Cytomegalovirus (CMV) in Pregnancy

Overview

Cytomegalovirus (CMV) is a double-stranded DNA herpesvirus; humans are its only known host. Like other herpesviruses, CMV establishes lifelong latency and may later reactivate. Maternal infection may be primary, reactivation, or reinfection with a different strain.

CMV is shed in saliva, urine, blood, genital/cervical secretions, semen, and breast milk. In pregnancy, the most important congenital route is transplacental fetal infection after maternal viremia. Exposure commonly occurs through saliva or urine from young children; peripartum exposure to cervical secretions or breast milk can cause neonatal acquisition but is much less likely to cause the classic congenital injury pattern.

Primary infection in the periconceptional period or first trimester carries the greatest risk for severe fetal injury. Transmission becomes more frequent later in pregnancy, but later infection is usually less likely to cause severe structural disease.

Updated: June 10, 2026.

Pregnancy CMV algorithm

Clinical trigger

Evaluate when there is compatible maternal illness, seroconversion, exposure concern, or ultrasound findings suggesting congenital infection.

Maternal testing

Order CMV IgG and IgM. Use IgG avidity when IgG is positive and timing of infection matters.

Date the infection

Compare with prior or stored first-trimester samples when available. Do not rely on IgM alone.

Assess fetus

Offer targeted ultrasound and amniotic fluid CMV PCR when prenatal diagnosis is desired and timing is appropriate.

Plan follow-up

Use serial ultrasound, fetal brain MRI when indicated, multidisciplinary counseling, and neonatal CMV PCR within 21 days.

If maternal infection suspected

Review symptoms, exposure, and prior serology.
Discuss hygiene precautions and transmission risk.
Refer to MFM/genetics when primary infection is likely.

If fetal infection confirmed

Serial ultrasound every 2-3 weeks.
Detailed fetal neurosonography.
Fetal brain MRI around 28-32 weeks.

At delivery

Notify pediatrics/neonatology.
Urine or saliva CMV PCR before 21 days of life.
Audiology follow-up, even if newborn appears well.

When to evaluate for CMV

Maternal clues

Mononucleosis-like illness, fever, malaise, myalgias, pharyngitis, or lymphadenopathy
Unexplained hepatitis or transaminitis
Known seroconversion or prior negative CMV IgG with new IgG positivity
High exposure to saliva or urine from young children

Ultrasound clues

Ventriculomegaly, microcephaly, intracranial calcifications, periventricular cysts
Echogenic bowel, hepatosplenomegaly, hepatic calcifications
Fetal growth restriction, placentomegaly, ascites, hydrops, or pericardial effusion
Multiple unexplained fetal abnormalities

Maternal diagnosis

Maternal serology should be interpreted by pattern and timing. IgM alone is neither specific enough to confirm recent primary infection nor sensitive enough later in pregnancy to exclude congenital CMV.

Pattern	Likely interpretation	Clinical next step
IgG negative / IgM negative	No serologic evidence of prior infection.	Hygiene counseling; repeat testing only if new symptoms or high-risk exposure.
IgG positive / IgM negative	Usually past infection, but congenital infection is not excluded if fetal findings are suspicious.	If ultrasound is concerning, consider IgG avidity, prior stored sample review, and amniotic fluid CMV PCR.
IgG positive / IgM positive	Could represent recent primary infection, persistent IgM, reactivation, or reinfection.	Obtain IgG avidity and compare with prior serology if available.
Low IgG avidity	Supports recent primary infection.	Specialist counseling; discuss fetal diagnosis and serial imaging.
High IgG avidity	Most reassuring if obtained in the first trimester. Later high avidity does not fully exclude early pregnancy infection.	Interpret with gestational age, symptoms, prior samples, and fetal imaging.

Important limitation: A negative maternal CMV IgM in the second trimester should not be used to rule out congenital CMV when fetal findings are suggestive of infection.

Fetal diagnosis and surveillance

Diagnostic test

Amniotic fluid CMV PCR is the preferred prenatal diagnostic test. For best sensitivity, perform after 21 weeks and at least 6 weeks after suspected maternal infection.

Ultrasound

Use targeted ultrasound to evaluate growth, placenta, fluid, bowel, liver/spleen, hydrops, and CNS findings. Normal ultrasound does not exclude fetal infection or later hearing loss.

Fetal MRI

When fetal infection is confirmed or CNS findings are suspected, fetal brain MRI at approximately 28-32 weeks can complement neurosonography.

Practical follow-up: If maternal infection is suspected or fetal infection is confirmed, consider ultrasound surveillance every 2-3 weeks, with the interval individualized to gestational age and fetal findings.

Antiviral therapy and counseling

Management has changed rapidly and differs by country. SMFM 2016 did not recommend routine antenatal valacyclovir or hyperimmune globulin outside research protocols. More recent RCOG/ECCI-style guidance and newer studies support specialist-directed high-dose valaciclovir for primary maternal CMV infection acquired periconceptionally or in the first trimester, particularly when started promptly.

When valacyclovir is considered

Most studied scenario: primary maternal infection in the periconceptional period or first trimester.
Published regimen: valaciclovir/valacyclovir 8 g/day, commonly 2 g orally every 6 hours.
Best effect appears when therapy is started soon after suspected infection and continued at least until fetal diagnostic testing is completed.
Use should be MFM/infectious disease directed, with attention to renal function, hydration, drug interactions, and local practice.

Evidence and limitations

A 90-patient randomized trial reported fetal infection reduction from 29.8% with placebo to 11.1% with valaciclovir 8 g/day.
Individual patient data meta-analysis also found reduced vertical transmission after early primary infection, with low overall maternal adverse-event rates.
Evidence is strongest for early primary infection; benefit is less certain for periconceptional infection diagnosed late, second/third trimester infection, or non-primary infection.
High-dose therapy can rarely cause renal toxicity; reported acute renal failure generally resolved after stopping treatment. Monitor creatinine and counsel regarding hydration.

Clinical scenario	Practical counseling
Primary CMV likely before 12-14 weeks	Discuss urgent specialist referral; high-dose valacyclovir may be considered where consistent with local protocol.
Fetal infection already confirmed	Continue individualized counseling; available evidence for preventing transmission no longer applies once fetal infection is established. Some centers consider therapy for symptomatic fetal infection, but this is not uniform practice.
IgG positive / IgM negative with suspicious ultrasound	Do not dismiss CMV; consider avidity, stored first-trimester sample review, and amniotic fluid CMV PCR if amniocentesis is being performed.

NOTE: Antiviral therapy should not be considered routine for all CMV exposures. Treatment is time-sensitive, evidence-evolving, and dependent on infection timing, fetal status, maternal renal function, and specialist consultation.

Delivery and neonatal plan

Notify pediatrics/neonatology when maternal CMV infection is suspected or fetal infection is confirmed.
Test the newborn with urine or saliva CMV PCR within the first 21 days of life to confirm congenital infection.
Evaluate symptomatic infants with CBC, liver tests, ophthalmology, neuroimaging, and audiology.
Arrange hearing surveillance because hearing loss may be delayed or progressive.
Neonatal valganciclovir/ganciclovir decisions should be made by pediatrics/infectious disease specialists.

EMR-ready documentation

Suspected maternal CMV infection

CMV counseling reviewed. Maternal symptoms/exposure and fetal ultrasound findings were discussed. CMV IgG/IgM with IgG avidity was reviewed or recommended as clinically indicated. Counseling included limitations of IgM testing, timing-dependent fetal risk, option for amniotic fluid CMV PCR after 21 weeks and at least 6 weeks from suspected infection, and need for serial fetal assessment if infection is suspected or confirmed.

Confirmed or suspected fetal CMV

Suspected/confirmed fetal CMV infection reviewed. Recommend detailed ultrasound/neurosonography with serial follow-up, consideration of fetal brain MRI at approximately 28-32 weeks, multidisciplinary counseling, and neonatal CMV PCR testing from urine or saliva within 21 days of life. Pediatric/neonatology notification and postnatal audiology follow-up are recommended.

References

Archived prior page: Cytomegalovirus 2010

Society for Maternal-Fetal Medicine (SMFM). Diagnosis and antenatal management of congenital cytomegalovirus infection. Am J Obstet Gynecol. 2016. PMID: 26902990.
Khalil A, Heath PT, Jones CE, Soe A, Ville Y; Royal College of Obstetricians and Gynaecologists. Congenital cytomegalovirus infection: update on screening, diagnosis and treatment. BJOG. 2025;132:e42-e52. PMID: 39434207.
Shahar-Nissan K, Pardo J, Peled O, et al. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial. Lancet. 2020;396(10253):779-785. PMID: 32919517.
Chatzakis C, Ville Y, Makrydimas G, et al. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. Am J Obstet Gynecol. 2020. PMID: 32460972.