Two pregnant women with immune-mediated thrombotic thrombocytopenic purpura: A case report.

Thrombotic thrombocytopenic purpura (TTP) during pregnancy is life-threatening. We encountered two pregnant women with immune-mediated TTP (iTTP). A 40-year-old primigravida woman was referred at 19 gestational weeks (GWs) owing to iTTP. She received plasma exchange (PE) and steroid therapies and delivered a live infant at 27 GWs by cesarean delivery. A 29-year-old primigravida woman was referred owing to intrauterine fetal death and thrombocytopenia at 20 GWs. She was diagnosed with iTTP and received PE therapy. She required additional PE and steroid therapies owing to relapse. Before her second pregnancy, she received prednisolone and hydroxychloroquine according to the therapy for systemic lupus erythematosus (SLE). She had induced labor at 37 GWs owing to decrease plasma level of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity. Close monitoring of plasma ADAMTS13 activity level and treatments for underlying SLE may prevent iTTP relapse and lead to a good prognosis.

Rapid reduction of adenomyosis coexisting with leiomyoma volume during treatment with Relugolix.

OBJECTIVE: This study elucidated the efficacy of Relugolix (REL) on the reduction of uterine volume and clinical symptoms for the treatment of adenomyosis. METHODS: We conducted a retrospective cohort study of patients who received REL (40 mg for about 20 weeks) and who underwent a hysterectomy for adenomyosis or fibroids. We divided patients into two groups: adenomyosis coexisting with fibroids (Group A) and fibroids only (Group B); the groups were determined by a postoperative pathological examination. The primary end points were the percent reduction in uterine volume, adenomyotic lesion, and the largest fibroid volume at week 16. The secondary end points were the rate of amenorrhea, pelvic pain, and anemia at week 12. RESULTS: A total of 56 patients participated in the current study: 20 in Group A and 36 in Group B. Regarding the largest fibroid volume, there was no significant difference between the two groups. Uterine volume after REL treatment was significantly decreased in Group A (43%), as compared to Group B (27%) (p = .00972), In Group A, adenomyotic lesion was decreased by 61%. Irrespective of the group, adenomyosis showed a significant reduction compared to uterine fibroids (p < .001). There was no statistically significant difference in the mitigation of symptoms (amenorrhea, pelvic pain, and anemia) between the two groups. CONCLUSIONS: REL is more effective in reducing adenomyotic lesion than uterine fibroids and in relieving symptoms (amenorrhea, pelvic pain, and anemia). It can be expected that REL will also be used as a preoperative treatment for adenomyosis.

Uterine rupture in intramural ectopic pregnancy: A case report.

Intramural pregnancy is a rare form of ectopic pregnancy. It is defined by a gestation within the uterine wall, completely surrounded by myometrium and separated from the uterine cavity and the fallopian tube. We report a rare case of intramural ectopic pregnancy. If a patient has a history of intrauterine surgery or myomectomy, the possibility of intramural pregnancy, although rare, should not be ruled out.

Uterine endometrium microbiota and pregnancy outcome in women with recurrent pregnancy loss.

To evaluate whether uterine endometrium microbiota (UEM) is associated with pregnancy outcome in women with recurrent pregnancy loss (RPL). This prospective cohort study enrolled 67 women who had a history of two or more RPL. They underwent endometrial biopsy at midluteal phase for UEM analyses with 16 S ribosomal RNA sequence. Four women with inappropriate specimens were excluded. Therefore, 63 women were followed up for more than 14 months; 44 became pregnant, while 19 did not. Thirty of the 44 pregnancies ended in live births, including 24 full-term and six preterm deliveries. Three pregnancies were ongoing, and the remaining 11 ended in miscarriages, including eight miscarriages with normal chromosome karyotype and three miscarriages with abnormal karyotype. Clinical characteristics and UEM associated with risks for non-pregnancy, miscarriage with normal karyotype, and preterm delivery in subsequent pregnancies were evaluated. Multivariable logistic regression analyses revealed that the number of previous miscarriages (odds ratio 42.2, 95 % CI 1.19-1490, p = 0.040) and relative dominance rate of Ureaplasma species (odds ratio 24.2, 95 % CI 1.55-377, p = 0.023) in UEM were independent risk factors for subsequent miscarriage with normal karyotype; and relative dominance rate of Ureaplasma species in UEM was a risk factor for preterm delivery (odds ratio 109, 95 % CI 1.07-1110, p = 0.047). This study demonstrated for the first time that increases in Ureaplasma species in UEM of women with RPL were risks of miscarriage with normal chromosome karyotype and preterm delivery in subsequent pregnancies. UEM analysis for women with RPL before pregnancy may identify microbiota associated with adverse pregnancy outcomes.

Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies.

This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1-6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6-11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8-27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1-6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

Vaginal microbiota associated with preterm delivery.

OBJECTIVES: The aim of this study was to evaluate whether vaginal microbiota is associated with threatened premature labor and preterm delivery. METHODS: This prospective study enrolled 64 pregnant women who underwent vaginal microbiome analyses using 16S ribosomal RNA sequence method with informed consent. The 64 pregnant women consisted of 47 women with threatened premature labor and 17 women with other diseases (non-threatened premature labor) in a case-control study. In a cohort study of threatened premature labor group, 23 pregnancies ended in preterm delivery, and the remaining 24 ended in full-term deliveries. The differences in vaginal microbiota between threatened and non-threatened premature labor groups, and between preterm and full-term delivery groups were evaluated. RESULTS: There were no differences in vaginal microbiota between threatened and non-threatened premature labor groups. There were significant differences between preterm and full-term delivery groups in Nugent score [median 3 (range 0-7) vs. 0 (0-4), p < 0.05], percentage of Lactobacillus species [88% (0-100) vs. 99.8% (55.4-100), p < 0.01], the number of bacterial species [3 (1-13) vs. 2 (1-5), p < 0.05], and positivity of Ureaplasma species (61% vs. 17%, p < 0.01). Univariate and multivariable analyses revealed that positivity of Ureaplasma species was a predictive factor of preterm delivery in women with threatened premature labor (OR, 6.5; 95% CI, 1.3-33.0; p < 0.05). CONCLUSION: Increased positivity of Ureaplasma species in vaginal microbiota was a risk factor for preterm delivery among women with threatened premature labor. Vaginal microbiome analysis may identify high risk pregnancies for preterm delivery.

The ß 2 -Glycoprotein I/HLA-DR Complex As a Major Autoantibody Target in Obstetric Antiphospholipid Syndrome.

OBJECTIVE: The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, ß2 -glycoprotein I (ß2 GPI) complexed with HLA class II molecules (ß2 GPI/HLA-DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the ß2 GPI/HLA II complex as a potential risk factor for RPL in women. METHODS: Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti-ß2 GPI antibodies, and lupus anticoagulant as well as anti-ß2 GPI/HLA-DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross-sectional study, women with RPL and their partners underwent HLA-DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti-ß2 GPI/HLA-DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential). RESULTS: Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti-ß2 GPI/HLA-DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti-ß2 GPI/HLA-DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti-ß2 GPI/HLA-DR antibodies. CONCLUSION: The anti-ß2 GPI/HLA-DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.

A cohort study of the universal neonatal urine screening for congenital cytomegalovirus infection.

OBJECTIVES: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae. METHODS: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age. RESULTS: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment. CONCLUSIONS: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries.

Case report of eight pregnant women with syphilis.

Congenital syphilis may lead to severe sequelae in affected infants. The prevalence of syphilis in women of childbearing age has increased worldwide. From 2015 to 2018, we encountered eight pregnant women with syphilis including six with late latent and two with early latent syphilis. Seven pregnant women with syphilis received antibiotic therapies of oral amoxicillin, intravenous penicillin G, or the both. The syphilotherapies in four cases were considered effective, because rapid plasma reagin titers decreased. None of the seven pregnant women who received syphilotherapies had congenital syphilis. The remaining one woman who did not undergo a maternity checkup or syphilotherapy delivered a stillbirth with congenital syphilis at 29 gestational weeks.

Clinical factors associated with pregnancy outcome in women with recurrent pregnancy loss.

The aim of this prospective cohort study was to evaluate clinical factors associated with pregnancy outcomes in women with recurrent pregnancy loss (RPL). Women with a history of two or more pregnancy losses underwent workups for clinical factors of RPL and their pregnancies were followed-up with informed consent. Two hundred eleven (81.5%) of 259 women with RPL became pregnant. The multivariable analyses demonstrated that age (p < .01, OR 0.9, 95%CI 0.97-0.83), uterine abnormality (p < .05, OR 0.3, 95%CI 0.11-0.8), and protein C (PC) deficiency (p < .01, OR 0.14, 95%CI 0.03-0.6) were independent factors for becoming pregnancy in women with RPL. The number of previous pregnancy loss (p < .01, OR 0.57, 95%CI 0.43-0.75) and natural killer (NK) cell activity ≥33% (p < .01, OR 0.31, 95%CI 0.13-0.73) were independent factors for live birth in the subsequent pregnancy. Advanced age, the presence of uterine abnormality, and PC deficiency were risk factors for reduced pregnancy rate in women with RPL. Increased number of previous pregnancy loss and high NK cell activity were risk factors for miscarriage in the subsequent pregnancy. These results involve important information and are helpful for clinical practitioners.

Hepatitis B virus infection: Prevention of mother-to-child transmission and exacerbation during pregnancy.

The aims of this study were to assess the effect of maternal screening for hepatitis B (HB) virus and a perinatal prevention program of mother-to-child transmission, and to identify clinical characteristics and findings associated with HB exacerbation during pregnancy. This prospective cohort study enrolled 3796 pregnant women and their neonates with informed consent. Pregnant women underwent maternal universal screening for HBs antigen (Ag) in the first trimester. If HBs Ag was positive, serum levels of HBe Ag, alanine transaminase (AST), aspartate aminotransferase (ALT), and HB virus (HBV) DNA were measured. All neonates delivered from HBs Ag-positive women were given HB immune globulin and HB vaccine based on the guidelines of the perinatal prevention program. Of the 3796 pregnant women, 40 (1.05%) tested positive for HBs Ag. Three (7.5%) of the 40 HBs Ag-positive women experienced exacerbation of HBV infection during pregnancy. Serum levels of AST (median 776 vs. 22 mIU/ml, p < 0.01), ALT (median 325 vs. 15 mIU/ml, p < 0.01), and HBV-DNA (median 9.1 vs. 5.4 log copies/ml, p < 0.05), and frequencies of HBe Ag-positive (100% vs. 29.7%, p < 0.05) and symptoms of itching or general fatigue (66.7% vs. 0%, p < 0.01) in three women with exacerbation of HBV infection were significantly higher than those in 37 women without exacerbation. There was no case of mother-to-child transmission, suggesting the perinatal HBV prevention program was effective. Levels of HBe Ag, liver enzymes, and HBV-DNA as well as symptoms of itching and general fatigue should be carefully monitored for HBs Ag-positive women during pregnancy and the postpartum period.

Resonant terahertz transmissions through metal hole array on silicon substrate.

We have observed resonant terahertz transmission peaks in samples comprising perforated periodic hole array in a metal film, covered with a high dielectric substrate. These resonant transmissions arise from the interplay between waveguide modes in dielectric substrate and the periodic hole array in the metal film. Finite difference time domain (FDTD) simulations show good agreement with the data, in support of the proposed mechanism. Inducing additional resonant transmissions using guided modes can lead to the ease in tuning the transmission peak frequencies that are potentially useful to terahertz (THz) bio-sensing.