A randomized, double-blind, placebo-controlled investigation of the safety of intravenous immune globulin administration to preterm neonates

Intravenous immune globulin (750 mg/kg), or an equivalent volume of a placebo, was administered during the first week of life, in a randomized trial, to 20 preterm neonates weighing 710 to 1800 g. A variety of laboratory and clinical values were measured serially and analyzed for possible untoward effects. Serum IgG levels were also determined serially. No differences in heart rate, respiratory rate, urine output, blood glucose, serum osmolality, BUN, SGPT, pH, blood gasses, serum electrolytes, total or direct bilirubin, blood leukocyte concentration, absolute neutrophil count, or blood platelet concentration were observed between the intravenous immune globulin (IVIG) and placebo recipients before or following IVIG administration. The red blood cell concentration of IVIG recipients diminished transiently and only slightly (P less than .05). Serum IgG levels increased from 503 +/- 162 mg/dL (X +/- SD) to 1492 +/- 201 mg/dL 15 minutes after the IVIG administration (P less than .001). After 8 days, serum IgG levels were still elevated, at 675 +/- 297 mg/dL. All patients randomized to receive the placebo experienced a diminution in serum IgG over this 8-day period (P less than .01). All 20 patients survived and none in either group had a documented nosocomial infection. This study suggests that IVIG can safely be administered to preterm neonates, resulting in serum IgG levels comparable to those of term infants.     

Prevention of hypogammaglobulinemia of prematurity with intravenous immune globulin

We evaluated the effect of 1 g/kg intravenous immune globulin (IGIV) on immunoglobulin levels and half-life, the dose and frequency of IGIV administration necessary to maintain IgG levels at greater than 400 mg/dL, and IGIV effect on immunoglobulin levels after discharge in infants less than or equal to 32 weeks' gestation and less than or equal to 1500 g. Fifteen infants received 31 infusions at IgG levels less than or equal to 400 mg/dL. Immunoglobulin levels were obtained 24 hours postinfusion, weekly during hospitalization, and monthly after discharge. Mean IgG postinfusion was 980 mg/dL. Mean IgG half-life was 18 days (range 7 to 41). Smaller infants with greater than or equal to 5% of blood volume removed per week experienced shorter immunoglobulin half-lives. IGIV caused increased IgG levels after discharge and did not delay endogenous production of IgG. We conclude that 1 g/kg IGIV given to infants less than or equal to 32 weeks' gestation and less than or equal to 1500 g every 1 to 6 weeks during hospitalization, depending on weight and blood volume removed, prevents hypogammaglobulinemia of prematurity.     

Traditional care of the perineum during birth. A prospective,randomized, multicenter study of 1,076 women

OBJECTIVE: To investigate the influence of the traditional hands-on versus the innovative hands-poised method on the risk of perineal trauma during vaginal delivery and on neonatal outcomes. STUDY DESIGN: In a prospective, randomized, multicenter study, 1,161 of 1,505 women giving birth at the Departments of Obstetrics and Gynecology of the University Hospital of Vienna and Semmelweis Women's Hospital, Vienna, between February and September 1999, were randomized into the trial. In the hands-on method, the left hand of the midwife puts pressure on the infant's head, and the right hand is placed against the perineum. In the hands-poised method, the midwife guides the parturient through the birth without touching the perineum, prepared to apply light pressure on the infant's head. RESULTS: One hundred eighty-seven of 574 women (32.5%) in the hands-on group and 180 of 502 women (35.8%) in the hands-poised group experienced perineal tears (P = .5). Sixteen women (2.7%) treated with the hands-on method developed third-degree perineal tears as compared with five women (0.9%) treated with the hands-poised method (P < .05). In the hands-on group, 103 women (17.9%) underwent episiotomy as compared with 51 cases (10.1%) in the hands-poised group (P < .01). No significant differences in neonatal outcomes were observed between the two groups. CONCLUSION: Our data suggest that a policy of hands-poised care is more suitable for preserving the perineum during birth and is a safe and effective birthing alternative for women.     

Effect of oral misoprostol after second-trimester delivery: a randomized,blinded study

OBJECTIVE: To determine whether serial oral misoprostol shortens the third stage of labor in second-trimester pregnancy loss. METHODS: This was a randomized, double-blind, placebo-controlled study of women between 13 and 28 weeks' gestation admitted for spontaneous or induced pregnancy termination. Subjects were randomized to receive either misoprostol (200 microg) or placebo orally every hour for a maximum of three doses if the placenta had not delivered spontaneously within 10 minutes of the fetus. A dilute oxytocin infusion was given to women in both groups. The patients were managed expectantly until intervention was required or up to 6 hours when curettage was scheduled. RESULTS: One hundred eighteen women were randomized to misoprostol and 119 randomized to placebo. Fifty-eight (49%) and 55 (46%) of the misoprostol and placebo groups, respectively, did not receive their medication (P =.65, chi(2) test). There was no difference between the groups with regard to demographic features, method of pregnancy termination, or gestational age. Sixty-seven (57%) and 62 (52%) of the misoprostol and placebo groups, respectively, completed the third stage of labor within 2 hours (P =.47, chi(2) test). There was no statistically significant difference in the median time from fetus to placenta (60 versus 91 minutes in the misoprostol versus placebo group, P =.57, Mann-Whitney U test). There was no difference between the groups in the incidence of hemorrhage, need for transfusion, or curettage rate. CONCLUSION: The therapeutic use of oral misoprostol in the third stage of labor in second-trimester pregnancy loss does not reduce the time to complete spontaneous placental delivery.     

A randomized, blinded, placebo-controlled trial of antibiotics in idiopathic preterm labor

Because subclinical genital tract infection may play a major role in preterm birth, the efficacy of adjunctive antibiotic therapy in combination with standard parenteral tocolysis was examined in a randomized, blinded study of patients with idiopathic preterm labor. Labor was documented by three contractions in 20 minutes, cervical dilation of 1 cm or more, and the need for parenteral tocolysis. Enrollment was restricted to patients with intact membranes and without known causes for preterm labor. One hundred three patients at 24-34 weeks' gestation were randomized to intravenous ampicillin plus oral erythromycin or corresponding placebos. Compared with the placebo group, the adjunctive antibiotic group had a similar frequency of preterm birth (38 versus 44%), time to delivery (34 versus 34 days), birth weight (2847 versus 2855 g), and episodes of recurrent labor requiring parenteral tocolysis (0.43 versus 0.49). In our population, we found no benefit to the adjunctive use of ampicillin plus erythromycin. Significant differences in genital microflora between our patients and those of other studies may explain our results.     

A multicenter,double-blind,randomized, placebo-controlled study of rifaximin for the treatment of bacterial vaginosis

ObjectiveTo compare efficacy and tolerability between different regimens of rifaximin vaginal tablets and a placebo for treatment of bacterial vaginosis.MethodsIn a prospective study carried out at 13 sites in 3 European countries between August 2009 and October 2010, White, non-pregnant, premenopausal women with bacterial vaginosis were randomly assigned to receive rifaximin at 100 mg for 5 days (100 mg/5 days), 25 mg/5 days, or 100 mg/2 days, or placebo. Women were assessed at 7–10 and 28–35 days. Diagnosis and cure were based on Amsel criteria and Nugent score. Fisher exact test was used to compare cure rates.ResultsAmong 114 women recruited, 103 were evaluable for drug efficacy. Therapeutic cure rate at first follow-up was higher in the rifaximin 25 mg/5 days (48%, P = 0.04), 100 mg/2 days (36.0%), and 100 mg/5 days (25.9%) groups than in the placebo group (19.0%). At second follow-up, therapeutic cure rate was 28.0%, 14.8%, and 4.0% in the respective groups versus 7.7% in the placebo group. No difference in adverse events was observed.ConclusionRifaximin at 25 mg/5 days showed better therapeutic cure rates and maintenance of therapeutic cure after 1 month versus placebo. All treatment regimens were well tolerated.EudraCT number: 2009-011826-32.     

Glyceryl trinitrate and ritodrine in tocolysis: an international multicenter randomized study. GTN Preterm Labour Investigation Group.

OBJECTIVE: To compare the efficacy of transdermal glyceryl trinitrate and intravenous (IV) ritodrine as tocolytics. METHODS: Two hundred forty-five women with preterm labor and intact membranes between 24 and 36 weeks' gestation were randomized to transdermal glyceryl trinitrate or intravenous ritodrine. Treatment was continued until contractions stopped or a maximum of 7 days. Glyceryl trinitrate was administered as a 10- or 20-mg transdermal patch. Intravenous ritodrine was administered according to nationally available guidelines. The primary outcome was prolongation of gestation expressed as a percentage of the time from entry to 37 weeks. Secondary outcomes were proportion of women who delivered the same day, next day, or within 7 and 14 days of entry, and by 32, 34, and 37 weeks. Analysis was by intention to treat. RESULTS: Twelve women (5%) were lost to follow-up. Glyceryl trinitrate and ritodrine prolonged gestation by 74% of time to 37 weeks (difference glyceryl trinitrate-ritodrine 0%; 95% confidence interval (CI) -10%, +10%). There was no significant difference in the proportion of women receiving glyceryl trinitrate or ritodrine who delivered within the specified days from study entry or weeks of gestation; however, 42 women who received glyceryl trinitrate and 58 women who received ritodrine delivered by 37 weeks (difference -11%; 95% CI -24%, +2%). No serious maternal side effects were reported for ritodrine or glyceryl trinitrate. CONCLUSION: We found no overall difference between glyceryl trinitrate and ritodrine in the acute tocolysis of preterm labor but a suggested advantage of glyceryl trinitrate over ritodrine in reducing preterm delivery rate. The maternal side effect profile and treatment discontinuation rates were fewer for glyceryl trinitrate, suggesting it was a safer alternative to ritodrine.     

Induction of labor with intravenous oxytocin or vaginal PGE2 suppositories. A randomized study

Thirty-eight term pregnant women with a moderately unfavorable cervix (cervical score 4-5 p.) were randomly given intravenous oxytocin (Group A) or 3 mg PGE2 as a vaginal suppository (Group B) for labor induction. Eight out of 19 in Group A and 17 out of 19 in Group B gave birth vaginally within 24 h. The remaining 11 women in Group A had still an unfavorable cervix after 24 h. They were then given 3 mg PGE2 as a vaginal suppository and all but one had given birth vaginally without complications within 24 h. In Group B only 2 were still undelivered after 24 h. Both had a favorable cervix and were delivered vaginally within 12 h after intravenous infusion of oxytocin. The number of instrumental deliveries in Group A was one cesarean section and two vacuum extractions and in Group B three vacuum extractions. One woman in Group B reported nausea and vomiting and in one had strong uterine contractions in the second stage of labor. Otherwise no side effects were registered. All babies were born in good condition with Apgar scores greater than or equal to 7. In conclusion, vaginal application of 3 mg PGE2 as a suppository seems to be more effective than intravenous infusion of oxytocin for labor induction in women with half-ripened cervices, i.e. cervical scores of 4-5 p.     

Laparoscopic-assisted vaginal hysterectomy versus minilaparotomy hysterectomy: a prospective, randomized, multicenter study

STUDY OBJECTIVE: The aim of this study was to compare operative and early postoperative outcomes of laparoscopic-assisted vaginal hysterectomy (LAVH) and minilaparotomy in a randomized clinical trial including patients undergoing total hysterectomy for benign gynecologic disease and having 1 or more of the generally considered contraindications to vaginal route. DESIGN: Prospective, randomized, multicenter trial (Canadian Task Force classification I). SETTING: Departments of Gynecology from 3 major university hospitals in Rome. PATIENTS: Eighty-one patients who were candidates for abdominal hysterectomy. INTERVENTIONS: Laparoscopic-assisted vaginal hysterectomy and minilaparotomy hysterectomy. MEASUREMENTS AND MAIN RESULTS: Forty patients were randomized to LAVH and 41 to minilaparotomy. Characteristics of patients and indications for surgery in the 2 arms were comparable. In the minilaparotomy group, complications were as follows: 1 case (2.4%) of delayed laparotomy with 2 units of red blood cell transfusion, 2 cases (4.8%) of wound infection, and 3 cases (7.3%) of fever of unknown origin. No minor or major complications were observed in the LAVH group. Postoperative visual analog scale pain scores at days 1 and 2 were significantly lower in the LAVH group (p <.05). The complication rate between the 2 groups was significantly lower for LAVH (p = .026). CONCLUSION: Because LAVH was associated with significantly lower early postoperative pain scores and complication rates, in general LAVH should be preferred to minilaparotomy hysterectomy when the vaginal approach cannot be used.     

Treatment of candidal vaginitis. A prospective randomized investigator-blind multicenter study comparing topically applied econazole with oral fluconazole

Two hundred and thirty-five women with clinically and microbiologically proven candidal vaginitis were randomly allocated for treatment with either one topically applied vaginal tablet of 150 mg econazole (114 women) or one orally administered capsule of 150 mg fluconazole (121 women). The women returned for follow-up visits 7-10, 28-35, and 80-100 days after the recruitment visit. Women with clinical and/or mycological failures and/or a recurrence were successively excluded from the follow-up. At the 28-35-day follow-up visit, the women treated with fluconazole had a significantly higher clinical/microbiological cure rate than those given econazole (P = 0.022; Fisher's exact 2-tail test). No significant such differences were observed at the 7-10 and the 80-100-day follow-up visits, although fluconazole tended to be more efficacious. Nine women administered fluconazole, and 2 women given econazole reported minor systemic side effects of the treatment. Three women out of 4 preferred oral to local therapy of candidal vaginitis.