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Short fetal leukocyte telomere length and preterm prelabor rupture of the membranes.

ABSTRACT: BACKGROUND: Rupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS) and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM) or spontaneous preterm births with intact membranes (PTB), compared to term birth. METHODS: Telomere lengths were quantified in cord blood leukocytes (n = 133) from three major groups: 1) pPROM (n = 28), 2) PTB (n = 69) and 3) uncomplicated full term births (controls, n = 35), using real-time quantitative PCR. Placental membrane specimens (n = 18) were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths. RESULTS: In pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962 ± 3124 bp) that were significantly shorter than gestational age-matched PTB (11546 ± 4348 bp, p = 0.04), but comparable to term births (9011 ± 2497 bp, p = 0.31). Secondary analyses revealed no effects of race (African American vs. Caucasian) or intraamniotic infection on telomere length. A strong Pearson's correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p<0.01). CONCLUSIONS: Fetal leukocyte telomere length is reduced in pPROM compared to PTB but is similar to term births. pPROM represents a placental membrane disease likely mediated by OS-induced senescence.

SUBMITTER: Menon R

PROVIDER: S-EPMC3278428 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Project description:BackgroundGlobally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls.MethodsChorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses.ResultsA total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25.ConclusionsIn our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.

Project description:BackgroundEstimation of fetal weight (EFW) by ultrasound is useful in clinical decision-making. Numerous formulas for EFW have been published but have not been validated in pregnancies complicated by preterm premature rupture of membranes (PPROM). The purpose of this study is to compare the accuracy of EFW formulas in patients with PPROM, and to further evaluate the performance of the most commonly used formula - Hadlock IV.MethodsA retrospective cohort study of women with singleton gestations and PPROM, admitted to a single tertiary center between 2005 and 2017 from 220/7-330/7 (n = 565). All women had an EFW within 14 days of delivery by standard biometry (biparietal diameter, head circumference, abdominal circumference and femur length). The accuracy of previously published 21 estimated EFW formulas was assessed by comparing the Pearson correlation with actual birth weight, and calculating the random error, systematic error, proportion of estimates within 10% of birth weight, and Euclidean distance.ResultsThe mean gestational was 26.8 ± 2.4 weeks at admission, and 28.2 ± 2.6 weeks at delivery. Most formulas were strongly correlated with actual birth weight (r > 0.9 for 19/21 formulas). Mean systematic error was - 4.30% and mean random error was 14.5%. The highest performing formula, by the highest proportion of estimates and lowest Euclidean distance was Ott (1986), which uses abdominal and head circumferences, and femur length. However, there were minimal difference with all of the first 10 ranking formulas. The Pearson correlation coefficient for the Hadlock IV formula was strong at r = 0.935 (p < 0.001), with 319 (56.5%) of measurements falling within 10%, 408 (72.2%) within 15% and 455 (80.5%) within 20% of actual birth weight. This correlation was unaffected by gender (r = 0.936 for males, r = 0.932 for females, p < 0.001 for both) or by amniotic fluid level (r = 0.935 for mean vertical pocket < 2 cm, r = 0.943 for mean vertical pocket ≥2 cm, p < 0.001 for both).ConclusionsIn women with singleton gestation and PPROM, the Ott (1986) formula for EFW was the most accurate, yet all of the top ten ranking formulas performed quite well. The commonly used Hadlock IV performed quite similarly to Ott's formula, and is acceptable to use in this specific setting.

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Short fetal leukocyte telomere length and preterm prelabor rupture of the membranes.

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