neonatal infections

Neonatal Infections

Catherine M. Bendel, M.D.Associate Professor of PediatricsDirector, Neonatal-Perinatal Medicine Fellowship Program

Questions?

• Why are infants, especially premies, more susceptible to infections?

• What are the clinical manifestations of neonatal infections?

• Bacterial?• HSV?• How to prevent

infections?

• Antibiotics - indications, contraindications, cautions, resistance, etc.

• How to interpret labs?• Any precautions with

lines?

Objectives

• To briefly review neonatal immunology and why neonates are so susceptible to infections

• To review the epidemiology, clinical presentation, diagnosis and treatment of the most common bacterial and HSV neonatal infections.

• To review modes of infection prevention.• To differentiate between preterm and term infants

in all these areas

“Prematurity is an infectious disease.”

- James Todd, M.D.

Why are infants, especially premies, more susceptible to

infections?

Neonatal Immune SystemNeonatal Immune System

• All neonates relatively immunocompromised

• Immature and Ineffective:

– Antibodies

– Complement

– Neutrophils

– Skin / mucosal barriers

Antibody

Figure 1.1 Antibodies (anti- foreign bodies) are produced by host while cells on contact with the invading micro-organism which is acting as an antigen (e.g. generates antibodies). The individual may then be immune to further attacks.

(Modified From: Roitt, I: Essential Immunology, 4th edition, Blackwell Scientific Publications, 1980)

Antibodies

Infectious agent

Immunity

No contact with infectious agents = no antibody production

Antibodies

Infectious agent

Immunity

x x

Remington and Klein, Sixth Edition, 2006

Maternal Transfer of Antibodies

• Antibody transfer increases with GA

• Most during 3rd trimester

• No guarantee maternal antibodies present to the infecting organism

Complement

Neutrophils

Neonatal Neutrophils

• Immature Chemotaxis Deformability Phagocytosis Storage pool

• Adults 14-fold > circulating pool

• Neonates only 2-fold

Manroe et al, J Pediatr, 1979

“Normal” VLBW neonates

Mouzinho et al, Pediatr 94:76, 1994

Neonatal Barriers to Infection

Neonatal Anatomic Barriers

• Immature skin and mucosal surfaces layers junctions between cells secretory IgA

• Umbilical cord

• Breaches - catheters, tape

Invasive Fungal Dermatitis in a VLBW infant

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

JL Rowen, Sem Perinatal 27:406-413, 2003

Epidemiology

Neonatal Sepsis: Incidence

• 2/1000 live births with culture proven sepsis

– Bacterial / Viral / Fungal

– 80% infants develop bacterial sepsis

– 20% infants perinatally acquired viral infections

– ~ 25% of infected infants have meningitis

• Higher rate with preterm birth

– 26/1000 preterm infants with BW < 1000g

– 8-9/1000 preterm infants with BW 1000-2000g


Neonatal Bacterial Sepsis:Disease Patterns

• Early Onset Neonatal Sepsis (EONS)– Fulminant, multi-

system illness– < 5 days old– Obstetrical

complications– Prematurity– Perinatal acquisition– High mortality, 5-50%

• Late Onset Neonatal Sepsis (LONS)– Sepsis or meningitis– 5 days to 3 months old– Perinatal or postnatal

acquisition– Lower mortality, 2-6%

Neonatal InfectionsNeonatal Infections

Sepsis MeningitisPneumonia

Otitis MediaDiarrheal Disease

UTIOsteomyelitis

Suppurative ArthritisConjunctivitis

Orbital CellulitisCellulitis - - Omphalitis

Bacterial / Viral / Fungal

Etiologic Agents of Neonatal SepsisEtiologic Agents of Neonatal Sepsis

Frequency(%) Group B Streptococci 40 Escherichia coli 17Streptococcus viridans 7Staphylococcus aureus 6Enterococcus spp 6Coagulase-negative staphylococci 5Klebsiella pneumoniae 4Pseudomonas spp 3Serratia marcescans 2Others 10

*Schuchat et al, Pediatrics 105: 21-26, 2000

Etiologic Agents of Neonatal MeningitisEtiologic Agents of Neonatal Meningitis

Gram Positive Bacteria; Frequency (%) Group B Streptococci 53Listeria monocytogenes 7Miscellaneous gram-positives 6

Gram Negative Bacteria: Escherichia coli 19Klebsiella species 8Haemophilus influenzae 1Miscellaneous gram-negatives 8

Anaerobes 3

Feigen & Cherry, Fifth Edition, 2004

Incidence of Neonatal Group B Streptoccal Sepsis

• 5-35% Pregnant women colonized

• 1/100-200 colonized women will have an infant with early onset disease

• 1-7/1000 live births in 1993

• 0.44/1000 live births in 1999


0

0.5

1

1.5

2

2.5

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Year

Cases per 1000 live births

Early-onset Late-onset

Rate of Early- and Late-onset Rate of Early- and Late-onset GBS Disease GBS Disease in the 1990s, U.S. the 1990s, U.S.

Consensus guidelines

1st ACOG & AAP statements

Group B Strep Association formed CDC draft

guidelines published

Schrag, New Engl J Med 2000 342: 15-20

Rate of Early-Onset Disease by Race Rate of Early-Onset Disease by Race 1993-19981993-1998

0

0.5

1

1.5

2

2.5

1993 1994 1995 1996 1997 1998

Cases per 1000 live births

Black

White

Healthy People 2010

Schrag, New Engl J Med 2000 342: 15-20

Current Estimates of Annual GBS Current Estimates of Annual GBS Early-Onset Disease in the U.S. Early-Onset Disease in the U.S.

(2001 provisional, from ABCs/EIP Network)(2001 provisional, from ABCs/EIP Network)

1720 cases still occurring annually

70 - 90 deaths Remains leading infectious cause of neonatal morbidity and mortality

~4,400 cases prevented per year

What do we know about trends in “other pathogens”?

• Most studies: stable rates of ‘other’ sepsis

• Concerns for increased rates of E. coli, all gram negatives, or amp-R infections

• Population-based (multicenter) studies find stable rates of total non-GBS and E. coli

• One multicenter study of very LBW infants found a decrease in GBS by 4.2 /1,000, but an increase in E coli rates of 3.6/1,000 (Stoll et al, NEJM, 2002, 347:240-7)

• % of E. coli sepsis w/ amp resistance may be increasing

• Increases restricted to low birth weight or preterm deliveries

0123456789

1998 1999 2000

Year

Number of Cases

Sensitive Resistant

N=22, p=0.52, linear trend

Ampicillin Susceptibility of Ampicillin Susceptibility of E. coliE. coli from Early- from Early-Onset Sepsis Cases, Full-Term Infants, ABCs, Onset Sepsis Cases, Full-Term Infants, ABCs,

Selected Counties CA and GA, 1998-2000Selected Counties CA and GA, 1998-2000

Hyde et al, Pediatrics 2002;110(4):690-5.

0

5

10

15

20

1998 1999 2000

Year

Number of Cases

Sensitive Resistant

N=37, p=0.02, linear trend

Ampicillin Susceptibility of Ampicillin Susceptibility of E. coliE. coli from Early- from Early-Onset Sepsis Cases Preterm Infants, ABCs, Onset Sepsis Cases Preterm Infants, ABCs,

Selected Counties CA and GA, 1998-2000Selected Counties CA and GA, 1998-2000

Hyde et al, Pediatrics 2002;110(4):690-5.

Susceptibility of GBS: Susceptibility of GBS: ABC/EIP Isolates, 1995-2000ABC/EIP Isolates, 1995-2000

• 1280 isolates from MN, GA, NY, OR (1173 invasive, 107 colonizing):

– All susceptible to penicillin, ampicillin, cefotaxime and vancomycin

– 19% erythromycin resistance

– 11% clindamycin resistance

Risk Factors for Early Onset Risk Factors for Early Onset Neonatal SepsisNeonatal Sepsis

• Primary (significant) Prematurity or low birth weight– Preterm labor– Premature or prolonged rupture of membranes Maternal fever / chorioamnionitis– Fetal hypoxia– Traumatic delivery

• Secondary– Male– Lower socioeconomic status– African-American race


Factors associated with early-onset Factors associated with early-onset GBS disease: multivariable analysisGBS disease: multivariable analysis

Characteristic Adjusted RR (95% CI)

GBS screening 0.46 (0.36-0.60)

Prolonged ROM (> 18 h) 1.41 (0.97-2.06)

Pre-term delivery 1.50 (1.07-2.10)

Black race 1.87 (1.45-2.43)

Maternal age <20 y 2.22 (1.59-3.11)

Previous GBS infant 5.54 (1.71-17.94)

Intrapartum fever 5.36 (3.60-7.99)

Schrag et al, NEJM 2002, 347:233-9

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Risk Factors - Maternal FeverRisk Factors - Maternal Fever

• Maternal fever is a significant risk factor for EONS and may add in the identification of infected but initially asymptomatic infant.

• 5.36 = adjusted RR

• 25% of asymptomatic infants, with culture positive sepsis, had maternal fever as the ONLY criteria for evaluation.

Chen et al, J of Perinatal, 2002, 22:653-657

Early Onset Neonatal Sepsis:Presentation and Diagnosis

Early Onset Neonatal Sepsis:Signs/Symptoms

??

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Signs/SymptomsSigns/Symptoms

Strongly suggestivehypoglycemia / hyperglycemiahypotensionmetabolic acidosisapneashockDIChepatosplenomegalybulging fontanelleseizurespetechiaehematocheziarespiratory distress

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Signs/SymptomsSigns/Symptoms

Nonspecificlethargy, irritability

temperature instability -- hypothermia or fever

poor feeding

cyanosis

tachycardia

abdominal distention

jaundice

tachypnea

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Signs/Symptoms - FeverSigns/Symptoms - Fever

• The infant with sepsis may have an elevated, depressed or normal temperature.

• Fever is seen in up to 50% of infected infants.

• Fever is more common in term infants, while hypothermia is more common in preterm infants

• A single elevated temperature reading or fever as an isolated finding is infrequently associated with sepsis.

• Persistent fever for greater than 1 hour is more frequently associated with infection.

• Fever occurs more frequently with LONS or with viral, rather than bacterial, sepsis.

Klein, Sem in Perinat, 5:3-8

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Laboratory EvaluationLaboratory Evaluation

Cultures

• Chest Radiograph

• Complete Blood Cell Count

• Glucose

• Bilirubin

• Liver Function Tests

• Coagulation studies

• C-reactive Protein (CRP)

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Cultures -- Who and Which?Cultures -- Who and Which?

• Blood culture -- indicated in ALL infants with suspected sepsis. Repeat cultures indicated if initial culture positive.

• Urine culture -- low yield in EONS

– + in 1.6% EONS compared to 7.47% LONS

Klein, Sem in Perinat, 5:3-8

Early Onset Neonatal Sepsis:Cultures -- Who and Which?

• CSF culture -- should always be considered Meningitis frequently accompanies sepsis

- 50-85% meningitis cases have + blood culture

- Yield reportedly low if respiratory distress is the only major sign of infection

- Specific signs & symptoms occur in less than 50% of infants with meningitis

- Using “selective criteria” for obtaining CSF may result in missed or delayed diagnosis in up to 37% of infants with meningitis

Wiswell et al, Pediatrics, 1995

Laboratory Diagnosis of Laboratory Diagnosis of Neonatal MeningitisNeonatal Meningitis

CSF - - > 32 WBC/mm3

> 60% PMN

glucose < 50% - 75% of serum

protein > 150 mg/dl

organisms on gram stain

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Complete Blood Cell CountsComplete Blood Cell Counts

• Is the CBC helpful as an indicator of early onset neonatal sepsis?

– Thrombocytopenia frequently associated with sepsis

– WBC may be high, low or “normal” --timing of the sample important

– Persistent low WBC more predictive of sepsis than elevated WBC (ANC < 1200)

– I:T quotient unreliable

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Complete Blood Cell CountsComplete Blood Cell Counts

Early Onset Neonatal Sepsis:Complete Blood Cell Counts

• Single or serial neutrophil values DO NOT assist in the diagnosis of EONS or determining the duration of therapy

• 99% of asymptomatic, culture-negative neonates > 35 weeks GA had 1 or more “abnormal” WBC values

Early Onset Neonatal Sepsis:C-Reactive Protein


• Measure of inflammation -- NOT specific for infection

• Elevated CRP, > 10 mg/L (>1 mg/dl), highly associated with sepsis --- but NOT diagnostic

• Limited by lack of “normal” reference values for <24 hours old or preterm infants

• Trend with multiple samplings correlates with infection as takes time to rise -- two samples ~24 hours apart useful

• Potentially useful when maternal antibiotics given - pretreatment interferes with cultures

Early Onset Neonatal Sepsis: Empiric Treatment

Initial:Ampicillin and Gentamicin IV(Cefotaxime discouraged)

Duration:“Rule out sepsis” 48 - 72 hours

Pneumonia 5 - 7 days

Sepsis 7 - 10 days

Meningitis 14 - 21 days

Primarily determined by etiologic organism culturedSecondarily determined by clinical course/response

?CRP-guided determination of duration?


Early Onset Neonatal Sepsis: Supportive Therapy


• Ventilation• BP support - fluids, Dopamine/Dobutamine/HCTZ

• TPN• FFP - clotting factors, C3, antibodies• G-CSF - stimulate WBC production/release• Steroids not indicated as anti-inflammatory

Treatment of GBS Infections

Initial- Ampicillin and Gentamycin IV

(Gent synergy for first 3 days)

- May switch to Penicillin G IV (with confirmation of diagnosis/sensitivities)

Duration (from first negative culture)Uncomplicated sepsis 10 - 14 days

Meningitis 14 days minimum

Treatment of E. Coli Infections

Ampicillin and an Aminoglycoside IVWith confirmation of diagnosis /sensitivities:- drop Amp- substitute a third generation cephalosporin

Duration (from first negative culture)

Uncomplicated sepsis 10 -14 days


Treatment of Listeria Monocytogenes Infections

Ampicillin and an Aminoglycoside IV





Pediatrics, 1997, 99:216-221

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:C-reactive ProteinC-reactive Protein

• CRP levels <10mg/L, determined >24 hours after beginning therapy correctly identified 99% of infants not needing further therapy.

• May be useful in determining end-point for “rule-out sepsis” evaluations, especially with maternal antibiotic treatment.

• CRP-guided determination of length of therapy, shortened the treatment course for most infected infants without increasing the rate of relapse.

• Limitations: no studies evaluating meningitis or infections other than bacterial sepsis.

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Treatment & CRPTreatment & CRP

• “Exposure to antibiotics during labor did not change the clinical spectrum of disease or onset of clinical signs of infection within 24 hours of birth for term infants with EOGBS infection.”

• Normal CRP values at 24 hours of age supported these observations.

Pediatrics, 2000, 106:244-250

PrognosisPrognosis

Neonatal SepsisMortality 20 - 30% overall - highest in premature infants

Morbidity ?? 25% ??

Neonatal Bacterial MeningitisMortality 15 - 30% - - 5% if infant survives the first 24 hr

Morbidity up to 50%

30 - 35% mild to moderate neurologic sequelae5 - 10% severe neurologic impairment

Early Onset Neonatal Sepsis:Early Onset Neonatal Sepsis:Prognosis - PrematurityPrognosis - Prematurity

Organism Mortality for

BW <1500g Mortality for BW 1500-2500g

Mortality for BW >2500g

Group B

Streptococci

73% 20% 10%

Escherichia coli 73% 42% 13%

Staphylococcus aureus

44% 15% 5%

Other 67% 33% 13%

Total 67% 28% 10%


Early Onset Neonatal Sepsis:Summary

• GBS is still the predominant organism isolated in EONS

• Our efforts at IAP have reduced, but not eliminated, early onset GBS sepsis

• Obstetrical risk factors, including premature/near-term delivery and maternal intrapartum fever, help to identify the infants at highest risk for EONS

• Ancillary laboratory evaluations, including the CRP value, may assist in determination of the most appropriate length of therapy

Late Onset Neonatal Sepsis

Late Onset Neonatal Sepsis

• Perinatal acquisition with later onset– Term or preterm– Bacterial: GBS, Chlamydia– Viral: HSV, CMV, HepB, HIV– Fungal: Candida

• Nosocomial acquisition– Health care associated infections– Preterm or sick term infant

Late Onset GBS

• Transmission - Perinatally or postnatally -- intrapartum prophylaxis or neonatal treatment of early onset disease does not decrease risk of late onset disease

• Symptoms - 7days - 3 months. Typically 3-4 weeks old.

Occult bacteremia or meningitis most common. However, focal infections (pneumonia, UTI, cellulitis, osteomylelitis, septic arthritis) may occur.

• Diagnosis - Culture of blood, sputum, urine, abscess or other body fluid.

• Treatment - Penicillin, as with early onset disease.

Herpes Simplex Virus (HSV)

• Incidence• 1/3000-20,000 live births

• 1/200 pregnant women

• > 75% asymptomatic

• Enveloped DS-DNA

• 75% HSV II

• HSVI

• Transmission• 5-8% transplacental (congenital) • 85-90% perinatally

• Primary infection (risk 30-50%)• Secondary infection (risk <5%)• Impossible to distinguish 1o vs 2o

• 5-10% postnatally• Parent, caregiver

• Usually non-genital - hand, mouth

• Nosocomial spread from other infants via hands of health care professionals

HSV Specific Symptoms1. Disseminated Disease

• Multi-organ involvement• Sepsis syndrome, DIC• Liver, CNS, lung predominance• Severe liver & CNS dysfunction common• Wide temp variations characteristic

2. Localized Central Nervous System Disease• Seizures common

3. Disease localized to the skin, eye and mouth• Vesicles, cloudy cornea.conjunctivitis, ulcers

4. Onset 1-4 weeks of age5. Clinical overlap exists6. Skin lesions absent or appear late with

disseminated/CNS disease

HSV Diagnosis• High index of suspicion

– History ±– Age (1-4 weeks)– Sepsis Syndrome unresponsive to antibiotic therapy

• PE - classic vesicular lesions

• Culture - readily grows within 1-3 days– Mouth, nasopharynx, conjunctivae rectum -- swabs >48 hours of age– Skin vesicles, urine, stool, blood and CSF

PCR - diagnostic method of choice - best on CSF, other fluids possible

• CSF pleocytosis (especially monos) and elevated protein• Coagulopathy/DIC, thrombocytopenia, severe liver dysfunction• EEG

HSV Therapy - Prognosis

• Acyclovir IV– 21 days for disseminated or CNS

– 14 days for skin, eye and mouth

• Mimimal toxicity - primarily liver - large volume IV

• Decreases mortality with disseminated disease from ~75% to 25-40%

• Decreases morbidity from 90% to 65%

• Improvements in both mortality and morbidity dependent upon early initiation of Acyclovir

Neonatal Herpes: Number of Patients and Neonatal Herpes: Number of Patients and Outcome by Body Site Involved in Infants Outcome by Body Site Involved in Infants

with a Pre-Mortem Diagnosis and Not with a Pre-Mortem Diagnosis and Not Treated with Antivirals*Treated with Antivirals*

* Modified from Nahmias et al. 265

† Primary severe neurologic sequelae.‡ No apparent sequelae from available follow-up information.

Type of Infection Patients (%) Death (%) Outcome in Infant (%) Normal‡(%)Sequelae†

Disseminatedwithout CNS involvement 38 (16) 87 3 10with CNS involvement 78 (33) 71 15 14

LocalizedCNS 61 (26) 37 51 12skin 39 (17) 10 26 64eye 13 (5) 0 31 69mouth 4 (2) 0 0 100

Asymptomatic 2 (1) 0 0 100

TOTAL 235 (100) 49 25 26


Neonatal Nosocomial Infections

Risk Factors for Neonatal Nosocomial Sepsis

• Prematurity • ELBW > VLBW• Increased LOS• Abdominal surgery / NEC• Hyperalimentaion / Intralipids• Neutropenia, Thrombocytopenia• Catheters

– UAC, UVC, ETT, Foley, CT, Peritoneal drains, etc

Umbilical Arterial and Venous Catheters

• Life-saving tools on the NICU• Necessary evil• Increased of infections

– Minimally at 7 days– Significantly at 10-14 days or when clot present

• UVC > UAC– Stasis, hyperal/IL, thrombin formation

Umbilical Arterial and Venous Catheters

• Require strict protocols regarding use and care to reduce infection rates

• Remove:– when no longer needed– when evidence of infection or clot formation

• Replace when required >14 days– PICC / broviac / percutaneous a-line

Neonatal InfectionsNeonatal Infections

Sepsis MeningitisPneumonia

Otitis MediaDiarrheal Disease

UTI Osteomyelitis

Suppurative ArthritisConjunctivitis

Orbital CellulitisCellulitis - - Omphalitis

Bacterial / Viral / FungalMulti-organ involvement common

Neonatal Nosocomial Infections: Microbiology

• Skin flora Coagulase negative Staphylococcus Candida spp• Methicillin-resistant Staphylococcus aureus

– Source: infant, care-givers, parents

• Gram-negative bacteria Enterococcus spp, Enterobacter spp, E. coli• Pseudomonas spp, Klebsiella spp, Seratia spp

– Source:• Infant GI tract• Person-to-person transmission from Nursery personnel• Nursery environmental sites: sinks, multiple use solutions, countertops, respiratory

therapy equipment…

Late Onset Neonatal Sepsis: Empiric Treatment

Initial:Vancomycin and Aminoglycoside IV(Cefotaxime discouraged)

Duration (from first negative culture):“Rule out sepsis” 48 - 72 hours

Pneumonia 5 - 7 days

Sepsis 10 -14 days


Primarily determined by etiologic organism culturedSecondarily determined by clinical course/response

?CRP-guided determination of duration?


Concerns for Antibiotic-resistant organisms

• Vancomycin- resistant enterococcus (VRE)– Theoretic risk on

NICU risk with multiple

course of vanco– Strict contact

isolation

• Methicillin-resistant Staphylococcus aureus (MRSA)– Real risk on NICU– Community /

maternal acquired– Vanco use required– Strict contact

isolation

Treatment of Coagulase Negative Treatment of Coagulase Negative Staphylococcal InfectionsStaphylococcal Infections

Vancomycin IV (± Rifampin if difficult to clear)




Removal of indwelling intravascular catheters

Treatment of Gram-Negative InfectionsTreatment of Gram-Negative Infections

Aminoglycoside IV + “something” (based on sensitivities)




Removal of indwelling intravascular catheters

PrognosisPrognosis

Dependent upon organism and early initiation of

appropriate therapy

LOS increased in all cases

Morbidity also variable dependent upon organ involvement - worse with meningitis

Thanks for all your excellent care on the

NICU!

Indications for GBS Intrapartum Prophylaxis

AAP Redbook, 2006 Report of the Committee on Infectious Diseases

Empiric management of the infant after maternal IAP

AAP Redbook, 2006 Report of the Committee on Infectious Diseases

Common Manifestations of Viral Infections in the Newborn Infant

Specific Features (acute)Hyper- or hypothermiaGeneral: irritability, lethargy, jitters, poor feeding, vomiting CNS: seizures, hyper- or hypotonia, full fontanelle, meningitis, encephalitisSkin: icterus, petechiae, purpura, vesicle, maculopapular rashEye: conjunctivitis, keratitisHeart: myocarditis, hypotensionAbdomen: hepatosplenomegaly, hepatitisLung: pneumonitis, respiratory distress, cyanosis


Early Onset Neonatal Sepsis:Enteroviral infections

• Diagnosis:– Culture of stool, rectum pharynx best– Culture of urine, blood and CSF may be positive– Culture of mother may be diagnostic– PCR more rapid, but less specific

• Therapy: supportive only

Time/Mode of Acquisition of Viral Agent

Time Prenatal Perinatal PostnatalMode Transplacental Birth Canal or Ascending Contact

MotherMaternal colonizedviremia, in vagina Nosocomialamnioitis or GI tract or horizontal

Implications + symptoms + symptoms transmission

CMV + + +Rubella + - +Herpes II + + +EBV + (rare) - +Echo + + +Coxsackie + + +HTLV-III + - +Influenza + - +Hepatitis B + + +Varicella + - +Adeno - - +Rotavirus - - +RSV - - +Parainfluenza type 3 - - +Rhinovirus - - +

Time Prenatal Perinatal PostnatalMode Transplacental Birth Canal or Ascending Contact

MotherMaternal colonizedviremia, in vagina Nosocomialamnioitis or GI tract or horizontal

Implications + symptoms + symptoms transmission

CMV + + +Rubella + - +Herpes II + + +EBV + (rare) - +Echo + + +Coxsackie + + +HTLV-III + - +Influenza + - +Hepatitis B + + +Varicella + - +Adeno - - +Rotavirus - - +RSV - - +Parainfluenza type 3 - - +Rhinovirus - - +

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