NEWBORN NEWS
Educational Objectives
| The goal of this program is to improve the diagnosis and management of infectious diseases in newborns. After hearing
and assimilating this program, the clinician will be better able to:
|
 | 1. Recognize and appropriately treat cases of neonatal herpes simplex virus (HSV) infection.
|
| 2. Identify the pathway for acquisition of perinatal HSV and describe the factors that influence the rate of transmission.
|
| 3. Diagnose and manage other infectious diseases in newborns, including neonatal cervical adenitis, omphalitis,
ophthalmia neonatorum, and pertussis.
|
| 4. Describe causes of jaundice in newborns and effectively test for and manage hyperbilirubinemia.
|
| 5. Summarize the factors that influence the incidence of neonatal sepsis from group B streptococci, and manage
symptomatic and asymptomatic patients.
|
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, Dr. Harrison reported serving on the Speakers’ Bureaus for Sanofi-aventis and Merck and receiving
research grant funding from sanofi-aventis, Merck, GlaxoSmithKline, Cubist Pharmaceuticals, Lupin Pharmaceuticals, Astellas
Pharma, and Johnson & Johnson. Dr. Wang and the planning committee reported nothing to disclose.
Acknowledgements
Dr. Harrison’s lecture was recorded at the 25th Annual Care of the Sick Child Conference, held November 12-15,
2008, in Orlando, FL, presented by Orlando Health, the Arnold Palmer Hospital for Children, and the College of
Medicine, Florida State University. Dr. Wang addressed Primary Care Pediatrics, held December 3-5, 2008, in Boston,
MA, presented by Mass General Hospital for Children, and sponsored by Harvard Medical School. The Audio-
Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
ID Challenges in the Newborn
Christopher J. Harrison, MD, Professor of Pediatrics, University of Missouri-Kansas City School of Medicine, Children’s
Mercy Hospital, Pediatric Infectious Diseases Section and Director of the Pediatric Infectious Disease Research Laboratory, Children’s
Mercy Hospitals and Clinics, Kansas City, MO
Herpes Simplex Virus (HSV)
| Case 1: infant born vaginally to mother with visible genital lesions; no history of genital herpes, so probably her first infection
(worst case scenario)
|
| Factors influencing risk for transmission: mother’s viral load at delivery; antibody titer passed to infant (zero if first infection
in mother); duration of membrane rupture; breaks in skin, eg, scalp electrode
|
| Neonatal infections: usually symptomatic and highly lethal; subclinical cases possible, but infections usually recognized
at 1 to 3 wk of age; premature infants at greater risk
|
| Acquisition of HSV: HSV enters skin, replicates once, finds sensory nerve endings, infects spinal cord ganglion, replicates, and
spreads; >80% of infections occur intrapartum; infection in utero rare and produces scarring and other signs (eg, small head,
cataracts, scleral thickening); postpartum infection from infected family members with fever blisters relatively common
|
| Presentation: disseminated disease—target organs include liver, lung, and brain; HSV, group B streptococci (GBS), Escherichia
coli, and enterovirus can cause diffuse intravascular coagulation (DIC); central nervous system (CNS) infection—
produces seizures, lethargy, irritability, poor feeding, and temperature instability (mimicking sepsis); skin, eye, and mucous
membrane lesions (SEM)—easily detected visible lesions
|
| Incidence: disseminated, CNS, and SEM diseases occur in 25%, 30%, and 45% of cases, respectively
|
| Management: diagnosis—includes culture of cerebrospinal fluid (CSF), polymerase chain reaction (PCR), blood culture,
chest x-ray, liver function tests (LFTs), and examination of skin and mucous membranes; therapy—empiric high-dose
acyclovir; if culture results positive, continue treating for 21 days, unless infection limited to SEM (treat 14 days); if
CNS involvement possible, consider imaging
|
| Signs of perinatal HSV: ophthalmia neonatorum; small clusters of sores; white infarcts in liver; scattered infiltrate in
lung; brain abnormalities
|
| Maternal recurrence: maternal antibodies have crossed placenta; premature infants receive less antibody; if mother has recurrent
lesions, perform cultures; some experts recommend withholding antiviral treatment pending results of culture; if
mother has no lesions, observe infant but do not test or treat unless symptoms appear
|
| Transmission rate: 57% for first maternal outbreak, but only 2% for recurrent disease; ≈25% if first genital episode, but
not primary disease; minimal infectious dose across mucous membrane or abraded skin amounts to 103.5 log virions; maternal
antibody—study showed neutralizing titer of 1:20 in infant gives significant protection
|
| Case 2: preterm infant (8 days of age) born vaginally with clusters of vesicles; mother had no known HSV genital disease
(true of most infected babies)
|
| Disseminated disease: 25% of all cases; onset at 1 to 3 wk of age; signs include sepsis-like syndrome; look for liver dysfunction
and coagulopathy; may present as respiratory distress (5-day window before dissemination)
|
| Presenting signs and symptoms: skin vesicles easily identified; vesicles or SEM disease may result from CNS infection;
acyclovir virostatic (neutralizes virus; immune system must then kill virus)
|
| Findings from lumbar puncture (LP): CSF shows predominantly mononuclear white blood cells (WBCs) (median of
≈120 cells, similar to enteroviral meningitis); high protein levels; may show excess of red blood cells (RBCs) despite
“clean” LP; Gram stain not helpful; PCR—sensitivity not 100%, even in presence of CNS disease (primary encephalitis);
96% of missed cases detected if LP repeated 2 to 3 days later; culture of CSF not sensitive
|
| Recurrence: early acyclovir treatment increases recurrence rate and shortens time to recurrence; if recurrence occurs before
3 mo of age, full testing and treatment needed
|
| Treatment outcomes: study showed outcome fair vs placebo in disseminated disease, poor in CNS disease, but 100% successful
in SEM
|
| Poor prognostic factors: for disseminated disease—presence of damage to target organ or CNS findings (eg, seizures); for
CNS disease—prematurity or seizures
|
| Disease patterns: onset of disseminated disease between 9 and 15 days; later for other forms
|
| Neonatal cervical adenitis
|
| Case 3: infant (9 days of age, 36-wk gestation) with poor feeding, “fussiness”, no fever, but decreased muscle tone; samples
taken for complete blood cell count (CBC), urinalysis, and blood culture; later observed swelling in neck and
erythema
|
| Pathogens: GBS; 25% have concurrent meningitis, and 75% have positive blood culture results; infants require empiric
antibiotics; in past 7 yr, methicillin-sensitive Staphylococcus aureus (MSSA) important cause; now, methicillin-resistant
S aureus (MRSA) increasingly common; S aureus rarely causes meningitis but causes dissemination to lung and septic
thrombophlebitis; in neonates, S aureus often produces mediastinitis (especially in black infants)
|
| Treatment plan: complete testing for sepsis, including CSF; begin empiric therapy with vancomycin plus ampicillin and
gentamicin; narrow treatment when culture data available
|
| Expected test results: WBCs in CSF (mostly polymorphonuclear); low glucose and high protein levels; GBS grown from
culture
|
| Treatment: if GBS identified, discontinue vancomycin; continue high-dose ampicillin with gentamicin for 3 to 7 days; total
course 14 days if uncomplicated, 21 days if complicated (eg, meningitis present)
|
| Late-onset GBS disease: not prevented by maternal screening or intrapartum treatment
|
Omphalitis
| Case 4: infant (11 days of age) with decreased feeding and fussiness, no fever, vomiting, or diarrhea; erythema present
around umbilicus
|
| Pathogens: usually polymicrobial; MSSA and MRSA usually dominant, but group A or B streptococci, and coliforms
also possible; underlying anatomic abnormalities possible (eg, patent urachus, unclosed duct, cyst)
|
| Tempo and severity: if baby appears ill—admit, perform full diagnostic testing, and treat with vancomycin and cefotaxime
against staphylococci and gram-negative organisms; if baby appears well—perform diagnostic tests and consider blood culture;
treat with oral clindamycin and cefixime; re-examine in 24 hr
|
| Warning signs: admission required; flame sign—with lymphangitis in tip of flame (indicates dissemination);
pseudocrepitus—indicates fasciitis needing surgery; small vesicular lesions—scattered evenly over trunk and abdomen
(more on anterior aspect) indicates >72 hr of bacteremia; consider admission to intensive care unit
|
Ophthalmia Neonatorum (Neonatal Purulent Conjunctivitis)
| Case 5: infant (4 days of age) with bilateral “pink eye”; no fever
|
| Pathogens: include Neisseria gonorrhea, Chlamydophila trachomatis (most common), viruses (eg, HSV and adenovirus);
most acquired in birth canal, but adenovirus also acquired postnatally; N gonorrhea (GC) infection causes early and severe
swelling; C trachomatis can cause pneumonitis 3 wk to 3 mo later in ≈30% (not prevented by topical therapy); also caused
by MRSA (more commonly) and MSSA (less commonly)
|
| Management: culture results positive for N gonorrhea and negative for other sexually transmitted infections (STIs);
treated with one dose of ceftriaxone and topical erythromycin (to reduce infectivity of secretions); GC—can penetrate
corneal epithelium and may enucleate eye; commonly causes ulceration, which can lead to partial blindness; rapid progression;
treat empirically; high rate of resistance to penicillin and quinolones, so ceftriaxone drug of choice; treat with
cefotaxime if infant has problems with bilirubin
|
| Treatment plan: American Academy of Pediatrics Redbook recommends hospitalizing infant and looking for other sites
of infection (eg, scalp abscesses, joints, CSF); test for susceptibility and for other STIs; notify mother and partners
|
Pertussis
| Case 6: infant (24 days of age) with rapid breathing, difficulty feeding, coarse sounds in both bases, nasal flaring, and intercostal
and subcostal retractions; became apneic during examination; chest x-ray showed infiltrate with mild hyperinflation
and interstitial thickening; C-reactive protein (CRP) slightly elevated; culture pending; LP appeared normal
|
| Management: gave ampicillin and cefotaxime because of possibility of late-onset GBS; sent respiratory secretions for PCR
pertussis test; erythromycin added to therapy; maternal grandmother had history of sinus cough for 3 mo
|
| Bordetella pertussis: shown by culture and PCR; catarrhal stage rarely seen in infants; adolescents and adults act as reservoir;
secondary attack rate 80%, symptoms in adults and teens include paroxysmal cough, whoop, and post-tussive emesis;
onset insidious, with minimal fever; infants may present with apnea; complications—pneumonia, hospitalization
(20%), death (more common in infants), and encephalopathy; eradication challenges—mild cases underrecognized; vaccination
rates inadequate; diphtheria-tetanus-acellular pertussis (Tdap) booster dose may improve duration of immunity;
adults and adolescents—often transmit disease to children; 1 in 6 adults seeking treatment for cough lasting >3 wk have
B pertussis; immunization of adolescents in Canada reduced incidence drastically; prevention—immunize family of neonate
(“cocooning”); immunization of infants at birth blocks response to Haemophilus influenzae type b (Hib) vaccine
|
Common Problems in the Newborn Nursery
Marvin Wang, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Pediatrician and Director, Newborn
Nurseries, Massachusetts General Hospital, Boston, MA
Hyperbilirubinemia
| Bilirubin encephalitis (kernicterus): staining for bilirubin in brain (especially basal ganglia); occurs in ≈1 in
100000 infants; 5 to 40 in1000 infants receive phototherapy before discharge from hospital
|
| Bilirubin level: study showed children with bilirubin levels of 13 mg/dL may incur minor neurologic problems; some children
do better with slight jaundice, possibly because bilirubin has antioxidant properties; another study showed increased
levels of unbound bilirubin can cause auditory problems
|
| Metabolism: degradation of RBCs (hemolysis) releases bilirubin; some becomes bound to albumin; unbound bilirubin
goes to liver, which conjugates and converts it to bile; bilirubin needs fat in lumen to exit gut; if no fat present, bilirubin
transported across luminal wall, deconjugated, and cycle repeats (enterohepatic circulation)
|
| Physiologic jaundice: due to shorter half-life of RBCs and immature liver in full-term infant; increased enterohepatic circulation
may develop, due to low volume of milk in early days of breastfeeding; breast milk jaundice— after 1 wk of
breastfeeding, something in breast milk may increase enterohepatic circulation; stop breastfeeding for 24 hr
|
| Pathologic jaundice: caused by any disorder that increases degradation of RBCs (eg, isoimmune immunization, glucose 6-
phosphate dehydrogenase [G6PD] deficiency, spherocytosis), enzymatic defects in liver, gut obstruction
|
| Management: test infants <24 hr of age with jaundice; encourage frequent breastfeeding; hydration not helpful; test for
ABO/Rh incompatibilities; check direct bilirubin level if continued high after 3 wk of treatment; test for G6PD (carried
rate 13% in blacks); follow up in 2 to 3 days
|
| Universal screening options: quantitative screening—serum level or transcutaneous monitoring; Bhutani curve—uses
normative values from population study ±2 standard deviations; American Academy of Pediatrics (AAP) 2004 guidelines—
recommend adding treatment curve stratified by term and risk factors (eg, high serum levels of bilirubin, jaundice in first 24
hr, prematurity, family history, bruising, or East Asian ethnicity); study—found prematurity most predictive of bilirubin >20
mg/dL; combined use of nomograms and analysis of risk factors gives best predictive ability
|
| Treatment:phototherapy (PTx)—treatment of choice; uses blue light; success depends on extent of body exposed and intensity
of radiation; rate of response to PTx depends on bilirubin load in skin (lower loads take longer); rebound—significant
spike in levels may occur after stopping PTx; white curtains—increase efficacy of PTx; PTx not indicated—for
direct hyperbilirubinemia or porphyria
|
GBS Sepsis
| Screening: mothers screened at 35 to 36 wk; 3 primary pathogens cause sepsis in newborns (ie, GBS, E coli, and Listeria
monocytogenes); ≈30% of mothers colonized with GBS; among these, 1 in 1000 have babies who develop invasive disease;
if mother has fever, risk increases to 40 in 1000; early-onset disease—90% of early-onset GBS presents within first
24 hr after birth; late-onset disease—mostly bacteremia, but focal disease and meningitis possible; many mothers of infected
babies test negative for GBS; risk factors—include prolonged ruptured membranes, previous child with GBS disease,
GBS bacteriuria, prematurity <35 wk, and fever; prophylactic intrapartum treatment—no increase in antibiotic
resistance but increased incidence of invasive E coli observed
|
| Practical management of neonatal GBS infections: symptomatic infants—work up and treat with ampicillin and
gentamicin; LP of symptomatic child controversial; study showed 40% of all children who had positive CSF culture had
negative blood cultures; asymptomatic infants—observe if mother GBS negative; if mother GBS positive and had ≥4 hr intrapartum
antibiotic therapy, observe infant; if mother GBS positive and had <4 hr antibiotic therapy, perform blood culture
and CBC; if WBC count <7 cells and differential (ratio of immature [I] over total [T] neutrophils) >20%, consider antibiotic
therapy, realizing that I/T ratio has poor sensitivity and specificity; if mother’s GBS status unknown, and risk factors present,
proceed as if GBS positive; if chorioamnionitis (maternal intrapartum fever >100.5°F) present, Centers for Disease Control
and Prevention guidelines recommend obtaining CBC and blood culture and starting antibiotic therapy
|
Suggested Reading
Arkwright PD, Abinun M: Recently identified factors predisposing children to infectious diseases. Curr Opin Infect
Dis 21:217, 2008; Dulin MF et al: Management of cervical lymphadenitis in children. Am Fam Physician 78:1097, 2008;
Fraser N et al: Neonatal omphalitis: a review of its serious complications. Acta Pediatr 95:519, 2006; Gabutti G: The
value of booster vaccinations against diphtheria, tetanus, pertussis and poliomyelitis. J Prev Med Hyg 49:47, 2008; Hulzebos
CV et al: Usefulness of the bilirubin/albumin ration for predicting bilirubin-induced neurotoxicity in premature infants.
Arch Dis Child Fetal Neonatal Ed 93:F384, 2008; Kapellen TM et al: Higher Rate of Cord-Related Adverse Events
in Neonates with Dry Umbilical Cord Care Compared to Chlorhexidine Powder. Results of a Randomized Controlled Study
to Compare Efficacy and Safety of Chlorhexidine Powder versus Dry Care in Umbilical Cord Care of the Newborn. Neonatology
96:13, 2009; Kirk JM: Neonatal jaundice: a critical review of the role and practice of bilirubin analysis. Ann Clin
Biochem 45:452, 2008; Larsen JW, Sever JL: Group B Streptococcus and pregnancy: a review. Am J Obstet Gynecol
198:440, 2008: MacDonald N et al: Gonococcal infections in newborns and in adolescents. Adv Exp Med Biol 609:108,
2008; Maisels MJ, McDonagh AF: Phototherapy for neonatal jaundice. N Eng J Med 358:920, 2008; McDonaugh
AF et al: Photoisomers: obfuscating factors in clinical peroxidase measurements of unbound bilirubin? Pediatrics 123:67,
2009; Piling R et al: Ophthalmia neonatorum: a vanishing disease or underreported notification? Eye Dec 12, 2008
[Epub ahead of print]; Smits-Wintjens VE et al: Rhesus haemolytic disease of the newborn: Postnatal management,
associated morbidity and long-term outcome. Semin Fetal Neonatal Med 13:265, 2008; Westerberg BD et al: A systematic
review of the incidence of sensorineural hearing loss in neonates exposed to herpes simplex virus (HSV). Int J Pediatr
Otorhinolaryngol 72:931, 2008; Weston WM, Klein NP: Kinrix: a new combination TdaP-IPV vaccine for children
aged 4-6 years. Expert Rev Vaccines 7:1309, 2008; Whitely RJ: Therapy of herpes virus infections in children. Adva Exp
Med Biol 609:216, 2008; Wood N, McIntyre P: Pertussis: review of epidemiology, diagnosis, management and prevention.
Paediatr Respir Rev 9:201, 2008.
|
