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.

Aggressive Granulosa Cell Tumor of the Ovary with Rapid Recurrence: a Case Report and Review of the Literature.

Aggressive adult granulosa cell tumor (AGCT) of the ovary remains uncommon. We report a case of aggressive AGCT of the ovary who had rapid recurrence at two months after surgery. A patient was referred for further examination of a pelvic tumor. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. In the areas showing a sarcomatoid pattern, the mitotic count were 25/10 HPFs, and the mitoses were most prominent in foci composed of pleomorphic cells with enlarged and bizarre nuclei. In some areas, tumor cells with relatively uniform nuclei proliferated in a trabecular pattern. The mitotic count was 4/10 HPFs. Tumor cells were diffusely positive for α-inhibin. She was diagnosed as having aggressive AGCT. The Ki-67 labeling index in the sarcomatoid AGCT was higher (40%) than that in the areas of typical AGCT (3%). Immunostaining for p53 in the sarcomatoid AGCT was almost strongly positive, but that in typical AGCT was negative. Two months later after the initial surgery, a recurrent abdominal 12 cm-sized mass developed after performing adjuvant chemotherapy consisting of paclitaxel and carboplatin. She died of the disease at 3 months after initial surgery. A markedly higher mitotic count, a higher Ki-67 labeling index, and strong immunoreactivity of p53 in AGCT suggests highly malignant potential. In such a case, a careful follow-up is warranted due to the possibility of rapid recurrence.

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.

Prophylactic intravenous immunoglobulin injections to mothers with primary cytomegalovirus infection.

The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.5-5.0 g/day for consecutive 3 days to mothers with primary CMV infection. Four pregnant women were enrolled. One pregnancy ended in no congenital infection, while two pregnancies ended in congenital CMV infection. The other one pregnancy was terminated. The mother-to-fetus CMV transmission rate was found to be high as 66.7% (2/3). This preliminary result suggests that intravenous immunoglobulin injections are not effective for the prevention of mother-to-fetus CMV transmission in the present protocol.

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.

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.

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.

Coexistence of endometrioid adenocarcinoma in atypical polypoid adenomyoma.

Atypical polypoid adenomyoma (APA) is a rare polypoid tumor of the uterus composed of atypical endometrial glands and smooth muscle cells. Concomitant development of endometrial adenocarcinoma in APA remains infrequent. We report a case of the coexistence of endometrioid adenocarcinoma in APA. A 41-year-old patient presented with abnormal genital bleeding. A polypoid mass was extruded from the external cervical os. She underwent transcervical resection of the polypoid mass arising from the lower uterine segment. Pathological examination revealed APA with the foci of well-differentiated endometrioid adenocarcinoma. Subsequently, she underwent total hysterectomy and bilateral salpingo-oophorectomy. No residual malignant lesions were found. Awareness of the close association of APA with the development of endometrial cancer is warranted. A meticulous pathological evaluation of specimen of APA is necessary for the detection of the coexistence of endometrial cancer.

Large cell neuroendocrine carcinoma originating from the uterine endometrium: a report on magnetic resonance features of 2 cases with very rare and aggressive tumor.

Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC) of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR) images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.

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.

Argatroban therapy for heparin-induced thrombocytopenia during pregnancy in a woman with hereditary antithrombin deficiency.

A 33-year-old woman developed deep venous thrombosis at 7 gestational weeks (GW). Heparin-induced thrombocytopenia was evident at 9 GW during unfractionated heparin infusion. Immediately, anticoagulation therapies together with antithrombin (AT) infusion were commenced with the use of argatroban from 9 GW, and fondaparinux was substituted for argatroban after 24 GW. The patient had hereditary AT deficiency type I determined by laboratory findings and results of genomic DNA analysis. The pregnancy ended in full-term vaginal delivery of a healthy male without adverse effects of the anticoagulation therapies. This was the first report of a pregnant woman who developed heparin-induced thrombocytopenia caused by heparin therapy for deep venous thrombosis due to AT deficiency.