A randomized, prospective study of adjunctive ceftizoxime in preterm labor. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen. A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis. Ampicillin and metronidazole treatment in preterm labour: a multicentre, randomised controlled trial. Preterm labour--is bacterial vaginosis involved? The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.
Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnancies receiving tocolysis for preterm labor.
                A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients with preterm labor between 24 and 35 weeks' gestation. A total of 545 patients with intact membranes and without chorioamnionitis who were receiving magnesium sulfate were screened. Exclusions were for advanced cervical dilatation, penicillin allergy, current antibiotic therapy, and failure to give informed consent. Of these, 117 consecutive, eligible, consenting patients were randomized to receive either 2 gm of ceftizoxime or a placebo every 8 hours. The primary end point was prolongation of gestation. Statistical comparisons were performed by use of unpaired two-tailed t tests and chi 2 analysis.
                Of the 58 ceftizoxime and 59 placebo patients, there was no difference in the interval to delivery (34.5 +/- 21.1 days vs 34.6 +/- 24.5 days, p = 0.99) and no difference in the rate of delivery before 37 weeks' gestation (60% in the ceftizoxime group vs 58% in the placebo group, p = 0.91). Subanalyses of 61 subjects who received nine or more doses and who were group B streptococci negative, 69 patients at < or = 32 weeks on presentation, and 22 sets of twins all showed no differences in delivery interval or rate of delivery at < 37 weeks. The sample size of this study was sufficient to detect a 9-day difference in prolongation of pregnancy (alpha = 0.05, beta = 0.2).
                Ceftizoxime had no effect on interval to delivery or duration of pregnancy in women treated for preterm labor. Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks' gestation.
                In 624 pregnant women at risk for delivering prematurely, vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks' gestation. We then performed a 2:1 double-blind randomization to treatment with metronidazole and erythromycin (433 women) or placebo (191 women). After treatment, the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time (a mean of 27.6 weeks' gestation).
                A total of 178 women (29 percent) delivered infants at less than 37 weeks' gestation. Eight women were lost to follow-up. In the remaining population, 110 of the 426 women assigned to metronidazole and erythromycin (26 percent) delivered prematurely, as compared with 68 of the 190 assigned to placebo (36 percent, P = 0.01). However, the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis (rate of preterm delivery, 31 percent with treatment vs. 49 percent with placebo; P = 0.006). Of the 358 women who did not have bacterial vaginosis when initially examined, 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely (P = 0.55). The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery (preterm delivery in the treatment group, 39 percent; and in the placebo group, 57 percent; P = 0.02) and in women who weighed less than 50 kg before pregnancy (preterm delivery in the treatment group, 14 percent; and in the placebo group, 33 percent; P = 0.04).
                Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery. To screen for bacterial vaginosis (BV) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks (primary outcome).
                Randomised consent design for clinical trials according to Zelen.
                Southeast region of Sweden.
                A total of 9025 women were screened in early pregnancy.
                A total of 819 women with a Nugent score of 6 and above were considered to have BV and treated according to Zelen allocation. The incidence of late miscarriage and spontaneous (noniatrogenic) preterm birth was assessed.
                Late miscarriage and spontaneous preterm delivery before 37 weeks.
                Therapy with vaginal clindamycin had no significant impact on the incidence of spontaneous preterm delivery prior to 37 completed weeks; OR 0.90, 95% CI 0.40-2.02 (primary outcome variable). However, only 1 of 11 women in the treatment group versus 5 of 12 in the control group delivered prior to 33 completed weeks; OR 0.14, 95% CI 0.02-0.95. Treatment was associated with 32 days longer gestation for the 23 participants who had late miscarriage or spontaneous preterm birth (P= 0.024, Mann-Whitney U test) and significantly fewer infants had a birthweight below 2,500 g (secondary outcome). A follow up of infants born preterm 4 years postnatally indicated that extending gestational age did not increase the number of sequelae.
                Clindamycin vaginal cream therapy was associated with significantly prolonged gestation and reduced cost of neonatal care in women with BV. Early screening for BV and treatment with clindamycin saved approximately 27 euro per woman. Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial.
                Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay.
                Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation.
                Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis. To ascertain whether adjuvant ampicillin and metronidazole given to women in preterm labour with intact membranes would prolong pregnancy and decrease the perinatal mortality and morbidity.
                A multicentre, prospective, randomised controlled trial.
                Three perinatal centres serving an indigent population.
                Eighty-one women in active preterm labour with otherwise uncomplicated singleton pregnancies between 26 and 34 weeks gestation or an ultrasound fetal weight estimate of 800 g to 1500 g.
                The study group received ampicillin and metronidazole for five days. The control group received no antibiotics. In all women contractions were suppressed with hexoprenaline and indomethacin for 24 h, and betamethasone was given for fetal lung maturity.
                Days gained and perinatal mortality and morbidity.
                The study (n = 43) and control groups (n = 38) were comparable at entry. In those receiving ampicillin and metronidazole the pregnancy was significantly prolonged (median 15 days versus 2.5 days, P = 0.04) with significantly more women still pregnant after seven days (63% versus 37%, P = 0.03, OR 0.34 95% CI 0.13-0.94). Significantly more infants in the control group developed necrotising enterocolitis than in the study group (5 versus 0, P = 0.02).
                Adjuvant ampicillin and metronidazole in the management of women in preterm labour with intact membranes significantly prolonged the pregnancy and decreased neonatal morbidity. To assess the efficacy of treatment of bacterial vaginosis (BV) using metronidazole to reduce preterm labour in primigravidae and multigravidae with previous midtrimester abortion or preterm labour.
                Randomised controlled trial.
                Tertiary academic hospital.
                Two different groups of patients were screened for BV at the first antenatal visit, namely primigravidae and high-risk multigravidae who had had a previous midtrimester abortion or preterm delivery. Patients where BV was diagnosed clinically or on Gram's stain of a smear taken from the posterior vaginal fornix, received either 400 mg metronidazole, or 100 mg vitamin C orally twice daily for 2 days. The Gram's stain was repeated after 4 weeks. If BV was found again, treatment with the same drug was repeated.
                Preterm delivery, birth weight and perinatal deaths.
                One thousand and five patients entered the study, but 40 were excluded for various reasons and 10 were lost to follow-up. There were 464 primigravidae, of whom 150 (32%) had BV. Except for the 5-minute Apgar score, no significant differences were found between primigravidae negative for BV and those who received either metronidazole or vitamin C. There were 491 high-risk multigravidae, of whom 127 (26%) had BV. The mean gestational age in the BV-negative group was 37 weeks, in contrast to 37.4 weeks in the vitamin C group and 35.6 weeks in the metronidazole group. Birth weights in these three groups were 2,752 g, 2,759 g and 2,475 g respectively, significantly less (P = 0.0109) in the metronidazole group in comparison with the BV-negative group. Delivery before 37 weeks occurred in 29% of high-risk multigravidae with no BV but in 24% of those who took vitamin C and in 43% who took metronidazole. Differences were significant between the BV-negative and metronidazole groups (P = 0.0231) and also between the metronidazole and vitamin C groups (P = 0.0274). Delivery before 28 weeks occurred in 4% of the high-risk multigravidae with no BV but in 10% of those with BV who took metronidazole. The difference was significant (P = 0.0430). Analysis for maximum likelihood estimates for preterm labour identified only previous preterm labour or midtrimester abortion as risk factors.
                Metronidazole does not seem to reduce the prevalence of preterm labour when given for BV before 26 weeks' gestation. Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae.
                The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability. Secondary outcomes studied were: somatic growth, tolerance, rates of sepsis and necrotizing enterocolitis.
                In a prospective randomized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied. The study group received a preterm formula supplemented with Bifidobacter lactis (2 x 10(7) cfu/g of dry milk) while the control group received the same formula but without supplementation. Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test. Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula.
                All infants tolerated the study formula well. Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable. After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group (p=0.0356) and they remained higher to the end of the study (p at day 30=0.075). The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group (p=0.003). Head growth was significantly higher in the study group (p=0.001).
                The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth. A prospective, double-blind, randomized, controlled trial was conducted to evaluate the effect of low-dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance.
                Two groups of preterm infants (birth weight </= 1500 g) with feeding intolerance were randomized to either low-dose erythromycin (5 mg/kg every 8 hours) or 5% dextrose placebo, both of which were discontinued 1 week after full enteral feedings were tolerated. The primary outcome variable was the time taken to attain full enteral feedings of at least 130 mL/kg/d.
                The gestational age at birth was similar in the two groups (erythromycin, 27.1 +/- 1.9 weeks; placebo, 27.5 +/- 2.9 weeks). The mean birth weight of the erythromycin group was lower (806.3 +/- 215.6 g) than the placebo group (981.4 +/- 285.4 g; P = 0.18), and included more infants who were small for gestational age (4/13 = 31% versus 1/11 = 9%; P = 0.224). There was no difference between the two groups with regard to the volume of feedings they were receiving at the time of enrollment. Reduction in symptoms of gastroesophageal reflux was similar in the two groups. 3 of 13 in the erythromycin group and 4 of 11 in the placebo group improved during the study (P = 0.565). The mean time to attain full enteral feedings after enrollment was 24.9 + 2.9 days in the erythromycin group and 30.8 +/- 4.1 days in the placebo group, a difference that did not reach statistical significance (P = 0.17).
                Low-dose erythromycin did not reduce the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. Gastroesophageal reflux decreased as a consequence of maturation of the gastrointestinal tract and not because of erythromycin. These preliminary results justify verification in larger multicenter trials. Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.
                Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.
                From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).
                The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes.
Two studies with a total of 59 mothers suggest modest improvements in short-term EBM volumes when a medication is used after insufficient EBM occurs in mothers following preterm delivery. In both studies, the medication was commenced ≧14 days post delivery and following insufficient EBM supply with other lactation supports.
Currently, no studies support prophylactic use of a galactagogue medication at any gestation. Use of any galactagogue medication has only been examined at more than 14 days post delivery and after full lactation support has been given. Further trials should examine larger groups of preterm mothers and consider breastfeeding outcomes over a longer period.