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598: Umbilical cord telomere length and folate levels – a potential pathway for fetal re-programming
Poster Session IV
ajog.org
absent, or reversed end-diastolic flow). Management occurred per departmental guidelines. If discordant results were obtained, the most abnormal measurement was used to dictate patient care. If a fetus was initially diagnosed with FGR but grew to an EFW greater than the tenth percentile, weekly visits continued until a second growth ultrasound confirmed normal growth. RESULTS: Abnormal UAD measurements were seen in 48 fetuses during 141 visits. During the course of follow-up, eleven fetuses (23%) demonstrated improvement in fetal growth to an EFW greater than the tenth percentile. There were 8 fetuses (38%) with abnormal S/D ratios in a single artery that demonstrated resolution of FGR; five (63%) had abnormal UAD measurements when measuring above the tenth percentile. Only 3 fetuses (11%) with abnormalities in both arteries demonstrated growth above the tenth percentile; all 3 (100%) had abnormal S/D ratios during the period of improved growth. CONCLUSION: Abnormal UAD measurements were seen in 73% of the fetuses in our study with resolved FGR. This may reflect imprecision in the classification of FGR. Alternatively, another mechanism, such as incomplete maturation of placental anastomoses, may be present to cause abnormal UAD measurements.
birth. Given the relationship between shortened telomere length and future morbidity and mortality, the results could potentially provide a pathway of understanding and preventing adult-onset disease and mortality through intra-uterine re-programming.
Distribution of abnormal UAD measurements among fetuses with resolved growth restriction
599 A receptor for danger signals, advanced glycation end products (RAGE) in fetal systemic inflammation and clinical chorioamnionitis
Ahmed Ahmed1, Piya Chaemsaithong1, Tinnakorn Chaiworapongsa1, Dong Zhong1, Majid Shaman1, Kia Lannaman1, Lami Yeo1, Sonia Hassan1, Bo Hyun Yoon2, Roberto Romero1
1 NICHD/ NIH/ DHHS, Perinatology Research Branch, Detroit, MI; Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, MI, 2Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Seoul, Republic of Korea
598 Umbilical cord telomere length and folate levels e a potential pathway for fetal re-programming 1
1
2
Adetola Louis-Jacques , Rachel Sinkey , Arnut Paothong , Lindsey King2, Anupam Pradhan3, Valerie Whiteman1, Karen Bruder1, Roger Zoorob4, Hamisu Salihu2
1 Morsani College of Medicine, Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine, Tampa, FL, 2University of South Florida, Department of Epidemiology and Biostatistics, College of Public Health, Tampa, FL, 3University of South Florida, Department of Global Health, College of Public Health, Tampa, FL, 4Baylor College of Medicine, Department of Family and Community Medicine, Houston, TX
OBJECTIVE: Telomere length has been studied in adults but little is known about factors that influence it in-utero. The objective of this study is to investigate the relationship between fetal folate levels and telomere length. STUDY DESIGN: This was part of a cohort study conducted from 20112012 in pregnant women with a singleton gestation who were admitted for labor and delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene (T/S) ratio method was used to determine telomere length. Cord blood folate levels were also measured. Statistical analysis was performed using bootstrap and generalized linear modeling (GLM). RESULTS: A total of 96 maternal-fetal dyads were enrolled in this study. The mean gestational age was 39.44 weeks. Figure 1 illustrates the histogram of all p-values generated using GLM from the 10,000 bootstrapping simulations. The distribution of the coefficient of folate showed all values to be greater than 0 confirming that folate had a positive correlation with T/S ratio. The figure shows that in 9,553 of the 10,000 (95.53%) iterations performed, p-value was <0.05, demonstrating statistical significance. This means that fetuses exposed to higher folate levels had a longer telomere length. CONCLUSION: Our study is the first of its kind to show a positive association between umbilical cord folate and fetal telomere length at
OBJECTIVE: Fetal Systemic Inflammatory Response Syndrome (FIRS)
is considered the counterpart of the Systemic Inflammatory Response Syndrome of adults, which can be caused by infection and non-infection-related insults. The receptor for advanced glycation end products (RAGE) participates in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines. The soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) have both anti-inflammatory and proinflammatory properties. The objective of this study was to determine whether FIRS is associated with changes in the umbilical cord (UC) plasma concentration of sRAGE and esRAGE. STUDY DESIGN: UC blood was collected from the following groups: 1) preterm deliveries with (n¼31) and without FIRS (n¼42); and 2) Term deliveries divided into 3 groups: i) Term clinical chorioamnionitis (n¼23), ii) Term without labor (n¼23) and iii) Term labor (n¼23). FIRS was diagnosed by UC blood IL-6 (>17.5 pg/mL). Plasma concentrations of sRAGE, esRAGE and IL-6 were determined by ELISA. RESULTS: 1) Preterm neonates with FIRS had a lower median UC plasma concentration of sRAGE (ng/mL) and esRAGE (ng/mL) than those without FIRS (sRAGE: 1381 vs. 2574; p¼0.0006; esRAGE 0.44 vs. 0.78: p¼0.0004); 2) There was a negative correlation between the UC plasma concentration of sRAGE or esRAGE and IL-6 in preterm neonates (sRAGE: Spearman Rho¼ -0.41, p<0.001, esRAGE: Spearman Rho¼ -0.4, p<0.002); 3) The median UC plasma sRAGE and esRAGE concentration were lower in term labor than in those without labor (sRAGE: 1318 vs. 2166, esRAGE 0.32 vs. 0.57; each p¼0.006); and 4) there were no significant differences in the median sRAGE and esRAGE UC plasma concentrations between term neonate with labor and those with clinical chorioamnionitis (each p>0.05). CONCLUSION: We provide evidence for differential expression of a receptor for Danger signals in fetal systemic inflammation and clinical chorioamnionitis at term.
S298 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
ajog.org
absent, or reversed end-diastolic flow). Management occurred per departmental guidelines. If discordant results were obtained, the most abnormal measurement was used to dictate patient care. If a fetus was initially diagnosed with FGR but grew to an EFW greater than the tenth percentile, weekly visits continued until a second growth ultrasound confirmed normal growth. RESULTS: Abnormal UAD measurements were seen in 48 fetuses during 141 visits. During the course of follow-up, eleven fetuses (23%) demonstrated improvement in fetal growth to an EFW greater than the tenth percentile. There were 8 fetuses (38%) with abnormal S/D ratios in a single artery that demonstrated resolution of FGR; five (63%) had abnormal UAD measurements when measuring above the tenth percentile. Only 3 fetuses (11%) with abnormalities in both arteries demonstrated growth above the tenth percentile; all 3 (100%) had abnormal S/D ratios during the period of improved growth. CONCLUSION: Abnormal UAD measurements were seen in 73% of the fetuses in our study with resolved FGR. This may reflect imprecision in the classification of FGR. Alternatively, another mechanism, such as incomplete maturation of placental anastomoses, may be present to cause abnormal UAD measurements.
birth. Given the relationship between shortened telomere length and future morbidity and mortality, the results could potentially provide a pathway of understanding and preventing adult-onset disease and mortality through intra-uterine re-programming.
Distribution of abnormal UAD measurements among fetuses with resolved growth restriction
599 A receptor for danger signals, advanced glycation end products (RAGE) in fetal systemic inflammation and clinical chorioamnionitis
Ahmed Ahmed1, Piya Chaemsaithong1, Tinnakorn Chaiworapongsa1, Dong Zhong1, Majid Shaman1, Kia Lannaman1, Lami Yeo1, Sonia Hassan1, Bo Hyun Yoon2, Roberto Romero1
1 NICHD/ NIH/ DHHS, Perinatology Research Branch, Detroit, MI; Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, MI, 2Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Seoul, Republic of Korea
598 Umbilical cord telomere length and folate levels e a potential pathway for fetal re-programming 1
1
2
Adetola Louis-Jacques , Rachel Sinkey , Arnut Paothong , Lindsey King2, Anupam Pradhan3, Valerie Whiteman1, Karen Bruder1, Roger Zoorob4, Hamisu Salihu2
1 Morsani College of Medicine, Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine, Tampa, FL, 2University of South Florida, Department of Epidemiology and Biostatistics, College of Public Health, Tampa, FL, 3University of South Florida, Department of Global Health, College of Public Health, Tampa, FL, 4Baylor College of Medicine, Department of Family and Community Medicine, Houston, TX
OBJECTIVE: Telomere length has been studied in adults but little is known about factors that influence it in-utero. The objective of this study is to investigate the relationship between fetal folate levels and telomere length. STUDY DESIGN: This was part of a cohort study conducted from 20112012 in pregnant women with a singleton gestation who were admitted for labor and delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene (T/S) ratio method was used to determine telomere length. Cord blood folate levels were also measured. Statistical analysis was performed using bootstrap and generalized linear modeling (GLM). RESULTS: A total of 96 maternal-fetal dyads were enrolled in this study. The mean gestational age was 39.44 weeks. Figure 1 illustrates the histogram of all p-values generated using GLM from the 10,000 bootstrapping simulations. The distribution of the coefficient of folate showed all values to be greater than 0 confirming that folate had a positive correlation with T/S ratio. The figure shows that in 9,553 of the 10,000 (95.53%) iterations performed, p-value was <0.05, demonstrating statistical significance. This means that fetuses exposed to higher folate levels had a longer telomere length. CONCLUSION: Our study is the first of its kind to show a positive association between umbilical cord folate and fetal telomere length at
OBJECTIVE: Fetal Systemic Inflammatory Response Syndrome (FIRS)
is considered the counterpart of the Systemic Inflammatory Response Syndrome of adults, which can be caused by infection and non-infection-related insults. The receptor for advanced glycation end products (RAGE) participates in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines. The soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) have both anti-inflammatory and proinflammatory properties. The objective of this study was to determine whether FIRS is associated with changes in the umbilical cord (UC) plasma concentration of sRAGE and esRAGE. STUDY DESIGN: UC blood was collected from the following groups: 1) preterm deliveries with (n¼31) and without FIRS (n¼42); and 2) Term deliveries divided into 3 groups: i) Term clinical chorioamnionitis (n¼23), ii) Term without labor (n¼23) and iii) Term labor (n¼23). FIRS was diagnosed by UC blood IL-6 (>17.5 pg/mL). Plasma concentrations of sRAGE, esRAGE and IL-6 were determined by ELISA. RESULTS: 1) Preterm neonates with FIRS had a lower median UC plasma concentration of sRAGE (ng/mL) and esRAGE (ng/mL) than those without FIRS (sRAGE: 1381 vs. 2574; p¼0.0006; esRAGE 0.44 vs. 0.78: p¼0.0004); 2) There was a negative correlation between the UC plasma concentration of sRAGE or esRAGE and IL-6 in preterm neonates (sRAGE: Spearman Rho¼ -0.41, p<0.001, esRAGE: Spearman Rho¼ -0.4, p<0.002); 3) The median UC plasma sRAGE and esRAGE concentration were lower in term labor than in those without labor (sRAGE: 1318 vs. 2166, esRAGE 0.32 vs. 0.57; each p¼0.006); and 4) there were no significant differences in the median sRAGE and esRAGE UC plasma concentrations between term neonate with labor and those with clinical chorioamnionitis (each p>0.05). CONCLUSION: We provide evidence for differential expression of a receptor for Danger signals in fetal systemic inflammation and clinical chorioamnionitis at term.
S298 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015