Increased levels of C19MC microRNAs in maternal plasma are a characteristic phenomenon of established severe pre-eclampsia, and it has been shown for the first time that the upregulation of C19MC miRNAs occurred as a consequence of, not in advance of, the onset of pre-eclampsia.

Background: The reliable diagnosis of human T-cell leukemia virus type 1 (HTLV-1) infection is important, particularly as it can be vertically transmitted by breast feeding mothers to their infants. However, current diagnosis in Japan requires a confirmatory western blot (WB) test after screening/primary testing for HTLV-1 antibodies, but this test often gives indeterminate results. Thus, this collaborative study evaluated the reliability of diagnostic assays for HTLV-1 infection, including a WB-based one, along with line immunoassay (LIA) as an alternative to WB for confirmatory testing. Results: Using peripheral blood samples from blood donors and pregnant women previously serologically screened and subjected to WB analysis, we analyzed the performances of 10 HTLV-1 antibody assay kits commercially available in Japan. No marked differences in the performances of eight of the screening kits were apparent. However, LIA determined most of the WB-indeterminate samples to be conclusively positive or negative (an 88.0% detection rate). When we also compared the sensitivity to HTLV-1 envelope gp21 with that of other antigens by LIA, the sensitivity to gp21 was the strongest. When we also compared the sensitivity to envelope gp46 by LIA with that of WB, LIA showed stronger sensitivity to gp46 than WB did. These findings indicate that LIA is an alternative confirmatory test to WB analysis without gp21. Therefore, we established a novel diagnostic test algorithm for HTLV-1 infection in Japan,

The aim of this study was to clarify the association between circulating pregnancy-associated, placenta-specific microRNAs (miRNAs) in maternal plasma and placental abruption. All samples were obtained after receiving written informed consent, and the study protocol was approved by the institutional review board. Maternal blood samples (7 mL) were obtained at 25 to 40 weeks of gestation from 15 cases of placental abruption (placental abruption group) and from 24 cases of uncomplicated pregnancies (uncomplicated pregnancy group). The plasma concentrations of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) were measured by quantitative real-time reverse transcription-polymerase chain reaction. There were no significant differences in clinical characteristics between the 2 groups. The median concentration of plasma cell-free miR-517c in the placental abruption group was 21 672.2 copies/mL, whereas that in the uncomplicated pregnancy group was 13 452.0 copies/mL (Mann-Whitney U test, P = .047). Receiver operating characteristic curve analysis revealed that plasma cell-free miR-517c levels discriminated placental abruption from uncomplicated pregnancy with an area under the curve of 0.692. When a cutoff negative/positive value of 15 669.6 copies/mL was selected, the sensitivity and specificity were 73.3% and 62.5%, respectively. In addition, the positive and negative predictive values were 55.0% and 78.9%, respectively. Plasma cell-free miR-517a and miR-517c levels in the large abruption (degree of abruption ≥50% of placenta) group were significantly higher than in the small abruption (<50%) group ( P = .03 for both miRNAs). In conclusion, the circulating level of cell-free miR-517c in maternal plasma was increased as a consequence of placental abruption and may be a potential biomedical marker for placental abruption.

Maternal blood during pregnancy, cord blood, and placental villous tissues at the time of delivery were obtained from subjects to measure the HTLV-1 proviral load (PVL) using real-time PCR. As shown in Figure 1A, HTLV-1 provirus was detected in the maternal blood of 248 of 254 subjects (97.6%), in the placental villous tissues of 140 of 254 subjects (55.1%), and in the cord blood samples of 6 of 254 subjects (2.4%). Overall, 248 women had PVL in the maternal blood, of whom 140 also had PVL in the placenta. Of these 140 women, 6 had PVL in the cord blood. Significant differences in the PVL were observed between the maternal blood, cord blood, and placental villous tissues (Figure 1A). The 248 pregnant carriers with PVL in the maternal blood were divided into those with PVL (n = 140) and without PVL (n = 108) in the placental tissue, and their clinical backgrounds were compared. Women with PVL in the placental tissue had a significantly higher peripheral blood PVL, higher antibody titers, and more multiparas compared with women with no PVL in the placental tissue (Table 1 and Figure 1B). These 2 groups did not differ in terms of birth weight and pregnancy complications (Table 1). There was no significant difference in the clinical backgrounds of pregnant women with HTLV-1 in the placenta when divided into those who tested positive versus negative for HTLV-1 in the cord blood (Supplemental Table 1). This was at least in part due to the small number of pregnant women testing positive for HTLV-1 in the cord blood. In addition, there were insufficient numbers of follow-up surveys of cases of MTCT by intrauterine transmission to allow statistical analysis. These issues are subjects for future investigation. A weak positive correlation between the PVLs in the maternal blood and in the placental villous tissues was observed (Figure 1C), whereas PVL in HTLV-1-positive cord blood samples did not correlate with PVL in the maternal blood or placental villous tissues of the same subject (Figure 1, D and E). To test the possibility that HTLV-1 provirus detected in cord blood was derived from maternal blood contamination of cord blood, microsatellite analysis was performed using short tandem repeat (STR) markers (25). Differences in the patterns of representative STR markers were observed between maternal blood-derived DNA and fetal placental villous tissue-and cord blood-derived DNA (Figure 1F). Similar results were obtained for all 6 samples that tested positive for HTLV-1 provirus in the cord blood. Furthermore, STR analysis and HTLV-1 PVL assay were used to examine how much maternal blood in the cord blood was required to detect a positive signal. A mixing rate of 20% (maternal/fetal cell ratio = 20:80) was the detection limit in the STR analysis, and a mixing rate of 5% (maternal/fetal cell ratio = 5:95) was the detection limit in the HTLV-1 PVL assay (Supplemental Figure 1). A previous study reported that the median rates of maternal blood contamination in the cord blood were 0.27% and 0.

The measurement of human T-cell leukemia virus type 1 (HTLV-1) proviral DNA levels by using polymerase chain reaction has been beneficial for confirming HTLV-1 infection during pregnancy. However, the influence of pregnancy on HTLV-1 infection and proviral DNA levels among pregnant women with HTLV-1 has not been clarified. We prospectively gathered blood samples from 36 pregnant women in whom HTLV-1 carriage was previously diagnosed and sequentially measured their proviral DNA levels. The HTLV-1 proviral DNA levels remained at a plateau during pregnancy but were elevated after delivery. Moreover, flow cytometry and serological analyses revealed that the regulatory T-cell population and soluble interleukin 2 receptor levels were similarly elevated after birth in comparison with those in control pregnant women. This study is the first to provide data on sequential changes in HTLV-1 proviral DNA levels during and after pregnancy. These findings will guide the establishment of a better program to prevent mother-to-child transmission of HTLV-1.

In this study, associations between invasive cervical cancer and four cervical cancer susceptibility loci (rs13117307 at 4q12, rs8067378 at 17q12, and rs4282438 and rs9277952 at 6p21.32) in the Han Chinese population were investigated in a Japanese population. Human leukocyte antigen (HLA)-DPB1 alleles were also investigated for their association with cervical cancer risk in the Japanese population. After receiving written informed consent, 214 unrelated Japanese women with invasive cervical cancer and 288 cancer-free Japanese women were recruited, and DNA samples were obtained (study protocol approved by Institutional Review Board of Nagasaki University). Of the four single-nucleotide polymorphisms, rs8067378 showed a significant association with invasive cervical cancer (P=0.0071). Under a recessive model, the minor allele G of rs8067378 contributed to the risk of invasive cervical cancer (odds ratio=2.92, 95% confidence interval=1.40-6.36; P=0.0021). No association was detected between HLA-DPB1 alleles and cervical cancer risk in the Japanese population. In conclusion, we show for the first time, to the best of our knowledge, that an association between increased risk of invasive cervical cancer and rs8067378 in the Han Chinese population is replicated in a Japanese population. In addition, Japanese women with the GG genotype of rs8067378 are a candidate high-risk group for invasive cervical carcinoma.

41This questionnaire survey was conducted at 11 hospitals in Japan to determine 42 vaccination coverage against seasonal influenza and the prevalence rate of influenza 43 among pregnant Japanese women. Of 2808 postpartum women who gave birth at the 11 44 hospitals during the study period from March 1, 2014, to July 31, 2014, 1713 influenza infection rate by 35% (3.9% vs. 6.3% for women with and without 55 vaccination, respectively; P=0.0272). Seventy-two (83%) of the 87 women took 56 antiviral agents for the treatment of influenza and two (2.3%) required hospitalization. 57These results suggested that pregnant Japanese women had a high level of concern 58 regarding seasonal influenza. However, campaigns targeting young pregnant Japanese 59 women as well as multiparous women for vaccination are needed to further reduce the 60 incidence of influenza among pregnant Japanese women. 61 62

Objectives: This study was performed to determine whether multiparous pregnant women are prone to influenza. Methods:A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected.Results: Seventy-eight percent (n = 5,197) of women given questionnaires responded.Of these, 2,661 (51%) and 364 (7.0%) women reported having been vaccinated and having contracted influenza, respectively. Multiparous women had a higher risk of compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8% (100/2,089), 7.5%, (121/1,618), 9.0%, (71/785), and 10.4% (58/557) for women with 1, 2, 3, and ≥ 4 cohabitants, respectively. Conclusions:Family size is a risk factor for influenza infection in pregnancy.