Cell-mediated and humoral immune responses to human cytomegalovirus in pregnant women with vertically transmitted infection following primary infection: A case report.

Human cytomegalovirus (HCMV) is the major cause of neurological sequelae in infants. Immune control of primary HCMV infection appears to depend on the interaction between humoral and cell-mediated immune responses. We report the case of an HCMV-transmitter mother observed with dissociation between humoral and cell-mediated immune responses. The patient had immunoglobulin (Ig) G and M positivity at 11 weeks of gestation and showed fetal hyperechoic bowel and minimal ascites at 21 weeks of gestation. At 25 weeks of gestation, the polymerase chain reaction result for HCMV using amniotic fluid was positive. The numbers of spots in the enzyme-linked immunosorbent spot (ELISPOT) assay at 25, 36, and 39 weeks of gestation were three, five, and six spots/2 × 105 peripheral blood mononuclear cells, respectively. Furthermore, IgG avidity indexes (AIs) at 21, 25, 36, and 39 weeks of gestation were 37.6, 49.7, 72.5, and 74.3, respectively. At 40+1 weeks of gestation, the patient delivered a symptomatic infected newborn with a weight of 2,384 g (-2.6 SD) and a head circumference of 30 cm (-2.6 SD). The neonate had a petechial rash and bilateral hearing loss although did not show liver dysfunction or thrombocytopenia. Cranial magnetic resonance imaging revealed mild ventriculomegaly, left lateral/parietal polymicrogyria, and a punctate white matter lesion. This case showed that IgG AI increased with increasing gestational age, whereas the numbers of spots in the ELISPOT assay had no change. The dissociation between humoral and cell-mediated immune responses may be characteristic of the immune response of a transmitter mother.

Revision of Cytomegalovirus Immunoglobulin M Antibody Titer Cutoff in a Maternal Antibody Screening Program in Japan: A Cohort Comparison Involving a Total of 32,000 Pregnant Women.

Cytomegalovirus (CMV) is associated with congenital infections. We aimed to validate the revised CMV immunoglobulin (Ig) M titer cutoff for IgG avidity measurements as a reflex test in maternal screening to identify women with primary CMV infection and newborn congenital cytomegalovirus (cCMV). We screened maternal CMV antibodies (the Denka assay) in Japan, from 2017 to 2019, using a revised IgM cutoff (≥4.00 index). Participants were tested for IgG and IgM antibodies, and for IgG avidity if IgM levels exceeded the cutoff. We compared these with corresponding results from 2013 to 2017 based on the original cutoff (≥1.21) and recalculated using the revised cutoff. Newborn urine CMV DNA tests were performed for women with low avidity (≤35.0%). Among 12,832 women screened in 2017-2019, 127 (1.0%) had IgM above the revised cutoff. Thirty-five exhibited low avidity, and seven infants developed cCMV. Of 19,435 women screened in 2013-2017, 184 (1.0%) had IgM above the revised cutoff, 67 had low avidity, and 1 had cCMV. The 2017-2019 results were not significantly different from the 2013-2017 results. The revised IgM cutoff improves maternal screening in identifying primary infection and newborn cCMV; however, further study related to other assays than Denka is required.

Prevalence of congenital cytomegalovirus infection according to the type of maternal infection in Japan.

INTRODUCTION: Variable rates of cytomegalovirus (CMV) seropositivity in mothers from different individual's background may translate to distinct epidemiological patterns of congenital CMV infection. METHODS: The prospective cohort study was conducted in Japan to evaluate the prevalence of vertical transmission rate according to the type of maternal infection. Post hoc power as a follow-up analysis was evaluated to compare the statistical power with other studies from France, Finland and Brazil. One thousand one hundred sixty-three pregnant women were measured IgG, IgM and IgG avidity index. The urine samples of neonates of these women were evaluated using polymerase chain reaction to diagnose the vertical transmission. RESULTS: The prevalence of congenital CMV infection in the study population was 0.4%. The proportions of patients with primary and nonprimary infections were 60% and 40%, respectively, with a maternal seroprevalence of 82.5%. The rate of vertical transmission among the seronegative pregnant women before pregnancy was statistically higher than that among the seropositive pregnant women before pregnancy (p < 0.05), with a study power of 52.7%. The same difference was observed in France and Finland for maternal seroprevalence of 61% and 72% and statistical power of 56.9% and 66.7%, respectively. CONCLUSION: The maternal seroprevalence of the present study conducted in Japan was much higher than that of studies in France and Finland. Nevertheless, seronegative pregnant women had a higher risk of vertical transmission before pregnancy.

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan.

OBJECTIVE: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection. MATERIALS AND METHODS: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection. RESULTS: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00-12.00 titers and 100% with 1.21-3.99 IgM titers) (p = 0.048). CONCLUSIONS: Nulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.

Primary cytomegalovirus infection during pregnancy and congenital infection: a population-based, mother-child, prospective cohort study.

OBJECTIVE: This study assessed maternal cytomegalovirus antibodies, and the occurrence of primary and congenital cytomegalovirus infections, and risk factors of congenital infection after a maternal primary infection. STUDY DESIGN: We included 19,435 pregnant women in Japan, who were tested for serum cytomegalovirus antibodies before 20 gestational weeks. Immunoglobulin (Ig) G avidity was evaluated in women with both IgG and IgM antibodies; tests were repeated at ≥28 gestational weeks among women without IgG and IgM antibodies. RESULT: Primary and congenital infections were 162 and 23 cases, respectively. The risk ratios for congenital infection were 8.18 (95% confidence interval: 2.44-27.40) in teenage versus older women, and 2.25 (95% confidence interval: 1.28-3.94) in parity ≥ 2 versus parity ≤ 1. Of 22 live birth congenital infection cases, three had abnormal neurological findings. CONCLUSION: We demonstrated teenage and parity ≥ 2 pregnant women as risk factors of post-primary congenital infection.

Low Maternal Immunoglobulin G Avidity and Single Parity as Adverse Implications of Human Cytomegalovirus Vertical Transmission in Pregnant Women with Immunoglobulin M Positivity.

Human cytomegalovirus (CMV) is the leading cause of neurological sequelae in infants. Understanding the risk factors of primary CMV infection is crucial in establishing preventive strategies. Thus, we conducted a retrospective cohort study to identify risk factors of vertical transmission among pregnant women with immunoglobulin (Ig) M positivity. The study included 456 pregnant women with IgM positivity. Information on age, parity, occupation, clinical signs, IgM levels, and IgG avidity index (AI) was collected. The women were divided into infected and non-infected groups. The two groups showed significant differences in IgM level, IgG AI, number of women with low IgG AI, clinical signs, and number of pregnant women with single parity. In the multiple logistic regression analysis, pregnant women with single parity and low IgG AI were independent predictors. Among 40 women who tested negative for IgG antibody in their previous pregnancy, 20 showed low IgG AI in their current pregnancy. Among the 20 women, 4 had vertical transmission. These results provide better understanding of the risk factors of vertical transmission in pregnant women with IgM positivity.

Immunoglobulin fetal therapy and neonatal therapy with antiviral drugs improve neurological outcome of infants with symptomatic congenital cytomegalovirus infection.

Infants with symptomatic congenital cytomegalovirus infection (cCMV) suffer from long-term sequelae. This study aimed at evaluating the efficacy of combining immunoglobulin (Ig) fetal therapy (FT) and neonatal therapy (NT) with antiviral drugs to improve neurological outcomes of affected infants. Women whose fetuses had symptomatic cCMV received Ig injection into the fetal peritoneal cavity and/or maternal blood as FT, while affected newborns received oral valganciclovir or intravenous ganciclovir as NT. We compared the neurological outcomes at ≥18 months old between infants receiving FT with or without NT (FT group) and those receiving NT only (NT group). From 2009-2019, 15 women whose fetuses had symptomatic cCMV received FT, while 19 newborns received NT only. In FT group, two newborns died, and two were <18 months old. Neurological outcomes of the remaining 11 infants in FT group were as follows: normal 45.5 %, mild impairments 36.4 %, and severe impairments 18.2 %. In NT group, one newborn died, one's parents refused the follow-up, one was <18 months old, and two had only chorioretinitis as symptoms. Neurological outcomes of the remaining 14 infants in NT group were as follows: normal 21.4 %, mild impairments 14.3 %, and severe impairments 64.3 %. The proportion of infants with severe impairments in FT group was significantly lower than that in NT group (18.2 % vs 64.3 %, p < 0.05). This is the first trial demonstrating that the combination of Ig FT and NT with antiviral drugs may be more effective in improving neurological outcomes of newborns with symptomatic cCMV as compared to NT only.

A multiple regression model for predicting a high cytomegalovirus immunoglobulin G avidity level in pregnant women with IgM positivity.

OBJECTIVE: To establish a model to predict high cytomegalovirus (CMV) immunoglobulin (Ig)G avidity index (AI) using clinical information, to contribute to the mental health of CMV-IgM positive pregnant women. METHODS: We studied 371 women with IgM positivity at ≤14 w of gestation. Information on the age, parity, occupation, clinical signs, IgM and G values, and IgG AI was collected. The IgG AI cut-off value for diagnosing congenital infection was calculated based on a receiver operating characteristic curve analysis. Between-group differences were assessed using the Mann-Whitney U-test or χ2 analysis. The factors predicting a high IgG AI were determined using multiple logistic regression. RESULTS: The women were divided into high or low IgG AI groups based on an IgG AI cut-off value of 31.75. There were significant differences in the IgG and IgM levels, age, clinical signs, and the number of women with one parity between the two groups. In a multiple logistic regression analysis, IgM and the number of women with one parity were independent predictors. This result helped us establish a mathematical model that correctly classified the IgG AI level for 84.6% of women. CONCLUSION: We established a highly effective model for predicting a high IgG AI immediately after demonstrating IgM positivity.

A cross-sectional study on maternal anxiety levels after cytomegalovirus screening.

Purpose: we aimed to estimate the anxiety levels of pregnant women following maternal serum screening for CMV infection.Materials and methods: In this case-control study conducted from April 2016 to June 2017, we enrolled all pregnant women referred to our hospital who were CMV immunoglobulin (Ig) M antibody positive (IgM-positive group, n = 51); further, those who were CMV IgG positive but IgM negative (IgM-negative group, n = 51) during the same period were included as study controls. Data were collected on patient characteristics, CMV IgM levels, and whether patients were accompanied by their partners during the first hospital visit after CMV IgM testing. The State-Trait Anxiety Inventory was used to assess anxiety levels.Results: Both groups were age matched [mean age (years): IgM-positive, 30 ± 4.2 and IgM-negative, 29.9 ± 4.6]. The mean state-anxiety score was higher in the IgM-positive group (53 ± 9.6) than in the IgM-negative group (38.5 ± 7.0, p < .05) with no between-group differences in trait-anxiety scores. Similarly, a higher number of women were accompanied by their partners in the IgM-positive group. The state-anxiety scores and CMV IgM levels were not correlated in the IgM-positive group.Conclusion: Counseling support is essential for IgM-positive pregnant women following serum screening, and the screening should be avoided if support systems are unavailable.

Clinical Factors Associated With Congenital Cytomegalovirus Infection: A Cohort Study of Pregnant Women and Newborns.

BACKGROUND: The aim of this prospective cohort study was to determine clinical factors associated with the occurrence of congenital cytomegalovirus infection (cCMV) in pregnant women. METHODS: Between March 2009 and November 2017, newborns born at a primary maternity hospital received polymerase chain reaction (PCR) analyses for CMV DNA in their urine with informed consent of the mothers at a low risk. Clinical data, including age, gravidity, parity, body mass index, occupation, maternal fever/flulike symptoms, pregnancy complications, gestational weeks at delivery, birth weight, and automated auditory brainstem response, were collected. Logistic regression analyses were performed to determine clinical factors associated with cCMV. RESULTS: cCMV was diagnosed by positive PCR results of neonatal urine in 9 of 4125 pregnancies. Univariate and multivariable analyses revealed that the presence of fever/flulike symptoms (odds ratio [OR], 17.9; 95% confidence interval [CI], 3.7-86.7; P < .001) and threatened miscarriage/premature labor in the second trimester (OR, 6.0; 95% CI, 1.6-22.8; P < .01) were independent clinical factors associated with cCMV. Maternal fever/flulike symptoms or threatened miscarriage/premature labor in the second trimester had 100% sensitivity, 53.2% specificity, and a maximum Youden index of .85. CONCLUSIONS: This cohort study for the first time demonstrated that these clinical factors of pregnant women and newborns were associated with the occurrence of cCMV. This is useful information for targeted screening to assess risks of cCMV in low-risk mothers, irrespective of primary or nonprimary CMV infection.

Prospective Cohort Study of Congenital Cytomegalovirus Infection during Pregnancy with Fetal Growth Restriction: Serologic Analysis and Placental Pathology.

OBJECTIVE: To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR). STUDY DESIGN: Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth. RESULTS: One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine ß-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection. CONCLUSIONS: Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection.

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection.

The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0-55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4-37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5-48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy.

Universal Screening With Use of Immunoglobulin G Avidity for Congenital Cytomegalovirus Infection.

BACKGROUND: The aim of this prospective cohort study was to evaluate the efficacy of maternal screening for congenital cytomegalovirus infection (CCI) using cytomegalovirus (CMV) immunoglobulin G (IgG) and the IgG avidity index (AI). METHODS: Pregnant women underwent screening of CMV IgG and AI measurements. IgG-negative women underwent remeasurement of IgG after educational intervention. Women with an AI ≤45% received further examinations, including measurement of CMV IgM. All newborns received polymerase chain reaction analyses of the urine, and CCI was diagnosed by the detection of CMV-DNA in the urine. Primary infection was defined as an AI <35% and/or positive IgM (>1.20 index). Serum samples from women with an AI >45% were stored, and the IgM levels were measured after delivery. The efficacy of AI and IgM for CCI screening was compared. RESULTS: A total of 1562 (71.2%) women tested positive for IgG. In this study, 10 newborns with CCI were detected. The presence of infection in 3 newborns from mothers with primary infection was predicted by screening of IgG and AI <35%. However, infection in 7 newborns from women with nonprimary infection could not be predicted by screening of CMV IgG, AI <35%, or IgM. The application of an AI <35% for CCI screening yielded 22.2% sensitivity, 95.0% specificity, 2.5% positive predictive value, and 99.5% negative predictive value and was similar to that of IgM (11.1% sensitivity, 93.2% specificity, 0.9% positive predictive value, and 92.7% negative predictive value). CONCLUSIONS: Maternal screening using CMV IgG and AI can identify pregnancies with CCI from primary infection, but overlooks a number of those from nonprimary infection.

Prediction of Congenital Cytomegalovirus Infection in High-Risk Pregnant Women.

BACKGROUND: This prospective study aimed to determine maternal clinical, laboratory, and ultrasound findings that effectively predict the occurrence of congenital cytomegalovirus (CMV) infection (CCI) in high-risk pregnant women. METHODS: Three hundred CMV immunoglobulin (Ig) M-positive pregnant women were enrolled. The maternal clinical and laboratory findings, including serum CMV IgM and IgG; IgG avidity index (AI); antigenemia assay (C7-HRP); polymerase chain reaction (PCR) for the detection of CMV-DNA in the maternal serum, urine, and uterine cervical secretion; and prenatal ultrasound findings, were evaluated. To determine predictive factors for the occurrence of CCI, logistic regression analyses were performed. RESULTS: In 22 of the 300 women, CCI was confirmed using PCR for CMV-DNA in newborn urine. Univariate analyses demonstrated that the presence of maternal flu-like symptoms, presence of ultrasound fetal abnormalities, serum titers of CMV IgM, positive results for C7-HRP, CMV IgG AI <40%, and positive PCR results in the uterine cervical secretion were statistically associated with the occurrence of CCI. Multivariable analysis revealed that the presence of ultrasound fetal abnormalities (odds ratio [OR], 31.9; 95% confidence interval [CI], 8.5-120.3; P < .001) and positive PCR results in the uterine cervical secretion (OR, 16.4; 95% CI, 5.0-54.1; P < .001) were independent predictive factors of CCI in CMV IgM-positive women. CONCLUSIONS: This is the first prospective cohort study to suggest that the presence of CMV-DNA in the maternal uterine cervical secretion and ultrasound fetal abnormalities are predictive of the occurrence of congenital CMV infection in high-risk pregnant women.

Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection.

BACKGROUND: The immunoglobulin (Ig) G avidity index (AI) is useful to detect primary cytomegalovirus (CMV) infection. However, because IgG matures with time, this index is not useful to detect a primary infection, unless measured at an appropriate time. OBJECTIVES: We aimed to clarify the difference between using IgG AI and IgM positivity according to the stage of pregnancy to identify congenital CMV infection risk. STUDY DESIGN: We collected the serum samples from 1115 pregnant women who underwent maternal screening for primary infection (n = 956) and were referred to our hospital because of CMV IgM positivity (n = 155) or had abnormal fetal ultrasonography findings (n = 4). The same sera samples were used to measure CMV IgM, IgG, and IgG AI. An IgG AI of <35% was defined as low. Neonatal urine collected within 5 days after birth was examined by polymerase chain reaction to confirm congenital infection. RESULTS: Fourteen mothers gave birth to infected neonates. The sensitivity, specificity, and negative predictive values of the low IgG AI group with IgM-positive samples to discriminate between women with congenital infection at ≤14 weeks of gestation were 83.3, 83.8, and 99.1, respectively, which were higher than those of other subjects. Uni- and multivariate analyses revealed that IgM positivity and low IgG AI were independent variables associated with congenital infection at any stage of pregnancy, except low IgG AI at ≥15 weeks of gestation. CONCLUSION: Low IgG AI with IgM positivity at ≤14 weeks of gestation was a good indicator of congenital infection, which should prove useful in obstetric practice.

Rapid increase in the serum Cytomegalovirus IgG avidity index in women with a congenitally infected fetus.

BACKGROUND: Human Cytomegalovirus (CMV) is the virus most frequently responsible for severe diseases of the fetus and newborn. The reported intrauterine transmission rate of CMV following primary maternal infection is approximately 40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV infection. OBJECTIVES: The aim of this study was to evaluate whether the rapidity of change in the CMV IgG avidity index (AI) is associated with the presence of congenital CMV infection among mothers with suspected primary CMV infection. STUDY DESIGN: The serum CMV IgG AI was repeatedly measured in 17 pregnant women with positive or borderline test results for CMV IgM together with an initial IgG AI value of <40%. Their neonates underwent polymerase chain reaction analyses for the presence of CMV DNA in the urine. The rapidity of change in the IgG AI per 4 weeks was defined as the ΔAI (%). The ΔAI of women with congenital CMV infection was compared with that of women with no infection. RESULTS: The ΔAI of nine mothers with congenital CMV infection (median,15.7%; range,7.8-42.8%) was significantly higher than that of eight mothers with no infection (median, 6.5%, range, 2.0-8.8%; p<0.001). The incidences of congenital CMV infection were 100.0%, 16.7%, and 0.0% among mothers with a ΔAI of >10, 5-10, and <5%, respectively. CONCLUSIONS: Measurement of the ΔAI in pregnant women might be useful for estimating the risk of mother-to-neonate CMV transmission.

The IgG avidity value for the prediction of congenital cytomegalovirus infection in a prospective cohort study.

BACKGROUND: Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. OBJECTIVES: To evaluate the maternal IgG avidity value for the prediction of congenital CMV infection. STUDY DESIGN: The serum IgG avidity in all mothers was measured, and the urine of their neonates was assessed for CMV DNA in a prospective cohort study. RESULTS: Of 759 women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG avidity indices in the congenital infection group (median 35.1%) were significantly lower than those in the non-congenital infection group (70.4%). A cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3% sensitivity for congenital infection was determined by receiver operating characteristic curve analyses. The highest sensitivity (88.9%), 96.2% specificity, 27.6% positive predictive value, 99.8% negative predictive value, and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of gestation. CONCLUSION: The IgG avidity measurement with a cutoff value of <40% IgG avidity index might be helpful in predicting congenital CMV infection, especially in <28 weeks of gestation.

Quantitative evaluation of ventricular dilatation using computed tomography in infants with congenital cytomegalovirus infection.

BACKGROUND: Infants with congenital cytomegalovirus infection (CCMVI) may develop brain abnormalities such as ventricular dilatation, which may potentially associate with sensorineural hearing loss. There is currently no recognized method for quantitative evaluation of ventricle size in infants with CCMVI. Our objectives were to establish a method for quantitative evaluation of ventricle size using computed tomography (CT) in infants with CCMVI, and determine a cut-off value associated with abnormal auditory brainstem response (ABR) early in life. DESIGN/SUBJECTS: This study enrolled 19 infants with CCMVI and 21 non-infected newborn infants as a control group. Infants with CCMVI were divided into two subgroups according to ABR at the time of initial examination: normal ABR (11 infants) or abnormal ABR (8 infants). Ventricle size was assessed by calculating Evans' index (EI) and lateral ventricle width/hemispheric width (LVW/HW) ratio on brain CT images, and was compared among groups. A cut-off ventricle size associated with abnormal ABR was determined. RESULTS: EI and LVW/HW ratio were significantly higher in the CCMVI with abnormal ABR group than the control and CCMVI with normal ABR groups. Cut-off values of 0.26 for EI and 0.28 for LVW/HW ratio had a sensitivity of 100% and 100%, respectively, and a specificity of 73% and 91%, respectively, for association with abnormal ABR. CONCLUSIONS: We established a method for quantitative evaluation of ventricle size using EI and LVW/HW ratio on brain CT images in infants with CCMVI. LVW/HW ratio had a more association with abnormal ABR in the early postnatal period than EI.

Cytomegalovirus (CMV) glycoprotein H-based serological analysis in Japanese healthy pregnant women, and in neonates with congenital CMV infection and their mothers.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is caused by maternal primary infection as well as CMV reinfection or reactivation during pregnancy, although differences in the clinical impact between these modes of infection remain to be clarified. OBJECTIVES: To investigate the latest prevalence and risk of multiple CMV infection in healthy pregnant women, as well as the types of maternal CMV infection associated with congenital CMV infection. STUDY DESIGN: Seroprevalence against CMV and IgG subclasses were determined in 344 serum samples from healthy pregnant women in Japan. CMV genotype and serotype were also determined in 18 pairs of mothers and neonates with congenital CMV infection identified in our CMV screening program. RESULTS: Thirty-two percent of the pregnant women were seronegative, while 66% of CMV seropositive women had IgG3 antibodies against one epitope on glycoprotein H (gH) as the major subclass, and 52% had IgG1 antibodies against one epitope on glycoprotein B (gB). Only a single genotype determined by CMV gH neutralizing epitope was found in the urine from the 18 neonates with congenital CMV infection, even though one case possessed antibodies against multiple CMV strains. In that case, the antibodies against the strain not detected in the urine from the infant disappeared within one month after birth, whereas the antibodies against the infecting CMV strain continued to be detected at 12 months after birth. CONCLUSIONS: Two (11%) of 18 cases of congenital CMV infection occurred via maternal CMV reinfection. Maternal humoral immunity did not prevent congenital CMV infection with another gH subtype.

Low IgG avidity and ultrasound fetal abnormality predict congenital cytomegalovirus infection.

Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. The aim of this study was to assess whether prenatal clinical or laboratory findings in pregnant women who had high risks for primary CMV infection predicted the presence of congenital infection. Fifty pregnant women who had serum CMV IgG and positive or borderline tests for serum CMV IgM were included in this prospective study. Serum IgG avidity was measured, and PCR was conducted for CMV DNA in maternal serum, urine, and uterine cervical secretion. All neonates underwent PCR testing for CMV DNA in the urine for the presence of congenital infection. Risk factors were compared between congenital infection group and group without congenital infection. As a result, nine neonates (18%) were diagnosed as having congenital infection. The frequencies of ultrasound fetal abnormality and positive test for CMV DNA in cervical secretion, CMV IgM titer and IgM/IgG ratio in the congenital infection group were significantly higher than those in the group without congenital infection. Conversely, IgG avidity index in the congenital infection group was significantly lower than that in the group without congenital infection. By multivariate logistic regression analyses, IgG avidity index (Odds ratio 0.91, 95% CI: 0.83-0.99) and ultrasound fetal abnormality (291.22, 2.72-31125.05), were selected independently as significant signs predictive of congenital CMV infection. Among pregnant women with positive or borderline tests for CMV IgM, when they have findings of low serum CMV IgG avidity or ultrasound fetal abnormality, the probability of congenital CMV infection may increase.