Risk Of Congenital Cytomegalovirus Infection Research Articles

Results of Routine Antenatal Screening for Cytomegalovirus at a Tertiary Center.

Cytomegalovirus (CMV) is the most common viral infection. In this study, we discussed the results of pregnant women who underwent antenatal CMV screening in a tertiary center and the value of CMV antenatal screening. For this retrospective study, the data of pregnant patients with antenatal CMV screening test results between 2019 and 2022 were obtained from hospital records. CMV immunoglobulin M (IgM), CMV IgG, anti-IgG avidity test results, amniocentesis, CMV polymerase chain reaction (PCR), and the outcome of the babies were recorded. A total of 31,912 CMV IgM and 26,969 CMV IgG tests were performed. CMV IgG seropositivity was observed in 78.99% of pregnant women, and 0.09% of the pregnant women were confirmed to have a positive CMV IgM test result. Pregnant women with positive IgM accompanying low avidity were referred to perinatology clinics for detailed ultrasonography and amniocentesis. Only 3 of the 44 pregnant women who underwent amniocentesis were confirmed to have positive CMV PCR testing. CMV screening should be preserved for pregnant women with ultrasonographic findings at high risk of congenital CMV infection.

Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis.

Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection. MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy. Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I2 = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I2 = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I2 = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low. Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Cross-sectional study to assess awareness of cytomegalovirus infection among pregnant women in Germany

BackgroundStudy aimed to assess awareness of congenital cytomegalovirus (CMV) infection and its determinants in pregnancy.MethodsCross-sectional survey was conducted in five hospital-based maternity units in Germany. Pregnant women attending the maternity departments completed interviewer/self-administered survey questionnaire. High-risk group was defined according to contact with children under five years of age (at home or at work). Quantitative analyses using multivariable logistic regression were performed.ResultsOne thousand two hundred thirty-three pregnant women were included. 48.5% (n = 598) of women reported any knowledge about risk of CMV infection during pregnancy. CMV infection was less known than other infections or diseases (education about toxoplasmosis 95.5% (n = 1,177), listeriosis 60.5% (n = 746). 38% (n = 468) of participants received education about CMV. CMV awareness was associated with the level of education and employment in childcare or medical care. Only 32% (n = 394) of the women made use of serological screening for CMV during pregnancy (individual health service). 40.8% (n = 503) of pregnant women were classified as high-risk group. They had significantly higher knowledge and education about CMV, and msignificantlycant more often use of the serological screening.ConclusionsLess than half of pregnant women surveyed were aware of potential risk associated with CMV infection during pregnancy. In our study,one-third third of pregnant women made use of the serological screening for CMV.Regarding the lack of current consensus on the role of serological CMV screening for pregnant women, hygiene preventive measures are the only evidence-based recommendation for pregnant women and knowledge increase could potentially have major public health impact.

In Utero Human Cytomegalovirus Infection Is Associated With Increased Levels of Putatively Protective Maternal Antibodies in Nonprimary Infection: Evidence for Boosting but Not Protection.

Although primary maternal cytomegalovirus infections are associated with higher risk of in utero transmission, most fetal infections worldwide result from nonprimary maternal infections. Antibodies directed at glycoprotein B (gB) and the gH/gL/pUL128-130-131 pentamer can neutralize virus, and higher levels of antibody directed at several particular pentamer epitopes defined by monoclonal antibodies (mAbs) are associated with reduced risk of fetal cytomegalovirus (CMV) transmission during primary maternal infection. This had not been explored in maternal nonprimary infection. In a setting where most maternal CMV infections are nonprimary, 42 mothers of infants with congenital CMV infections (transmitters) were compared to 75 CMV-seropositive mothers whose infants were CMV-uninfected (nontransmitters). Control infants were matched by sex, maternal human immunodeficiency virus (HIV) status, and gestational age. We measured the ability of maternal antibodies to block 3 key pentameric epitopes: one in the gH subunit, another straddling UL130/UL131, and the third straddling gH/gL/UL128/UL130. We tested if levels of antibodies directed at these epitopes were higher in nontransmitters compared to transmitters. Levels of all 3 putatively protective pentamer-directed antibodies were significantly higher in transmitters compared to nontransmitters. In contrast, antibodies targeting an epitope on gB were not different. Total antibody specific for pentamer and for gB were also higher in transmitters. We found no evidence that higher levels of any CMV-specific antibodies were associated with reduced risk of congenital CMV infection in nonprimary maternal infection. Instead, we found higher maternal antibody targeting epitopes on CMV pentamer in transmitters than nontransmitters, providing evidence for antibody boosting but not protection.

Current status of vaccines against congenital cytomegalovirus infection: The paradox of previous immunity

Human cytomegalovirus (CMV) is a very ubiquitous virus that is transmitted very efficiently among the population through saliva, urine, lactation or blood transfusions. Around 75% of people at age 15 are already seropositive, have acquired immunity, against this virus. The majority (85%) of congenital CMV infections are due to gestational reactivation (latency) and reinfection by different CMV strains and only 15% to a primary infection during it. These data support the concept of the paradox of previous immunity, that is, the risk of congenital CMV infection is higher in seropositive pregnant women.One of the possibilities of avoiding congenital CMV infections is universal vaccination in the first months of life. In this way women would reach fertile age with immunity and without CMV in their body.Despite the efforts made in the last forty years, there is still no vaccine against CMV that can be applied effectively in humans. Of all the multiple platforms developed, only six of them (attenuated Towne vaccine, gB/MF59 subunits, gB/AS03, DNA bivalent, viral vector recombinant and peptide vaccine) have been tested in humans and recently the gB / MF59 and the bivalent DNA have completed Phase II assays. Due to safety concerns, attenuated and vector-based vaccines seem to be ruled out for the future; Therefore it is very possible that the future is in vaccines based on recombinant proteins (gB) and especially those formed by the pentameric complex. Keywords: cytomegalovirus; congenital infection; vaccination; gB glycoprotein; pentameric complex.

Ante- and postnatal diagnostics and complex treatment of congenital cytomegalovirus infection

Timely diagnostics and treatment of cytomegalovirus infection in pregnant women and newborns allow to avoid serious consequences, preserving the life and health of the child. The article provides an example of antenatal diagnosis of congenital cytomegalovirus infection in the fetus (positive result of polymerase chain reaction in umbilical cord blood), treatment with umbilical transfusion of donor red blood cells, postnatal therapy with antiviral drugs, including ganciclovir and specific immunoglobulin. The issues of assessing the risk of congenital cytomegalovirus infection, approaches to its prevention and treatment during pregnancy are discussed.

Ultrasound screening and clinical manifestations of congenital cytomegalovirus infection in fetuses

Objective To investigate the value of ultrasound screening for congenital cytomegalovirus (CMV) infection in fetuses and to summarize the clinical manifestations. Methods From January 2012 to December 2017, we retrospectively analyzed the clinical data of 905 gravidas who received invasive prenatal diagnosis in Fujian Provincial Maternity and Children's Hospital for abnormal prenatal ultrasound findings including ventriculomegaly, intracranial calcification, microcephaly, echogenic bowel and fetal growth restriction (FGR). CMV DNA loads in amniotic fluid and neonatal urine were detected by real-time polymerase chain reaction. CMV-specific IgM and IgG in umbilical cord and neonatal peripheral blood were detected by commercial enzyme 1inked immunosorbent assay kits. Eighteen fetuses with normal karyotype were diagnosed as congenital CMV infection. Relationships of ultrasound features and CMV DNA loads in amniotic fluid to pregnancy outcomes were analyzed with χ2 test or Fisher's exact test. Results (1) Congenital CMV infection was detected in 18 fetuses in this study with an detection rate of 1.99% (18/905). Three pregnancies were terminated immediately after the diagnosis was confirmed, two terminated when the ventriculomegaly progressed, five terminated for hydrocephaly and eight continued to delivery. (2) Congenital CMV infection rate was significantly higher in those with two or more ultrasound abnormalities than that in those with only one abnormal indicator [3.92%(8/204) vs 1.28%(9/701), χ2=4.619, P=0.032]. Fetuses with craniocerebral abnormalities were more likely to have congenital CMV infection than those without [3.11%(13/418) vs 0.82%(4/487), χ2=6.392, P=0.012]. (3) Among the 18 fetuses with congenital CMV infection, those with serious ultrasound abnormalities had a significantly higher rate of adverse outcomes than those without (11/11 vs 3/7, Fisher's exact test, bilateral P=0.043). No significant difference in the rate of adverse outcomes was found between fetuses with low and high CMV DNA loads in amniotic fluid (3/4 vs 12/14, Fisher's exact test, bilateral P=1.000). Conclusions Ultrasound abnormalities including ventriculomegaly, intracranial calcification, microcephaly, echogenic bowel and FGR, especially those with multiple abnormalities and brain abnormalities, increased risk of congenital CMV infection. Congenital CMV fetuses with serious ultrasound abnormalities has adverse outcomes. Key words: Cytomegalovirus infections; Fetal diseases; Ultrasonography, prenatal; Pregnancy outcome

Use of Cytomegalovirus-Specific Hyperimmunoglobulins in Pregnancy: A Retrospective Cohort.

There is no consensus on the use of cytomegalovirus (CMV)-specific hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during pregnancy, but this therapy is currently used in some countries. The objectives of this study were to describe tolerability and pregnancy outcome following treatment with monthly intravenous CSHIG and compare rates of positive PCR and postnatal symptoms according to whether CSHIGs were given or not. This retrospective cohort study included all pregnant women who were diagnosed with primary CMV infection or congenital CMV infection at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was discussed with pregnant women who received positive CMV PCR results from amniotic fluid or if ultrasound anomalies suggested congenital infection and there was serologic evidence of maternal primary infection (therapeutic group). CSHIG was also offered as prophylaxis in pregnant women without fetal ultrasound anomalies but with evidence of maternal primary infection, when amniocentesis either had negative results or was not performed (prophylactic group). A matched analysis was performed to control for timing of maternal infection, amniocentesis, and type and timing of ultrasound anomaly. Sixteen women received CSHIG, and 55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In bivariate analyses, the risk of congenital CMV infection and postnatal symptoms did not significantly decrease with CSHIG treatment, in both the therapeutic and the prophylactic groups. After matching, there was still no difference in outcomes between CSHIG-treated and untreated women. The effectiveness of CSHIG in preventing congenital CMV infection and its clinical manifestations could not be demonstrated.

The Effect of Human Immunodeficiency Virus and Cytomegalovirus Infection on Infant Responses to Vaccines: A Review.

The success of prevention of mother to child transmission programs over the last two decades has led to an increasing number of infants who are exposed to human immunodeficiency virus (HIV), but who are not themselves infected (HIV-exposed, uninfected infants). Although the morbidity and mortality among HIV-exposed, uninfected infants is considerably lower than that among HIV-infected infants, they may remain at increased risk of infections in the first 2 years of life compared with their HIV-unexposed peers, especially in the absence of breastfeeding. There is some evidence of immunological differences in HIV-exposed, uninfected infants, which could play a role in susceptibility to infection. Cytomegalovirus (CMV) may contribute to the increased immune activation observed in HIV-exposed, uninfected infants. Infants born to HIV-infected women are at increased risk of congenital CMV infection, as well as early acquisition of postnatal CMV infection. In infants with HIV infection, CMV co-infection in early life is associated with higher morbidity and mortality. This review considers how HIV infection, HIV exposure, and CMV infection affect infant responses to vaccination, and explores possible immunological and other explanations for these findings. HIV-infected infants have lower vaccine-induced antibody concentrations following tetanus, diphtheria, pertussis, hepatitis B, and pneumococcal vaccination, although the clinical relevance of this difference is not known. Despite lower concentrations of maternal-specific antibody at birth, HIV-exposed, uninfected infants respond to vaccination at least as well as their HIV-unexposed uninfected peers. CMV infection leads to an increase in activation and differentiation of the whole T-cell population, but there is limited data on the effects of CMV infection on infant vaccine responses. In light of growing evidence of poor clinical outcomes associated with CMV infection in HIV-exposed, uninfected infants, further studies are particularly important in this group. A clearer understanding of the mechanisms by which maternal viral infections influence the developing infant immune system is critical to the success of maternal and infant vaccination strategies.

Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11–4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25–3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

Cytomegalovirus infection in pregnancy.

Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and contact with young children. Primary infection occurs in approximately 1 to 4% of pregnancies, and is mostly asymptomatic in immunocompetent adults. However, primary infection may manifest as a mild mononucleosis or flu-like syndrome with persistent fever and fatigue. CMV can be transmitted from mother-to-child in utero, intrapartum, or during breastfeeding. Intrauterine transmission can lead to congenital CMV infection, a leading cause of permanent hearing and vision loss and neurological disability among children. Congenital CMV transmission rates are as high as 50% in women who acquire primary CMV infection during pregnancy, and less than 2% in women with nonprimary infection. There is no licensed CMV vaccine. Good hygiene practices and avoiding intimate contact with young children (e.g., kissing on the mouth and sharing utensils) have been suggested as an approach to prevent maternal primary CMV infection during pregnancy, but remains an unproven method of reducing the risk of congenital CMV infection. Approximately 1 in 10 infants who acquire CMV in utero will have clinical signs at birth, and an additional 10 to 15% will go on to develop late-onset sequelae. Antiviral treatment prenatally and postnatally has not proven effective at preventing congenital or postnatal CMV infection, and is not recommended for routine clinical care. However, antiviral treatment when initiated in the first month of life for symptomatic congenital CMV infection is recommended for improved neurodevelopmental and audiologic outcomes. Birth Defects Research 109:336-346, 2017. © 2017 Wiley Periodicals, Inc.

Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy.

Congenital cytomegalovirus (cCMV) infection is common among infants born to HIV-infected women. Nelfinavir (NFV), an antiretroviral drug that is safe during pregnancy, inhibits CMV replication in vitro at concentrations that standard doses achieve in plasma. We hypothesized that infants born to women receiving NFV for prevention of mother-to-child transmission of HIV (PMTCT) would have a reduced prevalence of cCMV infection. The prevalence of cCMV infection was compared among HIV-uninfected infants whose HIV-infected mothers either received NFV for >4 weeks during pregnancy (NFV-exposed) or did not receive any NFV in pregnancy (NFV-unexposed). CMV PCR was performed on infant blood samples collected at <3 weeks from birth. Of the 1,255 women included, 314 received NFV for >4 weeks during pregnancy and 941 did not receive any NFV during pregnancy. The overall prevalence of cCMV infection in the infants was 2.2%, which did not differ by maternal NFV use. Maternal CD4 T cell counts were inversely correlated with risk of cCMV infection, independent of the time NFV was initiated during gestation. Infants with cCMV infection were born 0.7 weeks earlier (P = 0.010) and weighed 170 g less (P = 0.009) than uninfected infants. Among HIV-exposed uninfected infants, cCMV infection was associated with adverse perinatal outcomes. NFV use in pregnancy was not associated with protection against cCMV. Safe and effective strategies to prevent cCMV infection are needed.

Seroprevalence and Absence of Cytomegalovirus Infection Risk Factors among Pregnant Women in St. Paul?s Hospital Millennium Medical College

Background: The human cytomegalovirus (CMV) is one of the major causes of congenital infections. Maternal infection poses the risk of congenital CMV infection and occurs in 0.5%-22% of all life births. CMV is more widespread in developing countries and in communities with lower socioeconomic status. Objective: The aim of the study was to determine the prevalence of CMV infection and identify risk factors of CMV seropositivity. Method: Using cross sectional study design a total of 200 pregnant women were consecutively recruited from ANC attendees from June to July 2014. Blood samples were collected from all study participants and structured questionnaire was introduced to gather socio-demographic and risk factor related data. ELISA was used to detect anti-CMV IgG and IgM. SPSS version 20 was used to analyze the data, and regression was also applied to see the strength of association. Results: Out of 200 participants CMV-IgG and CMV-IgM were detected from 177 (88.5%), and 31 (15.5%) respectively. Women who were immune/positive only for IgG were 147 (73.5%). The second group was those who had primary infection {IgG (+) plus IgM (+)} and this consisted of 30 (15.0%) participants. Eleven percent of those participants had no anti-CMV infection. In the last category, one pregnant woman was identified as having a recent primary infection. There was no statistical significant factor detected between CMV positivity rate with any obstetrical, and socio-demographical characteristic (P-value<0.05). Conclusion: This study provides recent information regarding CMV seroprevalence. Despite the high rate of seropositivity, the importance of CMV testing during pregnancy should not be undermined. A comprehensive study with a long term follow-up examination of pregnant women and their offspring born to CMV IgM-positive mothers may be required for estimation of symptomatic congenital infection.

Educating women about congenital cytomegalovirus: assessment of health education materials through a web-based survey

Congenital cytomegalovirus (CMV) is the most common congenital infection in the U.S. and can result in permanent disabilities, such as hearing and vision loss, intellectual disability, and psychomotor and language impairments. Women can adopt prevention behaviors in an attempt to reduce their exposure to CMV. Currently, few women are familiar with CMV. To increase awareness of CMV, the Centers for Disease Control and Prevention (CDC) developed draft health education materials. The purpose of this study was to pilot test two health education materials to gauge their appeal and to determine if they increase knowledge about CMV and motivate audiences to seek additional information on CMV and adopt CMV prevention behaviors. African-American (n = 404) and Caucasian women (n = 405), who had a young child and were either pregnant or planning a pregnancy, were recruited to participate in a 15-minute web survey. Participants were randomly assigned to view one of two CMV health education materials, either a factsheet or video. Pre and post survey measures were used to assess changes in knowledge of CMV and motivation to adopt prevention behaviors. We also examined audience preferences regarding materials and motivation. CMV knowledge score increased significantly after presentation of either the video or factsheet (from 3.7 out of 10 to 9.1 out of 10, p <0.001). The average materials appeal score was high, with a mean of 3.6 on a four-point scale, indicating women responded very positively to both materials. Regression analyses indicated that appeal, message involvement (e.g., information seeking, discussing with others), post materials knowledge score, and viewing the video (vs. factsheet) were significantly positively associated with increased support for CMV prevention behaviors. Overall, we found that the health education materials improved women’s knowledge of CMV and encouraged them to adopt prevention behaviors. Given the low awareness levels among women currently, these findings suggest that appropriate education materials have the potential to greatly increase knowledge of CMV. As women become more knowledgeable about CMV and transmission routes, we expect they will be more likely to adopt prevention behaviors, thereby reducing their risk of CMV infection.

REACTIVATION OF LATENT CYTOMEGALOVIRUS INFECTION AS A CAUSE OF CONGENITAL DISEASES (CLINICAL CASE)

It is considered that the risk of congenital cytomegalovirus infection does not exceed 2-5% if it reactivates in pregnancy. According to some authors up to 75% of children born with this disease were infected as the result of reactivation of latent infection in the mother. The clinical case illustrates this situation. Attention is paid to the experts need to examine all the available information about the risk of congenital infection in pregnant women and newborns.

Detection of cytomegalovirus (CMV) antibodies or DNA sequences from ostensibly healthy Iranian mothers and their neonates

Cytomegalovirus (CMV) remains the most common cause of viral intrauterine infection. The objective of this research was to determine the prevalence of at-risk pregnancies for congenital cytomegalovirus transmission in a randomly selected pregnant women and their newborns. Enzyme Link Immunosorbent Assay (ELISA) and real-time polymerase chain reaction (PCR) were utilized to screen the sera of mothers (n = 100) and consecutive umbilical cord blood samples from their newborn (n = 100). Of the 100 mother's sera analyzed, 100 (100%) and 3 (3%) were positive for cytomegalovirus IgG and IgM antibodies, respectively. Of the 100 cord serum specimens analyzed, 99 (99%) and 2 (2%) were positive for cytomegalovirus IgG and IgM antibodies, respectively. Cytomegalovirus DNA was detected in 4 out of 100 (4%) cord blood samples of newborns. From four CMV DNA positive cases, Case 1 had no IgM in cord serum, but had IgM in mother's sera. Cases 2 and 4 were positive for IgM in both mother's sera and cord serum. Case 3 had no detectable CMV IgM in sera and cord serum. As many as 66 and 100% of CMV IgM-positive women in this study also had CMV IgM and CMV DNA in their delivery cord blood samples, respectively suggesting an increased risk of congenital CMV infection in those pregnancies. A paired women sera/cord blood CMV IgM-negative was found to be positive for CMV DNA. The data may also suggest the utility of PCR in place of CMV IgM as a diagnostic method for congenital CMV infection. Key words: Cytomegalovirus, cord blood, congenital disease, real-time polymerase chain reaction (PCR), antibodies

Decreased Risk of Congenital Cytomegalovirus Infection in Children Born to HIV‐1–Infected Mothers in the Era of Highly Active Antiretroviral Therapy

We evaluated the prevalence of congenital cytomegalovirus (CMV) infection before and after highly active antiretroviral therapy (HAART) availability among neonates born to human immunodeficiency virus type 1 (HIV-1)-infected mothers. We also identified maternal risk factors associated with in utero CMV transmission. Routine screening for congenital CMV infection was performed from 1993 through 2004 in children born to HIV-1-infected mothers included in the French Perinatal Cohort (Enquête Périnatale Française). Interpretable tests on urine samples collected within the first 10 days of life were available for 4797 of the 7563 live-born infants. Prevalence was estimated for different time periods. Univariate and multivariate logistic regression analyses were performed to identify factors associated with CMV transmission in the HAART era. Among live-born children, the overall prevalence of CMV infection was 2.3% (95% confidence interval, 1.9%-2.8%). Prevalence was higher among HIV-1-infected neonates (10.3%; 95% confidence interval, 5.6%-17.0%) than among HIV-1-uninfected neonates (2.2%; 95% confidence interval, 1.8%-2.7%; P < .01). Among HIV-1-uninfected neonates, the prevalence of CMV infection decreased over time, from 3.5% in 1997-1998 to 1.2% in 2003-2004. Delivery period, maternal age, time at antiretroviral treatment initiation, and maternal CD4(+) cell count <200 cells/mm(3) close to delivery were independently associated with CMV infection in logistic regression analysis. The percentage of symptomatic CMV infections was 23.1% among HIV-1-infected newborns and 6.7% among HIV-1-uninfected neonates. The prevalence of congenital CMV infection was high and associated with high morbidity rates among HIV-1-infected neonates. Conversely, the prevalence of CMV infection decreased over time among neonates not infected with HIV-1, reaching levels similar to those observed in the general population, following the introduction and increasing use of HAART for prevention of mother-to-child HIV-1 transmission.

Risk Factors for Congenital Cytomegalovirus Infection in the Offspring of Young Women: Exposure to Young Children and Recent Onset of Sexual Activity

Two recognized sources of maternal cytomegalovirus infection are young children and sexual activity. Previous studies evaluated either maternal exposures to young children or sexual activity, but these studies did not evaluate whether both of these maternal cytomegalovirus sources contribute to increases in congenital cytomegalovirus infections within populations with a high prevalence of infection among women of childbearing age. Our objective with this study was to investigate whether maternal cytomegalovirus exposure through young children and by sexual activity increases the risk for congenital cytomegalovirus infection in their offspring. A case-control study of 519 women from a delivery population in Birmingham, AL, between December 1992 and July 1998 was undertaken to measure the association between maternal cytomegalovirus exposures and an increased risk for congenital cytomegalovirus infection in their infants. Routine newborn cytomegalovirus screening at the hospital identified infants with congenital cytomegalovirus infection. The cases (n = 150) were women who delivered an infant with congenital cytomegalovirus infection, and the control subjects (n = 369) were randomly selected from the delivery population of women whose newborns were uninfected. Investigation of exposures included using a standardized maternal interview, prenatal and medical chart abstraction, and laboratory confirmation of cytomegalovirus infection. Significant associations between congenital cytomegalovirus infection and caring for preschool children in the year before delivery, onset of sexual activity < 2 years before delivery, sexually transmitted diseases during pregnancy, household size > 3 people, and maternal age < 25 years were identified. Women who cared for preschool children in the year before delivery and also became sexually active within the 2 years before delivery were at greatest risk for delivering an infant with congenital cytomegalovirus infection. Caring for young children and recent onset of sexual activity contribute to an increased risk for congenital cytomegalovirus infection in the offspring of young 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.

Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection

Currently, there is no effective intervention for a primary cytomegalovirus (CMV) infection during pregnancy. We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks' gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously). In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, -infinity to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) 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 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects. 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 now be appropriate.