Cytomegalovirus in pregnancy: prevention, maternal screening, and the role of antivirals

SUMMARY

Cytomegalovirus (CMV) is the most common congenital infection in Australia and a leading cause of preventable childhood disability.

Current Australian guidelines recommend targeted antenatal screening of women at higher risk for CMV infection. Serology testing should also be considered in women with clinical symptoms suggestive of CMV.

Women with suspected CMV infection in pregnancy should be promptly referred to a maternal–fetal medicine or infectious diseases specialist.

High-dose valaciclovir can reduce in utero transmission to the fetus following first-trimester maternal primary infection; however, long-term safety data are limited. Valaciclovir should only be prescribed by clinicians with specific expertise in CMV, such as maternal–fetal medicine or infectious diseases specialists.

Universal hygiene counselling, targeted screening, careful timing of conception after infection, and structured psychological support are essential components of care.

 

Introduction

Cytomegalovirus (CMV) is a ubiquitous herpesvirus that establishes lifelong latency after infection, meaning the virus persists, resting in the body for life. The virus is transmitted through close contact with infected body fluids, including saliva and urine, as well as through sexual contact and breastfeeding. Young children under the age of 5 years are a major reservoir for CMV and commonly shed the virus in saliva and urine.¹ Childcare workers and carers of young children are therefore at increased risk of CMV infection.^1,2

Congenital CMV affects approximately 1 in 200 live births with 10 to 15% of affected infants developing long-term sequelae such as sensorineural hearing loss, cerebral palsy, or intellectual disability.^3-5 Despite this burden, awareness among pregnant women and clinicians is low.^6-9 Hygiene counselling on risk reduction behaviours, such as handwashing, avoiding sharing food utensils, and refraining from kissing toddlers on the mouth, remains the cornerstone of prevention (Figure 1). Australian healthcare authorities^10,11 and international consensus groups^12,13 all recommend embedding such advice in routine antenatal care. Hygiene education delivered to seronegative women at high risk of CMV exposure has been shown to reduce the risk of primary infection in pregnancy to 1.6% from 7.6%.¹⁴ Australian education resources for healthcare practitioners and pregnant women have been developed and shown to improve knowledge and implementation of CMV risk reduction strategies.^15,16

 

Risk of fetal infection

Transplacental transmission is required for the occurrence of congenital CMV, and infection may result in complications for the fetus and infant, with potential lifelong impacts.

Like other members of the herpesvirus family, fetal CMV infection can be acquired via primary and non-primary maternal infection. Primary maternal CMV infection (i.e. infection in a person without pre-existing CMV-specific IgG antibodies) carries the greatest risk of fetal transmission. Maternal primary infection in the first trimester of pregnancy has a significant risk of severe fetal and newborn complications (Table 1).¹⁸

Table 1 Timing of maternal primary CMV infection, rates of fetal infection and consequences¹⁸

Timing of maternal primary CMV infection	Risk of fetal CMV infection	Risk of fetal or newborn CNS complications [NB1]		Risk of childhood complications [NB2]
		If fetal infection confirmed	If fetal infection unknown [NB3]	If fetal infection confirmed	If fetal infection unknown [NB3]
Periconception [NB4]	21%	29%	6%	not reported	not reported
First trimester	37%	19%	7%	23%	8.4%
Second trimester	40%	0.9%	0.4%	0.1%	less than 0.1%
Third trimester	66%	0.4%	0.3%	less than 0.1%	less than 0.1%
CMV = cytomegalovirus; CNS = central nervous system NB1: Termination of pregnancy for CMV-associated CNS anomalies, or newborn neurological symptoms NB2: Severe sensorineural hearing loss or neurodevelopmental delay NB3: Derived by multiplying risk of infection by risk of complications NB4: Defined as 4 weeks before last menstrual period to 6 weeks after last menstrual period

In contrast, non-primary maternal infection (CMV reinfection or reactivation of latent infection) has a 4-fold lower risk of vertical transmission,¹⁹ but can still be associated with severe fetal consequences.²⁰

 

Indications for CMV serology testing in pregnancy

Screening for CMV

Universal antenatal CMV screening has not been a widespread practice in most countries due to the absence of cost-effectiveness studies, potential risks of harm from false positive results, and lack of proven interventions for maternal infection in pregnancy.^21,22 However, emerging data on the effectiveness of antiviral treatment for reducing the risk of vertical transmission after maternal primary infection in the first trimester have ignited interest in routine screening in pregnancy.^23,24 Several European countries have now embarked on prospective trials of CMV screening.^25-27

Australian Pregnancy Care Guidelines currently recommend that women at increased risk of infection be offered and recommended CMV serology.¹⁰ These guidelines recommend against universal CMV screening in pregnancy and, where testing is done, recommend CMV IgG only due to the risk of false positive IgM results. This is because approximately 5% of pregnant women will have a detectable CMV IgM on testing, most of whom do not have evidence of a recent primary infection after avidity testing (see 'Testing and interpretation' below).^28,29

Suspected CMV infection

Women should be offered serology testing if they have symptoms suggestive of CMV that are not attributable to another specific infection, or when imaging findings suggest fetal infection.

Maternal indications for testing

Maternal symptoms of CMV infection include fever, lymphadenopathy, or a flu-like illness, with laboratory features such as atypical lymphocytosis, thrombocytopenia, elevated transaminases, or haemolytic anaemia. Only 54% of women are symptomatic during a CMV infection, so clinically indicated testing will only detect about half of maternal infections.³⁰

Fetal indications for testing

The main fetal indication for testing is the presence of fetal ultrasound findings suspicious for infection. These include highly suggestive changes such as cerebral ventriculomegaly (especially with a periventricular halo or intraventricular synechiae), brain or liver calcifications, or others such as echogenic bowel or nonimmune hydrops fetalis.³¹

 

Testing and interpretation

Where there is a clinical suspicion of CMV infection in pregnancy, women should be tested for CMV IgG and IgM antibodies, and IgG avidity.CMV IgG avidity is a measure of how well the antibody binds to the virus and is a marker of the recency of infection, not efficacy of the antibody. A diagnosis of primary maternal CMV is based on seroconversion (appearance of CMV IgG in a woman who was previously CMV IgG negative), or the presence of CMV IgG and IgM antibodies, with low IgG avidity (Table 2). Low IgG avidity indicates infection typically within the past 3 months, while high IgG avidity indicates infection more than 3 months prior. However, IgG avidity maturation can vary between individuals and may take longer than 3 months.

Table 2 CMV serology interpretation and management in the first trimester

IgM	IgG	IgG avidity [NB1]	Interpretation	Management
Negative	Negative	Unmeasurable	No prior CMV infection	Educate about transmission (susceptible to primary infection)
Positive	Negative	Unmeasurable	Possible recent infection	Repeat serology at 2 and 4 weeks
Positive	Positive	Low	Primary infection within the past 3 to 4 months	Refer to a maternal–fetal medicine or infectious diseases specialist
Positive	Positive	Intermediate	Possible primary infection within the past 3 to 4 months	Test stored sera from early pregnancy, or manage as recent primary infection and refer to a maternal–fetal medicine or infectious diseases specialist
Positive	Positive	High	Past infection more than 3 to 4 months prior	Refer to a maternal–fetal medicine or infectious diseases specialist, or seek advice about interpretation
Negative	Positive	High	Past infection more than 3 to 4 months prior	Educate about transmission (potential reinfection)
CMV = cytomegalovirus NB1: IgG avidity is a measure of how well the antibody binds to the virus and is a marker of the recency of infection (more than or less than 3 months).

Women with evidence of first-trimester or periconceptional primary infection (within 4 weeks of last menstrual period) should be promptly referred to specialists in perinatal infections, such as maternal–fetal medicine or infectious diseases physicians.^10-13 This ensures appropriate interpretation of serology, expert counselling regarding fetal risks and diagnostic tests, and timely consideration of valaciclovir where appropriate.

If maternal serological testing is performed in the second or third trimester (e.g. following an abnormal midtrimester morphology ultrasound) and the CMV IgG is positive with high avidity, a primary infection in early pregnancy cannot be excluded. In such cases, requesting CMV IgG testing on the maternal serum sample collected at the booking visit may be helpful for determining whether seroconversion occurred during pregnancy. Pathology laboratories are required to store serum samples from pregnant patients for 12 months, enabling retrospective analysis when needed.

 

Role of antivirals

Valaciclovir, the oral prodrug of aciclovir, achieves therapeutic concentrations in maternal serum and amniotic fluid. It is the first antiviral intervention shown in a double-blinded, randomised controlled trial to reduce the vertical transmission of CMV.²⁴ This landmark trial demonstrated high-dose valaciclovir (8 g/day in 2 divided doses) reduced fetal transmission from 48 to 11% for those with first-trimester primary infections. A 2021 meta-analysis incorporating this trial and 2 observational studies confirmed reduced congenital infection rates after first-trimester primary infection, although heterogeneity and lack of long-term developmental outcome data remain significant limitations.²³ Other observational studies in France and Italy support the meta-analysis findings for first-trimester primary infections.^32-34 However, the efficacy of valaciclovir in reducing vertical transmission of CMV for patients with periconceptional infections remains uncertain.

It has been speculated that valaciclovir treatment may alter the maternal immune response to primary CMV infection. A large multicentre observational study found that women treated with valaciclovir were more likely to deliver CMV-positive infants despite a negative amniocentesis, compared with untreated women (15.5% versus 6.7%).³⁴ This phenomenon is thought to reflect rebound maternal viraemia and transplacental transmission after treatment cessation. However, infants in the valaciclovir group were significantly less likely to be symptomatic at birth than the untreated group (7.1% versus 35.2%).³⁴

Given these complexities, valaciclovir should only be prescribed by clinicians with specific expertise in congenital CMV, such as maternal–fetal medicine or infectious diseases specialists. The use of valaciclovir for prevention of congenital CMV is off label in Australia. Women should be counselled about the limited evidence base, lack of long-term safety data, and the fact that valaciclovir reduces, but does not eliminate, the risk of fetal infection. Informed, shared decision-making should cover treatment uncertainties, alternative options, and the need for close monitoring (Box 1).

 

Ongoing antenatal management

Follow-up appointments with the maternal–fetal medicine team should be scheduled every 2 to 4 weeks until amniocentesis. Patients should be assessed regularly for adverse events. Monitoring of renal function and blood cell counts should also be performed at least 2- to 4-weekly, or more frequently if indicated. In all cases where amniotic fluid polymerase chain reaction is positive for CMV, follow-up ultrasound assessment should be recommended, including detailed fetal anatomy and growth evaluation. Dedicated fetal neuroimaging, such as targeted neurosonography and fetal brain magnetic resonance imaging, should also be discussed and considered following appropriate patient counselling.

 

Future pregnancies

There is limited evidence to guide management of future pregnancies after maternal CMV infection. Women who have experienced primary infection develop CMV IgG antibodies, but these do not confer complete protection, and non-primary infection can still occur. Some experts recommend waiting at least 6 to 12 months before attempting conception, but there is no evidence to indicate a specific optimal interval. Documentation of high-avidity CMV IgG prior to conceiving has also been suggested, but this approach may be problematic for women who have delayed IgG maturation. Shared decision-making regarding the appropriate interpregnancy interval should consider individual factors such as maternal age, other fertility considerations, and reproductive goals.

 

Patient support and resources

Australian research on women with lived experience of CMV infection in pregnancy highlighted the profound anxiety, uncertainty and emotional distress associated with this condition.³⁶ These findings underscore the need for compassionate care that goes beyond medical management to include empathic communication, psychological support, and timely referral to counselling services. Alongside clinical guidance, patients value reliable, accessible resources (Box 2). Integrating these resources into routine care pathways can help reduce the isolation and uncertainty many women experience when navigating CMV in pregnancy.

 

Conclusion

Cytomegalovirus is the most common congenital infection in Australia and a leading cause of preventable childhood disability. The updated Australian Pregnancy Care Guidelines emphasise universal hygiene counselling, targeted serological testing for women with increased risk, and timely referral to maternal–fetal medicine or infectious diseases specialists when infection is suspected. Valaciclovir is the first pharmacological intervention shown to reduce (but not prevent) vertical transmission, but its use is limited by pill burden, potential toxicity and the absence of long-term outcome data; therefore, it should only be prescribed under the guidance of maternal–fetal medicine or infectious diseases specialists. Clinicians should recognise the profound psychosocial impact of a CMV diagnosis in pregnancy and provide information on psychological support and reliable patient resources.

This article was finalised on 17 February 2026.

Acknowledgements: The authors thank Dr Antonia Shand for her expert feedback on the manuscript.

Conflicts of interest: Lisa Hui has received a research fellowship from the Norman Beischer Medical Research Foundation for the project 'ESE-CMV study: education, serology and evaluation for the prevention of congenital CMV'. This project focuses on improving knowledge of congenital CMV and adherence to recommended hygiene behaviours among pregnant women, as well as evaluating a first-trimester CMV screening protocol for women at risk of primary infection.

Lisa has developed patient information brochures on CMV for the Cerebral Palsy Alliance and UpToDate. She received payment from Wolters Kluwer for editing the 'Cytomegalovirus infection in pregnancy' chapter in UpToDate.

Lisa has received funding for travel, registration and accommodation as an invited speaker at conferences of the International Society of Ultrasound in Obstetrics and Gynecology, the International Society for Prenatal Diagnosis, and the New Zealand Maternal Fetal Medicine Network. She was previously an elected Board Director of the International Society for Prenatal Diagnosis and Associate Editor of Prenatal Diagnosis.

Lisa Hui and Natasha Holmes contributed to a free online learning module on congenital CMV hosted by Praxhub and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG).

Lisa Hui and William Rawlinson were contributors to the RANZCOG 'Prevention of congenital cytomegalovirus (CMV) infection' statement. Lisa Hui, William Rawlinson and Michelle Giles were co-authors of 'Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy'.¹²

This article is peer reviewed.

 

References

1. Pass RF, Little EA, Stagno S, Britt WJ, Alford CA. Young children as a probable source of maternal and congenital cytomegalovirus infection. N Engl J Med 1987;316:1366-70.
2. Balegamire SJ, McClymont E, Croteau A, Dodin P, Gantt S, Besharati AA, et al. Prevalence, incidence, and risk factors associated with cytomegalovirus infection in healthcare and childcare worker: a systematic review and meta-analysis. Syst Rev 2022;11:131.
3. Buca D, Di Mascio D, Rizzo G, Giancotti A, D'Amico A, Leombroni M, et al. Outcome of fetuses with congenital cytomegalovirus infection and normal ultrasound at diagnosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2021;57:551-9.
4. Smithers-Sheedy H, Raynes-Greenow C, Badawi N, Fernandez MA, Kesson A, McIntyre S, et al. Congenital Cytomegalovirus among Children with Cerebral Palsy. J Pediatr 2017;181:267-71 e1.
5. Ssentongo P, Hehnly C, Birungi P, Roach MA, Spady J, Fronterre C, et al. Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries With Universal Screening: A Systematic Review and Meta-analysis. JAMA Netw Open 2021;4:e2120736.
6. Lazzaro A, Vo ML, Zeltzer J, Rawlinson W, Nassar N, Daly K, et al. Knowledge of congenital cytomegalovirus (CMV) in pregnant women in Australia is low, and improved with education. Aust N Z J Obstet Gynaecol 2019;59:843-9.
7. Shand AW, Luk W, Nassar N, Hui L, Dyer K, Rawlinson W. Cytomegalovirus (CMV) infection and pregnancy-potential for improvements in Australasian maternity health providers' knowledge. J Matern Fetal Neonatal Med 2018;31:2515-20.
8. Sartori P, Baud D, de Tejada BM, Farin A, Rossier MC, Rieder W, et al. Cytomegalovirus infection during pregnancy: cross-sectional survey of knowledge and prevention practices of healthcare professionals in French-speaking Switzerland. Virol J 2024;21:45.
9. Vena F, D'Ambrosio V, Pajno C, Boccherini C, Corno S, Di Mascio D, et al. Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study. J Perinat Med 2021;49:327-32.
10. Australian Living Evidence Collaboration. Australian Pregnancy Care Guidelines. Version 8.1. 2025. [cited 2026 Feb 19]
11. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Prevention of congenital cytomegalovirus (CMV) infection. 2019. [cited 2025 Jul 2]
12. Rawlinson WD, Boppana SB, Fowler KB, Kimberlin DW, Lazzarotto T, Alain S, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 2017;17:e177-e88.
13. Leruez-Ville M, Chatzakis C, Lilleri D, Blazquez-Gamero D, Alarcon A, Bourgon N, et al. Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI). Lancet Reg Health Eur 2024;40:100892.
14. Revello MG, Tibaldi C, Masuelli G, Frisina V, Sacchi A, Furione M, et al. Prevention of Primary Cytomegalovirus Infection in Pregnancy. EBioMedicine 2015;2:1205-10.
15. Smithers-Sheedy H, Swinburn K, Rode N, Tripathi T, Holmes N, Waight E, et al. Educating antenatal patients about cytomegalovirus infection: An e-learning package improves general practitioners' knowledge and intention to implement clinical guidelines. Australian Journal of General Practice 2025;54:407-12.
16. Tripathi T, Watson J, Smithers-Sheedy H, Swinburn K, Rode N, Waight E, et al. A 2-Min Cytomegalovirus (CMV) Awareness Video Improves Pregnant Women's Knowledge and Planned Adherence to Hygiene Precautions. Aust N Z J Obstet Gynaecol 2025;65:662-70.
17. Cerebral Palsy Alliance. Reducing the risk of CMV during pregnancy. CMV Resource Hub; 2025. [cited 2025 Sep 22]
18. Chatzakis C, Ville Y, Makrydimas G, Dinas K, Zavlanos A, Sotiriadis A. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. Am J Obstet Gynecol 2020;223:870-83 e11.
19. Leruez-Ville M, Magny JF, Couderc S, Pichon C, Parodi M, Bussieres L, et al. Risk Factors for Congenital Cytomegalovirus Infection Following Primary and Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using Polymerase Chain Reaction in Saliva. Clin Infect Dis 2017;65:398-404.
20. Mussi-Pinhata MM, Yamamoto AY. Natural History of Congenital Cytomegalovirus Infection in Highly Seropositive Populations. J Infect Dis 2020;221:S15-S22.
21. Hui L, Shand A. Is it time to adopt routine cytomegalovirus screening in pregnancy? No! Am J Obstet Gynecol MFM 2021;3:100355.
22. Xie M, Tripathi T, Holmes NE, Hui L. Serological screening for cytomegalovirus during pregnancy: A systematic review of clinical practice guidelines and consensus statements. Prenat Diagn 2023;43:959-67.
23. D'Antonio F, Marinceu D, Prasad S, Khalil A. Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2023;61:436-44.
24. Shahar-Nissan K, Pardo J, Peled O, Krause I, Bilavsky E, Wiznitzer A, et al. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial. Lancet 2020;396:779-85.
25. Latapy C, Midy F. Assessment of screening for cytomegalovirus (CMV) infection in pregnant women in France. Haute Autorité de Santé; 2016. [cited 2025 Aug 12]
26. Sanchez-Duran MA, Maiz N, Liutsko L, Bielsa-Pascual J, Garcia-Sierra R, Zientalska AM, et al. Universal screening programme for cytomegalovirus infection in the first trimester of pregnancy: study protocol for an observational multicentre study in the area of Barcelona (CITEMB study). BMJ Open 2023;13:e071997.
27. TreatCMV. Voor zorgverleners. 2025. [cited 2025 Sep 15]
28. Munro SC, Hall B, Whybin LR, Leader L, Robertson P, Maine GT, et al. Diagnosis of and screening for cytomegalovirus infection in pregnant women. J Clin Microbiol 2005;43:4713-8.
29. Marzan MB, Tripathi T, Dumville L, Watson J, Holmes NE, Hui L. Modelling maternal cytomegalovirus seroprevalence in Australia using maternal country of birth: Implications for antenatal screening. medRxiv 2025:2025.08.21.25333872.
30. Munro SC, Trincado D, Hall B, Rawlinson WD. Symptomatic infant characteristics of congenital cytomegalovirus disease in Australia. J Paediatr Child Health 2005;41:449-52.
31. Khalil A, Sotiriadis A, Chaoui R, da Silva Costa F, D'Antonio F, Heath PT, et al. ISUOG Practice Guidelines: role of ultrasound in congenital infection. Ultrasound Obstet Gynecol 2020;56:128-51.
32. Faure-Bardon V, Fourgeaud J, Stirnemann J, Leruez-Ville M, Ville Y. Secondary prevention of congenital cytomegalovirus infection with valacyclovir following maternal primary infection in early pregnancy. Ultrasound Obstet Gynecol 2021;58:576-81.
33. Egloff C, Sibiude J, Vauloup-Fellous C, Benachi A, Bouthry E, Biquard F, et al. New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus. Ultrasound Obstet Gynecol 2023;61:59-66.
34. Zammarchi L, Tomasoni LR, Liuzzi G, Simonazzi G, Dionisi C, Mazzarelli LL, et al. Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study. Am J Obstet Gynecol MFM 2023;5:101101.
35. Pasternak B, Hviid A. Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects. JAMA 2010;304:859-66.
36. Tripathi T, Watson J, Skrzypek H, Stump H, Lewis S, Hui L. "The anxiety coming up to every scan-It destroyed me": A qualitative study of the lived experience of cytomegalovirus infection during pregnancy. Prenat Diagn 2024;44:623-34.