Antibiotics for treating bacterial vaginosis in pregnancy.

BACKGROUND: Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcome and, in particular, preterm birth. Identification and treatment may reduce the risk of preterm birth and its consequences. OBJECTIVES: To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (September 2002). SELECTION CRITERIA: Randomized trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trials and extracted data independently. Study authors were contacted for additional information. MAIN RESULTS: Ten trials involving 4249 women were included; all were of good quality. Antibiotic therapy was effective at eradicating bacterial vaginosis during pregnancy (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.18 to 0.24, eight trials of 3825 women). Treatment did not significantly reduce the risk of preterm birth before 37 weeks (OR 0.95, 95% CI 0.82 to 1.10, eight trials of 4062 women), 34 weeks (OR 1.20, 95% CI 0.69 to 2.07, five trials of 851 women), or 32 weeks (OR 1.08, 95% CI 0.70 to 1.68, three trials of 3080 women). However, antibiotic treatment did significantly decrease the risk of preterm prelabour rupture of membranes (OR 0.32, 95% CI 0.15 to 0.67, three trials of 562 women). In women with a previous preterm birth, treatment did not affect the risk of subsequent preterm birth (OR 0.83, 95% CI 0.59 to 1.17, five trials of 622 women) but it did decrease the risk of preterm prelabour rupture of membranes (OR 0.14, 95% CI 0.05 to 0.38, two trials of 114 women) and low birthweight (OR 0.31, 95% CI 0.13 to 0.75, five trials of 622 women). REVIEWER'S CONCLUSIONS: Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. However, the current evidence does not support screening and treating all pregnant women with asymptomatic bacterial vaginosis to prevent preterm birth and its consequences. For women with a previous preterm birth, there is little suggestion that detection and treatment of bacterial vaginosis will prevent a further preterm birth, but it may reduce the risk of low birthweight and preterm prelabour rupture of membranes.

Necrotizing enterocolitis.

Improvement in survival rates of low birth-weight infants particularly in the neonatal intensive care units of India appears to be accompanied by frequent recognition of Necrotizing enterocolitis (NEC) among early survivors. As the philosophy and practice of advanced care for tiny infants becomes more acceptable and affordable in the country, a steady increase in survival of such infants is predictable. However there is growing concern in India that NEC could become a significant contributor to morbidity and mortality in the future. NEC is currently regarded as the most common acquired gastrointestinal emergency in the newborn period, and the outcome of this disease is universally poor. Improved understanding of the pathophysiology and pathogenesis of this condition is required for formulating optimal principles of prevention and management.

Infection and preterm birth: evidence of a common causal relationship with bronchopulmonary dysplasia and cerebral palsy.

Subclinical genital tract infection has been clearly established as a significant cause of spontaneous preterm birth, particularly in early gestations. Bacterial vaginosis organisms rank highly among the pathogens involved in preterm labour and there is considerable beneficial evidence from the use of prophylactic antibiotics for women at high risk of preterm birth. The pathogenesis involves activation of macrophages and the generation of pro-inflammatory cytokines. Bronchopulmonary dysplasia is seen in the most immature of survivors and appears to be secondary to interruption of normal development and maturation of the lungs. The link between chorioamnionitis and lung injury in utero and subsequent development of bronchopulmonary dysplasia has now been substantiated. Exposure to pro-inflammatory cytokines is implicated in the impairment of the fetal lung. A significant body of evidence supports the association between chorioamnionitis, periventricular leukomalacia and cerebral palsy. Biological mechanisms that explain the association between chorioamnionitis and fetal brain injury involve pro-inflammatory cytokines. Similarity in the pattern of expression of cytokines suggests a common pathway for the initiation of preterm labour and also injury to the lung and the central nervous system of the fetus.

Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial.

OBJECTIVE: To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid-pregnancy would reduce the risk of spontaneous preterm birth. DESIGN: A multicentre, randomised, placebo-controlled trial. SETTING: Four metropolitan hospitals. PARTICIPANTS: Eight hundred and seventy-nine singleton women with a heavy growth of G. vaginalis or Gram stain indicative of bacterial vaginosis at 19 weeks of gestation. INTERVENTIONS: Oral metronidazole (400 mg) or placebo twice daily for two days at 24 weeks of gestation, and at 29 weeks if G. vaginalis found in test-of-cure swab four weeks after treatment. MAIN OUTCOME MEASURES: Spontaneous preterm birth less than 37 weeks. RESULTS: Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (31/429 [7.2%] vs 32/428 [7.5%]) or spontaneous preterm birth (20/429 [4.7%] vs 24/428 [5.6%]). Among the 480 women with bacterial vaginosis treatment had no effect on spontaneous preterm birth (11/242 [4.5%] vs 15/238 [6.3%]). In the subset of 46 women with a previous preterm birth, women in the metronidazole group showed a significant reduction in spontaneous preterm birth (2/22 [9.1%] vs 10/24 [41.7%], OR 0.14, 95% CI 0.01-0.84). A treatment effect was also found in compliant women with a previous preterm birth and bacterial vaginosis (0/14 [0%] vs 6/17 [35.3%], OR 0.0, 95% CI 0.0-0.94). CONCLUSION: Metronidazole treatment of women with a heavy growth of G. vaginalis or bacterial vaginosis did not reduce the preterm birth rate. Among women with a previous preterm birth, treatment reduced the risk of spontaneous preterm birth. Further studies are required to confirm these findings.

Prevention of early onset group B streptococcal sepsis in the newborn.

There is an urgent need for strategies to prevent early onset group B streptococcal sepsis in the newborn. The most effective mechanism is the identification of maternal carriers of the organism and interruption of transmission during labour. Vaginal culture is currently the most reliable method for the identification of carriers. Antibiotic prophylaxis for known carriers in labour has been demonstrated to be effective as standard management practice in a number of Australian institutions and is the best available strategy at this stage.

Bacterial vaginosis in pregnancy and efficacy of short-course oral metronidazole treatment: a randomized controlled trial.

OBJECTIVE: To characterize the natural history of bacterial vaginosis in pregnancy and to assess the efficacy of short courses of oral metronidazole therapy for long-term suppression of bacterial vaginosis flora. METHODS: This was a randomized, double-blind, placebo-controlled study of two 2-day courses of metronidazole (400 mg twice daily) in pregnant women with bacterial vaginosis (by Gram stain) and/or heavy growth of Gardnerella vaginalis. The first course was given at 24 weeks' gestation and a second course at 29 weeks if the follow-up vaginal swab grew G vaginalis. Follow-up swabs were performed at 28, 32, and 36 weeks' gestation. RESULTS: On the basis of their G vaginalis colonization, 196 women were enrolled, and 137 were evaluable for efficacy, including 66 with bacterial vaginosis. The microbial ecology of bacterial vaginosis in 36 women in the placebo group was relatively stable, with 72% persistence at 28 weeks and 57% at 32 weeks' gestation. Metronidazole effectively suppressed bacterial vaginosis for 4 weeks after the first course in 76%, compared with 28% in the placebo group, and had a cumulative efficacy of 87% compared to 44% 4 weeks after the second course (odds ratio 0.12, 95% confidence interval 0.03-0.5). CONCLUSIONS: The microbial ecology of bacterial vaginosis in pregnant women is relatively stable. Long-term suppression of bacterial vaginosis flora for 2-3 months can be achieved by short courses of metronidazole therapy in 87% of women in mid-pregnancy. Because bacterial vaginosis has been associated with an increased risk of preterm labor, these findings provide the foundation for an intervention study of women with bacterial vaginosis in pregnancy.

Changes in vaginal flora during pregnancy and association with preterm birth.

A prospective study of the vaginal flora changes between midtrimester and labor was undertaken in 560 women; 337 had intact membranes and were in labor when swabs were taken. Of these, 45 delivered preterm. Gardnerella vaginalis, Ureaplasma urealyticum (both associated with preterm birth when present in midtrimester), and Mycoplasma hominis commonly persisted between midtrimester and labor, particularly in the preterm cohort (24 [65%] of 37 midtrimester isolates), and these organisms were seldom acquired late in pregnancy. A second group, Bacteroides species, had both a high persistence (9 [60%] of 15 midtrimester isolates) and high late acquisition rate (10 [53%] of 19 labor isolates) in the preterm cohort. These findings provide a rationale for treatment of bacterial vaginosis in pregnancy. A third group, comprising enteropharyngeal bacteria and Peptostreptococcus species, were almost all acquired late in the preterm cohort (14 [88%] of 16 labor isolates), and persistence from midtrimester was rare.

Parachute-like sinus venosus remnant: echocardiographic and pathological appearance.

A female infant with multiple congenital abnormalities and a right atrial "mass" on echocardiography is reported. Her general condition at birth was poor, and the chest x-ray showed cardiomegaly. Echocardiography demonstrated the usual atrial arrangement and concordant atrioventricular and ventriculoarterial connections with a mobile right atrial mass. Death occurred at 3 days of age and subsequent postmortem examination revealed a hollow, tube-like sinus venosus remnant mobile between right atrium and ventricle with numerous other abnormalities of the heart, including left heart hypoplasia and tubular hypoplasia of the aortic arch. Filling of the sinus venosus remnant with blood had resulted in an echocardiographic appearance suggestive of a right atrial tumor.

Prenatal microbiological risk factors associated with preterm birth.

OBJECTIVE: To study the vaginal flora of pregnant women at 22-28 weeks gestation to determine whether the presence of specific micro-organisms is significantly associated with preterm birth and prelabour rupture of the membranes. DESIGN: A comprehensive descriptive prospective study of the vaginal micro-flora of women between 22-28 weeks gestation comparing those who gave birth preterm (less than 37 weeks) with those who gave birth at term. Microbiological assessment included cultures for aerobic and anaerobic bacteria, yeasts, genital mycoplasmas and Trichomonas vaginalis. Multiple logistic regression analysis was used to account for confounding obstetric and demographic variables. SETTING: The Queen Victoria Hospital, Adelaide, South Australia. SUBJECTS: 135 women who gave birth preterm compared to 651 women who gave birth at term. MAIN OUTCOME MEASURE: Preterm birth and preterm prelabour rupture of membranes (PROM) RESULTS: The prevalence of Gardnerella vaginalis between 22-28 weeks was significantly higher in women who gave birth preterm compared to women who gave birth at term (23% vs 15%; multiple logistic regression odds ratio (OR) 1.8, 95% confidence intervals (CI) 1.01-3.2, P less than 0.05. Ureaplasma urealyticum was also found in a higher proportion of women who gave birth preterm (49% vs 32% OR 1.7, 95% CI 1.1-2.6, P less than 0.0005). Preterm PROM occurred in 42% of whom 60% were carriers of U. urealyticum between 22-28 weeks, compared with 32% in the term group (OR 3.2, CI 1.7-6.1, P less than 0.0005). When women who received antibiotics between the midtrimester swab and labour were excluded, G. vaginalis was also significantly associated with preterm PROM (OR 2.7, CI 1.1-6.5, P less than 0.05). The presence of vaginal enteropharyngeal bacteria (E. coli, Klebsiella spp., Haemophilus spp., Staph. aureus) in the midtrimester was not predictive of preterm birth, but when these organisms were found in labour, they appeared to have been acquired later in the pregnancy. CONCLUSION: Women carrying G. vaginalis or U. urealyticum during the midtrimester had nearly twice the risk of preterm birth, while women positive for U. urealyticum had more than a threefold risk of preterm PROM.

Monocytosis in preterm infants.

In sick preterm neonates receiving intensive care a spectacular rise in monocyte count has frequently been observed in sequential full blood examinations. The etiology of this has not previously been investigated and this study examines clinical factors that may contribute to this finding. Thirty (5.1%) of the 587 neonates who required intensive care during the study period had significant monocytosis (absolute count greater than 1700/mm3). Their mean gestation was 29 weeks (range 26-32 weeks). Monocytic response occurred at an age of 5.5 +/- 3 (mean +/- S.D.) days with 20% occurring at birth, 57% in the first week and 23% in the second week of life and lasted for 19.8 +/- 16 days (mean +/- S.D.). Most reached peak levels within two weeks and these ranged between 2,170 and 7176 per mm3. Analysis of the clinical variables against 37 controls revealed lower mean birth weight and gestational age, and higher incidence of leukocytosis, multiple transfusions, albumin infusions and theophylline therapy in the study group in comparison to the controls (P less than 0.001). No significant difference was found in maternal risk factors (pre-eclampsia, diabetes and amnionitis), birth asphyxia, respiratory disease, parenteral nutrition, proven infection and antibiotic therapy. An unexpected association with maternal steroid therapy was demonstrated. It is speculated that monocytosis represents a physiological though immature response of the marrow of small premature infants to a variety of exogenous stimuli including drugs and foreign protein infusions.

Vaginal infection and preterm labour.

OBJECTIVE: To study the vaginal flora of women in preterm labour (PTL) and determine whether the presence of specific vaginal microflora is significantly associated with onset of PTL. DESIGN: A comprehensive prospective study of the vaginal microflora of women in early labour comparing women in PTL with term controls. Microbiological assessment included cultures for aerobic and anaerobic bacteria, yeasts, genital mycoplasmas and Trichomonas vaginalis. Multiple logistic regression analysis was used to adjust for confounding obstetric and demographic variables. SETTING: The Queen Victoria Hospital, Adelaide. PATIENTS: 428 Women in PTL compared to 568 women in labour at term. MAIN OUTCOME MEASURE: PTL and preterm prelabour rupture of membranes (PPROM) in relation to specific vaginal microflora. RESULTS: After multiple logistic regression analysis, two distinct bacteriological groupings were associated with PTL less than 37 weeks gestation, namely, the bacterial vaginosis group of organisms, Gardnerella vaginalis and Bacteroides spp., and a group of enteropharyngeal organisms, E. coli, Klebsiella spp., Haemophilus spp. and S. aureus. G. vaginalis was found in 12% of women in PTL compared to 6% at term [regression odds ratio (ROR) 1.8, 95% confidence intervals (CI) 1.1-3.1] whereas Bacteroides spp. were detected in 45% of women in PTL compared with 35% at term (ROR 1.6, CI 1.2-2.1). The prevalence of G. vaginalis (17%) and Bacteroides spp. (50%) was even higher in women in PTL less than 34 weeks gestation. The enteropharyngeal group of organisms were more commonly present in women in PTL less than 37 weeks (E. coli 10% vs 6%, ROR 1.4, CI 0.8-2.4; Klebsiella spp. 3% vs less than 1%, ROR 5.4, CI 1.1-26.7; Haemophilus spp. 2% vs less than 1%, ROR 5.5, CI 1.1-28.6; S. aureus 6% vs 4%, ROR 1.8, CI 0.9-3.3) and were isolated even more frequently in women in PTL less than 34 weeks (E. coli 15%; Klebsiella spp. 4%; S. aureus 7%). Bacteroides spp., Klebsiella spp., and Haemophilus spp. were all found to be associated with PPROM. CONCLUSION: There are two distinct bacteriological groupings commonly found in women in PTL, especially in PTL less than 34 weeks gestation. These bacteriological groups are women with bacterial vaginosis in pregnancy and women who demonstrate enteropharyngeal bacteria in the vagina.

Silastic cup vacuum extractor or forceps: a comparative study.

A retrospective analysis over a 2-year period was carried out to compare the limitations in the use of the Silastic Cup vacuum extractor and forceps as the preferred instrument for operative vaginal delivery. Whilst the use of the vacuum extractor was associated with less maternal morbidity (54.9% episiotomy rate; 20.9% nil analgesia) and comparable neonatal problems, an increased failure rate (6.5%) was demonstrated in comparison to forceps delivery (0.7% failed vaginal delivery rate). A comparison of their use for rotational vaginal delivery failed to reveal any significant difference in maternal or neonatal outcome apart from an increased failure rate (30%) to complete vaginal delivery after application of the vacuum extractor. It is concluded that the vacuum extractor is a comparable instrument for midcavity or lift-out instrumental delivery but Kielland's forceps may still be a more appropriate instrument for rotational vaginal delivery.

Group B streptococcal colonization and preterm labour.

Recent publications have highlighted the controversy regarding the significance of Lancefield Group B Streptococcal (GBS) colonization in pregnancy and preterm delivery. In this prospective study vaginal swabs from 692 women at approximately 24 weeks' gestation were cultured for GBS. GBS was detected in 91 (13.2%) women. The rate of preterm labour (PTL) (less than 37 weeks) was significantly higher in GBS positive women than in GBS negative women (18.7% versus 5.5%; p less than 0.001). This association remained significant even when patients with other recognized factors predisposing to PTL were excluded (11.5% versus 3.9%; p less than 0.001). The rate of premature rupture of membranes (PROM) was also significantly higher in GBS positive women (9.9% versus 2.7%; p less than 0.005) and remained significantly higher when patients with other recognized risk factors were excluded (6.1% versus 1.8%; p less than 0.025). These results unequivocably show that pregnant women who are vaginal carriers of GBS have a significantly increased risk of PROM and PTL.

Jaundice of the newborn. The use of phototherapy.

Jaundice is common in the newborn infant who is unique because of a limited ability to clear bilirubin from the plasma. In most babies it is physiological and benign. In some, however, jaundice is a sign of a serious underlying disorder. The challenge to the physician is to distinguish normal physiology from pathological jaundice.

The use of a new ultra-thin fiberoptic bronchoscope to determine endotracheal tube position in the sick newborn infant.

The various techniques available for determining endotracheal tube position after intubation of a newborn are auscultation of the chest, observation of distance rings on the endotracheal tube, and chest radiology. Radiology is considered to be the most reliable method. We evaluated the use of a new ultra-thin fiberoptic bronchoscope on 20 recently intubated newborn infants to determine the position of the endotracheal tube and compared the technique with radiology. The accuracy of the two methods was comparable (correlation 0.91, P less than 0.001). Adverse changes in transcutaneous PO2 were observed during both procedures but were more marked during radiology than bronchoscopy. We conclude that the bronchoscopic technique of determining endotracheal tube position is both as safe and as accurate as radiologic technique.