Abstract
Objective
To provide an update on current recommendations for cytomegalovirus (CMV) infection
during pregnancy. The objectives of this guideline are:
- •To improve perinatal care providers’ awareness of the consequences of maternal CMV infection for the fetus and the infant;
- •To emphasize the importance of educating patients about how to prevent CMV acquisition during pregnancy
- •To raise perinatal care providers’ awareness of new developments in CMV screening and treatment
- •To highlight that a substantial proportion of disability due to congenital CMV (cCMV) can be modified to some extent
Target Population
Patients of child-bearing age, pregnant patients, and patients planning a pregnancy.
Benefits, Harms, and Costs
The patient partners urged us to make awareness of preventive strategies a high priority,
despite concern that discussing CMV with patients could cause unnecessary anxiety.
CMV educational interventions have shown benefits from increased awareness of cCMV
prevalence and preventive strategies among providers, patients, and families.
Evidence
We searched MEDLINE, EMBASE, and CENTRAL databases for CMV in pregnancy. The search
terms were developed using MeSH terms and keywords (Appendix).
The results were filtered for articles published between January 2010 and October
2020 and systematic reviews, meta-analyses, clinical trials, and observational studies.
The main inclusion criteria were pregnant patients and infants, as the target population,
and CMV infection, as the diagnosis of interest. Recommendations are graded according
to the U.S. Preventive Services Task Force grade of recommendations and level of certainty.
Validation Methods
We collaborated with patient partners, including members of CMV Canada (cmvcanada.com).
In formulating our recommendations, we included patients’ voices to add a unique and
valuable perspective, thus ensuring that our recommendations are relevant to the patient–provider
partnership.
Intended Audience
All perinatal health care providers.
RECOMMENDATIONS (grade and level of certainty in parentheses)
- 1Pregnant patients with a mononucleosis-like illness or undifferentiated hepatitis should be investigated for cytomegalovirus infection (C, low).
- 2To diagnose maternal cytomegalovirus infections and to differentiate primary from non-primary infections, this guideline recommends a combination of seroconversion (defined as documentation of a change from cytomegalovirus immunoglobulin G negative to positive), cytomegalovirus immunoglobulin M, and cytomegalovirus immunoglobulin G avidity testing (B, moderate).
- 3A positive immunoglobulin M result alone should be interpreted with caution when determining when a CMV infection was acquired (C, moderate).
- 4Breastfeeding is considered safe in patients who had CMV infection during pregnancy (B, high).
- 5If primary maternal CMV infection is diagnosed during pregnancy, or abnormal sonographic findings suggest congenital CMV infection, pregnant patients should be offered an amniocentesis for confirmation of fetal congenital infection (cCMV) at least 8 weeks after the estimated time of maternal infection (B, high).
- 6This guideline recommends discussing education and hygiene measures to prevent CMV acquisition with all patients, regardless of serologic status, before conception and through pregnancy, especially early in the antepartum period (B, high).
- 7CMV hyperimmune globulin should not be used to prevent congenital CMV if a primary CVM infection is diagnosed during pregnancy (B, low).
- 8In the case of documented primary CMV infection in the first trimester, early treatment with valacyclovir can be considered (B, moderate).
- 9For established congenital CMV infections during pregnancy, decisions concerning treatment options should be made in a shared process involving patients and experienced teams (C, low).
- 10In provinces where CMV IgG avidity testing is available, screening for CMV primary infection in the first trimester (using IgG and IgM antibodies followed by IgG avidity testing if the patient is IgM-positive) can be offered, especially in women at high risk (those who have a child under 3 years at home). CMV screening in pregnancy is not recommended in provinces where CMV IgG avidity testing is unavailable (C, low).
Keywords
Abbreviations:
CMV (cytomegalovirus), cCMV (congenital cytomegalovirus infection), CVS (chorionic villus sampling), ELISA (enzyme-linked immunosorbent assay), IUGR (intra uterine growth restriction), IgG (immunoglobulin G), IgM (immunoglobulin M), PCR (polymerase chain reaction), SGA (small for gestational age)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Obstetrics and Gynaecology CanadaAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
REFERENCES
- Survey of a neonatal population for the prevalence of cytomegalovirus.Scand J Infect Dis. 1975; 7 (Available at): 165-167
- Congenital cytomegalovirus infection in an urban canadian community.J Infect Dis. 1980; 142 (Available at): 647-653
- Long-term outcomes of congenital cytomegalovirus infection in sweden and the united kingdom.Clin Infect Dis. 2013; 56 (Available at): 1232-1239
- Long-term impairment attributable to congenital cytomegalovirus infection: A retrospective cohort study.Dev Med Child Neurol. 2017; 59 (Available at): 1261-1268
- Awareness of cytomegalovirus and risk factors for susceptibility among pregnant women, in montreal, canada.BMC Pregnancy Childbirth. 2016; 16 (Available at): 54
- Congenital cytomegalovirus infection in high-risk canadian infants: Report of a pilot screening study.Can J Infect Dis Med Microbiol. 2010; 21 (Available at): e12-e19
- Implementation of a cmv screening program for infants of hiv infected mothers by salivary pcr and/or culture: Results from a single center.Canadian Journal of Infectious Diseases and Medical Microbiology. 2015; SB: 72B
- Cytomegalovirus seroprevalence in the united states: The national health and nutrition examination surveys, 1988-2004.Clin Infect Dis. 2010; 50 (Available at): 1439-1447
- Predictive factors of cytomegalovirus seropositivity among pregnant women in paris, france.PLoS One. 2014; 9 (Available at): e89857
- Congenital human cytomegalovirus infection and the enigma of maternal immunity.J Virol. 2017; (Available at): 91
- Review and meta-analysis of the epidemiology of congenital cytomegalovirus (cmv) infection.Rev Med Virol. 2007; 17 (Available at): 253-276
- The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: A population-based prediction model.Rev Med Virol. 2013; 23 (Available at): 241-249
- Seroconversion for cytomegalovirus infection in a cohort of pregnant women in quebec, 2010-2013.Epidemiol Infect. 2016; 144 (Available at): 1701-1709
- Cytomegalovirus seroconversion rates and risk factors: Implications for congenital cmv.Rev Med Virol. 2010; 20 (Available at): 311-326
- Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome.JAMA. 1986; 256 (Available at): 1904-1908
- Quantifying the burden of congenital cytomegalovirus infection with long-term sequelae in subsequent pregnancies of women seronegative at their first pregnancy.Clin Infect Dis. 2020; 71: 1598-1603
- Quantifying the burden of congenital cytomegalovirus infection with long-term sequelae in subsequent pregnancies of women seronegative at their first pregnancy.Clinical Infectious Diseases. 2019; 71 (Available at): 1598-1603https://doi.org/10.1093/cid/ciz1067
- The occupational risk of cytomegalovirus infection among day-care providers.JAMA. 1991; 265 (Available at): 603-608https://doi.org/10.1001/jama.1991.03460050057020
- Molecular epidemiology of cytomegalovirus: Viral transmission among children attending a day care center, their parents, and caretakers.The Journal of Pediatrics. 1988; 112 (Available at): 366-372
- Increased rate of cytomegalovirus infection among parents of children attending day-care centers.N Engl J Med. 1986; 314: 1414-1418
- Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age.J Clin Virol. 2011; 52 (Available at): 244-246
- Sequelae of congenital cytomegalovirus (ccmv) following maternal primary infection are limited to those acquired in the first trimester of pregnancy.Clin Infect Dis. 2018; (Available at)
- Universal cytomegalovirus screening: Time for reappraisal?.Fetal and Maternal Medicine Review. 2014; 25 (Available at): 117-133
- Universal cytomegalovirus screening: Time for reappraisal?.Fetal and Maternal Medicine Review. 2014; 25 (Available at)
- Neonatal screening for congenital cmv infection stresses the importance of maternal nonprimary infection even in an area where prenatal serology testing is common.J Matern Fetal Neonatal Med. 2017; (Available at): 1-4
- Seroconversion for cytomegalovirus infection during pregnancy and fetal infection in a highly seropositive population: "The brachs study".J Infect Dis. 2018; 218 (Available at): 1200-1204
- Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity.J Pediatr. 2006; 148 (Available at): 332-336
- Spectrum of disease and outcome in children with symptomatic congenital cytomegalovirus infection.J Pediatr. 2014; 164 (Available at): 855-859
- Primary versus non-primary maternal cytomegalovirus infection as a cause of symptomatic congenital infection - register-based study from finland.Infect Dis (Lond). 2017; 49 (Available at): 445-453
- Maternal immunity and the natural history of congenital human cytomegalovirus infection.Viruses. 2018; : 10
- Report on a long-term study of maternal and congenital cytomegalovirus infection in sweden. Review of prospective studies available in the literature.Scand J Infect Dis. 1999; 31 (Available at): 443-457
- Chapter 24: Cytomegalovirus.in: Wilson CB Remington and klein's infectious diseases of the fetus and newborn infant. 8th ed. Elsevier Saunders, Philadelphia, Pennsylvania2016: 724-781
- Chapter 140: Cytomegalovirus.in: Bennett JE Dolin R Blaser MJ Mandell GL Douglas RG Mandell, douglas, and bennett's principles and practice of infectious diseases. 8th ed. Elsevier, Philadelphia,PA2015: 1738-1753
- Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity.N Engl J Med. 2001; 344 (Available at): 1366-1371
- Cytomegalovirus reinfections in healthy seroimmune women.J Infect Dis. 2010; 201 (Available at): 386-389
- Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population.Am J Obstet Gynecol. 2010; 202 (297 e1-8Available at)
- Diagnosis and management of infants with congenital cytomegalovirus infection.Paediatr Child Health. 2017; 22 (Available at): 72-74
- Cytomegalovirus infection of breast milk and transmission in infancy.Pediatrics. 1983; 72 (Available at): 295-299
- Postnatal cytomegalovirus infection and the risk for bronchopulmonary dysplasia.JAMA Pediatr. 2015; 169 (Available at)e153785
- Outcome of preterm infants with postnatal cytomegalovirus infection.Pediatrics. 2018; (Available at): 141
- Maternal igm antibody status in confirmed fetal cytomegalovirus infection detected by sonographic signs.Prenat Diagn. 2012; 32 (Available at): 817-821
- Ultrasound prediction of symptomatic congenital cytomegalovirus infection.Am J Obstet Gynecol. 2008; 198 (380 e1-7Available at)
- Congenital cytomegalovirus infection in pregnancy and the neonate: Consensus recommendations for prevention, diagnosis, and therapy.Lancet Infect Dis. 2017; 17 (e177-e88Available at)
- Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant.Clin Microbiol Rev. 2002; 15 (Available at): 680-715
- Development and evaluation of a capture elisa for igm antibody to the human cytomegalovirus major DNA binding protein.J Virol Methods. 1991; 35: 315-329
- Positive predictive value of anti-hcmv igm as an index of primary infection.J Virol Methods. 2010; 168 (Available at): 121-125
- Role of cytomegalovirus (cmv) igg avidity testing in diagnosing primary cmv infection during pregnancy.Clin Vaccine Immunol. 2014; 21 (Available at): 1377-1384
- Evaluation of the new architect cytomegalovirus immunoglobulin m (igm), igg, and igg avidity assays.J Clin Microbiol. 2009; 47: 1695-1699
- Analytical issues possibly affecting the performance of commercial human cytomegalovirus igg avidity assays.Eur J Clin Microbiol Infect Dis. 2014; 33 (Available at): 1579-1584
- Prenatal indicators of congenital cytomegalovirus infection.J Pediatr. 2000; 137 (Available at): 90-95
- Avidity of immunoglobulin g directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects.Clin Diagn Lab Immunol. 1997; 4 (Available at): 469-473
- Diagnosis and antenatal management of congenital cytomegalovirus infection.Am J Obstet Gynecol. 2016; 214 (Available at): B5-B11
- Detailed in utero ultrasound description of 30 cases of congenital cytomegalovirus infection.Prenat Diagn. 2014; 34 (Available at): 518-524
- Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy.Clin Microbiol Infect. 2011; 17 (Available at): 1285-1293
- Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome.Prenat Diagn. 2001; 21 (Available at): 362-377
- Accuracy of amniotic fluid testing before 21 weeks' gestation in prenatal diagnosis of congenital cytomegalovirus infection.Prenat Diagn. 1994; 14 (Available at): 1055-1059
- Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases: A 5 years' single center experience.Prenat Diagn. 2017; 37 (Available at): 389-398
- Primary maternal cytomegalovirus infections: Accuracy of fetal ultrasound for predicting sequelae in offspring.Am J Obstet Gynecol. 2016; 215 (638 e1- e8Available at)
- Does normal fetal brain ultrasound predict normal neurodevelopmental outcome in congenital cytomegalovirus infection?.Prenat Diagn. 2011; 31 (Available at): 360-366
- Value of prenatal ultrasound and magnetic resonance imaging in assessment of congenital primary cytomegalovirus infection.Ultrasound Obstet Gynecol. 2010; 36 (Available at): 709-717
- Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging.Ultrasound Obstet Gynecol. 2013; 41 (Available at): 508-514
- Congenital cytomegalovirus infection: Contribution and best timing of prenatal mr imaging.Eur Radiol. 2016; 26 (Available at): 3760-3769
- Clinical evaluation of the new roche platform of serological and molecular cytomegalovirus-specific assays in the diagnosis and prognosis of congenital cytomegalovirus infection.J Virol Methods. 2017; 248 (Available at): 250-254
- Clinical predictive value of real-time pcr quantification of human cytomegalovirus DNA in amniotic fluid samples.J Clin Microbiol. 2009; 47 (Available at): 660-665
- Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood.BJOG. 2011; 118 (Available at): 448-456
- Hearing outcome of infants with congenital cytomegalovirus and hearing impairment.Arch Dis Child. 2016; 101 (Available at): 433-438
- Vaccination against the human cytomegalovirus.Vaccine. 2018; (Available at)
- Vaccine prevention of maternal cytomegalovirus infection.N Engl J Med. 2009; 360: 1191-1199
- Observational study to assess pregnant women's knowledge and behaviour to prevent toxoplasmosis, listeriosis and cytomegalovirus.BMC Pregnancy Childbirth. 2013; 13 (Available at): 98
- Awareness of cytomegalovirus infection among pregnant women in geneva, switzerland: A cross-sectional study.Int J Environ Res Public Health. 2015; 12 (Available at): 15285-15297
- Perspectives of women on screening and prevention of cmv in pregnancy.Eur J Obstet Gynecol Reprod Biol. 2021; 258: 409-413
- Maternal cytomegalovirus infection prevention: The role of dutch primary care midwives.Midwifery. 2014; 30 (Available at): 1196-1201
- What information do dutch midwives give clients about toxoplasmosis, listeriosis and cytomegalovirus prevention? An exploratory study of videotaped consultations.Patient Educ Couns. 2014; 96 (Available at): 29-35
- Prevention of primary cytomegalovirus infection in pregnancy.EBioMedicine. 2015; 2 (Available at): 1205-1210
- A brief prenatal intervention of behavioral change to reduce the risk of maternal cytomegalovirus: A randomized controlled trial.Obstet Gynecol. 2017; 130 (Available at): 726-734
- Prevention of child-to-mother transmission of cytomegalovirus by changing behaviors: A randomized controlled trial.Pediatr Infect Dis J. 1996; 15 (Available at): 240-246
- Does hygiene counseling have an impact on the rate of cmv primary infection during pregnancy? Results of a 3-year prospective study in a french hospital.J Clin Virol. 2009; 46 (Available at): S49-S53
- Educating women about congenital cytomegalovirus: Assessment of health education materials through a web-based survey.BMC Womens Health. 2014; 14 (Available at): 144
- Women's attitudes toward practicing cytomegalovirus prevention behaviors.Prev Med Rep. 2016; 4 (Available at): 517-524
- Effectiveness of message framing on women's intention to perform cytomegalovirus prevention behaviors: A cross-sectional study.BMC Womens Health. 2017; 17 (Available at): 134
Balegamire S, McClymont E, Croteau A, et al. Systematic review and meta-analysis of the prevalence, incidence, and risk factors of cytomegalovirus infection in occupationally exposed populations. Under review.
- Acyclovir exposure and birth defects: An important advance, but more are needed.JAMA. 2010; 304 (Available at): 905-906https://doi.org/10.1001/jama.2010.1214
- Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects.JAMA. 2010; 304 (Available at): 859-866https://doi.org/10.1001/jama.2010.1206
- Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection.BJOG: An International Journal of Obstetrics & Gynaecology. 2007; 114 (Available at): 1113-1121
- Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: A randomised, double-blind, placebo-controlled trial.Lancet. 2020; 396: 779-785
- Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection.BJOG. 2007; 114 (Available at): 1113-1121
- In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase ii study.Am J Obstet Gynecol. 2016; 215 (462 e1-e10Available at)
- Passive immunization during pregnancy for congenital cytomegalovirus infection.N Engl J Med. 2005; 353 (Available at): 1350-1362
- Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: A retrospective analysis.J Perinat Med. 2012; 40 (Available at): 439-446
- A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus.N Engl J Med. 2014; 370 (Available at): 1316-1326
- Use of cytomegalovirus-specific hyperimmunoglobulins in pregnancy: A retrospective cohort.J Obstet Gynaecol Can. 2018; 40 (Available at): 1409-1416
- Prevention and treatment of fetal cytomegalovirus infection with cytomegalovirus hyperimmune globulin: A multicenter study in madrid.J Matern Fetal Neonatal Med. 2019; 32 (Available at): 617-625
- Prevention of maternal-fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration.Ultrasound Obstet Gynecol. 2019; 53 (Available at): 383-389
- Lb17. Randomized trial to prevent congenital cytomegalovirus (cmv).Open Forum Infectious Diseases. 2019; 6 (Available at): S1000-S10S1https://doi.org/10.1093/ofid/ofz415.2500
- Regression of fetal cerebral abnormalities by primary cytomegalovirus infection following hyperimmunoglobulin therapy.Prenat Diagn. 2008; 28 (Available at): 512-517
- Fetal hyperechogenic bowel may indicate congenital cytomegalovirus disease responsive to immunoglobulin therapy.J Matern Fetal Neonatal Med. 2012; 25 (Available at): 2202-2205
- Early primary cytomegalovirus infection in pregnancy: Maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age.Clin Infect Dis. 2012; 55 (Available at): 497-503
- Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy–a case-control study of the outcome in children.J Infect Dis. 2012; 205 (Available at): 215-227
- A trial of immunoglobulin fetal therapy for symptomatic congenital cytomegalovirus infection.J Reprod Immunol. 2012; 95 (Available at): 73-79
- Valganciclovir for symptomatic congenital cytomegalovirus disease.N Engl J Med. 2015; 372 (Available at): 933-943
- Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: A randomized, controlled trial.J Pediatr. 2003; 143 (Available at): 16-25
- Universal newborn screening for congenital cmv infection: What is the evidence of potential benefit?.Rev Med Virol. 2014; 24 (Available at): 291-307
- Cost-effectiveness of universal and targeted newborn screening for congenital cytomegalovirus infection.JAMA Pediatr. 2016; 170 (Available at): 1173-1180
- Outcomes from a hearing-targeted cytomegalovirus screening program.Pediatrics. 2017; : 139
- Ammi canada: Response to faqs about the management of children with congenital cytomegalovirus infection in canada.Official Journal of the Association of Medical Microbiology and Infectious Disease Canada. 2019; 4 (Available at): 208-214
- A targeted approach for congenital cytomegalovirus screening within newborn hearing screening.Pediatrics. 2017; : 139
Article info
Publication history
Published online: June 01, 2021
No. 420, July 2021 (Replaces No. 240, April 2010)Footnotes
This document reflects emerging clinical and scientific advances as of the publication date and is subject to change. The information is not meant to dictate an exclusive course of treatment or procedure. Institutions are free to amend the recommendations. The SOGC suggests, however, that they adequately document any such amendments.
Informed consent: Everyone has the right and responsibility to make informed decisions about their care together with their health care providers. In order to facilitate this, the SOGC recommends that health care providers provide patients with information and support that is evidence-based, culturally appropriate, and personalized.
Language and inclusivity: The SOGC recognizes the importance to be fully inclusive and when context is appropriate, gender-neutral language will be used. In other circumstances, we continue to use gendered language because of our mission to advance women's health. The SOGC recognizes and respects the rights of all people for whom the information in this document may apply, including but not limited to transgender, non-binary, and intersex people. The SOGC encourages health care providers to engage in respectful conversation with their patients about their gender identity and preferred gender pronouns and to apply these guidelines in a way that is sensitive to each person's needs.
Identification
Copyright
© 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Directive clinique no 420 : Infection à cytomégalovirus pendant la grossesseJournal of Obstetrics and Gynaecology Canada Vol. 43Issue 7
- Corrigendum to ‘Guideline No. 420: Cytomegalovirus Infection in Pregnancy’ [Journal of Obstetrics and Gynaecology Canada 43/7 (2021) 893-908]Journal of Obstetrics and Gynaecology Canada Vol. 43Issue 12
