Ljubomir Petricevic

Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery

Abstract Objective To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women. Design Multicentre, prospective, randomised controlled trial. Setting Non-hospital based antenatal clinics. Participants 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection. In the intervention group, the womens obstetricians received the test results and women received standard treatment and follow up for any detected infection. In the control group, the results of the vaginal smears were not revealed to the caregivers. Main outcome measures The primary outcome variable was preterm delivery at less than 37 weeks. Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage. Results Outcome data were available for 2058 women in the intervention group and 2097 women in the control group. In the intervention group, the number of preterm births was significantly lower than in the control group (3.0% v 5.3%, 95% confidence interval 1.2 to 3.6; P = 0.0001). Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and ≤ 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group. Conclusion Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women.

Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women.

OBJECTIVE The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the influence of the orally administered probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the quality of the vaginal flora in postmenopausal women. STUDY DESIGN Postmenopausal women with Nugent scores between 4 and 6 in initial vaginal swab, were randomized into two groups. Women in the intervention group received probiotic capsules containing 2.5x10(9)CFU (colony forming units) each of lyophilized L. rhamnosus GR-1 and L. reuteri RC-14 and women in the control group received an oral placebo once daily, in both groups for 14 days. Final vaginal swabs were taken 1 day after the last administration of the medication. The primary efficacy variable was a change in the Nugent score between baseline and the end of the study of at least two grades in each individual patient. RESULTS Seventy two women were recruited in the study, 35 assigned to the intervention group and 37 to the control group. Twenty-one of the 35 subjects (60%) in the intervention group and 6 of the 37 subjects (16%) in the control group showed a reduction in the Nugent score by at least two grades. The difference in the number of patients with improvement was highly significant (p=0.0001). The median difference in Nugent scores between baseline and the end of the study was 3 in the intervention group and 0 in the control group (p=0.0001). CONCLUSION Our results provide evidence for an alternative modality to restore the normal vaginal flora using specific probiotic strains administered orally.

Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery

The presence of an abnormal vaginal microflora in early pregnancy is a risk factor for preterm delivery. There is no investigation on vaginal flora dominated by lactic acid bacteria and possible association with preterm delivery. We assessed the dominant vaginal Lactobacillus species in healthy pregnant women in early pregnancy in relation to pregnancy outcome. We observed 111 low risk pregnant women with a normal vaginal microflora 11 + 0 to 14 + 0 weeks of pregnancy without subjective complaints. Vaginal smears were taken for the identification of lactobacilli using denaturing gradient gel electrophoresis (DGGE). Pregnancy outcome was recorded as term or preterm delivery (limit 36 + 6 weeks of gestation). The diversity of Lactobacillus species in term vs. preterm was the main outcome measure. L. iners alone was detected in 11 from 13 (85%) women who delivered preterm. By contrast, L. iners alone was detected in only 16 from 98 (16%) women who delivered at term (p < 0.001). Fifty six percent women that delivered at term and 8% women that delivered preterm had two or more vaginal Lactobacillus spp. at the same time. This study suggests that dominating L. iners alone detected in vaginal smears of healthy women in early pregnancy might be associated with preterm delivery.

Vaginal Lactobacillus microbiota of healthy women in the late first trimester of pregnancy

Objective  This study was undertaken to characterise the dominant species of Lactobacillus colonising the vagina of healthy pregnant women, to examine some of their phenotypic and genotypic properties, and to gain a better understanding of the potential role of species, which might be associated with infection‐free status.

IL-8 concentrations in maternal serum, amniotic fluid and cord blood in relation to different pathogens within the amniotic cavity.

Abstract Objective: The association between elevated interleukin (IL)-8 concentrations in amniotic fluid and preterm delivery is well described. Little consideration has been given to the impact of different groups of microorganisms within the amniotic cavity on IL-8 concentration. Methods: We collected amniotic fluid, placental tissue and amniotic membranes during preterm cesarean sections for bacterial culture. In addition, we determined IL-8 concentrations in maternal serum, amniotic fluid and cord blood and correlated them with the various intra-amniotic pathogens isolated by bacterial culture. Results: IL-8 concentrations were determined in amniotic fluid in 107 cases, in cord blood in 185 cases and in maternal blood in 158 cases. Women with intra-amniotic Ureaplasma urealyticum infection had significantly higher amniotic fluid concentrations of IL-8 than those without (P<0.001). In cord blood, we found significantly elevated IL-8 concentrations due to intra-amniotic infection with U. urealyticum (P=0.045) and other pathogens (P=0.04). In maternal sera, we found no significant elevation of maternal IL-8 in any of the groups. Conclusion: Intrauterine infection with U. urealyticum seems to play a profound role in the cascade of inflammation and increases IL-8 concentrations in amniotic fluid and cord blood.

Characterisation of the oral, vaginal and rectal Lactobacillus flora in healthy pregnant and postmenopausal women

OBJECTIVE To investigate the hypothesis that the rectum may be an important reservoir for vaginal colonisation by Lactobacillus species. STUDY DESIGN We included 60 pregnant women aged 18-35 years and 80 postmenopausal women aged 55-65 years in this cross-sectional observational study. Participants had to be without clinical signs of vaginal infection and without hormone replacement therapy. Only women with normal vaginal microflora (Nugent scores 0-3) were included in the evaluation. The first oral, vaginal, and rectal smears were taken for the enumeration of lactobacilli by cultural methods and identification of dominating lactobacilli based on multiplex polymerase chain reaction (PCR). The second oral, vaginal, and rectal smears were taken for molecular lactobacilli profiling using PCR denaturing gradient gel electrophoresis (DGGE). RESULTS 30 pregnant and 30 postmenopausal women were evaluated. On multiplex PCR, 99 colonies isolated from 30 pregnant women and 37 colonies isolated from 30 postmenopausal women were identified as being members of the genus Lactobacillus: 50% of pregnant and 33% of postmenopausal women had one or more Lactobacillus spp. recovered from their oral specimens. Around 80% of pregnant and 40% of postmenopausal women harboured one or more Lactobacillus spp. in the vagina and rectum. On PCR-DGGE, 80% of pregnant and 40% of postmenopausal women harboured the same lactobacilli isolates in both the vagina and rectum. CONCLUSION This study supports the hypothesis that the rectum may play an important role as a reservoir for some strains of lactobacilli that colonise the vagina.

Antibiotic prophylaxis before surgery vs after cord clamping in elective cesarean delivery: a double-blind, prospective, randomized, placebo-controlled trial.

CONTEXT Perioperative antibiotic prophylaxis during elective cesarean delivery at term to reduce postoperative maternal infectious morbidity is generally used but may not be effective on the basis of the available data. Also, the optimal timing of prophylactic antibiotic administration is unclear. OBJECTIVE To compare the effectiveness of cefazolin administered before skin incision vs cefazolin administered after umbilical cord clamping vs placebo in a 3-arm randomized trial. The primary objective of the study was to compare postoperative infectious morbidity, defined as wound infection, endometritis, or urinary tract infection (primary end point), in women with cefazolin vs placebo. The comparison between the 2 arms administering cefazolin before skin incision vs after umbilical cord clamping was a secondary end point. DESIGN Double-blind, prospective, randomized, placebo-controlled trial. SETTING The Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria. PATIENTS We recruited 1112 women undergoing elective cesarean delivery at term from March 1, 2004, through January 31, 2010. INTERVENTIONS In group 1, cefazolin (2 g) was administered 20 to 30 minutes before skin incision. In group 2, cefazolin (2 g) was administered immediately after clamping of the cord. In group 3, placebo was administered before skin incision. RESULTS The primary outcome was observed in 18 of 370 women in group 1 (4.9%) and in 14 of 371 women in group 2 (3.8%), whereas it was noted in 45 of 371 women in group 3 (12.1%) (P < .001 for group 1 plus group 2 vs group 3). The number needed to treat to avoid 1 primary outcome was 13 (95% CI, 9 to 24). Between groups 1 and 2, there was no statistically significant difference regarding postoperative infectious morbidity (P = .60). CONCLUSION We were able to demonstrate the usefulness in elective cesarean delivery of prophylactic cefazolin vs placebo in reducing postoperative maternal infectious morbidity.

DNA Hybridization Test: Rapid Diagnostic Tool for Excluding Bacterial Vaginosis in Pregnant Women with Symptoms Suggestive of Infection

ABSTRACT This prospective comparative study evaluated a DNA hybridization test (Affirm VPIII) as an alternative to Gram stain for the diagnosis of bacterial vaginosis. We examined vaginal smears from 1,725 pregnant women between the 12th and 36th weeks of gestation with clinical signs of vaginal infection. The DNA hybridization test compared well with Gram stain and can be used as a rapid diagnostic tool to exclude bacterial vaginosis.

Effect of asymptomatic vaginal colonization with Candida albicans on pregnancy outcome

Vaginal infection is a major causative factor of preterm delivery. The present study was performed to evaluate the effect of asymptomatic vaginal colonization with Candida albicans at early gestation on pregnancy outcome.

Mycoplasma/Ureaplasma infection in pregnancy: to screen or not to screen

Abstract Mycoplasmata have been linked to pregnancy complications and neonatal risk. While formerly a limited number of species could be discovered by cultures, molecular biology nowadays discovers both lower quantities and more diverse species, making us realize that mycoplasmata are ubiquitous in the vaginal milieu and do not always pose a danger for pregnant women. As the meaning of mycoplasmata in pregnancy is not clear to many clinicians, we summarized the current knowledge about the meaning of different kinds of mycoplasmata in pregnancy and discuss the potential benefits and disadvantages of treatment. Currently, there is no general rule to screen and treat for mycoplasmata in pregnancy. New techniques seem to indicate that Ureaplasma parvum (Up), which now can be distinguished from U. urealyticum (Uu), may pose an increased risk for preterm birth and bronchopulmonary disease in the preterm neonate. Mycoplasma hominis (Mh) is related to early miscarriages and midtrimester abortions, especially in the presence of abnormal vaginal flora. Mycoplasma genitalium (Mg) is now recognized as a sexually transmitted infection (STI) that is involved in the causation of cervicitis, pelvic inflammatory disease (PID) in non-pregnant, and preterm birth and miscarriages in pregnant women, irrespective of the presence of concurrent other STIs, like Chlamydia or gonorrhoea. Proper studies to test for efficacy and improved pregnancy outcome are scarce and inconclusive. Azythromycin is the standard treatment now, although, for Mg, this may not be sufficient. The role of clarithromycin in clinical practice still has to be established. There is a stringent need for new studies based on molecular diagnostic techniques and randomized treatment protocols with promising and safe antimicrobials.