Dataset Information

Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis.

ABSTRACT:

Objective

The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM).

Study design

A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo.

Results

Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group.

Conclusion

Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.

SUBMITTER: Spinnato JA

PROVIDER: S-EPMC2723730 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Publications

Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis.

Spinnato Joseph A JA Freire Salvio S Pinto e Silva Joao Luiz JL Rudge Marilza Vieira Cunha MV Martins-Costa Sérgio S Koch Matthew A MA Goco Norman N Santos Cleide de Barros Cde B Cecatti Jose Guilherme JG Costa Roberto R Ramos José Geraldo JG Moss Nancy N Sibai Baha M BM

American journal of obstetrics and gynecology 20081001 4

<h4>Objective</h4>The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM).<h4>Study design</h4>A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with ...[more]

PMID: 18928997

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Project description:OBJECTIVE: Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects. STUDY DESIGN: Paired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM?=?14, preterm labor (PTL?=?8), preterm no labor (PTNL?=?8), term labor (TL?=?10), and term no labor (TNL?=?8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student's t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC). RESULTS: In all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p?=?0.05). CONCLUSIONS: Fetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects.

Project description:Background. Preterm Premature Rupture of Membranes (PPROM) is a major leading cause of preterm births. While the cause for PPROM remains unidentified, it is anticipated to be due to subclinical infection, since a large proportion of PPROM patients display signs of chorioamnionitis. Since subclinical infections can be facilitated by dysbiosis, our goal was to characterize the vaginal microbiome and amniotic fluid discharge upon PPROM, through latency antibiotic treatment, and until delivery, to detect the presence of pathogens, microbiota alteration, and microbial response to treatment. Methods. Enrolled subjects (15) underwent routine institutional antenatal care for PPROM, including the administration of latency antibiotics. Serial vaginal swabs were obtained from diagnosis of PPROM through delivery and the sequencing of the V3-V5 region of the 16S rRNA gene was performed for all collected samples. Results. The results show that Lactobacilli species were markedly decreased when compared to vaginal swabs collected from uncomplicated pregnancy subjects with a matched gestational time. Prevotella and Peptoniphilus were the most prevalent taxa in PPROM subjects at presentation. The vaginal microbiome of the PPROM subjects varied substantially intra- and inter-subjects. Several taxa were found to be significantly reduced during and after the antibiotic treatment: Weeksella, Lachnospira, Achromobacter, and Pediococcus. In contrast, Peptostreptococcus and Tissierellaceae ph2 displayed a significant increase after the antibiotic treatment. However, the relative abundance of Lactobacillus, Prevotella, and Peptoniphilus was not substantially impacted during the hospitalization of the PPROM subjects. The deficiency of Lactobacillus, and constancy of known pathogenic species, such as Prevotella and Peptoniphilus during and after antibiotics, highlights the persistent dysbiosis and warrants further investigation into mitigating approaches. Discussion. PPROM is responsible for one third of all preterm births. It is thought that subclinical infection is a crucial factor in the pathophysiology of PPROM because 25-40% of patients present signs of chorioamnionitis on amniocentesis. Here we sought to directly assess the bacterial content of the vagina and leaking amniotic fluid of subjects at presentation, throughout treatment and up until delivery, in order to search for common pathogens, microbiota changes, and microbial response to latency antibiotic treatment. We have found that the vaginal microbiome of PPROM subjects is highly variable and displays significant changes to treatment. However, the unchanging deficiency of Lactobacillus, and persistence of known pathogenic species, such as Prevotella and Peptoniphilus from presentation, through antibiotic treatment and up until delivery, highlights the persistent dysbiosis and warrants further investigation into mitigating approaches.

Project description:IntroductionTo identify potential biomarkers in the plasma that could predict histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM), using shotgun and targeted proteomic analyses.MethodsThis retrospective cohort study included 78 singleton pregnant women with PPROM (24-34 gestational weeks) who delivered within 96 h of blood sampling. Maternal plasma samples were analyzed by label-free liquid chromatography-tandem mass spectrometry for proteome profiling in a nested case-control study design (HCA cases vs. non-HCA controls [n = 9 each]). Differential expression of 12 candidate proteins was assessed by multiple reaction monitoring-mass spectrometry (MRM-MS) analysis in individual plasma samples from cases and controls matched by gestational age at sampling (n = 40, cohort 1). A validation study was further performed in an independent study group (n = 38, cohort 2) using ELISA and turbidimetric immunoassay for three differentially expressed proteins.ResultsShotgun proteomics analyses yielded 18 proteins that were differentially expressed (P < 0.05) between HCA cases and non-HCA controls. MRM-MS analysis of 12 differentially expressed proteins further revealed that the CRP, C4A, and SAA4 levels were significantly increased in women with HCA. A multi-marker panel comprising plasma SAA4 and C4A showed enhanced potential for differentiating HCA from non-HCA women (area under the curve = 0.899). Additional validation of these findings by ELISA assays revealed that the CRP levels were significantly higher in women with HCA than in those without HCA, whereas the plasma levels of C4A and SAA4 did not significantly differ between the two groups.ConclusionsPlasma C4A, SAA4, and CRP were identified as potential biomarkers for detecting HCA in women with PPROM, based on targeted and shotgun proteomic analyses, showing good accuracy when used as a combined dual-biomarker panel (C4A and SAA4). Nevertheless, ELISA validation of these proteins, except for CRP, may not yield clinically useful markers for predicting HCA.

Dataset Information

Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis.

Objective

Study design

Results

Conclusion

Publications

Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis.

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