectrometer separates molecules based on mass and charge; patterns identify presence of particular molecules; height of peaks indicates quantity present in sample; second screening may be necessary (required in some states); 20 of 29 disorders in newborn screening panel identified by mass spectrometry; universalization of expanded panel—most states follow expanded screening guidelines (including screening for citrullinemia, arginosuccinic aciduria, tyrosinemia, fatty acid oxydase disorders, other amino acid disorders, and organic acidemias)

Fatty acid oxidation disorders: categorization based on chain length; medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency—occurs in 1 in 10,000 births (frequency varies in different ethnic populations); fatal in ≈33% of cases

Organic acidemias: enzyme defects result in accumulation of organic acids (usually derived from dietary amino acids); treatment involves dietary restriction; otherwise, severe acidosis and hypoglycemia result

Diagnostic algorithms: available on Web site of American College of Medical Genetics (www.acmg.net); site includes information about differential diagnosis, condition, diagnostic tests, and follow-up actions; use of algorithm helps diagnose 54 disorders

Cystic fibrosis: screening requires 2 steps (immunoreactive trypsinogen test, followed by genetic analysis)

Future: mass spectrometry also may be used to identify storage disorders (eg, mucopolysaccharidosis), infectious diseases (eg, infection with HIV, toxoplasmosis), and genetic anomalies; challenges—cutoff levels for each test must be established, based on local population and laboratory; low cutoff level increases frequency of false-positive results; false-positive results also may occur because of processing problems and presence of maternal metabolites; although false-negative results uncommon, hospital and laboratory practices may delay results

Development 101
David O. Childers Jr, MD, Assistant Professor of Pediatrics, and Chief, Division of Developmental Pediatrics, University of Florida College of Medicine, Jacksonville

Resource: National Dissemination Center for Children with Disabilities (www.nichcy.org) has links to many state and national groups and provides free downloadable educational material and sample letters

Developmental disabilities: primary conditions caused by dysfunctional or damaged central nervous system, and persist throughout lifespan; disabilities include vision and hearing impairment, autism spectrum disorders, mental retardation, learning disabilities, and attention-deficit/hyperactivity disorder (ADHD); although common in pediatric practice, clinicians receive relatively little training about these issues

Developmental quotient (DQ): expressed as percentage (developmental age divided by chronologic age, and result multiplied by 100); generally persists throughout development; significant developmental delay often identifiable within first 1 to 2 yr of life (eg, failure to reach age-appropriate developmental milestones); children with mild delays may catch up; persistently depressed DQ signals significant developmental problem; special cases—psychosocial deprivation may cause developmental delay, but children may catch up; using corrected ages to assess premature infants common practice, but may delay potentially beneficial interventions

Developmental streams: gross motor skills; visual problem-solving (includes fine motor skills and visual conception); adaptive skills (eg, activities of daily living); expressive language (ie, communicating thoughts); receptive language (key to cognition); global delay—DQ <75% in ≥3 developmental streams; deviancy—developmental milestones occur out of order; disassociation—one developmental stream substantially depressed relative to others (eg, motor skills in cerebral palsy; language in autism)

Developmental screening: often fails to identify children with mild delays (those most responsive to therapy); drawing—3-yr-olds draw circle; 3.5-yr-olds draw midline cross; 4-yr-olds draw square; 5-yr-olds draw triangle; 6- yr-olds draw Union Jack; blocks—children handle and stack blocks or build structures; simple screening for age- appropriate skills; mouthing—infants have 3 times as many taste buds as adults and experience world through mouth; by ≈14 mo of age, interaction with surroundings becomes more sophisticated (several other developmental milestones also occur at this age)

Development 1-2-3: 1) at 1 yr of age, child has one word (other than “dada” and “mama”), uses protodeclarative pointing; can follow one-step command, and can use one utensil (spoon); 2) at 2 yr of age, child uses 2-word syntax, can follow 2-step commands, and engages in 2-person parallel play; 3) at 3 yr of age, child uses 3- to 5-word syntax, has vocabulary of 300 to 500 words (including 3-letter word, “why?”), knows 3 primary colors, can answer first-, second-, and third-person questions, can build 3-block bridge, can walk up and down 3 stairs (alternating), and can pedal 3-wheeled vehicle

More on language development: language “downloading” occurs at 16 mo of age, allowing child to follow novel commands; autistic children generally delayed in reaching this milestone

Developmental red flags: behavioral—extreme irritability or docility in infancy; poor eye contact; absence of joint attention (ie, following eye gaze); more interest in objects than in people; perseverative or repetitive play; stereotypies or severe self-injurious behavior; sensory hyper- or hyporesponsiveness (eg, child does not respond to audio cues when visuospatially engaged, but terrified of loud noises); low frustration tolerance; poor self-control; gross motor—asymmetric movement during infancy; persistence of primitive reflexes after 6 mo of age; dystonia after 4 mo of age; visuomotor—fisting after 4 mo of age; handedness before 1 yr of age (may result from in utero infarct); mouthing after 14 mo of age; inconsistent visual and auditory attention; language—lack of protodeclarative point or joint attention span by 20 mo of age; language development best predictor of future functioning

Billing for screening: major third-party payors compensate for developmental screening; code 96110-25; more information on American Academy of Pediatrics Web site (www.aap.org)

Anxiety Disorders in Children and Adolescents
Martin T. Stein, MD, Professor of Pediatrics, University of California, San Diego, and Director, Department of Developmental-Behavioral Pediatrics, Rady Children’s Hospital, San Diego

Separation anxiety disorder: excessive fear about separation from parent or other loved ones; normal behavior for infants 9 to 15 mo of age; mild form also may occur at entry to preschool, kindergarten, or first grade or during other stressful events; presentation—school refusal; somatic symptoms (eg, recurrent abdominal pain, headaches); worries about harm to loved ones; reluctance to sleep away from parents; nightmares with themes of separation; desire to return to parents when away from home; children may exhibit \>1 of these behaviors; chronicity—better prognosis with early diagnosis and treatment and in children with mild symptoms; if untreated, chronic anxiety develops in up to one-half of these children; increased risk for panic disorder, agoraphobia, other anxiety disorders, and depression; diagnosis—symptoms must interfere with function; comprehensive evaluation includes physical examination; treatment—educate parents and child about disorder; recommend behavioral interventions (eg, gradual return to school, exposure and desensitization, relaxation techniques); suggest treatment for anxiety in relatives, when appropriate (positive family history of anxiety common); reserve medical therapy (eg, selective serotonin reuptake inhibitors [SSRIs]) for severe cases; school phobia—coexisting diagnoses include separation anxiety disorder, generalized anxiety disorder, and major depression

Selective mutism: child does not speak in certain social situations for ≥1 mo, despite speaking at home (exclusions include first month of child care or new school and children who have recently immigrated); expression of social anxiety in very shy child; social anxiety disorder develops in ≤90% of cases; prevalence ≈0.5%; family history often includes social phobia or selective mutism; delays in speech and language occur in ≤33% of cases; special cases—bilingual children may exhibit selective mutism that is not necessarily sign of anxiety disorder; treatment—treat anxiety and improve self-esteem; avoid forcing child to speak (may exacerbate condition); recommend behavioral therapy, including positive reinforcement for communication (including nonverbal communication and whispering); consider referral for cognitive behavioral therapy (CBT); consider SSRI (eg, fluoxetine 20 mg/day for 6 mo) only in resistant cases

Simple phobias: persistent fear of specific object or situation, associated with avoidance or significant distress; positive family history common; peak onset occurs at 11 to 13 yr of age; children generally respond well to therapy; treatment—educate parent (teach them to, eg, understand child’s behavior, avoid overcorrecting); encourage mastery of feared object and desensitization through gradual exposure

Obsessive-compulsive disorder (OCD): common presentations in children—fear of contamination, with excessive hand-washing or avoidance of contaminated objects; obsessive worry about safety of parents or self; checking behaviors or chronic doubting; prevalence—1% to 3.5% of population; mean age at onset, 10 yr; symptoms persist for several years in \>50% of cases; treatment—comprehensive evaluation includes physical examination and assessment of anxiety and depression; education important; CBT higly effective (but requires multiple visits); of medical therapies, SSRIs supported by most evidence (but clinical effects not evident for up to 12 wk); combination therapy of CBT and SSRIs associated with best outcomes

Psychosomatic symptoms: study showed children with anxiety disorders commonly have ≥1 somatic symptom (eg, restlessness, recurrent abdominal pain, blushing, palpitations, muscle tension, sweating, trembling); treatment—consider SSRI for severe cases, especially with family history of anxiety disorders

Assessment of anxiety: pediatric symptom checklist available free of charge from www.brightfutures.org; formal tests and rating scales also used

Selective serotonin reuptake inhibitors: paroxetine contraindicated in children because of association with increased aggression, psychomotor agitation, and suicidal ideation, compared to other SSRIs; adverse effects— generally resolve within first weeks; include nausea, drowsiness, nervousness, dizziness, difficulties with concentration and memory, and behavioral agitation (red flag); suicidal ideation—2-fold increase with SSRIs; behavioral agitation usually presents before suicidal ideation; most commonly occurs within first 9 days of initiating SSRI; regular follow-up (office visits or phone calls) important during first month; discontinuation syndrome—fluoxetine has long half-life (self tapers); other SSRIs require tapering period of 2 to 4 wk; depression and anxiety—30% to 40% of youth with major depressive disorder have comorbid anxiety disorder; SSRI may have impact on depression by reducing anxiety; SSRIs more effective in patients with mixed anxiety and depression, compared to those with depression alone