Satoshi Nagamata

Awareness of and knowledge about mother‐to‐child infections in Japanese pregnant women

To reduce the incidence of infants with congenital infections, women should be aware of and know prevention measures against maternal infection with mother‐to‐child infections during pregnancy. Our objective was to assess the awareness of and knowledge about mother‐to‐child infections in Japanese pregnant women. A survey of 343 Japanese pregnant women was completed. Awareness of 13 pathogens capable of mother‐to‐child transmission was surveyed. Knowledge about the transmission route, the most susceptible time of infection that may cause severe fetal disease during pregnancy, and methods to prevent maternal infection were investigated for four major pathogens (cytomegalovirus, rubella virus, Toxoplasma gondii, and parvovirus B19) and results were compared between these pathogens. The proportion of women aware of pathogens concerning TORCH syndrome was the following: rubella virus 76%, Treponema pallidum 69%, Toxoplasma gondii 58%, parvovirus B19 28%, herpes simplex virus 27%, and cytomegalovirus 18%. Only 8% knew how cytomegalovirus is transmitted, and only 12% knew how parvovirus B19 is transmitted; both were significantly lower than those who knew transmission routes for rubella virus or Toxoplasma gondii. The proportion of women who knew the most susceptible time for severe fetal infection by maternal acquisition of cytomegalovirus, Toxoplasma gondii, or parvovirus B19 was significantly lower than that for rubella virus. The vast majority of surveyed women were not aware of methods to prevent maternal infection with cytomegalovirus or parvovirus B19. In conclusion, current awareness of and knowledge about cytomegalovirus and parvovirus B19 infection are low in Japanese pregnant women.

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.

Abstract 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.

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.

Nationwide survey of mother-to-child infections in Japan.

OBJECTIVES The aim of this survey study was to evaluate a state of mother-to-child infections in Japan. METHODS A nationwide survey on 2714 obstetric facilities where regular maternity checkups were carried out was conducted. A primary questionnaire assessed numbers of pregnancies including induced abortion, spontaneous abortion, still-birth as well as live-birth, which were affected by congenital infections of 6 pathogens during a year of 2011. The secondary questionnaire assessed clinical information, diagnostic modality, and the outcome for each case. The clinical features and diagnostic problems were evaluated. RESULTS The high reply rates for the primary (73.7%) and the secondary questionnaire (100%) were achieved. The presence of congenital infections for 34 cases with cytomegalovirus (CMV), 1 with Toxoplasma gondii, 4 with rubella virus, 5 with Treponema pallidum, 8 with herpes simplex virus, and 69 with parvovirus B19 was confirmed after questionnaire assessment. The incidence of fetal demise among pregnancies with congenital parvovirus B19 infection was up to 71.0%. Eleven mothers with hydrops fetalis received prenatal fetal therapies involving fetal blood transfusion and immunoglobulin administration, whereas only three pregnancies (27.3%) ended in live-births. CONCLUSIONS This survey study for the first time revealed the annual frequency of pregnancies with mother-to-child infections of 6 pathogens in Japan. The results involve important information and are helpful for clinical practitioners. The majority of neonates with congenital infection of CMV or T. gondii might be undiagnosed in obstetric facilities.

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.

Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation

BACKGROUND CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. STUDY DESIGN Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4+ and CD8+ cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. RESULTS HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4+ T cells, p = .02 in CD8+ T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4+ T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). CONCLUSIONS This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT.

Nationwide survey of maternal screening for mother-to-child infections in Japan

Mother‐to‐child infections cause congenital infection with disease and sequelae. To evaluate a state of maternal blood screening for mother‐to‐child infections in Japan, we for the first time conducted a nationwide survey on obstetric facilities where regular maternity checkups were carried out. A questionnaire assessment involved an annual number of deliveries, scale of facilities and a state of maternal blood screening for eight pathogens. A high rate (73.7%) of reply to the questionnaire was achieved from 1990 facilities, covering 75.1% of annual number of delivery in 2011. The performance rates of blood screening were more than 99% for rubella virus, Treponema pallidum, human immunodeficiency virus (HIV), human T cell leukemia virus type 1 (HTLV‐1), hepatitis B virus, and hepatitis C virus, while the rate was found to be only 4.5% for cytomegalovirus (CMV), and 48.5% for Toxoplasma gondii with large differences in regions. Most of the facilities performed blood tests for rubella virus, Treponema pallidum, HIV, hepatitis B virus and hepatitis C virus once in early pregnancy, while approximately 28% of the facilities performed blood tests for HTLV‐1 once during the 2nd or 3rd trimester. Most of the facilities used HA tests for Toxoplasma gondii, whereas there was a wide variation in antibody measurement methods for CMV. Generally, the obstetric facilities in Japan have performed maternal blood screening properly according to the current recommendations. The results of this survey involve important information and are helpful for clinical practitioners.

Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation.

Ectopic pregnancy in a patient undergoing therapy for ovarian hyperstimulation syndrome: a case report

We report a case of an ectopic pregnancy removed via laparoscopic surgery in a patient undergoing therapy for ovarian hyperstimulation syndrome (OHSS). A 36-year-old woman, with a history of egg retrieval after ovulation induction with human menopausal gonadotropin and human chorionic gonadotropin (hCG), was referred to our hospital because of abdominal pain and bloating. Ultrasound examination showed an 8-9 cm bilateral adnexal mass and subphrenic ascites. She was diagnosed with moderate OHSS. Despite conservative therapy, symptoms did not improve and the bilateral adnexal mass did not decrease in size. Serum hCG level was 6339 mIU/ml. Ultrasound examination did not detect a gestational sac in the uterus. Magnetic resonance imaging indicated a cystic mass in the peritoneal cavity. We strongly suspected ectopic pregnancy in the abdominal cavity. Laparoscopic surgery and intrauterine curettage were performed. The histopathological diagnosis was peritoneal pregnancy. Symptoms disappeared and serum hCG levels decreased. We believe that the peritoneal pregnancy caused OHSS. Even if there is a period when of pregnancy failure via assisted reproductive technology, ectopic pregnancy should be considered. Pregnancy should be confirmed and egg retrieval performed before initiating medical treatment in patients with OHSS.