Less Than Perfect: Diseases and Disorders of Early Life

Educational Objectives

The goal of this program is to improve the diagnosis and management of neonatal disorders and developmental delay in children. After hearing and assimilating this program, the clinician will be better able to:

1.   Identify causes of respiratory distress and neonatal sepsis.

2.   Recognize disorders that cause bowel obstruction.

3.   Describe common birth injuries and neonatal skin conditions.

4.   Select appropriate screening tools for developmental delay.

5.   Counsel parents of children with a developmental delay about early intervention and medical evaluation.

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, Drs. Miller and LaRosa and the planning com­mittee reported nothing to disclose.

Acknowledgements

Dr. Miller spoke in San Francisco, CA, at Family Medicine: Board Review Course, presented July 6-9, 2009, by the Univer­sity of California, San Francisco, School of Medicine. Dr. LaRosa was recorded in Kiawah Island, SC, on June 8, 2009, at An Intensive Review of Family Medicine, presented by the Medical University of South Carolina, Charleston. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Problems of the Neonatal Period

Carol A. Miller, MD, Professor of Pediatrics, University of California, San Francisco, School of Medicine

Respiratory distress syndrome (RDS): risk factors include £34 wk gestation, male sex, diabetic mother, and multi­ple- gestation pregnancy; surfactant deficiency causes atelectasis and promotes epithelial injury and pulmonary in­flammation, with resulting lung edema; reducing RDS  — prevent preterm delivery; treat maternal infections; use antenatal steroids

Transient tachypnea of newborn: due to delayed clearance of fetal lung fluid; risk factors include elective cesarean delivery associated with little or no labor; predominant clinical symptoms include early-onset tachypnea and mild to moderate hypoxia (generally resolve in 2-5 days); typical chest x-ray findings include aeration with prominent pulmonary vascular markings

Meconium aspiration syndrome: occurs with increasing frequency with advancing gestational age; may be due to fetal hypoxia, which stimulates fetal gasping and subsequent aspiration; typical chest x-ray findings include coarse patchy infiltrates and hyperinflations; pneumothorax common complication

Perinatal infections: major risk factors for early-onset sepsis include prematurity, chorioamnionitis, rupture of mem­branes >24 hr before delivery, group B streptococci (GBS)-positive mother, and male sex; common organisms in­clude GBS, Escherichia coli, and Listeria; viral agents include herpes simplex virus (HSV) and hepatitis B and C viruses; toxoplasmosis, rubella, cytomegalovirus (CMV), and HSV (TORCH)  —  infections occur in »1% of infants; generally asymptomatic; infants affected in utero and may be born small for gestational age, with thrombocytope­nia, enlarged liver and spleen, and distinctive skin lesions; prevention strategies  —  prevent GBS infections; obtain routine antenatal cultures at 35 to 36 wk gestation to identify colonized women; prophylactic antibiotics at onset of labor recommended for women with positive culture, previous infant with GBS sepsis, or with history of GBS uri­nary tract infection; rapid GBS testing may be helpful; work-up for neonatal sepsis  —  obtain complete blood count (CBC), blood cultures, and cerebrospinal fluid (CSF) cultures; C-reactive protein (CRP) levels may be helpful for symptomatic infants with negative cultures; symptomatic neonates generally empirically started on ampicillin and gentamicin (adjust later according to culture results); if herpes strongly suspected, add acyclovir; duration of treat­ment determined by clinical and laboratory findings; infants at high risk for sepsis with few symptoms may be treated initially for 48 to 72 hr (discontinue if supported by clinical findings)

Hepatitis and other infections: hepatitis B  —  to prevent transmission, all newborns should receive hepatitis B vac­cine before discharge from nursery (if mother surface antigen-positive, add type-specific immune globulin); all in­fants should finish vaccine regimen; infants of antigen-positive mothers should undergo antigen testing at »9 mo of age; breastfeeding not contraindicated; hepatitis C  —  transmission rate, 5% to 10%; antibody titers or polymerase chain reaction (PCR) testing after neonatal period recommended; no vaccine available; breastfeeding controversial; HSV—  transmission increased in prolonged rupture of membranes, instrument-assisted deliveries, and preterm de­livery; in most cases, positive maternal history or skin lesions absent (treatment based on clinical presentation and high index of suspicion); infections present as 1) disseminated disease; onset during first week of life; 2) central nervous system (CNS) disease; onset in second to third year of life; presents with profound neuropathic symptoms; 40% to 50% of infants have residual neurodevelopmental problems; 3) localized disease; may involve skin, eyes, and/or mouth; diagnosing TORCH infections  —  obtain culture for CMV; check for toxoplasmosis with maternal an­tibody titer and neonatal IgM antibody; for syphilis, if rapid plasma reagin positive, obtain titers and order trepone­mal-specific antibody test; for herpes (exposure without symptoms), swab surfaces (eg, conjunctival, nasopharyngeal, and rectal) for direct fluorescent antibody [DFA] testing (within 1-2 days of birth); if vesicles pres­ent, scrape and obtain culture; for CNS disease, perform PCR of CSF

Hypoglycemia: treatment includes early and frequent oral feeding; in infants who require continuous intravenous (IV) glucose infusion, gradual weaning recommended over abrupt discontinuation to prevent rebound hypoglyce­mic episodes

Hyperbilirubinemia: causes of increased hemolysis  —  blood group incompatibility; enzyme defects (glucose-6-phosphate dehydrogenase [G6PD] deficiency most common); sepsis; red blood cell membrane defects; collections of extravascular blood; management  —  prevent bilirubin neurotoxicity; signs of pathologic hyperbilirubinemia in­clude early onset of jaundice, rapid rise in serum levels, and prolonged duration of elevated bilirubin of excessively high direct fraction; when to consider hemolysis  —  onset of jaundice in first 24 hr of life; rapid (ie, >0.5 mg/dL per hour) rise in serum levels; hepatosplenomegaly; pallor; positive family history of heritable disorder; “setup” with incompatibility (eg, Coombs-positive results, elevated reticulocytes, abnormal smear test); consider sepsis or in­born errors of metabolism if jaundice accompanied by systemic symptoms and hepatosplenomegaly, tachycardia, or temperature instability; more conservative treatment recommended for preterm and ill infants (eg, phototherapy)

Polycythemia: hematocrit >65%; treatment by dilutional exchange transfusion; screening recommended only for in­fants with risk factors (eg, intrauterine growth restriction [IUGR], infants of diabetic mothers) and symptomatic in­fants

Bowel obstruction: sporadic episodes of vomiting suggest partial obstruction, malrotation, duplications, or annular pancreas; sometimes diagnosis can be made by fetal ultrasonography; intestinal atresia results in complete obstruc­tion; stenosis may have intrinsic cause or may be due to compression by intrinsic lesions; x-rays may or may not be diagnostic; clinical symptoms depend on degree of obstruction; may be associated with other condition (eg, Down syndrome, cardiac malformation); initial management aimed at correcting dehydration and electrolyte problems in preparation for surgery; meconium ileus  —  char-acteristics include dilated loops of small bowel, calcifications, and “soap-bubbly” appearance of meconium in intestine; common in cystic fibrosis; abdominal distention and emesis may occur within first 48 hr of life; calcifications evidence of in utero meconium peritonitis; malrotation  —occurs early in gestation; can lead to volvulus and complete obstruction; 50% of children present in first month of life with volvulus (surgical emergency); volvulus occurs when small bowel twists around superior mesenteric artery, result­ing in vascular compromise to gut; causes abdominal distention, vomiting, peritonitis, sepsis, and shock; diagnosed by contrast studies; Hirschsprung disease  —  lesions usually start in rectum and seldom extend beyond sigmoid co­lon; may be associated with Down or Waardenburg syndrome; common presentations include delayed passage of meconium, abdominal distention, emesis, and obstipation; barium studies may identify narrow segment; biopsy showing absence of plexuses diagnostic; treated surgically; meconium plug syndrome  —  transient; may be due to immaturity of myenteric plexus; barium enema for diagnosis and therapy

Birth injuries: common injuries involve extrusions of blood or edema fluid, nerve injury, and fractures; head  —  most common; swelling of caputs shortly after delivery due to edema decreases by 24 hr; cephalohematomas caused by ruptured blood vessels between skull and periosteum associated with skull fractures (imaging of asymptomatic in­fants not recommended); abnormal arm position  —  may be due to nerve injury or fracture; brachial plexus  —  injuries involve upper nerve root (Erb’s palsy), lower nerve root (Klumpke-Dejerine syndrome or Horner syn­drome), or combination of upper and lower roots; clavicle fracture  —associated with decreased arm movement (with preservation of biceps reflex) and crepitus; presentation of brachial plexus injury  —  infant's arm adducted, in­ternally rotated, and extended; biceps and Moro reflexes on affected side absent; sensory function preserved; pres­ence of hand grasp indicates sparing of lower nerve roots; recovery usually complete, but may take 48 hr to 6 mo

Neonatal skin: erythema toxicum  —  individual lesions, sometimes clustered; erythematous macules with small pap­ules; evanescent; distribution diffuse and can change within hours; present 24 to 48 hr after delivery; can be seen at £2 wk of age; eosinophils inside papulovesicular lesions may be responsible for violaceous erythema; cause un­known; resolve without scarring; benign pustular melanosis  —  commonly seen in black infants; superficial pustular lesions that easily rupture, usually with scaling around lesion; hyperpigmented macule inside lesion; rash erupts in late third trimester, then evolves before delivery; not associated with systemic disease; strawberry hemangioma  —  occurs in »3% of neonates during first few weeks of life, grows rapidly during first months of life, and eventually involutes; infants with large lesions on face, eyelids, airway, or mouth, or with cavernous lesions should be referred for treatment; nevus flammeous  —  occur in up to 40% of neonates; flat macules over eyelids, between eyebrows, on lower portion of face, and nape of neck

Developmental Delay

Angela LaRosa, MD, Assistant Professor, Department of Pediatrics, Medical University of South Carolina, Charleston

Developmental disabilities: related chronic disorders of early onset; involve ³1 developmental domains (eg, gross and fine motor function, speech, language, communication, cognitive abilities, personal and social skills, activities of daily living); global developmental delay  —  significant (ie, performing 2 SDs below mean on age-appropriate, standardized test) delay in ³2 domains; developmental delay in children 5 to 6 yr of age likely to persist; children diagnosed with intellectual disability, learning disability, or behavioral disorder

Reasons for screening: better outcomes (eg, higher graduation and employment rates) for children who participate in early intervention; cost savings; only 30% of children detected by health care provider before entering school

American Academy of Pediatrics (AAP) policy statement on screening and surveillance schedule: at age 9, 18, and 30 mo  —  specific screening tool required; age 48 mo  —school readiness screening test; surveillance at every well child visit recommended; perform screening test when concerns raised by parent or provider; algorithm  —  perform surveillance (ie, identify concerns of parents or provider); if concerns present, use screening tool; if screening results negative, schedule early return visit (if positive, refer for developmental and medical evaluation and early intervention services); if no concerns present on surveillance, give screening tool if child visiting at 9, 18, or 30 mo of age (refer if results positive); if child not visiting at 9, 18, or 30 mo of age, and no risks identified on surveillance, schedule routine visit; evaluate and follow closely

Surveillance and screening: surveillance  —  informal assessment; longitudinal, continuous, and cumulative; ask par­ents about concerns about learning or behavior; observe child; consider prenatal and perinatal risk factors; medical history (eg, lead exposure, ear infections, hearing loss); document developmental and behavioral history; play and sleep habits; neurologic and genetic examinations; psychosocial risk factors  —  presense of >4 risk factors greatly increases risk for developmental delay; education status of parents; family income; marital status; number of chil­dren in home; history of parental mental health problems, or history of parental abuse; domestic violence in home; frequency of household moves; ³4 risk factors shown to affect IQ (average IQ, 100 points, with SD of »15 points); screening  —use family psychosocial screening test; consider using validated tool (eg, Parents Evaluation of Devel­opmental Status [PEDS]); parent-completed questionnaires easier to use (informal checklists for developmental skills do not cover all domains of development)

Screening tests: sensitivity and specificity of 70% to 80% acceptable; PEDS  —  for children 0 to 8 yr of age; takes 2 min to score; add up score and follow pathway on interpretation form (eg, path C [“nonsignificant concerns”; coun­sel, reassure, and follow up in 2 wk] or path B [“1 significant concern”; perform directly administered screening test, or refer for screening]); Ages & Stages Questionnaire (ASQ)  —  fast and easy to use; 30 items for each age range (4-60 mo of age); completed by parent in 10 to 15 min; takes 2 to 3 min to score; Ages & Stages Social-Emo­tional test  —  looks at temperament, behavior, early indicators for attention deficit/hyperactivity disorder (ADHD), impulsivity, and parent-child conflict; distinguishes gross motor, fine motor, problem-solving, and personal or so­cial problems; Modified Checklist of Autism in Toddlers (MCHAT)  —  23 yes-no questions looking at social reci­procity, language, and motor skills; validated for children 18 mo to 4 yr of age; failing ³2 critical items, or any 3 items fails screening test; takes 5 min to complete and 5 min to score; sensitivity, 70% to 90%; in low-risk popula­tions, specificity »40%; follow-up interview increases positive predictive value from 0.36 to 0.74; sensitivity »70% in children who fail screening test and MCHAT

Early intervention: multidisciplinary, community-based services for children up to school age; BabyNet  —available in South Carolina; free for children 0 up to 36 mo of age; individualized family service plan (IFSP); services should start within 45 days; offers family education or specific physical, occupational, or speech therapy, and nutrition; Child Find  —  for children 3 to 5 yr of age; speech, occupational, or physical therapy provided through school; indi­vidualized educational plan (IEP)

Medical evaluation: genetic counseling  —  3-generation family history of developmental disabilities and mental health conditions; important to ask, “Did anyone not finish high school?” and determine why not; genetic and neu­rologic examination; genetic testing based on clinical findings; if no specific diagnosis suspected and child men­tally delayed, high-resolution chromosome analysis, fluorescence in situ hybridization (FISH) for subtelomeric abnormalities, and fragile X syndrome testing recommended; metabolic studies not routinely performed, unless in­dicated by eg, poor growth, low tone; diagnostic yield, 4% to 20% with array comparative genomic hybridization; magnetic resonance imaging  —  diagnostic yield better than with computed tomography; risk associated with seda­tion; recommended for abnormal focal finding, microcephaly, or macrocephaly; vision and hearing screening test; electroencephalography only if indicated based on history

Suggested Reading

Davies S et al: A pilot of the Parents' Evaluation of Developmental Status tool. Community Pract 82:29, 2009; Drewett M et al: Late-onset volvulus without malrotation in preterm infants. J Pediatr Surg 44:358, 2009; Engle WA: American Academy of Pediat­rics Committee on Fetus and Newborn. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pedi­atrics 121:419, 2008; Glascoe FP: Parents' concerns about children's development: prescreening technique or screening test? Pediatrics 99:522, 1997; Holland L et al: Implementing and validating transcutaneous bilirubinometry for neonates. Am J Clin Pathol 132:555, 2009; Mosca F et al: Respiratory management of the premature infant in the delivery room. J Matern Fetal Neonatal Med 16 Suppl 2:17, 2004; Rahi JS et al: Meeting the needs of parents around the time of diagnosis of disability among their children: evaluation of a novel program for information, support, and liaison by key workers. Pediatrics 114:e477, 2004; Riou EM et al: Global developmental delay and its relationship to cognitive skills. Dev Med Child Neurol 51:600, 2009; Shahdadpuri R et al: Diag­nostic outcome following routine genetics clinic referral for the assessment of global developmental delay. Ir Med J 102:146, 2009; Stagno S: Diagnosis of viral infections of the newborn infant. Clin Perinatol 8:579, 1981; Stegmann BJ et al: TORCH Infections. Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections. Curr Womens Health Rep 2:253, 2002; Tsai MH et al: Clinical manifestations in infants with symptomatic meconium peritonitis. Pediatr Neonatol 50:59, 2009; Yee WF et al: New concepts in neonatal respiratory distress syndrome. Compr Ther 10:55, 1984.