In utero exposure to Ureaplasma spp. is associated with increased rate of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants

Kasper, David C.; Mechtler, Thomas P.; Böhm, Judith; Petricevic, Ljubomir; Gleiß, Andreas; Spergser, Joachim; Witt, Armin; Herkner, Kurt; Berger, Angelika

doi:10.1515/jpm.2011.022

Cited by 68 publications

(42 citation statements)

References 41 publications

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“…The shortcomings include that we did not assess the colonization status with bacteria other than ureaplasmas, and the short-term outcomes of preterm infants such as BPD, which have previously been associated with Ureaplasma exposure [5,21]. …”

Section: Discussionmentioning

confidence: 99%

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First Trimester Vaginal Ureaplasma Biovar Colonization and Preterm Birth: Results of a Prospective Multicenter Study

Rittenschober-Böhm¹,

Waldhoer²,

Schulz³

et al. 2017

Neonatology

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Background: While there is a proven association of upper genital tract Ureaplasma infection during pregnancy with adverse pregnancy outcome, the effect of vaginal Ureaplasma colonization on preterm delivery has been controversially debated. Objectives: We hypothesized that women with isolation of vaginal U. parvum but not U. urealyticum are at increased risk for spontaneous preterm birth (SPB) compared to women with negative results. Methods: A vaginal swab taken between 12 and 14 weeks of gestation was analyzed for the presence of Ureaplasma biovars by PCR in 4,330 pregnant women. Results: Of the study cohort, 37% were positive for U. parvum, 5.9% for U. urealyticum, and 3.1% for both. The rates of SPB were 10.4% (OR 1.7, 95% CI 1.3, 2.2, p < 0.001) and 8.9% (OR 1.4, 95% CI 0.9, 2.3, p = 0.193) in the groups with isolation of U. parvum and U. urealyticum, respectively, compared to 6.4% in the group with negative PCR results. Multiple logistic regression and interaction analyses showed that vaginal colonization with U. parvum but not U. urealyticum was a statistically significant risk factor for SPB (adjusted OR 1.6, 95% CI 1.2, 2.1, p < 0.001), independent of other risk factors such as bacterial vaginosis and history of SPB. Conclusion: Our study demonstrates a statistically significant and independent association between first-trimester vaginal colonization with U. parvum and subsequent SPB.

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Section: Discussionmentioning

confidence: 99%

“…Although Ureaplasma spp. are mostly considered as commensals of the lower genital tract [3], intrauterine infection during pregnancy is associated with adverse pregnancy outcome and neonatal morbidity [5,6,7,8]. The most common pathway of bacteria invading the intrauterine compartment is an ascending infection from the vagina [9].…”

Section: Introductionmentioning

confidence: 99%

First Trimester Vaginal Ureaplasma Biovar Colonization and Preterm Birth: Results of a Prospective Multicenter Study

Rittenschober-Böhm¹,

Waldhoer²,

Schulz³

et al. 2017

Neonatology

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“…Bacterial culture remains an important method to detect the bacteriologic cause of amniotic membrane rupture. However, recent publications have demonstrated that bacterial culture had a lower rate of detection (27.1%) compared to PCR (up to 72.9%) [35,40]. The use of amniotic fluid culture alone could miss up to 91% of genital mycoplasma [41].…”

Section: Inflammationmentioning

confidence: 99%

Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome

Tchirikov

Schlabritz‐Loutsevitch

Mäher

et al. 2017

Journal of Perinatal Medicine

171

142

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Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long-and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/anhydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane -either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intraamniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR) = 0.66), neonatal infections (RR = 0.67) and abnormal ultrasound scan of neonatal brain (RR = 0.67)]. The positive effect of continuo...

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“…Ureaplasma infection induces production of tumor necrosis factor-α and interleukin-6 [11] and also causes apoptosis of human type 2 lung epithelial cells and lung macrophages [12]. Apart from BPD, Ureaplasma has also been associated with retinopathy of prematurity [13], intraventricular hemorrhage [14,15], necrotizing enterocolitis (NEC) [16] and adverse neurodevelopmental outcome [17]; all these associations could be attributed to the ability of Ureaplasma to elicit an inflammatory reaction.…”

Section: Introductionmentioning

confidence: 99%

Azithromycin and Other Macrolides for Prevention of Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

2014

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Background and Objective:Ureaplasma spp. infection has been associated with bronchopulmonary dysplasia (BPD) in preterm infants. Macrolides have been used for the treatment of Ureaplasma spp. infection, with an intention to prevent BPD. The objective of this meta-analysis is to evaluate the use of macrolides in the prevention of BPD in preterm infants. Methods: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, abstracts of the major pediatric society meetings and bibliographies of retrieved articles. We included randomized controlled trials assessing the effects of macrolides therapy on BPD in preterm infants. A random/fixed-effect model was used to synthesize predefined outcomes. Results: Six studies involving 469 preterm infants were eligible for the analysis. Macrolides when used prophylactically (4 studies) did not show significant reduction in BPD (risk ratio, RR, 0.88, 95% confidence interval, CI, 0.75-1.03), death (RR 0.89, 95% CI 0.79-1.01) or in the composite outcome of BPD/death. Similarly, there was no significant reduction in BPD (RR 0.64, 95% CI 0.31-1.31) or the composite outcome of BPD/death (RR 0.41, 95% CI 0.05-3.13), when macrolides were used in Ureaplasma-positive infants. However, prophylactic azithromycin therapy (3 studies) was associated with significant reduction in BPD (RR 0.83, 95% CI 0.71-0.97; number needed to treat, NNT, 10) and composite outcome of BPD/death (RR 0.86, 95% CI 0.77-0.97; NNT 10). Conclusion: This meta-analysis demonstrates prophylactic azithromycin therapy was associated with statistically significant reduction in BPD and the composite outcome of BPD/death in preterm infants. However, given the limited information on pharmacokinetics and potential harmful effects, further studies should be done before routine use of azithromycin in the neonatal population.

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In utero exposure to Ureaplasma spp. is associated with increased rate of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants

Abstract: In our study population Ureaplasma spp. was associated with BPD and IVH in preterm infants even after adjustment for multiple risk factors.

Cited by 68 publications

References 41 publications

First Trimester Vaginal <b><i>Ureaplasma</i></b> Biovar Colonization and Preterm Birth: Results of a Prospective Multicenter Study

First Trimester Vaginal <b><i>Ureaplasma</i></b> Biovar Colonization and Preterm Birth: Results of a Prospective Multicenter Study

Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome

Azithromycin and Other Macrolides for Prevention of Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

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