Congenital CMV: Difference between revisions

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== Epidemiology ==
 +
==Background==
   
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*Infection with [[cytomegalovirus]] acquired in utero
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* Risk of transmission to fetus
  
  +
*See also [[CMV in pregnancy]]
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** '''Primary infection''': 30% risk of congenital CMV; higher risk later in pregnancy, but worse outcomes earlier
  
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** Non-primary
  
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*** '''Reinfection''': 5% risk
  
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*** '''Reactivation''': 1% risk
  
   
  +
===Epidemiology===
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== Clinical Presentation ==
  
   
  +
*Maternal seroconversion in about 2% of pregnancies
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* At birth
  
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**Higher in childcare workers
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** Microcephaly
  
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*Risk of transmission to fetus
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** Periventricular calcifications
  
  +
**About 1 in 200 live births in US
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** Chorioretinitis
  
  +
**'''Primary infection''': 30% risk of congenital CMV; higher risk later in pregnancy, but worse outcomes earlier
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** Sensorineural hearing loss
  
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**Non-primary
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** Optic nerve atrophy
  
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***'''Reinfection''': 5% risk
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** Hepatosplenomegaly
  
  +
***'''Reactivation''': 1% risk
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** Cytopenia
  
  +
*Risk of transmission to fetus following primary infection increases with gestational age, but risk of neurological sequelae decreases substantially[[CiteRef::enders2011in]]
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* Later
  
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** Cognitive deficits (7%)
  
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** Sensorineural hearing loss (20%)
  
   
  +
{| class="wikitable"
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== Diagnosis ==
  
  +
! rowspan="2" |Maternal Serostatus
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! rowspan="2" |Trimester
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! rowspan="2" |Transmission to Fetus
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! colspan="3" |Severity of Neurological Disease
  +
! rowspan="2" |Overall Probability
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(of any neurological disease)
  +
|-
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!Severe
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!Mild/Transient
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!None
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|-
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| rowspan="3" |Primary
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|first
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|30%
  +
|5%
  +
|30%
  +
|65%
  +
|10%
  +
|-
  +
|second
  +
|40%
  +
|0%
  +
|15%
  +
|85%
  +
|6%
  +
|-
  +
|third
  +
|70%
  +
|0%
  +
|0%
  +
|100%
  +
|0%
  +
|-
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|Reinfection
  +
|overall
  +
|5%
  +
| colspan="3" |
  +
|<1%
  +
|-
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|Reactivation
  +
|overall
  +
|1%
  +
| colspan="3" |
  +
|<1%
  +
|}
   
  +
*Overall, 20% of infected babies will have permanent neurological sequelae
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* In mom, IgM antibodies
  
  +
**50% of those symptomatic at birth and 15% of those asymptomatic
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* In baby, urine PCR within 2 weeks of birth
  
   
  +
==Clinical Manifestations==
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== Management ==
  
   
  +
*Mother may have had asymptomatic infection
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* Treatment is indicated for symptomatic babies
  
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*At birth (10%)
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** Brain
  
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**[[Causes::Microcephaly]] (35-50%)
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** Hearing
  
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**[[Causes::Periventricular calcifications]]
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** Eye
  
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**[[Causes::Seizure]] (5-10%)
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* IV [[Is treated by::ganciclovir]] or PO [[Is treated by::valganciclovir]], for 6 months
  
  +
**[[Causes::Chorioretinitis]] (10-15%)
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* Monitor CBC while on therapy
  
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**[[Causes::Sensorineural hearing loss]] (35%)
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**[[Causes::Optic nerve atrophy]]
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**[[Causes::Petechiae]] (50-75%)
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**[[Causes::Neonatal jaundice]] (40-70%)
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**[[Causes::Hepatosplenomegaly]] (40-60%)
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**Small size for gestational age (40-50%)
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**[[Causes::Lethargy]] and [[Causes::hypotonia]] (30%)
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**Poor suck (20%)
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**[[Causes::Cytopenias]]
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**[[Causes::Hemolytic anemia]] (5-10%)
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**[[Causes::Pneumonia]] (5-10%)
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*Later
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**[[Causes::Cognitive deficits]] (7%)
  +
**[[Causes::Sensorineural hearing loss]] (20%)
   
  +
==Diagnosis==
   
  +
*In mom, [[CMV in pregnancy#Diagnosis|serology]]
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[[Category:Pediatrics]]
  
  +
*Molecular
  +
**Urine PCR within 2 weeks of birth is the mainstay of diagnosis
  +
***Can also do saliva in the first 2 weeks of life
  +
**Universal screening with PCR of dried blood spot is now being done in some jurisdictions
  +
  +
==Management==
  +
  +
*Once diagnosed, all babies need:
  +
**CBC, liver enzymes and function, creatinine
  +
**Quantitative CMV PCR
  +
**Possibly lumbar puncture for CSF analysis
  +
**Neuroimaging, with head ultrasound
  +
***CT is best for calcifications, but has high radiation exposure
  +
***MRI is best for migration defects, but may require sedation
  +
**Ophthalmology and audiology assessments
  +
*Treatment is indicated for symptomatic babies, which is defined based on the consensus guidelines[[CiteRef::rawlinson2017co]]
  +
**'''Moderately to severely symptomatic'''
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***'''Multiple manifestations''' attributable to congenital cytomegalovirus infection: [[thrombocytopenia]], [[petechiae]], [[hepatomegaly]], [[splenomegaly]], [[intrauterine growth restriction]], [[hepatitis]] (raised transaminases or bilirubin), or
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***'''Central nervous system involvement''' such as [[microcephaly]], radiographic abnormalities consistent with cytomegalovirus central nervous system disease ([[ventriculomegaly]], [[intracerebral calcifications]], periventricular echogenicity, cortical or cerebellar malformations), abnormal cerebrospinal fluid indices for age, [[chorioretinitis]], [[sensorineural hearing loss]], or the detection of cytomegalovirus DNA in cerebrospinal fluid
  +
**'''Mildly symptomatic congenital cytomegalovirus disease'''
  +
***Might occur with one or two isolated manifestations of congenital cytomegalovirus infection that are mild and transient (eg, mild [[hepatomegaly]] or a single measurement of low platelet count or raised levels of alanine aminotransferase)
  +
**'''Asymptomatic congenital cytomegalovirus infection with isolated sensorineural hearing loss'''
  +
***No apparent abnormalities to suggest congenital cytomegalovirus disease, but sensorineural hearing loss (β‰₯21 decibels)
  +
**'''Asymptomatic congenital cytomegalovirus infection'''
  +
***No apparent abnormalities to suggest congenital cytomegalovirus disease, and normal hearing
  +
*For neonates with moderately to severely symptomatic congenital CMV
  +
**Treat with [[Is treated by::valganciclovir]] PO for 6 months
  +
**Alternative is [[Is treated by::ganciclovir]] IV
  +
**Started within 30 days of birth
  +
**Monitor neutrophils weekly for 6 weeks, then at 8 weeks, and monthly
  +
**Monitor ALT monthly
  +
*For neonates with mildly symptomatic congenital CMV, consensus guidelines do not recommend treatment
  +
*Some specialists will still treat infants with [[sensorineural hearing loss]] in an attempt to prevent deafness
  +
  +
== Prevention ==
  +
  +
* The focus of prevention is on [[CMV in pregnancy#Prevention|preventing maternal disease]]
  +
  +
[[Category:Congenital infections]]

Latest revision as of 12:21, 20 September 2020

Background

Epidemiology

  • Maternal seroconversion in about 2% of pregnancies
    • Higher in childcare workers
  • Risk of transmission to fetus
    • About 1 in 200 live births in US
    • Primary infection: 30% risk of congenital CMV; higher risk later in pregnancy, but worse outcomes earlier
    • Non-primary
      • Reinfection: 5% risk
      • Reactivation: 1% risk
  • Risk of transmission to fetus following primary infection increases with gestational age, but risk of neurological sequelae decreases substantially1
Maternal Serostatus Trimester Transmission to Fetus Severity of Neurological Disease Overall Probability

(of any neurological disease)

Severe Mild/Transient None
Primary first 30% 5% 30% 65% 10%
second 40% 0% 15% 85% 6%
third 70% 0% 0% 100% 0%
Reinfection overall 5% <1%
Reactivation overall 1% <1%
  • Overall, 20% of infected babies will have permanent neurological sequelae
    • 50% of those symptomatic at birth and 15% of those asymptomatic

Clinical Manifestations

Diagnosis

  • In mom, serology
  • Molecular
    • Urine PCR within 2 weeks of birth is the mainstay of diagnosis
      • Can also do saliva in the first 2 weeks of life
    • Universal screening with PCR of dried blood spot is now being done in some jurisdictions

Management

  • Once diagnosed, all babies need:
    • CBC, liver enzymes and function, creatinine
    • Quantitative CMV PCR
    • Possibly lumbar puncture for CSF analysis
    • Neuroimaging, with head ultrasound
      • CT is best for calcifications, but has high radiation exposure
      • MRI is best for migration defects, but may require sedation
    • Ophthalmology and audiology assessments
  • Treatment is indicated for symptomatic babies, which is defined based on the consensus guidelines2
    • Moderately to severely symptomatic
    • Mildly symptomatic congenital cytomegalovirus disease
      • Might occur with one or two isolated manifestations of congenital cytomegalovirus infection that are mild and transient (eg, mild hepatomegaly or a single measurement of low platelet count or raised levels of alanine aminotransferase)
    • Asymptomatic congenital cytomegalovirus infection with isolated sensorineural hearing loss
      • No apparent abnormalities to suggest congenital cytomegalovirus disease, but sensorineural hearing loss (β‰₯21 decibels)
    • Asymptomatic congenital cytomegalovirus infection
      • No apparent abnormalities to suggest congenital cytomegalovirus disease, and normal hearing
  • For neonates with moderately to severely symptomatic congenital CMV
    • Treat with valganciclovir PO for 6 months
    • Alternative is ganciclovir IV
    • Started within 30 days of birth
    • Monitor neutrophils weekly for 6 weeks, then at 8 weeks, and monthly
    • Monitor ALT monthly
  • For neonates with mildly symptomatic congenital CMV, consensus guidelines do not recommend treatment
  • Some specialists will still treat infants with sensorineural hearing loss in an attempt to prevent deafness

Prevention

References

  1. ^  Gisela Enders, Anja Daiminger, Ursula BΓ€der, Simone Exler, Martin Enders. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. Journal of Clinical Virology. 2011;52(3):244-246. doi:10.1016/j.jcv.2011.07.005.
  2. ^  William D Rawlinson, Suresh B Boppana, Karen B Fowler, David W Kimberlin, Tiziana Lazzarotto, Sophie Alain, Kate Daly, Sara DoutrΓ©, Laura Gibson, Michelle L Giles, Janelle Greenlee, Stuart T Hamilton, Gail J Harrison, Lisa Hui, Cheryl A Jones, Pamela Palasanthiran, Mark R Schleiss, Antonia W Shand, Wendy J van Zuylen. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. The Lancet Infectious Diseases. 2017;17(6):e177-e188. doi:10.1016/s1473-3099(17)30143-3.

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