Longitudinal Correlations between Molecular Compositions of Stratum Corneum and Breast Milk Factors during Infancy: A Prospective Birth Cohort Study.

Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-ß1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers' breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities.

High doses of intravenous immunoglobulin stimulate regulatory T cell and suppress natural killer cell in women with recurrent pregnancy loss.

The aim was to evaluate whether natural killer (NK) cells and regulatory T (Treg) cells were involved in mechanisms underlying beneficial effects of a high dose of intravenous immunoglobulin (IVIG) on recurrent pregnancy losses (RPL) of unexplained etiology. In a double-blind, randomized, placebo-controlled trial of IVIG (400 mg/kg, for 5 days in 4-6 weeks of gestation) in women with RPL, blood samples were collected pre-infusion, one week after infusion (1 w), and eight weeks of gestation/when miscarried (8 w). Levels of NK and Treg cells in peripheral blood were compared between women with IVIG (n = 50) and placebo (n = 49), and between women with IVIG who gave live birth (n = 29) and those who had miscarriage with normal chromosome (n = 12). Effector Treg cell percentages in IVIG group at 1 w (mean 1.43 % vs. 1.03 %) and at 8 w (1.91 % vs. 1.18 %) were higher than those in placebo group (p < 0.01). Total Treg cell percentages in IVIG group at 1 w (4.75 % vs. 4.08 %) and at 8 w (5.55 % vs. 4.47 %) were higher than those in placebo group (p < 0.05). In women with live birth, total Treg cell percentages increased at 8 w (5.52 %, p < 0.001) compared with pre-infusion (4.54 %) and 1 w (4.47 %), while NK cell activity decreased at 1 w (20.18 %, p < 0.001) compared with pre-infusion (26.59 %). IVIG increased Treg cell percentages and suppressed NK cell activity very early in pregnancy, and these were associated with subsequent live birth. Stimulation of Treg cells and suppression of NK cell activity very early in pregnancy may be a mechanism of pharmacological effects of high dose IVIG.

Association between Maternal Characteristics and Immune Factors TGF-ß1, TGF-ß2, and IgA in Colostrum: An Exploratory Study in Japan.

Colostrum is the first food for newborns and it contains various crucial immune factors. The concentrations of immune factors in breast milk may change depending on maternal characteristics such as body mass index, collection day, and age at first pregnancy. In this exploratory study, we investigated the association between TGF-ß1, TGF-ß2, and IgA in colostrum and rarely studied factors that affect breast milk components, including the use of labor-inducing medication, colostrum secretion, sex of newborns, breast or nipple problems, and nipple care. Breast milk samples were collected from 42 mothers and analyzed for TGF-ß1, TGF-ß2, and IgA. The results suggest that parity and mode of delivery may be correlated with the concentrations of immune factors in colostrum. However, we found no association between the immune factors in colostrum and the use of labor-inducing medications, colostrum secretion, sex of newborns, breast or nipple problems, and nipple care. These findings have some implications for further analysis of the effects of immune factors in breast milk on the prognosis of allergies in children.

Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: A double-blind, randomised, placebo-controlled trial.

Background: There is no effective treatment for women with unexplained recurrent pregnancy loss (RPL). We aimed to investigate whether treatment with a high dose of intravenous immunoglobulin (IVIG) in early pregnancy can improve pregnancy outcomes in women with unexplained RPL. Methods: In a double-blind, randomised, placebo-controlled trial, women with primary RPL of unexplained aetiology received 400 mg/kg of IVIG daily or placebo for five consecutive days starting at 4-6 weeks of gestation. They had experienced four or more miscarriages except biochemical pregnancy loss and at least one miscarriage of normal chromosome karyotype. The primary outcome was ongoing pregnancy rate at 22 weeks of gestation, and the live birth rate was the secondary outcome. We analysed all women receiving the study drug (intention-to-treat, ITT) and women except those who miscarried due to fetal chromosome abnormality (modified-ITT). This study is registered with ClinicalTrials.gov number, NCT02184741. Findings: From June 3, 2014 to Jan 29, 2020, 102 women were randomly assigned to receive IVIG (n = 53) or placebo (n = 49). Three women were excluded; therefore 50 women received IVIG and 49 women received placebo in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (31/50 [62·0%] vs. 17/49 [34·7%]; odds ratio [OR] 3·07, 95% CI 1·35-6·97; p = 0·009) and the live birth rate (29/50 [58·0%] vs. 17/49 [34·7%]; OR 2·60, 95% CI 1·15-5·86; p = 0·03) in the IVIG group were higher than those in the placebo group in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (OR 6·27, 95% CI 2·21-17·78; p < 0·001) and the live birth rate (OR 4·85, 95% CI 1·74-13·49; p = 0·003) significantly increased in women who received IVIG at 4-5 weeks of gestation as compared with placebo, but these increases were not evident in women who received IVIG at 6 weeks of gestation. Four newborns in the IVIG group and none in the placebo group had congenital anomalies (p = 0·28). Interpretation: A high dose of IVIG in very early pregnancy improved pregnancy outcome in women with four or more RPLs of unexplained aetiology. Funding: The Japan Blood Products Organization.

Spontaneously conceived heterotopic pregnancy with abdominal pregnancy implanted on the vesicouterine pouch: A case report and literature review.

We report the case of a 36-year-old woman with spontaneously conceived heterotopic pregnancy with abdominal pregnancy. She visited the hospital at 5 weeks and 4 days of gestation and transvaginal ultrasonography revealed a normal intrauterine pregnancy. Two days later, she was urgently transported to the hospital due to extreme abdominal pain. Emergent laparotomy was performed to investigate the cause of massive intraperitoneal bleeding, which was confirmed to have been due to an abdominal pregnancy that implanted on the vesicouterine pouch. The hematic mass, including chorionic villi, was successfully removed from the peritoneum. The subsequent course of the intrauterine pregnancy was uneventful and a healthy baby was born at term. To the best of our knowledge, this is an extremely rare case report of a spontaneously conceived heterotopic abdominal pregnancy, in which the intrauterine pregnancy showed a successful outcome despite the collapse of the abdominal pregnancy at a very early stage.

Maternal age, history of miscarriage, and embryonic/fetal size are associated with cytogenetic results of spontaneous early miscarriages.

PURPOSE: To clarify the associations of the maternal age, history of miscarriage, and embryonic/fetal size at miscarriage with the frequencies and profiles of cytogenetic abnormalities detected in spontaneous early miscarriages. METHODS: Miscarriages before 12 weeks of gestation, whose karyotypes were evaluated by G-banding between May 1, 2005, and May 31, 2017, were included in this study. The relationships between their karyotypes and clinical findings were assessed using trend or chi-square/Fisher's exact tests and multivariate logistic analyses. RESULTS: Three hundred of 364 miscarriage specimens (82.4%) had abnormal karyotypes. An older maternal age was significantly associated with the frequency of abnormal karyotype (ptrend < 0.001), particularly autosomal non-viable and viable trisomies (ptrend 0.001 and 0.025, respectively). Women with ≥ 2 previous miscarriages had a significantly lower possibility of miscarriages with abnormal karyotype than women with < 2 previous miscarriages (adjusted odds ratio [aOR], 0.48; 95% confidence interval [95% CI], 0.27-0.85). Although viable trisomy was observed more frequently in proportion to the increase in embryonic/fetal size at miscarriage (ptrend < 0.001), non-viable trisomy was observed more frequently in miscarriages with an embryonic/fetal size < 10 mm (aOR, 2.41; 95% CI, 1.27-4.58), but less frequently in miscarriages with an embryonic/fetal size ≥ 20 mm (aOR, 0.01; 95% CI, 0.00-0.07) than in anembryonic miscarriages. CONCLUSIONS: The maternal age, history of miscarriage, and embryonic/fetal size at miscarriage may be independently associated with the frequencies or profiles of cytogenetic abnormalities in early miscarriages.

Clinical feature and anti-phospholipid antibody profiles of pregnancy failure in young women with antiphospholipid antibody syndrome treated with conventional therapy.

OBJECTIVE: To elucidate clinical feature and anti-phospholipid antibody (aPL) profiles, including lupus anticoagulant (LA), anti-cardiolipin (CL) antibodies and anti-phosphatidylserine/prothrombin (PS/PT) antibodies, of pregnancy failure in patients with antiphospholipid antibody syndrome (APS) already treated with conventional therapy. MATERIALS AND METHODS: Thirty-four women with a history of pregnancy who were diagnosed with APS between 2008 and 2016 were included in the study. We defined the successful pregnancy group as women who gave birth to a healthy baby over 1500 g after 34 weeks of pregnancy under conventional treatment (heparin and/or low-dose aspirin). The unsuccessful pregnancy group was defined as women whose pregnancy outcomes did not meet the aforementioned criteria despite the conventional therapy. The clinical features and aPL profiles were compared between the two groups. RESULTS: Fifteen women were classified into the unsuccessful pregnancy group; seven women were in the successful pregnancy group. Having history of both thrombosis and pregnancy morbidity and LA positivity were significantly more prevalent in the unsuccessful pregnancy group than in the successful pregnancy group (p <.05, respectively). In contrast, single positivity of anti-CL antibody was negatively associated with APS-associated pregnancy morbidity under the conventional treatment (p <.01). The proportion of anti-PS/PT IgG-positive patients was significantly higher in the unsuccessful pregnancy group (p = .02, OR 18.7, 95% CI 1.50, 232.29) with high concordance rate with LA (97% consistence). CONCLUSION: History of both thrombosis and pregnancy morbidity and the positivity of LA and/or anti-PS/PT-IgG, not but anti-CL-antibodies were correlated with APS-associated pregnancy morbidity refractory to conventional treatment. Clinical feature and aPL profiles might help us to make risk assessment for adverse pregnancy outcomes in patients with APS.

[STD and mother to child transmission].

Sexually transmitted disease (STD) is the disease that is spread by sexual contact, including chlamydial infection, gonorrhea, genital warts, herpes, syphilis, and infection with human immunodeficiency virus (HIV). STDs are the most common contagious diseases among young people in Japan. People with an STD may not have any symptoms and may not know they have it. Even if there are no symptoms, their health can be affected. Advanced STDs can cause severe damage to body. Often, symptoms occur only if the disease becomes more advanced. Untreated chlamydia or gonorrhea can cause pelvic inflammatory disease (PID) in women. PID is an infection of the uterus, fallopian tubes, and ovaries. It can cause infertility and ectopic pregnancy. If patient who has STD is pregnant, it can cause abortion, premature delivery and intrauterine infection.

[Anti-phosphatidylserine-prothrombin antibody in patients with recurrent abortion and preeclampsia].

AIM: The aim of the study was to describe the frequency of anti-phosphatidylserine-prothrombin antibody(aPS/PTAb) in patients with recurrent abortion and preeclampsia, and to study the relationship between the presence of aPS/PTAb and clinical finding. Eighty six cases of recurrent abortion and 82 cases of preeclampsia were studied. A aPS/PTAb was measured by an enzyme linked immunosorbent assay (ELISA). RESULTS: In patients with recurrent abortion, 3 out of 86 cases(3.4%) were positive in IgG antibody measurements and 5 out of 86(5.8%) were positive in IgM antibody measurements. In patients with preeclampsia, 2 out of 82 cases(2.5%) were positive in IgG antibody measurements and 13 out of 82(16%) were positive in IgM antibody measurements. The positive rates of aPS/PTAb in severe hypertension-positive cases is greater than in hypertension-negative cases(p=0.045). The positive rates of aPS/PTAb is higher tendency with in severe type than in mild type(p=0.117). The positive rates of aPS/PTAb is higher tendency with proteinuria and/or hypertension than without proteinuria(p=0.098) or hypertension(p=0.096). CONCLUSION: We found that aPS/PTAb appears in some cases of patients with recurrent abortion and preeclampsia. Our data suggest that aPS/PTAb might be a risk factor in patients with recurrent abortion, and may relate to clinical finding in preeclampsia.

[Practical use of taxol-based chemotherapy for poor compliance gynecologic cancers in Japanese woman].

Today, the first line of chemotherapy for ovarian cancer is Taxol-carboplatin (T-J), but there are some problems including severe bone marrow depression and severe neuropathy, so-called poor compliance cases. By changing the method of administering Taxol, the key drug in chemotherapy for ovarian cancer, it is possible to make compliance more better, continue therapies and look after patients' PS and QOL. We have considered weekly Taxol based chemotherapy for early stage recurrence cases and poor compliance cases; For example, weekly Taxol in combination with carboplatin (monthly) for poor compliance cases, severe bone marrow depression and the like, and Taxol by drip infusion for 24 hours in cases of peripheral nerve disorder (severe neuropathy). Especially, weekly Taxol combination with carboplatin (monthly), with takes advantage of the repeated administration of Taxol and one time administration of carboplatin, is a highly beneficial therapy for ovarian cancer. With this protocol we can reduce side effects and continue long-term administration on an outpatient basis.