Tatsuro Kishida

Massive Intravenous Immunoglobulin Treatment in Women with Four or More Recurrent Spontaneous Abortions of Unexplained Etiology: Down-Regulation of NK Cell Activity and Subsets

PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets.
 METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies.
 RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre‐infusion NK cell activity (mean±SD, 40.9±17.0%) at 4.4±0.5 weeks of gestation (GW) decreased to 15.0±7.9% at post‐infusion status (5.4±0.5 GW). Pre‐infusion percentages of CD56+CD16− cells (3.5±2.1%) and CD56+CD16− cells (16.8±8.8%) decreased to 3.0±2.2% and 11.1±6.9%, respectively, after MIVIg treatment.
 CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery.

The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.

Management of Pregnancy with Congenital Antithrombin III Deficiency: Two Case Reports and a Review of the Literature

Women with antithrombin (AT) III deficiency are prone to pregnancy‐associated venous thromboembolism. We report 2 cases with genetically confirmed ATIII deficiency, one with a mutation in exon 3A and the other with an exon 4 deletion, in whom the pregnancies were successfully managed with prophylactic therapies for thrombosis. A 35‐year‐old pregnant woman was treated with intravenous infusions of ATIII concentrate alone, and the other 22‐year‐old pregnant woman was mainly treated with subcutaneous injections of heparin and oral low‐dose aspirin therapy. Both pregnancies resulted in vaginal deliveries of healthy neonates. The literature concerning prophylactic therapies for thrombosis in ATIII deficiency‐complicated pregnancy is reviewed, and the clinical problems, including the adverse effects of the therapies, are discussed.

Changes in uterine size after vaginal delivery and cesarean section determined by vaginal sonography in the puerperium.

Abstract There have been few reports on postpartum changes in the uterus during the three months after delivery. The aim of this study was to evaluate uterine morphological changes in women after vaginal delivery (n=262–351) and in women after cesarean section (n=64–82) and to evaluate the relation between breast-feeding and parity, and uterine involution at 1 and 3 months postpartum measured by vaginal ultrasonography. There were no significant differences in parity between the vaginal delivery group and the cesarean section group. The length of the uterus at one month (7.93±1.16 cm, mean±SD) and, three months (7.03± 1.19 cm) and the width of the uterus at three months (3.83±0.94 cm) after delivery in the cesarean section group were greater than in the transvaginal group (7.64±1.03 cm, 6.65±0.99 cm, 3.57±0.62 cm, respectively). Increasing maternal parity was associated slightly with larger uterine size at one month post partum. The length of the uterus of women with a breast-feeding rate of 80% or more per day was 6.35±0.85 cm, and shorter than in women with a rate of 20% or less 7.03±1.04 cm, at three months after delivery. The width of the uterine body of women with a breast-feeding rate of 80% or more per day was 3.32±0.45 cm, and shorter than in women with a rate of 20% or less 3.87±0.66 cm, at 3 months after delivery. Stepwise regression and multiple regression analysis among parity, the history of cesarean section, the breast-feeding rate at one and three months after the delivery, and the restoration of the menses at three months after the delivery showed that the uterine size at one month after the delivery was related to the cesarean section and that the uterine size at three months after delivery was mostly related to the rate of breast-feeding. These results indicated that uterine involution was related to delivery mode at one and three months postpartum, feeding mode at three months postpartum, the menses restoration, and parity. The rate of breast-feeding was mostly related to the uterine size at three months postpartum.

Diagnosis of premature rupture of the membranes in preterm patients, using an improved AFP kit: comparison with ROM-check and/or nitrazine test

OBJECTIVE We developed a new kit for detecting AFP in leaked amniotic fluid. Later, we developed an improved AFP kit utilizing the same anti alpha-fetoprotein (AFP) monoclonal antibody. In this study, we evaluate the clinical usefulness of this improved kit in the diagnosis of preterm premature rupture of membranes (PROM). METHODS We compared this improved AFP test with the ROM-check and/or the nitrazine tests in 46 preterm patients. RESULTS The ROM-check and nitrazine tests showed a diagnostic accuracy of 89.1 and 87.0%, respectively, compared with 95.7% with the improved AFP test. The sensitivity of the improved AFP test on cervical samples was significantly higher than that of the nitrazine test on vaginal samples (P < 0.05). The reaction time with the improved AFP kit test is 90 s. CONCLUSION This study has confirmed a great clinical utility of the improved AFP test kit as a method of PROM diagnosis.

Recent trends in the prevalence of Down syndrome in Japan, 1980–1997

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.

Factor XII Deficiency in Women with Recurrent Miscarriage

Congenital thrombophilia is known to cause significant maternal complications, and possibly has an adverse effect on normal fetal development. The aim of this study was to assess the prevalence of factor XII (FXII) deficiency in women with a history of recurrent miscarriage. Two hundred and forty-one consecutive Japanese women with a history of two or more recurrent miscarriages were prospectively assessed for their etiology by conventional screening methods. Seven women were found to have reduced FXII activity (19.2–46.1%) and prolonged activated partial thromboplastin time (33.3–51.3 s). Of these 7 women, 6 had experienced early pregnancy losses, while 1 woman had experienced repeated mid-trimester fetal losses with coincidental gestational thrombocytopenia. In 241 women with a history of recurrent miscarriage, the prevalence of FXII deficiency was 2.9%.

Hypocomplementemia Correlates with Intrauterine Growth Retardation in Systemic Lupus Erythematosus

PROBLEM: The aim of this study was to elucidate fetomaternal risks in systemic lupus erythematosus (SLE)‐complicated pregnancy.

Diagnosis of preterm premature rupture of the membranes using a newly developed AFP monoclonal antibody test kit

OBJECTIVE We have developed a new anti-AFP monoclonal antibody kit which is easier to use than other examination methods for detecting AFP in the leaked amniotic fluid. In this study, we investigate the clinical value of this test in the diagnosis of preterm premature rupture of the membranes (PROM). METHODS We employed 103 patients of less than 37 weeks of gestational age for this preliminary study. We compared the clinical usefulness of this new AFP test with that of the nitrazine test and measured the concentration of AFP in vaginal fluid or cervical secretion by EIA. RESULTS The nitrazine test showed a correct diagnostic rate of 62.1%, in contrast the AFP test kit had a 98.0% rate (P < 0.001). The reaction time using the kit is 3 min. CONCLUSION The AFP test is a simple and non-invasive test which can be easily carried out repeatedly as a bedside examination. This study has confirmed the high clinical efficacy of the newly developed AFP test kit as a method of PROM diagnosis.

Alpha-fetoprotein microheterogeneity: a potential biochemical marker for Down’s syndrome

Our purpose was to examine the utility of analyzing alpha-fetoprotein (AFP) microheterogeneity assessed by lectin affinity in Downs syndrome (DS) screening. Maternal sera and amniotic fluids were collected from 18 women who were carrying DS fetuses and 70 unaffected pregnancies around 16 weeks of gestation. The percentages of AFP which reacted with Lens culinaris agglutinin (AFP-L2,3) were determined by lectin affinity electrophoresis. AFP-L2,3 levels were significantly increased (P<0.0001) in both maternal serum and amniotic fluid from DS-affected versus unaffected pregnancies. The fractional areas under the receiver operating characteristic curves were 0.835 and 0.700 (P=0.106) for AFP-L3 and AFP MoM (multiples of the median) in maternal serum. No correlation was found between AFP-L3 and AFP MoM in maternal serum (r=0.006). Our data suggest that the measurement of AFP-L3 in maternal serum is a potential biochemical marker for DS.