The efficacy of adjunct tacrolimus treatment in pregnancy outcomes in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) involves multiple organ systems and primarily affects women during their reproductive years. Pregnancy in a woman with SLE may lead to higher rates of disease flares. Little is known regarding which medications are safe to maintain remission and/or treat flares throughout such pregnancies. Here we retrospectively analyzed the efficacy of tacrolimus (TAC) in the pregnancy outcomes of SLE patients. We studied the 54 deliveries of 40 SLE patients over an eight-year period from 2008 to 2016. We used analyses of covariance with adjustments for the propensity score and inverse probability of treatment weights to compare the patient backgrounds between the TAC users and non-TAC users. TAC was administered to the patient in 15 of the 54 (27.8%) pregnancies, and these patients had a significantly higher dose of prednisolone, hypocomplementemia, lower estimated glomerular filtration rate, past history of lupus nephritis, and complication with antiphospholipid syndrome. In the adjusted background of the TAC deliveries, the risks of decreased fetal body weight, low birth weight infant, non-reassuring fetal status (NRFS), and preterm birth were not increased compared to the non-TAC deliveries. Thrombocytopenia and hypertension during the pregnancy were extracted as independent predictive risk factors for decreased fetal body weight and NRFS, respectively. We had anticipated that the maternal and fetal outcomes in the TAC-use deliveries would be poor before the analysis; however, the TAC-use group showed no significant difference in risks contributing to outcomes compared to the non-TAC group, suggesting that adjunct TAC treatment corrected various risk factors during the lupus pregnancies.

S100P is a useful marker for differentiation of ovarian mucinous tumors.

The S100P protein stimulates cell proliferation and survival, thereby contributing to tumor progression. The purpose of this study was to evaluate S100P expression in the three subtypes of mucinous cystic tumors, cystadenomas, borderline tumors, and adenocarcinomas. The authors examined nuclear S100P expression in 60 mucinous ovarian tumor specimens, including 24 specimens of mucinous cystadenoma, 15 of borderline tumors, and 21 of adenocarcinomas. Immunohistochemistry revealed S100P expression followed one of three patterns: (1) Expressed in most nuclei of mucinous epithelial cells, (2) sporadic (spotted or patchy) expression, or (3) absent or rarely expressed in the nuclei of mucinous epithelial cells. Most adenomas showed the first expression pattern, and borderline tumors often showed a patchy expression pattern. Adenocarcinomas generally demonstrated absence of S100P expression. These data suggest that S100P is a useful histological marker to differentiate between benign, borderline, and malignant mucinous tumors of the ovary.

Midpregnancy serum C-peptide concentration and subsequent pregnancy-induced hypertension.

OBJECTIVE: To test the hypothesis that elevated midpregnancy serum insulin (IRI) and C-peptide (CP) concentrations are associated with later development of pregnancy-induced hypertension (PIH), independent of prepregnancy obesity and midpregnancy blood pressure. RESEARCH DESIGN AND METHODS: In this prospective study, a cohort of normotensive women, ages > or = years performed a 50-g glucose challenge test at 24-30 weeks' gestational age. Blood samples were collected after an overnight fast and 1 h after glucose ingestion. Serum IRI and CP concentrations were measured in each sample. Maternal height, blood pressure and proteinuria were measured at the time of glucose challenge testing and after 36 weeks' gestational age. RESULTS: Of 320 subjects enrolled 44 women (13.8%) had subsequent PIH. Crude odds ratios (ORs) for devevelopment of PIH associated with each 1 U rise in log fasting IRI, log lasting CP. and glucosed-induced increase in CP (expressed as log [postprandial CP/fasting CP]) were 2.0 (95% CI 1.3-3.3), 1.8 (CI 1.2-2.7), and 2.3 (CI 1.1-4.9) respectively. After controlling for prepregnancy BMI, gestational age, and midpregnancy mean arterial pressure, adjusted ORs corresponding to log fastig IRI and CP for the development of PIH were 1.3 (95% CI 0.7-2.3) and 1.7 (CI 1.1-2.7) respectively, and, afterq adjustment for fasting CP, the adjusted OR of the glucose-induced rise in log CP was 3.7 (CI 1.5-9.3). CONCLUSIONS: Mid-pregnancy tasting and postoral glucose CP levels are associated with subsequent development of PIH, independent of maternal obesity and midpregnancy baseline blood pressure. These findings many reflect an amplified beta3-cell response to glycemic stimulus, similar to that found in states of insulin resistance, that appears to be independently associated with PIH.

Hourly fetal urine production rate in the fasting and the postprandial state of normal and diabetic pregnant women.

OBJECTIVE: To examine whether maternal meal ingestion affects fetal urine production in normal and diabetic pregnancies and whether fetal urine production is increased in diabetic pregnancy. METHODS: The hourly fetal urine production rate was measured before and after breakfast in 17 fetuses of diabetic mothers and 14 of women with normal glucose tolerance. The rate was calculated by taking serial measurements of fetal bladder volume at 2-3-minute intervals by ultrasonography. RESULTS: In the control group, the hourly fetal urine production rate was significantly greater during the 2 hours after breakfast than that in the fasting state (P < .0005). In the diabetic group, the rate also tended to increase after breakfast (P = .07). In the postprandial state, the hourly fetal urine production rate was not significantly different between the groups. However, in the fasting state, it was significantly greater in the diabetic group than in the control group (P < .03). CONCLUSIONS: Maternal meal ingestion should increase fetal urine production. The increased fetal urine production in the fasting state in diabetics is assumed to be one cause of hydramnios.

Change in fetal urine production rate in growth-restricted fetuses after maternal meal ingestion.

OBJECTIVE: To determine if fetal urine production is affected by maternal meal ingestion in growth-restricted fetuses. METHODS: We studied 25 normal-growth fetuses in uncomplicated pregnancies and 15 growth-restricted fetuses, all after 30 weeks' gestation. Serial fetal bladder volume measurements were obtained at 2-3 minute intervals with ultrasonography 2 hours before and 2 hours after maternal breakfast. The hourly fetal urine production rate in each maternal state was calculated from the bladder volume measurements. The amniotic fluid index (AFI) and the pulsatility index of both umbilical and fetal middle cerebral arteries were also measured. RESULTS: Two of the 15 growth-restricted fetuses were excluded from analysis, one because it was anomalous and the other because it was not small for gestational age at birth. In the normal-growth fetuses, the hourly fetal urine production rate increased significantly after maternal breakfast (mean +/- standard deviation 30.2 +/- 11.7 versus 41.1 +/- 14.6 mL/hour, P < .001). In contrast, in the growth-restricted fetuses, the rate did not change after maternal breakfast (24.6 +/- 6.2 versus 24.9 +/- 5.7 mL/hour). Although the urine production rate before breakfast did not differ between groups, 2 hours after maternal breakfast it was significantly lower in the growth-restricted fetuses than in the control group (normal-growth) (P < .001). The AFI also was significantly lower in the growth-restricted fetuses than in the control group (15.0 +/- 3.5 versus 18.6 +/- 5.0 cm, P < .04). There were no significant differences in the pulsed Doppler studies. CONCLUSION: In contrast to normal-growth fetuses, maternal meal ingestion for growth-restricted fetuses does not increase fetal urine production. Decreased fetal urine production in the maternal fed state may lead to decreased amniotic fluid volume in growth-restricted fetuses without obvious hypoxia.

Effect of maternal meal ingestion on fetal renal artery resistance.

OBJECTIVE: To examine whether maternal meal ingestion affects the fetal circulation in uncomplicated pregnancies. METHODS: A simple crossover blinded study was designed for late uncomplicated singleton pregnancies. After overnight fasting, two different maternal meal states were tested. In one state, pregnant women had a standard 600-kcal breakfast at 8 AM (phase A). The other state consisted of maintaining fasting (phase B). Both states were assigned to each woman within 3 days in randomized order. Fetal Doppler studies of the umbilical, middle cerebral, and renal arteries and the descending aorta were performed at 7 AM (the fasting state) and at 10 AM (the fed state or the continuous fasting state). RESULTS: Twenty women underwent the crossover study. Regardless of the maternal meal state, no significant change was observed in the pulsatility index (PI) of either the umbilical artery (n = 20), the middle cerebral artery (n = 19), or the descending aorta (n = 15). However, the PI of the fetal renal artery decreased significantly after maternal meal ingestion (n = 14) (phase A, 2.36 +/- 0.16 versus 2.09 +/- 0.33; P = .021). There was no such change in the PI after prolonged fasting (phase B, 2.44 +/- 0.32 versus 2.39 +/- 0.44; P = .75). CONCLUSION: Fetal renal artery resistance decreased after maternal meal ingestion in normally grown fetuses during late pregnancy. This decrease in the resistance may be associated with increased fetal urine production after maternal meals.

Maternal serum triglyceride at 24--32 weeks' gestation and newborn weight in nondiabetic women with positive diabetic screens.

OBJECTIVE: To determine whether elevated midpregnancy maternal serum lipid levels predict newborn weight at term and the risk of large for gestational age (LGA) infants in women with positive diabetic screen but normal glucose tolerance test. METHODS: Japanese gravidas who had positive diabetic screens and normal 75-g oral glucose tolerance tests (GTT) at 24--32 weeks were enrolled. Subjects with complications, including diabetes, hypertension, or fetal anomalies were excluded, as were women with multifetal gestations. Fasting serum triglyceride, free fatty acids, and total cholesterol levels were measured at the time of GTT. We tested the association between maternal variables and birth weight by univariable analysis. We used multivariable analysis to test whether the association between fasting lipids and birth weight was independent of prepregnant maternal body mass index (BMI), maternal weight gain during pregnancy, and plasma glucose levels at GTT. We also used multiple logistic regression analysis to determine whether maternal hyperlipidemia, defined as more than the 75th percentile of each lipid, is a risk factor for having an LGA infant. RESULTS: We enrolled 146 subjects. Among measured maternal lipids, only triglyceride levels correlated with birth weight in univariable analysis (r = 0.22, P =.009). Birth weight also was correlated with prepregnant maternal BMI (r = 0.18, P =.04) and fasting plasma glucose levels (r = 0.17, P =.04). The association between maternal fasting triglyceride level and birth weight remained significant after adjusting for prepregnant BMI, maternal weight gain, fasting plasma glucose levels, fetal gender, and gestational age at birth (P =.01). Logistic regression analysis showed that fasting maternal hypertriglyceridemia (over 259 mg/dL) was the significant predictor of LGA infants, independent of prepregnant BMI, maternal weight gain, and maternal plasma glucose levels (odds ratio 11.6; 95% confidence interval 1.1, 122; P =.04). CONCLUSION: In women with positive diabetic screens but normal GTTs, fasting triglyceride levels at 24-32 weeks correlated positively with newborn weight at term, independent of maternal plasma glucose levels and obesity. Maternal fasting serum triglyceride levels in midpregnancy might be an independent predictor of fetal macrosomia in those women.

Hyperinsulinemia increases the risk of gestational hypertension.

OBJECTIVE: To determine whether hyperinsulinemia is related to gestational hypertension. METHODS: We measured the arterial blood pressure and the level of immunoreactive insulin (IRI) during a 75 g oral glucose tolerance test in a total of 84 pregnant women. Hyperinsulinemia was defined as a fasting IRI level > or = 9 IU/l, while gestational hypertension was defined as arterial blood pressure > or = 140/90 mmHg. RESULTS: The incidence of gestational hypertension was higher in the hyperinsulinemic group (n = 29) than in the control group (n = 55) (24.1% vs. 7.3%, respectively P < 0.05). After controlling for maternal age, parity, pre-pregnancy body mass index and the gestational age at the time of oral glucose tolerance test (OGTT), using a multiple regression model, the relative risk of developing gestational hypertension for a fasting insulin level was 1.19 (95% C.I., 1.03-1.38). CONCLUSION: Pregnant women with hyperinsulinemia are at increased risk of developing gestational hypertension.

[Pharmacokinetic, bacteriological and clinical studies of cefuzonam in the field of obstetrics and gynecology].

Cefuzonam (CZON, L-105), an antibiotic injectable of cephalosporin family, was studied pharmacokinetically, clinically and bacteriologically to examine its distribution to female genital tissues and the activity on infections in the field of obstetrics and gynecology. Maximum concentrations in serum and genital tissues achieved 19-46 minutes after intravenous injection of CZON 1 g were 69.6 micrograms/ml for serum, 63.1 micrograms/g for oviduct, 34.2 micrograms/g for ovary, 22.5 micrograms/g for endometrium, 33.4 micrograms/g for myometrium, 30.7 micrograms/g for cervix uteri, and 37.1 micrograms/g for portio vaginalis. Clinical efficacies on 15 cases of intrauterine infection and adnexitis were proved with 4 cases of 'marked improvement' and 11 cases of 'improvement', thus the efficacy rate was 100%. Of 21 strains of aerobes and anaerobes isolated from infectious lesions, 19 strains were eliminated after administration of the drug. No side effects were observed. From these results of fundamental and clinical studies CZON appeared to be a highly useful drug fro the obstetric and gynecological infections.

[Evaluation of the diagnostic criteria of gestational diabetes mellitus in Japan: a study of women with mild glucose intolerance during late pregnancy].

To evaluate the validity of the diagnostic criteria of gestational diabetes (GDM) recommended by the Japan Society of Obstetrics and Gynecology (JSOG), we investigated women with mild glucose intolerance during pregnancy, using the borderline criteria of the Japan Diabetes Society (JDS), cut-off values of which are lower than those of the JSOG criteria. Five hundred seventy one pregnant women were screened for GDM after 20 weeks' gestation using a 50g glucose challenge test. Only ten women (1.8% of total), who fulfilled the JSOG criteria, were found (GDM group). At the same time, eighteen women (3.2% of total), who did not fulfill the JSOG criteria but who met two or more abnormal values of the JDS borderline criteria, were also found (A2 group). There was no significant difference between the two groups in either mean maternal age or the percentage of women over 30 years of age. delta IRI/delta BS in a 75g glucose tolerance test in the A2 group was 0.58 (median), which was similar to that in the GDM group (0.42). This result, however, was significantly lower than that in both the normal control group (1.00, p less than 0.01) and the group of women with only one abnormal value among the JDS criteria (A1 group, 0.88, less than 0.01). Before therapy, there was no significant difference in the diurnal plasma glucose level between the GDM group, who could be treated with diet therapy, and the A2 group.(ABSTRACT TRUNCATED AT 250 WORDS)

[The predictive factor of postpartum impaired glucose tolerance in pregnant women with abnormal glucose tolerance].

To determine factors predictive of impaired glucose tolerance (IGT) in the postpartum period, we examined the maternal and perinatal characteristics of fifty-eight women with abnormal glucose tolerance during pregnancy. A 75g oral glucose tolerance test (OGTT) was performed on the women again around 4 weeks after delivery. Forty women who had a 2-hour plasma glucose level of 140mg/dl or more were defined as IGT in postpartum (group IGT), and the other eighteen women with a 2-hour plasma glucose level lower than 140mg/dl were defined as having normalized glucose tolerance (group N). The women in group IGT weighed more during pregnancy than those in group N (p < 0.05). Insulin secretion during the antepartum OGTT was lower in group IGT than in group N. On the basis of the prepregnant body mass index (BMI) for the obese group (BMI > or = 24), the women in group IGT weighed much more during pregnancy than those in group N (p < 0.03). In the non-obese group, the women in group IGT had higher glucose levels and lower insulin responses than those in group N. We concluded that, in obese women, excessive weight gain during pregnancy is predictive of postpartum IGT, while in non-obese women, the severity of glucose intolerance during pregnancy is related to poor postpartum prognosis.

A case of nondiabetic macrosomia with Simpson-Golabi-Behmel syndrome: antenatal sonographic findings.

The incidence of macrosomic infants weighing 5,000 g or more is rare. We experienced a case of nondiabetic macrosomia, in which the fetus weighed more than 5,000 g. The newborn was diagnosed as having Simpson-Golabi-Behmel syndrome. We discuss antenatal ultrasonographic findings in the case.

[Effect of prolonged intravenous ritodrine tocolysis on diurnal glucose profiles in pregnant women with normal carbohydrate tolerance].

Our purpose was to investigate an effect of prolonged intravenous ritodrine tocolysis on maternal carbohydrate metabolism in women with normal glucose tolerance. In patients with preterm labor, diurnal plasma glucose levels were measured both during the 24 hours after beginning the therapy (phase 1) and each day during over five days of continuous ritodrine tocolysis (phase 2). We also measured diurnal plasma glucose levels in normal pregnant women without any therapy (control group). In phase 1, in comparison with before therapy, a significant increase in the plasma glucose levels was observed with the highest level at 9 hours after starting ritodrine (146.4 +/- 31.6mg/dl). The higher plasma glucose levels persisted during phase 1. Although infusion rates were similar in both phases, maternal plasma glucose levels in phase 1 were significantly higher than in phase 2 (mean plasma glucose level, 128.1 +/- 21.3mg/dl vs. 92.7 +/- 11.6 mg/dl, p < 0.05; maximum plasma glucose level, 159.5 +/- 25.2mg/dl vs. 106.6 +/- 14.5mg/dl, p < 0.05). Diurnal glucose levels in phase 2 were similar to those in the control group. In phase 1, there seemed to be a dose-dependent relation between the ritodrine infusion rates and plasma glucose levels, but we did not find any relationship between them in phase 2. In conclusion, although hyperglycemia occurs during the initial phase of continuous ritodrine therapy (at least 24 hours), prolonged ritodrine infusion leads to normalization of the maternal plasma glucose levels.

Maternal Meal Ingestion Does Not Affect Amniotic Fluid Index during Short-period Observation in Normal Pregnancy

>Objective: To determine whether maternal meal ingestion affects amniotic fluid index (AFI) over a short period after maternal meal ingestion in normal growth fetuses with normal amniotic fluid volume in uncomplicated late pregnancies.Methods: Twenty-five women with an appropriate-for-gestational-age fetus with normal AFI were included in a simple crossover, blinded study during late pregnancy. After an overnight fast, two different maternal meal states were prepared. On day A, the subjects had a standard 600-kcal breakfast at 8 a.m. On day B, the fasting state was maintained until 10 a.m. Both states were randomly assigned to each woman within 3 days. On both days, the AFI was measured at 7 a.m. (the fasting state) and at 10 a.m. (the fed state on day A and the continuous fasting state on day B). A change in AFI between 7 and 10 a.m. was compared between the days by paired t test.Results: The mean gestational age (mean +/- SD) was 37.5 +/- 1.5 weeks on day A and 37.4 +/- 1.6 weeks on day B. The change in AFI between 7 and 10 a.m. was 1.1 +/- 3.0 cm on day A (with breakfast) and 2.1 +/- 2.6 cm on day B (keeping fast). These changes were not different between the days (P = 0.19).Conclusions: Maternal meal ingestion had no apparent acute effect on AFI in normal growth fetuses with normal amniotic fluid volume.

Decreased expression of the GLUT4 glucose transporter protein in adipose tissue during pregnancy.

Insulin resistance involves impaired activities of the glucose transport system in insulin target tissues. We therefore investigated the GLUT4 glucose transporter protein in adipose tissues from the pregnant women with normal glucose tolerance and from women with gestational diabetes mellitus, and compared these to nonpregnant women. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N = 6), pregnant women with normal glucose tolerance (N = 6, gestational week 38.0 +/- 0.3), and pregnant women with gestational diabetes mellitus (N = 3, gestational week 38.6 +/- 0.3). The abdominal subcutaneous adipose tissues obtained from each group were subjected to analysis of the GLUT4 glucose transporter protein. The presence of the GLUT4 glucose transporter protein in the three groups was quantitatively determined by Western blot analysis of detergent-soluble adipose tissue extracts using anti-GLUT4 antibody. GLUT4 glucose transporter protein concentration in the adipose tissue of pregnant women were significantly lower than that in nonpregnant women, and this difference was more profound in women with gestational diabetes mellitus. We demonstrated that the content of GLUT4 protein was decreased in adipose tissue from normal pregnancy compared to nonpregnant women.