Eyal Schiff

Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.

OBJECTIVE Our purpose was to determine whether aggressive or expectant management of severe preeclampsia at 28 to 32 weeks is more beneficial to maternal and neonatal outcome. STUDY DESIGN Ninety-five eligible patients were randomly assigned to either aggressive (n = 46) or expectant management (n = 49). Aggressive management patients were prepared for delivery, either by cesarean or induction, 48 hours after glucocorticoids were administered. Expectant management patients were managed with bed rest, oral antihypertensives, and intensive antenatal fetal testing. RESULTS At the time of randomization there were no differences between the two groups in mean systolic blood pressure (170 +/- 9.7 vs 172 +/- 9.4 mm Hg), diastolic blood pressure (110 +/- 5.4 vs 112 +/- 4.2 mm Hg), proteinuria (3.0 +/- 2.3 vs 3.6 +/- 2.3 gm per 24 hours), and gestational age (30.4 +/- 1.6 vs 30.7 +/- 1.5 weeks) for the aggressive and expectant management groups. The average latency period in the expectant management group was 15.4 days (range 4 to 36), and this period was not affected by the amount of proteinuria at randomization. There was no eclampsia or perinatal death in either group. The two groups had similar incidences of abruptio placentae (4.1% vs 4.3%) and similar days of postpartum hospital stay. The expectant management group had a significantly higher gestational age at delivery (32.9 +/- 1.5 vs 30.8 +/- 1.7 weeks, p < 0.0001), higher birth weight, lower incidence of admission to the neonatal intensive care unit (76% vs 100%, p = 0.002), lower mean days of hospitalization in the intensive care unit (20.2 +/- 14 vs 36.6 +/- 17.4, p < 0.0001), and lower incidence of neonatal complications. CONCLUSION Expectant management, with close monitoring of mother and fetus at a perinatal center, reduces neonatal complications and neonatal stay in the newborn intensive care unit.

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies

We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for pre-eclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A2 to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pregnancy-induced hypertension and pre-eclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin.

Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients

BACKGROUND Storing ovarian tissue for fertility preservation in cancer patients carries the risk of the presence of malignant cells that could lead to recurrence of cancer after reimplantation. Methods to exclude presence of cancer cells were used to improve the safety of cryopreservation-reimplantation procedures. METHODS Fifty-eight patients with hematological malignancies were referred for the storage of ovarian tissue for fertility preservation. Investigation included preoperative imaging and histological evaluation of fresh ovarian tissue. After thawing markers to detect minimal residual disease (MRD) were used and compared with patients disease used as positive control (five patients). RESULTS Preoperative imaging detected disease in the ovaries (two patients). Conventional histology post-tissue harvesting did not disclose malignant cells (56 patients). MRD results post-thawing were negative in Hodgkins disease (CD30 immunohistochemical staining), in T- and B-cell lymphoma (PCR for T-cell receptor and Ig clones, respectively) and in two chronic myelogenous leukemia patients (RT-PCR for BCR-ABL gene expression). However, highly sensitive real-time RT-PCR was positive in one CML patient and, this alarming result avoided tissue transplantation. CONCLUSIONS Preoperative imaging prevented operations and storage of tissue with cancer. Evaluation of stored ovarian tissue for MRD using sensitive markers is essential to increase safety and to prevent reimplantation of tissue with malignant cells.

Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis

Abstract.Acute exacerbations may complicate the course of pregnancy and the postpartum period in patients with relapsing-remitting multiple sclerosis (RRMS). To evaluate relapse rate and the effect of immunomodulatory treatment with intravenous immunoglobulin (IVIg) during pregnancy and the postpartum period we retrospectively analysed the data of 108 pregnant RRMS patients. Group I patients were not treated, Group II patients were treated with IVIg 0.4 g/kg body weight/day for 5 consecutive days within the first week after delivery with additional booster doses of 0.4 g/kg body weight/day at 6 and 12 weeks postpartum (defined as 12 weeks after labor), and Group III patients were treated continuously with IVIg during gestation and the postpartum period (0.4 g/kg body weight/day for 5 consecutive days within the 6–8 weeks of gestation with additional booster doses of 0.4 g/kg body weight/day once every 6 weeks until 12 weeks postpartum). All patients underwent antenatal care and fetal ultrasonographic surveillance examinations. Relapse rate per woman per year during the pregnancy and the postpartum period as well as neonatal outcome data and IVIg related adverse events were analysed.Relapse rate per woman per year for patients treated with IVIg for the whole pregnancy and postpartum period (Group III, N = 28) compared with the untreated Group I patients (N = 39) were as follows: first trimester 0.43 vs. 0.72, second trimester 0.15 vs. 0.61, third trimester 0.0 vs. 0.41, and postpartum period 0.28 vs.1.33 (p < 0.05). Patients treated with IVIg only during the postpartum period (Group II, N = 41) also showed a decrease in relapse rate compared with untreated Group I patients, 0.58 vs. 1.33 (p = 0.012). The mean maternal age, disease duration, gestational age at delivery and fetal delivery weight did not significantly differ between the three groups. Mode of delivery, obstetrical complications, the use of epidural analgesia and breast-feeding, did not affect postpartum relapse rate. No severe adverse events were associated with IVIg treatment either during the pregnancy or postpartum period for the patients and newborns.We conclude that in RRMS patients IVIg treatment could be considered as an optional treatment to reduce the incidence of pregnancy and postpartum-related relapses. Further randomized double-blind studies are needed to confirm our findings.

Biochemical corroboration of endothelial involvement in severe preeclampsia

This prospective, nested, case-control study investigated whether elevated plasma cellular fibronectin concentrations previously reported in preeclamptic women likely reflect endothelial dysfunction. In addition to higher maternal plasma concentrations of cellular fibronectin, we found higher levels of von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1 in maternal plasma, providing biochemical corroboration of endothelial dysfunction in severe preeclampsia.

Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery

Objective To determine outcomes of pregnancies in women at least 44 years of age and to determine factors predicting cesarean delivery in these patients. Methods Between January 1988 and December 1995, 109 women at least 44 years old delivered in our medical center. These women were matched to a group of 309 women 20–29 years of age. Multiple logistic regression analysis was used to evaluate the association between maternal age and outcome variables, controlling for possible confounding factors. Based on the logistic regression, a predictive model was calculated for cesarean delivery and validated prospectively in a separate group of 30 consecutive women at least 44 years old, who delivered during the first 8 months of 1996. Results Very advanced maternal age, compared with younger age, was associated with a significantly higher rate of medical complications (hypertensive disorder and diabetes) (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5, 4.1; P < .001), instrument-assisted vaginal delivery (OR 7.5; 95% CI 2.2, 25.0; P < .004), and cesarean delivery (OR 7.3; 95% CI 2.2, 16.7; P < .001). The incidences of preterm labor, premature rupture of membranes, emergency cesarean delivery, meconium-stained amniotic fluid, small for gestational age newborns, and 5-minute Apgar scores of 7 or lower were not influenced by maternal age. The regression model showed an increased risk for cesarean delivery associated with age of at least 44 years (OR 7.3; 95% CI 2.2, 16.7), primiparity (OR 3.5; 95% CI 1.3, 9.8), infertility treatment (OR 3.6; 95% CI 1.5, 8.8), and egg donation (OR 19.5; 95% CI 6.1, 62.2), with positive and negative predictive values of 94 and 86%, respectively. Conclusion Maternal age of at least 44 years is associated with medical complications in pregnancy and more interventions during labor. However, overall pregnancy outcomes are favorable. Cesarean delivery can be predicted accurately based on maternal age, parity, and infertility treatment.

Clinical improvement and shrinkage of uterine fibroids after thermal ablation by magnetic resonance‐guided focused ultrasound surgery

Hysterectomy or myomectomy are the accepted treatments for symptomatic uterine fibroids. Heat ablation of uterine fibroids has been shown to be an effective alternative treatment. The aim of this study was to determine the clinical efficacy of non‐invasive thermal ablation by transcutaneous magnetic resonance‐guided high‐intensity focused ultrasound (MRgFUS) for the treatment of symptomatic uterine fibroids.

Maternal serum adiponectin levels during human pregnancy.

Objective:Pregnancy is a unique situation characterized by insulin resistance. The role of adiponectin, an insulin-sensitizing hormone, has not been completely clarified during pregnancy. The aim of this cross-sectional study was to evaluate adiponectin levels during pregnancy and postpartum.Study design:Adiponectin and leptin levels were tested in 80 pregnant women, 20 in each trimester (mean gestational age 10.5±1.9; 19.3±4.9; 39.3±0.8 weeks,) as well as 4 days postpartum.Results:Adiponectin levels during first (13.3±3.6 μg/ml), second (12.6±4.4 μg/ml) and third trimester (11.2±3.7 μg/ml) did not differ and were significantly higher than postpartum levels (8.8±2.1 μg/ml; P<0.0001, P<0.004 and P<0.02, respectively).Conclusion:Despite increased insulin resistance during pregnancy, no significant alterations in adiponectin levels were observed. This may imply that the regulation of adiponectin during gestation is altered. The elevated gestational adiponectin levels are consistent with increased ‘adiponectin resistance’ during pregnancy.

Pregnancy Outcome After Age 50

OBJECTIVE: To evaluate pregnancy complications occurring after age 50. METHODS: We compared the pregnancy outcomes of women aged 50–64 years with those aged 45–49 years and with the general population. RESULTS: During 5 years from January 1, 1999, to June 30, 2004, 123 women aged 45 years and older gave birth. Fifty-five percent were nulliparous, 24 of 123 were aged 50–64 years, and 99 of 123 women were aged 45–49 years. All women older than age 50 conceived via in vitro fertilization with oocyte donation. For these 123 women, the overall mean gestational age at delivery was 37.6±2.6 weeks. The mean birth weight was 2,684±754 g, significantly lower than the general population, and the incidences of multifetal pregnancies, diabetes, and hypertension were high. Women aged 50 years and older were more likely to be hospitalized during pregnancy than women younger than 50 years (63% versus 22%, P<.001). Neonatal outcome was generally good. Women aged 50 years and older gave birth to significantly more low birth weight babies than those younger than age 50 years (61% versus 32%, P=.002). Gestational age and birth weight were both significantly lower for singletons and multiples in women older than age 50 years compared with those younger than age 50 years (gestational age of singletons 36.9 versus 38.4 weeks, P=.005; birth weight of singletons 2,694 versus 3,027 g, P=.019; gestational age of multiples 35.1 versus 36.4 weeks, P=.01; birth weight of multiples 1,976 versus 2,310 g, P=.038, respectively). CONCLUSION: Pregnant women aged 50–64 years have increased risks of preterm birth, low birth weight babies, diabetes mellitus, hypertension, and hospitalization. LEVEL OF EVIDENCE: II-2

Immunoreactive circulating endothelin-1 in normal andhypertensive pregnancies

Summary OBJECTIVE : The purpose of this study was to measure the circulatory levels of endothelin-1 inthe serum of pregnant women with hypertension. STUDY DESIGN : Endothelin-1 levels were measured by means of radioimmunoassay in the serum of 26 pregnant women with hypertension (14 with pregnancy-induced preeclamptic toxemia, 12 with chronic hypertension) and in the serum of 17 control pregnant women and 18 control nonpregnant women. The mean levels in the different groups were subject to statistical analysis with the analysis of variance RESULTS : The mean level among the women with preeclampsia (29.9 ± 13.2 fmol/ml) was significantlyhigher than those of the chronically hypertensive women (16.1 ± 7.3 fmol/ml, p = 0.002) and of the control pregnant women (19.7 ± 9.2 fmol/ml, p = 0.011). The mean level of the control nonpregnant women (26.9 ± 9.3) was significantly higher than that of the control pregnant women ( p = 0.029). Among the patients with preeclampsia there was no correlation between endothelin-1 levels and the mean arterial blood pressure. Six to 10 weeks after delivery the mean levels of 15 studied patients (7 with preeclampsia, 8 with chronic hypertension) were similar to the levels of the nonpregnant control women CONCLUSION : We conclude that increased endothelin-1 production may play a role in the pathogenesisof preeclampsia