The Iranian Journal of Obstetrics, Gynecology and Infertility

The Iranian Journal of Obstetrics, Gynecology and Infertility

Cytomegalovirus Infection in Pregnant Women and Its Maternal and Neonatal Outcomes: A Review of Studies

Document Type : Review Article

Authors
Bagher Moradi 1
Ashraf Saber 2
1 Assistant Professor, Department of Basic Sciences, Esfrayen School of Medical Sciences, Esfrayen, Iran.
2 Instructor, Department of Nursing and Midwifery, Esfrayen School of Medical Sciences, Esfrayen, Iran.
10.22038/ijogi.2026.82127.6181
Abstract
Introduction: Cytomegalovirus (CMV) infection during pregnancy can cause miscarriage, stillbirth, or premature birth because of crossing the placenta. Considering population policies and the importance of having a young and healthy generation, the present review study was conducted with aim to explain cytomegalovirus infection as a threatening factor during pregnancy, as well as to review aspects of diagnosis, treatment, and prevention of cytomegalovirus in order to increase the knowledge of health and treatment experts.
Methods: This study was conducted by search in PubMed, Scopus, Web of Science (ISI), and Google Scholar databases using relevant keywords of Cytomegalovirus, Pregnant Women, Newborn, Outcome, and Health Care System. Terms were selected from the Mesh Medical Dictionary, and finally 117 articles in both Persian and English were selected, which examined cytomegalovirus infection in pregnant women and newborns without any time limit.
Results: Most pregnant women with CMV infection were IgG, IgM seropositive and asymptomatic. Nevertheless, numerous reports of miscarriage, premature birth, intrauterine growth restriction, stillbirth, neonatal death secondary to pneumonia and congenital hydrocephalus, and sensorineural hearing loss (SNHL) indicate the importance of this infection on the fetus and newborns. It seems that mother's survival after delivery is not much affected by diseases caused by cytomegalovirus.
Conclusion: Cytomegalovirus infection is underestimated in pregnant women due to its asymptomatic nature, which has a negative impact on the health of the fetus and newborn. The study also found that despite the serious consequences of CMV, pregnant women generally have little or no knowledge of the disease, and doctors and nurses who care for these patients are not accustomed to informing them about it.
Keywords
Cytomegalovirus
Newborn
Outcomes
Pregnancy
Subjects
1.        Kotton C. CMV: prevention, diagnosis and therapy. American Journal of Transplantation 2013; 13:24-40.
2.        Heldman MR, Dunn B, Clemens E, Henderson M, Fisher CE, Rakita RM, et al. A practical guide to real‐world implementation of pre‐emptive therapy for cytomegalovirus disease prevention in high‐risk seronegative liver transplant recipients with seropositive donors. Transplant Infectious Disease 2024; 26(3):e14229.
3.        Maltezou PG, Kourlaba G, Kourkouni Ε, Luck S, Blazquez-Gamero D, Ville Y, et al. Maternal type of CMV infection and sequelae in infants with congenital CMV: Systematic review and meta-analysis. Journal of Clinical Virology 2020; 129:104518.
4.        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 in Obstetrics & Gynecology 2021; 57(4):551-9.
5.        Benou S, Dimitriou G, Papaevangelou V, Gkentzi D. Congenital cytomegalovirus infection: do pregnant women and healthcare providers know enough? A systematic review. The Journal of Maternal-Fetal & Neonatal Medicine 2022; 35(25):6566-75.
6.        Mussi-Pinhata MM, Yamamoto AY. Natural history of congenital cytomegalovirus infection in highly seropositive populations. The Journal of infectious diseases 2020; 221(Supplement_1):S15-22.
7.        Alford CA, Stagno S, Pass RF, Britt WJ. Congenital and perinatal cytomegalovirus infections. Reviews of infectious diseases 1990; 12(Supplement_7):S745-53.
8.        Fowler KB, Pass RF. Risk factors for congenital cytomegalovirus infection in the offspring of young women: exposure to young children and recent onset of sexual activity. Pediatrics 2006; 118(2):e286-92.
9.        Plosa EJ, Esbenshade JC, Fuller MP, Weitkamp JH. Cytomegalovirus infection. Pediatrics in review 2012; 33(4):156-63.
10.     Bowden R. Cytomegalovirus infections in transplant patients: methods of prevention of primary cytomegalovirus. InTransplantation Proceedings 1991; 23(3):136-8.
11.     Chandler SH, Holmes KK, Wentworth BB, Gutman LT, Wiesner PJ, Alexander ER, et al. The epidemiology of cytomegaloviral infection in women attending a sexually transmitted disease clinic. Journal of Infectious Diseases 1985; 152(3):597-605.
12.     Bale JF, Zimmerman B, Dawson JD, Souza IE, Petheram SJ, Murph JR. Cytomegalovirus transmission in child care homes. Archives of pediatrics & adolescent medicine 1999; 153(1):75-9.
13.     Nigro G. Maternal–fetal cytomegalovirus infection: From diagnosis to therapy. The Journal of Maternal-Fetal & Neonatal Medicine 2009; 22(2):169-74.
14.     White DO, Fenner FJ. Medical virology. Gulf Professional Publishing; 1994.
15.     Bardanzellu F, Fanos V, Reali A. Human breast milk-acquired cytomegalovirus infection: certainties, doubts and perspectives. Current pediatric reviews 2019; 15(1):30-41.
16.     Nigro G, Anceschi MM, Cosmi EV, Congenital Cytomegalic Disease Collaborating Group. Clinical manifestations and abnormal laboratory findings in pregnant women with primary cytomegalovirus infection. BJOG: an international journal of obstetrics and gynaecology 2003; 110(6):572-7.
17.     Fisher S, Genbacev O, Maidji E, Pereira L. Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: implications for transmission and pathogenesis. Journal of virology 2000; 74(15):6808-20.
18.     Fowler KB, Stagno S, Pass RF. Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980–1990. Journal of Infectious Diseases 1993; 168(3):552-6.
19.     Cannon MJ, Griffiths PD, Aston V, Rawlinson WD. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?. Reviews in medical virology 2014; 24(5):291-307.
20.     Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systematic review. Pediatrics 2014; 134(5):972-82.
21.     Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Reviews in medical virology 2007; 17(5):355-63.
22.     Hamilton ST, van Zuylen W, Shand A, Scott GM, Naing Z, Hall B, et al. Prevention of congenital cytomegalovirus complications by maternal and neonatal treatments: a systematic review. Reviews in medical virology 2014; 24(6):420-33.
23.     Kenneson A, Cannon MJ. Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Reviews in medical virology 2007;17(4):253-76.
24.     Enders G, Daiminger A, Bäder U, Exler S, Enders M. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. Journal of Clinical Virology 2011;52(3):244-6.
25.     Moradi B, Meshkat Z. Evaluation of tuberculosis infection in pregnant women and its effects on newborns: an overview. The Iranian Journal of Obstetrics, Gynecology and Infertility 2015; 18(178):21-36.
26.     Saber A, Abedi A, Moradi B. Listeriosis infection in pregnant women and its effects on pregnancy and infants;(review of studies); 2022.
27.     Price SM, Bonilla E, Zador P, Levis DM, Kilgo CL, Cannon MJ. Educating women about congenital cytomegalovirus: assessment of health education materials through a web-based survey. BMC Women's Health 2014; 14(1):144.
28.     Xie M, Tripathi T, Holmes NE, Hui L. Serological screening for cytomegalovirus during pregnancy: A systematic review of clinical practice guidelines and consensus statements. Prenatal Diagnosis 2023; 43(7):959-67.
29.     Romero Starke K, Kofahl M, Freiberg A, Schubert M, Gross ML, Schmauder S, et al. The risk of cytomegalovirus infection in daycare workers: a systematic review and meta-analysis. International archives of occupational and environmental health 2020; 93(1):11-28.
30.     Zuhair M, Smit GS, Wallis G, Jabbar F, Smith C, Devleesschauwer B, et al. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta‐analysis. Reviews in medical virology 2019; 29(3):e2034.
31.     Coppola T, Mangold JF, Cantrell S, Permar SR. Impact of maternal immunity on congenital cytomegalovirus birth prevalence and infant outcomes: a systematic review. Vaccines 2019; 7(4):129.
32.     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. The Lancet 2020; 396(10253):779-85.
33.     Swanson EC, Schleiss MR. Congenital cytomegalovirus infection: new prospects for prevention and therapy: for pediatric clinics of North America: advances in evaluation, diagnosis and treatment of pediatric infectious disease. Pediatric Clinics of North America 2013; 60(2):10-16.
34.     Njue A, Coyne C, Margulis AV, Wang D, Marks MA, Russell K, et al. The role of congenital cytomegalovirus infection in adverse birth outcomes: a review of the potential mechanisms. Viruses 2020; 13(1):20.
35.     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. American journal of obstetrics and gynecology 2020; 223(6):870-83.
36.     Dinsmoor MJ, Fette LM, Hughes BL, Rouse DJ, Saade GR, Reddy UM, et al. Amniocentesis to diagnose congenital cytomegalovirus infection following maternal primary infection. American journal of obstetrics & gynecology MFM 2022; 4(4):100641.
37.     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. American journal of obstetrics & gynecology MFM 2023; 5(10):101101.
38.     McCarthy FP, Giles ML, Rowlands S, Purcell KJ, Jones CA. Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Cochrane database of systematic reviews 2011(3).
39.     Leruez-Ville M, Ghout I, Bussières L, Stirnemann J, Magny JF, Couderc S, et al. In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study. American journal of obstetrics and gynecology 2016; 215(4):462-e1.
40.     Fabbri E, Revello MG, Furione M, Zavattoni M, Lilleri D, Tassis B, et al. Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood. BJOG: An International Journal of Obstetrics & Gynaecology 2011; 118(4):448-56.
41.     Vos B, Noll D, Whittingham J, Pigeon M, Bagatto M, Fitzpatrick EM. Cytomegalovirus—a risk factor for childhood hearing loss: a systematic review. Ear and hearing 2021; 42(6):1447-61.
42.     Calvert A, Vandrevala T, Parsons R, Barber V, Book A, Book G, et al. Changing knowledge, attitudes and behaviours towards cytomegalovirus in pregnancy through film-based antenatal education: a feasibility randomised controlled trial of a digital educational intervention. BMC pregnancy and childbirth 2021; 21(1):565.
43.     Riga M, Korres G, Chouridis P, Naxakis S, Danielides V. Congenital cytomegalovirus infection inducing non-congenital sensorineural hearing loss during childhood; a systematic review. International Journal of Pediatric Otorhinolaryngology 2018; 115:156-64.
44.     Shears A, Yan G, Mortimer H, Cross E, Sapuan S, Kadambari S, et al. Vestibular and balance dysfunction in children with congenital CMV: a systematic review. Archives of Disease in Childhood-Fetal and Neonatal Edition 2022; 107(6):630-6.
45.     Gabrani C, Mitsikas D, Giannakou K, Lamnisos D. Congenital cytomegalovirus infection and ophthalmological disorders: a systematic review. Journal of Pediatric Ophthalmology & Strabismus 2023; 60(2):86-94.
46.     Choodinatha HK, Jeon MR, Choi BY, Lee KN, Kim HJ, Park JY. Cytomegalovirus infection during pregnancy. Obstetrics & Gynecology Science 2023; 66(6):463-76.
47.     Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A, et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. New England Journal of Medicine 2014; 370(14):1316-26.
48.     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 in Obstetrics & Gynecology 2021; 58(4):576-81.
49.     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 in Obstetrics & Gynecology 2023; 61(4):436-44.
50.     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 in Obstetrics & Gynecology 2023; 61(1):59-66.
51.     Seidel V, Feiterna-Sperling C, Siedentopf JP, Hofmann J, Henrich W, Bührer C, et al. Intrauterine therapy of cytomegalovirus infection with valganciclovir: review of the literature. Medical microbiology and immunology 2017; 206(5):347-54.
52.     Song X, Li Q, Diao J, Li J, Li Y, Zhang S, et al. Association between first-trimester maternal cytomegalovirus infection and stillbirth: a prospective cohort study. Frontiers in Pediatrics 2022; 10:803568.
53.     Nankervis GA, Kumar ML, Cox FE, Gold E. A prospective study of maternal cytomegalovirus infection and its effect on the fetus. American journal of obstetrics and gynecology 1984; 149(4):435-40.
54.     Picone O, Vauloup‐Fellous C, Cordier AG, Guitton S, Senat MV, Fuchs F, et al. A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome. Prenatal diagnosis 2013; 33(8):751-8.
55.     Pomar L, Contier A, Stojanov M, Guenot C, Sichitiu J, Truttmann AC, et al. Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland. American journal of obstetrics and gynecology 2024; 231(6):643-e1.
56.     Eletreby R, Abdelaziz R, Shousha HI, Hammam Z, Hany A, Sabry D, et al. Screening for maternal cytomegalovirus infection during pregnancy and pregnancy outcome in patients with liver disease: an observational study. BMC Infectious Diseases 2023; 23(1):210.
57.     Mocanu AG, Stoian DL, Daescu AM, Motofelea AC, Ciohat IM, Navolan DB, et al. The impact of latent cytomegalovirus infection on spontaneous abortion history and pregnancy outcomes in Romanian pregnant women. Microorganisms 2024; 12(4):731.
58.     Seneviratne M, Fernando ME, Kandasamy Y, White A, Sabesan V, Norton R. Cytomegalovirus infection in a single‐centre Australian neonatal cohort. Journal of Paediatrics and Child Health 2022; 58(7):1136-44.
59.     Nakamura E, Isoda K, Kotani T, Hiramatsu Y, Wada Y, Fujiki Y, et al. Congenital cytomegalovirus infection after maternal primary infection in a patient with systemic lupus erythematosus: a case report and literature review. Lupus 2022; 31(2):256-60.
60.     Wu PH, Lee CY, Huang JY, Yang SF, Shih CP. The correlation between neonatal parameters and late‐onset inner ear disorders in congenital cytomegalovirus infection: a 10‐year population‐based cohort study. Clinical Otolaryngology 2022; 47(1):107-14.
61.     Vicente M, Carocha AI, Rijo C, Cohen Á, Martins ML. Cytomegalovirus congenital infection: long-term outcomes in a valaciclovir treated population. Journal of Perinatal Medicine 2024; 52(7):778-82.
62.     Razonable RR, Inoue N, Pinninti SG, Boppana SB, Lazzarotto T, Gabrielli L, et al. Clinical diagnostic testing for human cytomegalovirus infections. The Journal of infectious diseases 2020; 221(Supplement_1):S74-85.
63.     Leruez-Ville M, Foulon I, Pass R, Ville Y. Cytomegalovirus infection during pregnancy: state of the science. American journal of obstetrics and gynecology 2020; 223(3):330-49.
64.     Gerna G, Fornara C, Furione M, Lilleri D. Congenital human cytomegalovirus infection: a narrative review of maternal immune response and diagnosis in view of the development of a vaccine and prevention of primary and non-primary infections in pregnancy. Microorganisms 2021; 9(8):1749.
65.     Wang H, Oyeniran SJ. Diagnosis of congenital and maternal cytomegalovirus infection—an up-to-date review. Clinical Microbiology Newsletter 2023; 45(9):69-76.
66.     Erenel H, Tuna G, Alpay V, Polat İ. Fetal cytomegalovirus infection in the absence of maternal cytomegalovirus-IgM seropositivity. Reproductive Sciences 2024; 31(6):1533-40.
67.     Vicente M, Carocha AI, Rijo C, Cohen Á, Martins ML. Cytomegalovirus congenital infection: long-term outcomes in a valaciclovir treated population. Journal of Perinatal Medicine 2024; 52(7):778-82.
68.     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 in Obstetrics & Gynecology 2023; 61(1):59-66.
69.     Zammarchi L, Lazzarotto T, Andreoni M, Campolmi I, Pasquini L, Di Tommaso M, et al. Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?. Clinical Microbiology and Infection 2020; 26(9):1151-4.
70.     Chatzakis C, Shahar-Nissan K, Faure-Bardon V, Picone O, Hadar E, Amir J, et al. The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis. American journal of obstetrics and gynecology 2024; 230(2):109-17.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 29, Issue 2
April 2026
Pages 69-83