Primary, Secondary, and Tertiary Prevention of Congenital Cytomegalovirus Infection

Abstract

Cytomegalovirus infection is the most common congenital infection, affecting about 1% of births worldwide. Several primary, secondary, and tertiary prevention strategies are already available during the prenatal period to help mitigate the immediate and long-term consequences of this infection. In this review, we aim to present and assess the efficacy of these strategies, including educating pregnant women and women of childbearing age on their knowledge of hygiene measures, development of vaccines, screening for cytomegalovirus infection during pregnancy (systematic versus targeted), prenatal diagnosis and prognostic assessments, and preventive and curative treatments in utero.

Maternal serological screening for cytomegalovirus infection may play an important role nowadays

“…1 This strategy is often legitimized by valid and complex reasons, such as the inability of laboratory tests to predict which newborn will develop long-term hearing loss or other neurodevelopmental complications, and the potentially increased rate of unnecessary abortions. 2,3 However, we fully agree with the authors that the current recommendations are characterized by limited and low-level evidence, 1 and we would like to emphasize some important concepts.…”

“…In their comprehensive systematic review, the authors found that none of the clinical practice guidelines or consensus statements recommended universal serological screening for cytomegalovirus (CMV) in pregnant women 1 . This strategy is often legitimized by valid and complex reasons, such as the inability of laboratory tests to predict which newborn will develop long‐term hearing loss or other neurodevelopmental complications, and the potentially increased rate of unnecessary abortions 2,3 …”

“…In our opinion, it should be highlighted that maternal serological screening for CMV infection may promote (1) primary prevention (to reduce the risk of maternal primary infection and reinfection) by inducing greater adherence to hygienic-behavioral rules in CMVseronegative pregnant women; (2) secondary prevention (to reduce the risk of maternal-fetal transmission) by ensuring that valaciclovir treatment can be initiated as soon as possible after maternal CMV seroconversion; (3) tertiary prevention (to reduce the impact of congenital CMV infection on children's hearing and neurodevelopmental outcomes) by fostering targeted newborn CMV screening that can ensure proper follow-up and possible timely use of valganciclovir in children diagnosed with congenital CMV infection. 2,3 Indeed, pregnant women who are aware that they are susceptible to primary CMV infection based on serology are more likely to practice proper hygiene measures, such as avoid changing diapers or practicing unsafe sex. 2 Moreover, early diagnosis of maternal primary infection may allow timely administration of oral valaciclovir, which could be effective in reducing the rate of fetal CMV infection.…”

Congenital Cytomegalovirus and Hearing Loss: The State of the Art

“…As a matter of fact, the development of a vaccine capable of conferring effective protection against primary CMV infection may be a valid solution to reduce the serious consequences of intrauterine CMV infection. However, it should be emphasized that a strategy aimed at preventing only primary maternal infection would not address HL and other severe neurological sequelae secondary to cCMV in children born to mothers with pre-existing CMV immunity [ 79 ]. Indeed, maternal non-primary CMV infection during pregnancy is considered the greatest burden due to the high seroprevalence of CMV among women of childbearing age [ 9 , 30 ].…”

“…However, a recent mathematical model by Byrne et al has predicted that even modestly protective CMV vaccination of young children would significantly reduce both CMV transmission to pregnant women and the prevalence of cCMV [ 84 ]. Currently, several CMV vaccines are under development, based on different strategies: live-attenuated and disabled-infectious single-cycle vaccines, adjuvanted recombinant protein vaccines, DNA vaccines, messenger RNA (mRNA) vaccines, virus-like particle vaccines, viral vectored vaccines, and peptide vaccines [ 79 ]. One of the most promising approaches seems to be the expression of several antigens within a single vaccine, which could be ensured by vector vaccines and mRNA vaccines, thus stimulating more areas of the immune system [ 85 ].…”