Congenital CMV: Difference between revisions
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***'''Reinfection''': 5% risk |
***'''Reinfection''': 5% risk |
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***'''Reactivation''': 1% risk |
***'''Reactivation''': 1% risk |
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*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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{| class="wikitable" |
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! 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 |
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! rowspan="2" |Overall Probability |
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(of any neurological disease) |
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|- |
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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% |
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|5% |
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|30% |
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|65% |
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|10% |
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|- |
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|second |
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|40% |
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|0% |
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|15% |
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|85% |
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|6% |
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|- |
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|third |
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|70% |
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|0% |
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|0% |
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|100% |
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|0% |
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|- |
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|Reinfection |
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|overall |
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|5% |
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| colspan="3" | |
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|<1% |
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|- |
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|Reactivation |
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|overall |
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|1% |
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| colspan="3" | |
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|<1% |
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|} |
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*Overall, 20% of infected babies will have permanent neurological sequelae |
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**50% of those symptomatic at birth and 15% of those asymptomatic |
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==Clinical Manifestations== |
==Clinical Manifestations== |
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==Diagnosis== |
==Diagnosis== |
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*In mom, |
*In mom, [[CMV in pregnancy#Diagnosis|serology]] |
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*Molecular |
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| ⚫ | |||
**Urine PCR within 2 weeks of birth is the mainstay of diagnosis |
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***Can also do saliva in the first 2 weeks of life |
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**Universal screening with PCR of dried blood spot is now being done in some jurisdictions |
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==Management== |
==Management== |
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*Once diagnosed, all babies need: |
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*Treatment is indicated for symptomatic babies |
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**CBC, liver enzymes and function, creatinine |
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**Brain |
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**Quantitative CMV PCR |
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**Hearing |
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**Possibly lumbar puncture for CSF analysis |
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**Eye |
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**Neuroimaging, with head ultrasound |
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*IV [[Is treated by::ganciclovir]] or PO [[Is treated by::valganciclovir]], for 6 months |
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***CT is best for calcifications, but has high radiation exposure |
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*Monitor CBC while on therapy |
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***MRI is best for migration defects, but may require sedation |
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**Ophthalmology and audiology assessments |
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*Treatment is indicated for symptomatic babies, which is defined based on the consensus guidelines[[CiteRef::rawlinson2017co]] |
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**'''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 |
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**'''Mildly symptomatic congenital cytomegalovirus disease''' |
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***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) |
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**'''Asymptomatic congenital cytomegalovirus infection with isolated sensorineural hearing loss''' |
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***No apparent abnormalities to suggest congenital cytomegalovirus disease, but sensorineural hearing loss (≥21 decibels) |
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**'''Asymptomatic congenital cytomegalovirus infection''' |
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***No apparent abnormalities to suggest congenital cytomegalovirus disease, and normal hearing |
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*For neonates with moderately to severely symptomatic congenital CMV |
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**Treat with [[Is treated by::valganciclovir]] PO for 6 months |
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**Alternative is [[Is treated by::ganciclovir]] IV |
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| ⚫ | |||
**Monitor neutrophils weekly for 6 weeks, then at 8 weeks, and monthly |
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**Monitor ALT monthly |
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*For neonates with mildly symptomatic congenital CMV, consensus guidelines do not recommend treatment |
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*Some specialists will still treat infants with [[sensorineural hearing loss]] in an attempt to prevent deafness |
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== Prevention == |
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* The focus of prevention is on [[CMV in pregnancy#Prevention|preventing maternal disease]] |
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[[Category: |
[[Category:Congenital infections]] |
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Latest revision as of 16:21, 20 September 2020
Background
- Infection with cytomegalovirus acquired in utero
- See also CMV in pregnancy
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
- Mother may have had asymptomatic infection
- At birth (10%)
- Microcephaly (35-50%)
- Periventricular calcifications
- Seizure (5-10%)
- Chorioretinitis (10-15%)
- Sensorineural hearing loss (35%)
- Optic nerve atrophy
- Petechiae (50-75%)
- Neonatal jaundice (40-70%)
- Hepatosplenomegaly (40-60%)
- Small size for gestational age (40-50%)
- Lethargy and hypotonia (30%)
- Poor suck (20%)
- Cytopenias
- Hemolytic anemia (5-10%)
- Pneumonia (5-10%)
- Later
- Cognitive deficits (7%)
- Sensorineural hearing loss (20%)
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
- Urine PCR within 2 weeks of birth is the mainstay of diagnosis
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
- Multiple manifestations attributable to congenital cytomegalovirus infection: thrombocytopenia, petechiae, hepatomegaly, splenomegaly, intrauterine growth restriction, hepatitis (raised transaminases or bilirubin), or
- 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 (≥21 decibels)
- Asymptomatic congenital cytomegalovirus infection
- No apparent abnormalities to suggest congenital cytomegalovirus disease, and normal hearing
- Moderately to severely symptomatic
- 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
- The focus of prevention is on preventing maternal disease
References
- ^ Gisela Enders, Anja Daiminger, Ursula Bäder, 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.
- ^ William D Rawlinson, Suresh B Boppana, Karen B Fowler, David W Kimberlin, Tiziana Lazzarotto, Sophie Alain, Kate Daly, Sara Doutré, 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.
