Mayumi Morizane

Prospective Study of Congenital Toxoplasmosis Screening with Use of IgG Avidity and Multiplex Nested PCR Methods

ABSTRACT Acute infection with Toxoplasma gondii during pregnancy can cause congenital toxoplasmosis. The aim of this study was to evaluate whether screening with the use of IgG avidity and multiplex nested PCR methods was effective to detect a high-risk pregnancy. In a prospective study, serum T. gondii IgG avidity was measured in consecutive 146 pregnant women testing positive for T. gondii antibody and either positive or equivocal for IgM. Multiplex nested PCR for T. gondii DNA on amniotic fluid, maternal blood, and umbilical cord blood were performed with informed consent. A total of 51 (34.9%) women presented with low IgG avidity (<30%), 15 (10.3%) presented with borderline avidity (30 to 35%), and 80 (54.8%) presented with high avidity (>35%) indices. Amniotic fluid obtained at amniocentesis or birth yielded positive PCR results in nine women with low IgG avidity indices. Of these nine women, three had congenital toxoplasmosis. None of women with high or border line IgG avidity indices had a positive PCR result in the amniotic fluid or congenital toxoplasmosis. No congenital toxoplasmosis was detected in women whose amniotic fluids yielded negative PCR results. Ingestion of raw or undercooked meat was found to be the main risk factor for acute T. gondii infection. Congenital toxoplasmosis screening with a combination of IgG avidity in the maternal blood and multiplex nested PCR in the amniotic fluid was useful for detecting a high risk pregnancy and diagnosing congenital toxoplasmosis.

No association of endometriosis with glutathione S-transferase M1 and T1 null mutations in a Japanese population.

Objective: Endometriosis is inherited as a complex trait, which means that multiple susceptibility genes interact with each other and with environmental factors to produce the phenotype. We investigated the frequency of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) null mutations in women with endometriosis in a Japanese population. Methods: One hundred fourteen unrelated women with endometriosis were enrolled. Samples of umbilical cord blood obtained from 179 female newborn infants were used as population controls. Genomic DNA isolated from endometriosis patients and controls were subjected to multiple polymerase chain reactions to determine the GSTM1 and GSTT1 genotypes. Results: There were no significant differences in the frequencies of the GSTM1 (P = .83, odds ratio 0.95) and GSTT1 (P = .24, odds ratio 0.75) null mutations between endometriosis patients and controls. The endometriosis group was divided into a subgroup of stage IV disease only, but no statistically significant differences were observed in the frequency of the GSTM1 null mutation (P = .88, odds ratio 0.96, 95% confidence interval 0.57-1.63) and the GSTT1 null mutation (P = .33, odds ratio 0.77, 95% confidence interval 0.45-1.30) between any of these groups and the controls. Conclusion: These findings suggest that the GSTM1 and GSTT1 null mutations are not likely to be associated with an increased risk of endometriosis in a Japanese population.

Lack of association between endometriosis and the CYP17 MspA1 polymorphism in UK and Japanese populations.

Endometriosis is a complex trait, which means that multiple susceptibility genes interact with one another and the environment to produce the phenotype. One of the genes previously implicated in the disease is CYP17; this encodes the enzyme P450c17α, which plays a vital role in steroid biosynthesis in the ovary. The presence of a single nucleotide polymorphism (T→C) in the 5′-promoter region of the gene creates a new recognition site for the restriction enzyme MspA1 producing a mutant allele (A2), which affects circulating estrogen levels. In this study, we compared the frequency of the CYP17 MspA1 polymorphism in two different ethnic populations. DNA was obtained from (1) 94 women with revised American Fertility Society (rAFS) stage III–IV endometriosis and 97 male blood donors in the UK, and (2) 130 women with rAFS stage III–IV endometriosis and 179 female newborn infants in Japan. No significant differences in allele or genotype frequencies were seen in either population. The genotype distribution in the UK population was 33/94 [35.1%] (cases) and 39/97 [40.2%] (controls) for A1A1 (homozygous wild-type); 43/94 [45.7%] (cases) and 44/97 [45.4%] (controls) for A1A2; and 18/94 [19.1%] (cases) and 14/97 [14.4%] (controls) for A2A2. The genotype distribution in the Japanese population was 31/130 [23.9%] (cases) and 57/179 [31.8%] (controls) for A1A1; 73/130 [56.2%] (cases) and 89/179 [49.7%] (controls) for A1A2; and 26/130 [20.0%] (cases) and 33/179 [18.4%] (controls) for A2A2. The CYP17 MspA1 polymorphism is probably not associated with endometriosis in either the UK or the Japanese population.

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.

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. J. Med. Virol. 84:1928–1933, 2012.

Risk factors for postpartum glucose intolerance in women with gestational diabetes mellitus

Abstract Objectives: To determine the risk factors for glucose intolerance (GI) during the postpartum period in women with gestational diabetes mellitus (GDM). Methods: This prospective cohort study included 72 Japanese women with GDM who underwent 75 g oral glucose tolerance tests (OGTT) at 12 weeks after delivery. These women were divided into the GI group and the normal group based on postpartum OGTT. Risk factors for GI, including levels of blood glucose (BG), area under the curve (AUC) of glucose, AUC insulin, HbA1c, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-β, insulinogenic index (II) and the oral disposition index (DI) in antepartum OGTT, were analyzed by logistic regression analyses. Results: Of the 72 women, 60 (83.3%) were normal and 12 (16.7%) had GI. By univariate logistic regression analyses, fasting BG, AUC glucose, HOMA-β, II and oral DI were selected as risk factors for GI. Multivariate logistic regression analysis revealed that the level of II in antepartum OGTT was a significant factor that predicted GI after delivery (odds ratio, 0.008; 95% CI, 0.0001–0.9; p < 0.05). Conclusions: II measured by OGTT during pregnancy might be a useful predictor of GI within the early postpartum period in women with GDM.

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.

Neuropathological features of the brain in acardius acormus

Abstract Acardia is the most severe complication in monozygotic twinning. Acardius acormus is an uncommon phenotype among acardias. We report on an acardius acormus using thorough gross and light microscopic examination of the brain. Neuropathological examination revealed a severely disorganized cerebral cortex, agenesis of cerebellum and brain stem, and undeveloped basal ganglia and thalamus. In particular, the cerebral cortex was characterized by no clear lamination, almost complete loss of neurons, extensive gliosis, angiogenesis and focal mineralization. Neurohistology of the acardius acormus clearly demonstrated two types of lesions: developmental arrest of the brain and hypoxic-asphyxic damage to the brain with reactive gliosis and angiogenesis. Both types of lesions may be induced by the same teratogen: early onset of persisting hypoxia due to a reversed arterial perfusion. The quality of the description contributes valuably to a better understanding of the basic mechanism underlying the acardius phenotype.