Prevention Of Congenital Cytomegalovirus Infection Research Articles

Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study

Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020. This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus. The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth). A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension. Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

New therapeutic perspective in the prevention of congenital cytomegalovirus infection

IntroductionHyperimmune globulin Cytotect CP® is a candidate for cytomegalovirus congenital infection prevention. We previously demonstrated its efficacy to prevent villi infection in our first-trimester placenta explants up to day 7, but with an inefficiency at day 14 (Coste-Mazeau et al., Microorganisms, 2021). As this could impact clinical efficacy, we now study the effect of weekly administration of Cytotect CP® on the prevention of villi infection. MethodsHuman embryonic lung fibroblast cells were infected at confluence with the endothelial strain TB40/E. Placentae were collected from voluntary pregnancy terminations (8–14 weeks of gestation) from cytomegalovirus-seronegative women. After 5 days of infection of the cells, villi explants were simultaneously added on sponges with Cytotect CP® at various concentrations. After 7 days, Cytotect CP® was renewed in only half of the plates. Villi were collected at days 7 and 14 with or without medium renewal. We compared the viral load by duplex quantitative PCR cytomegalovirus/albumin and the toxicity by measuring β-hCG concentrations in the supernatants with and without medium renewal. ResultsWe did not find any efficacy of Cytotect CP® at day 14 when Cytotect CP® is not renewed, but a regular decrease of the viral load when the immunoglobulins were renewed at day 7, with an EC50 = 0.52 U/mL. We did not observed toxicity of Cytotect CP® with or without renewal of the molecule. ConclusionCytotect CP® is more effective when renewed at day 7. The prevention of congenital cytomegalovirus infection could be enhanced by reducing the spacing of doses.

Prevention of Congenital Cytomegalovirus Infection: Review and Case Series of Valaciclovir versus Hyperimmune Globulin Therapy.

Cytomegalovirus (CMV) is the most common cause of congenital infections in developed countries because is capable of infecting the fetus after both primary and recurrent maternal infection, and because the virus may be spread for years through infected children. Moreover, CMV is the most serious congenital infection associated with severe neurological and sensorineural sequelae, which can occur at birth or develop later on. Hygienic measures can prevent CMV transmission, which mainly involve contact with children under 3 years of age and attending a nursery or daycare. In animal and human pregnancies, many observational and controlled studies have shown that CMV-specific hyperimmune globulin (HIG) is safe and can significantly decrease maternal-fetal transmission of CMV infection and, mostly, the occurrence of CMV disease. Recently, valaciclovir at the dosage of 8 g/day was also reported to be capable of decreasing the rates of congenital infection and disease. However, comparing the results of our two recent case series, the infants born to women treated with HIG showed significantly lower rates of CMV DNA positivity in urine (9.7% vs. 75.0%; p < 0.0001) and abnormalities after follow-up (0.0% vs. 41.7%; p < 0.0001). The implementation of CMV screening would enable primary prevention via hygiene counseling, improve the understanding and awareness of congenital CMV infection, and increase the knowledge of the potential efficacy of preventive or therapeutic HIG or antiviral administration.

Revised protocol for secondary prevention of congenital cytomegalovirus infection with valaciclovir following infection in early pregnancy.

A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol. All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study. Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (p<0.001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; OR=0.15; 95% CI 0.05-0.45, p <0.001), as well as among those infected in the periconception period (0/59 vs 3/24, OR=0; 95% CI 0-0.97, p=0.02). This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.

Primary, Secondary, and Tertiary Prevention of Congenital Cytomegalovirus Infection.

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.

The epidemiology and disease burden of congenital TORCH infections among hospitalized children in China: A national cross-sectional study.

Congenital TORCH (Toxoplasma gondii (T. gondii), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV)) infections are associated with a variety of adverse prenatal and neonatal events, including miscarriage, malformations and developmental abnormalities, and they remain an issue that cannot be neglected in China. However, the current research focuses more on the general screening of TORCH in women of childbearing age, and the medical information of children hospitalized due to congenital and perinatal TORCH infections has not been described in detail. This study summarized and analyzed the epidemiological characteristics, clinical manifestations, length of stay (LOS), and the disease burden of hospitalized children diagnosed with congenital TORCH infections in 27 children's hospitals in China. Based on the face sheet of discharge medical records (FSMRs) of hospitalized children in 27 tertiary children's hospitals collected in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE), we summarized and analyzed the epidemiological characteristics, clinical manifestations, LOS, the disease burden (in US dollars, USD) and potential risk factors for hospitalized children diagnosed with congenital toxoplasmosis, congenital rubella syndrome, congenital cytomegalovirus infection, and congenital HSV in 27 children's hospitals in China from 2015 to 2020. One hundred seventy-three patients aged 0-<1 year were hospitalized for congenital TORCH infections. Among infections with TORCH, hospitalization with congenital toxoplasmosis was the least common, with only five cases were reported (2.89%), while the LOS was the highest. The proportion of patients with congenital rubella syndrome (CRS) was 15.61%, and 86% of children hospitalized with CRS had cardiovascular malformations, and the economic burden was the highest. Congenital CMV infection cases accounted for the largest proportion (76.30%). Overall, 5.20% of patients were infected with HSV, and the expense of hospitalization for congenital HSV infection was relatively low. In the present study, the hospitalization proportion due to congenital TORCH infection was extremely low (17.56 per 100,000 neonates), indicating that China's congenital TORCH infection prevention and control policies remain effective. The lowest proportion of patients was hospitalized with congenital toxoplasmosis, while the LOS was the longest. The economic burden of CRS was heavy, and infants are recommended be vaccinated against RV in a timely manner. Congenital CMV infections accounted for the largest proportion of patients, suggesting that the disease burden of congenital CMV infection cannot be ignored, and the prevention of congenital CMV infection during pregnancy is still an important issue that needs to pay attention. The expense of hospitalization for congenital HSV infection was relatively low, while the disease burden increases significantly when patients develop complications. These data illustrate the importance of improving screening for congenital TORCH infections in the early diagnosis and treatment of neonatal patients.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. www.clinicaltrials.gov (NCT03973359).

Prevention strategies for congenital cytomegalovirus infection.

Cytomegalovirus (CMV) is the most common viral cause of congenital infection, occurring in approximately 1-2% of live births worldwide. Given our increasing knowledge of risk, advances in the identification of maternal infection, and the extremely limited options for the treatment of fetal infection, the prevention is a promising direction for research efforts. Recently, there have been several exciting studies assessing different ways of preventing congenital infection in the fetus and one in particular has focused on the use of valaciclovir. A recent study reported a 71% reduction in vertical transmission of CMV with the use of oral valaciclovir following maternal primary CMV infection early in pregnancy. The clinical impact of this study could be enormous and it has particular implications for considerations around maternal serological screening in the first trimester of pregnancy. Further research assessing behaviour modifications during early pregnancy could also provide evidence for an effective primary prevention technique. Prevention of congenital CMV infection, whether primary, secondary or tertiary, is possible, however, there are barriers to its utilisation in a clinical setting. The main limitation is the requirement for early, effective and large-scale serological screening of mothers to detect asymptomatic primary infection.

Prevention of Congenital Cytomegalovirus Infection with Vaccines: State of the Art.

Cytomegalovirus (CMV) is the most common cause of congenital infection and non-genetic sensorineural hearing loss in childhood. Up to 2% of neonates, with the highest percentages found in developing countries, are congenitally infected with CMV. At birth, most of these infants are asymptomatic. However, approximately 10% have signs and symptoms of the disease, and 40–60% of symptomatic neonates will later develop permanent neurologic sequelae. To reduce congenital CMV (cCMV) infection, a vaccine able to prevent primary infection is essential. In this narrative review, actual ongoing research about the development of a CMV vaccine is discussed. The progressive increase in knowledge on the ways in which the host’s immune system and CMV relate has made it possible to clarify that the development of a vaccine that is certainly capable of reducing the risk of cCMV infection, and preventing both primary and nonprimary infections is extremely difficult. Many of the ways in which the virus evades the immune system and causes cCMV infection are not yet fully understood, especially in cases of nonprimary infection. Moreover, the schedule that should be recommended and that subjects must be vaccinated to obtain the greatest effect have not been precisely defined. Further studies are needed before the problem of cCMV infection and its related challenges can be totally solved.

Secondary prevention of congenital cytomegalovirus infection

Secondary prevention of congenital cytomegalovirus infection

The modern view of congenital cytomegalovirus infection: diagnosis, treatment and prevention

A literature review of the works of foreign and domestic authors is devoted to modern approaches to the diagnosis, treatment and prevention of congenital cytomegalovirus infection (cCMV). The data of international consensuses are presented: «Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management» adopted by the cCMV group from the European society for pediatric infectious diseases (ESPID) in Leipzig, Germany in 2015, and «Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy» by an informal International Congenital Cytomegalovirus Recommendations Group (ICCRG), established in Brisbane, Australia in 2015 as part of the 5th International cCMV Conference about evidence-based treatment cCMV using antiviral drugs and immunotherapy. Particular attention is paid to the prevention of cCMV in both pregnant and newborns, as well as data from international studies on the cytomegalovirus vaccination.

Increasing awareness and promoting strategies for prevention of congenital cytomegalovirus infection among young pregnant women

Previous data indicate that most women have never heard of congenital cytomegalovirus (cCMV) and the risk of cCMV’s damaging sequelae for their newborns, or how to prevent CMV exposures. The objective of this study is to evaluate whether a cognitive-behavioral intervention can, 1) increase knowledge about cCMV and 2) decrease self-reported risk behaviors.

Hyperimmune globulin in pregnancy for the prevention of congenital cytomegalovirus disease

ABSTRACTIntroduction: Cytomegalovirus (CMV) is the most common and serious cause of congenital infections in developed countries since it is capable of infecting the fetus after both primary and recurrent maternal infection, and can be spread for years by infected children.Areas covered: Animal and human pregnancy studies about the prevention of congenital CMV infection and disease by CMV-specific hyperimmune globulin (HIG). Commercial HIG is manufactured from the plasma of selected donors with high anti-CMV antibody avidity and titers.Expert commentary: Currently available experimental and clinical studies and case reports support the possible effectiveness and safety of HIG infusions in pregnancy for the prevention of congenital CMV disease. The knowledge about the potential efficacy of preventive or therapeutic HIG administration should be enlarged by multi-center randomized studies, which may be favored by the implementation of CMV screening. Meanwhile, if ultrasound examinations show signs of fetal injury, or CMV is detected in the amniotic fluid, the patients should be advised about the possible option of HIG therapy.

Advances in the prevention and treatment of congenital cytomegalovirus infection.

Cytomegalovirus (CMV) is the most common cause of congenital infection in the world. Symptomatic infants are at increased risk of developing permanent sequelae, including sensorineural hearing loss and neurodevelopmental delay. Advances in the treatment and prevention of congenital CMV infection are a high priority nationally and globally. In symptomatic infants, antiviral therapy with 6 months of oral valganciclovir improves hearing and neurodevelopmental outcomes. Strategies to prevent congenital or maternal CMV infections, including the use of CMV hyperimmune globulin and development of a maternal vaccine, have yet to yield positive results. The clinical significance of congenital CMV infection, developments in antiviral therapy, and efforts to prevent congenital disease are herein reviewed.

Prevention of Congenital Cytomegalovirus Infection

Congenital cytomegalovirus (CMV) infection is potentially devastating. Although nonrandomized studies have suggested benefit from hyperimmune globulin administered to pregnant women with primary CMV infection, no randomized trials had been done for verification. Now, researchers in Italy have conducted a phase II, double-blind, multicenter study to evaluate the efficacy of this agent. Pregnant women with primary infection at 5 to 26 weeks of gestation and presumed onset …

Early high CMV seroprevalence in pregnant women from a population with a high rate of congenital infection

Congenital cytomegalovirus (CMV) infection rates increase with maternal seroprevalence due to transmission from maternal non-primary infection. CMV seroprevalence estimates of pregnant women are needed for planning strategies against congenital CMV transmission. We aimed to determine the age-specific prevalence of serum antibodies for CMV in a representative age-stratified sample of unselected pregnant women from a Brazilian population. A total of 985 pregnant women, aged 12–46 years (median 24 years), were enrolled. Overall CMV seroprevalence was 97% (95% confidence interval 95.8–98.0), with age-specific (years) prevalence as follows: 12–19 (96.3%), 20–24 (97.7%), 25–29 (97.1%), and 30–46 (96.7%). CMV seroprevalence is almost universal (97%) and is found at similar levels in pregnant women of ages ranging from 12 to 46 years. Because high CMV seroprevalence is found even in women of a younger age in this population, this finding suggests that the majority of primary CMV infections occur early, in infancy or childhood. As a consequence, vaccines currently under development to prevent primary infection may not be a solution for the prevention of congenital CMV infection in this population.

PIN23 Cost of Diagnosis and Prevention of Congenital Cytomegalovirus Infection

PIN23 Cost of Diagnosis and Prevention of Congenital Cytomegalovirus Infection

Problems and challenges in the diagnosis of vertical infection with human cytomegalovirus (CMV): Lessons from two accidental cases

Human cytomegalovirus (CMV) is considered as the most common cause of congenital infection in humans and the overall burden for the public health system is rather high. About 1/10 of vertically infected newborns present or develop severe signs of cytomegalic inclusion disease (CID), with the classical triad of chorioretinitis, microcephaly and cerebral calcifications. However the most symptomatic cases are detected postnatal and methods of diagnostic virology raised the questions for the gold standard in laboratory screening. The current problems in diagnosis and therapy are outlined in two different cases: An acute primary CMV infection with no clinical signs of illness in both mother and child and a secondary CMV-infection resulting in necrotizing CMV encephalitis in the fetus. Beside virus detection in whole blood samples and other fluids, newly adopted laboratory assays like the destination of CMV-IgG avidity were necessary. Furthermore a serologic screening for pregnant women should be implicated routinely. Passive IgG treatment of the mother was helpful but the ultimate goal in prevention of congenital CMV infection is to develop a vaccine, which would be administered to seronegative women.

Passive Immunization During Pregnancy for Congenital Cytomegalovirus Infection

Purpose of the Study. To investigate the effectiveness of cytomegalovirus (CMV)-specific hyperimmune globulin for primary CMV infection during pregnancy as a preventive therapy for fetal CMV infection. Study Population. One hundred fifty-seven pregnant women from 8 Italian cities with a primary CMV infection diagnosed via serologic testing. Methods. Women were placed in 1 of 2 groups. The therapy group comprised women who underwent amniocentesis and whose amniotic fluid contained either CMV detected by culture or CMV DNA detected by polymerase chain reaction. The group was offered intravenous CMV-specific hyperimmune globulin at a dose of 200 U per kg of maternal weight. Additional intravenous, intraumbilical-cord, or intra-amniotic doses were administered if evidence of persistent fetal involvement was present on ultrasound. Women with CMV-positive amniotic fluid who declined to receive hyperimmune-globulin infusions were followed as a comparison group. Those in the prevention group, consisting of women with a recent primary infection before 21 weeks’ gestation or who declined amniocentesis, were offered monthly hyperimmune globulin (100 U/kg intravenously). Pregnant women who declined monthly administration of hyperimmune globulin were followed as a comparison group. Results. In the therapy group, 31 women received hyperimmune globulin, only 1 (3%) of whom gave birth to an infant with symptomatic CMV disease, compared with 7 (50%) of 14 women who did not receive hyperimmune globulin. Thus, hyperimmune-globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio: 0.02; 95% confidence interval: −∞ to 0.15; P &amp;lt; .001). In the prevention group, 37 women received hyperimmune globulin, 6 (16%) of whom had infants with congenital CMV infection, compared with 19 (40%) of 47 women who did not receive hyperimmune globulin. Thus, hyperimmune-globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio: 0.32; 95% confidence interval: 0.10 to 0.94; P = .04). No adverse effects resulted from CMV-specific hyperimmune globulin administration. Conclusions. Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may be appropriate. Reviewer Comments. The risk of congenital CMV infection is high after primary maternal CMV infection. Although the majority of congenitally acquired CMV infections are asymptomatic, symptomatic infections result in significant morbidity and possible mortality. The implementation of CMV-specific hyperimmune globulin may reduce or prevent the devastating effects of symptomatic congenital CMV.

The Epidemiology and Prevention of Congenital Cytomegalovirus Infection and Disease: Activities of the Centers for Disease Control and Prevention Workgroup

Perhaps no single cause of birth defects and developmental disabilities in the United States currently provides greater opportunity for improved outcomes in more children than congenital cytomegalovirus (CMV). --Cannon and Davis. BMC Public Health 2005;5:70 Each year in the United States, thousands of children and their families are affected by congenital cytomegalovirus (CMV) infection. More children may be affected by congenital CMV than by other, better known childhood conditions, such as Down syndrome, fetal alcohol syndrome, and spina bifida. The Centers for Disease Control and Prevention (CDC) has formed a Workgroup on Congenital CMV, led by the National Center on Birth Defects and Developmental Disabilities and the National Center on Infectious Diseases. This report provides background on congenital CMV infection and describes the goals and activities of the workgroup for reducing the burden of sequelae of congenital CMV infection.