The Experts below are selected from a list of 48 Experts worldwide ranked by ideXlab platform
Ronald J Wapner - One of the best experts on this subject based on the ideXlab platform.
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timing of elective repeat cesarean delivery at term and neonatal outcomes
Obstetrical & Gynecological Survey, 2009Co-Authors: Alan T N Tita, Mark B Landon, Catherine Y Spong, Yinglei Lai, Kenneth J Leveno, Michael W Varner, Atef H Moawad, Steve N Caritis, Paul J Meis, Ronald J WapnerAbstract:The risk of neonatal adverse respiratory outcomes is higher among infants delivered before 39 weeks' gestation than after 39 weeks', and among infants delivered by prelabor cesarean compared to those delivered vaginally. Thus, elective cesarean section before 39 weeks is discouraged in the absence of fetal lung maturity. This prospective study compared neonatal outcomes among infants delivered by elective cesarean delivery at 37, 38, and 39 weeks' gestation. The study cohort was pregnant women with viable singleton pregnancies undergoing repeat cesarean delivery at 19 academic medical centers. The women were delivered before onset of labor and had no medical or obstetrical indications for delivery before 39 weeks. The primary study outcome was a composite of any adverse neonatal outcome or death. Adverse outcomes included respiratory complications, admission to the neonatal intensive care unit (ICU), Newborn Sepsis, treated hypoglycemia, and hospitalization for 5 days or longer. Logistic regression models were used to calculate adjusted odds ratios for the association between neonatal outcomes and gestational age at birth relative to 39 completed weeks. Among the study cohort, 13,258 women underwent elective repeat cesarean section at term. Of these, 49.1% had the procedure at 39 weeks', and 35.8% had the procedure before 39 completed weeks' gestation (6.3% at 37 weeks and 29.5% at 38 weeks). With increasing gestational age at birth, the risk of the primary outcome decreased. Unadjusted analysis showed that the incidence of the primary outcome was 15.3% at 37 weeks, 11.0% at 38 weeks, and 8.0% at 39 weeks (P for trend <0.001). The differences remained after adjusting for variables (P for trend <0.001). The adjusted risk of individual adverse outcomes including adverse respiratory complications, admission to the neonatal ICU, Newborn Sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks, relative to births at 39 weeks' gestation. There was only 1 neonatal death, of an infant born at 39 weeks. These findings suggest that postponing elective delivery to 39 weeks might prevent a significant number of adverse neonatal outcomes or deaths, and support recommendations to delay elective delivery until 39 weeks' gestation.
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timing of elective repeat cesarean delivery at term and neonatal outcomes
The New England Journal of Medicine, 2009Co-Authors: Alan T N Tita, Mark B Landon, Catherine Y Spong, Yinglei Lai, Kenneth J Leveno, Michael W Varner, Atef H Moawad, Steve N Caritis, Paul J Meis, Ronald J WapnerAbstract:BACKGROUND Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes. METHODS We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively (i.e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, Newborn Sepsis, and admission to the neonatal intensive care unit (ICU). RESULTS Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation (6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome (adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend <0.001). The rates of adverse respiratory outcomes, mechanical ventilation, Newborn Sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks. CONCLUSIONS Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.
Ofer Levy - One of the best experts on this subject based on the ideXlab platform.
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a neonatal murine escherichia coli Sepsis model demonstrates that adjunctive pentoxifylline enhances the ratio of anti vs pro inflammatory cytokines in blood and organ tissues
Frontiers in Immunology, 2020Co-Authors: Esther M Speer, Elizabeth Diagonavarro, Lukasz S Ozog, Mahnoor Raheel, Bettina C Fries, Ofer LevyAbstract:Introduction: Neonatal Sepsis triggers an inflammatory response that contributes to mortality and multiple organ injury. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses pro-inflammatory cytokines, is a candidate adjunctive therapy for Newborn Sepsis. We hypothesized that administration of PTX in addition to antibiotics decreases live bacteria-induced pro-inflammatory and/or enhances anti-inflammatory cytokine production in septic neonatal mice without augmenting bacterial growth. Methods: Newborn C57BL/6J mice (< 24 h old) were injected intravenously with 105 colony forming units (CFUs)/g weight of a bioluminescent derivative of the encapsulated clinical isolate Escherichia coli O18:K1. Adequacy of intravenous injections was validated using in vivo bioluminescence imaging and Evans blue. Pups were treated with gentamicin (GENT), PTX, (GENT + PTX) or saline at 0, 1.5, or 4 h after Sepsis initiation, and euthanized after an additional 4 h. CFUs and cytokines were measured from blood and homogenized organ tissues. Results: GENT alone inhibited bacterial growth, IL-1β, and IL-6 production in blood and organs. Addition of PTX to GENT profoundly inhibited E. coli-induced TNF and enhanced IL-10 in blood of Newborn mice at all timepoints, whereas it primarily upregulated IL-10 production in peripheral organs (lung, spleen, brain). PTX, whether alone or adjunctive to GENT, did not increase microbial colony counts in blood and organs. Conclusion: Addition of PTX to antibiotics in murine neonatal E. coli Sepsis promoted an anti-inflammatory milieu through inhibition of plasma TNF and enhancement of IL-10 production in plasma and organs without increasing bacterial growth, supporting its utility as a potential adjunctive agent for Newborn Sepsis.
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pentoxifylline alone or in combination with gentamicin or vancomycin inhibits live microbe induced proinflammatory cytokine production in human cord blood and cord blood monocytes in vitro
Antimicrobial Agents and Chemotherapy, 2018Co-Authors: Esther M Speer, Elizabeth Diagonavarro, Lukasz S Ozog, David J Dowling, Mahnoor Raheel, Bettina C Fries, Ofer LevyAbstract:Introduction: Neonatal Sepsis and its accompanying inflammatory response contribute to substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses transcription and production of pro-inflammatory cytokines, is a candidate adjunctive therapy for Newborn Sepsis. We hypothesized that PTX decreases live microbe-induced inflammatory cytokine production in Newborn blood. Methods: Cord blood was stimulated with live microorganisms commonly encountered in Newborn Sepsis ( Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis , or Candida albicans ), and simultaneously treated with antimicrobial agents (gentamicin, vancomycin, or amphotericin B) and/or clinically relevant concentrations of PTX. Microbial colony counts were enumerated by plating, supernatant cytokines measured by multiplex assay, intracellular cytokines and signaling molecules by flow cytometry, and mRNA by qRT PCR. Results: PTX inhibited concentration-dependent E. coli -, S. aureus-, S. epidermidis- , and C. albicans -induced TNF and E. coli -induced IL-1β production in whole blood, with greater suppression of pro-inflammatory cytokines in combination with antimicrobial agents. Likewise, PTX suppressed E. coli -induced monocytic TNF and IL-1β, whereby combined PTX and gentamicin led to significantly greater reduction of TNF and IL-1β. The anti-inflammatory effect of PTX on microbe-induced pro-inflammatory cytokine production was accompanied by inhibition of TNF mRNA expression, and was achieved without suppressing the production of the anti-inflammatory IL-10. Of note, microbial colony counts in Newborn blood were not increased by PTX. Conclusion: Our findings demonstrated that PTX inhibited microbe-induced pro-inflammatory cytokine production, especially when combined with antimicrobial agents, without enhancing microbial proliferation in human cord blood in vitro , thus supporting its utility as candidate adjunctive agent for Newborn Sepsis.
Alan T N Tita - One of the best experts on this subject based on the ideXlab platform.
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timing of elective repeat cesarean delivery at term and neonatal outcomes
Obstetrical & Gynecological Survey, 2009Co-Authors: Alan T N Tita, Mark B Landon, Catherine Y Spong, Yinglei Lai, Kenneth J Leveno, Michael W Varner, Atef H Moawad, Steve N Caritis, Paul J Meis, Ronald J WapnerAbstract:The risk of neonatal adverse respiratory outcomes is higher among infants delivered before 39 weeks' gestation than after 39 weeks', and among infants delivered by prelabor cesarean compared to those delivered vaginally. Thus, elective cesarean section before 39 weeks is discouraged in the absence of fetal lung maturity. This prospective study compared neonatal outcomes among infants delivered by elective cesarean delivery at 37, 38, and 39 weeks' gestation. The study cohort was pregnant women with viable singleton pregnancies undergoing repeat cesarean delivery at 19 academic medical centers. The women were delivered before onset of labor and had no medical or obstetrical indications for delivery before 39 weeks. The primary study outcome was a composite of any adverse neonatal outcome or death. Adverse outcomes included respiratory complications, admission to the neonatal intensive care unit (ICU), Newborn Sepsis, treated hypoglycemia, and hospitalization for 5 days or longer. Logistic regression models were used to calculate adjusted odds ratios for the association between neonatal outcomes and gestational age at birth relative to 39 completed weeks. Among the study cohort, 13,258 women underwent elective repeat cesarean section at term. Of these, 49.1% had the procedure at 39 weeks', and 35.8% had the procedure before 39 completed weeks' gestation (6.3% at 37 weeks and 29.5% at 38 weeks). With increasing gestational age at birth, the risk of the primary outcome decreased. Unadjusted analysis showed that the incidence of the primary outcome was 15.3% at 37 weeks, 11.0% at 38 weeks, and 8.0% at 39 weeks (P for trend <0.001). The differences remained after adjusting for variables (P for trend <0.001). The adjusted risk of individual adverse outcomes including adverse respiratory complications, admission to the neonatal ICU, Newborn Sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks, relative to births at 39 weeks' gestation. There was only 1 neonatal death, of an infant born at 39 weeks. These findings suggest that postponing elective delivery to 39 weeks might prevent a significant number of adverse neonatal outcomes or deaths, and support recommendations to delay elective delivery until 39 weeks' gestation.
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timing of elective repeat cesarean delivery at term and neonatal outcomes
The New England Journal of Medicine, 2009Co-Authors: Alan T N Tita, Mark B Landon, Catherine Y Spong, Yinglei Lai, Kenneth J Leveno, Michael W Varner, Atef H Moawad, Steve N Caritis, Paul J Meis, Ronald J WapnerAbstract:BACKGROUND Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes. METHODS We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively (i.e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, Newborn Sepsis, and admission to the neonatal intensive care unit (ICU). RESULTS Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation (6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome (adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend <0.001). The rates of adverse respiratory outcomes, mechanical ventilation, Newborn Sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks. CONCLUSIONS Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.
Bettina C Fries - One of the best experts on this subject based on the ideXlab platform.
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a neonatal murine escherichia coli Sepsis model demonstrates that adjunctive pentoxifylline enhances the ratio of anti vs pro inflammatory cytokines in blood and organ tissues
Frontiers in Immunology, 2020Co-Authors: Esther M Speer, Elizabeth Diagonavarro, Lukasz S Ozog, Mahnoor Raheel, Bettina C Fries, Ofer LevyAbstract:Introduction: Neonatal Sepsis triggers an inflammatory response that contributes to mortality and multiple organ injury. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses pro-inflammatory cytokines, is a candidate adjunctive therapy for Newborn Sepsis. We hypothesized that administration of PTX in addition to antibiotics decreases live bacteria-induced pro-inflammatory and/or enhances anti-inflammatory cytokine production in septic neonatal mice without augmenting bacterial growth. Methods: Newborn C57BL/6J mice (< 24 h old) were injected intravenously with 105 colony forming units (CFUs)/g weight of a bioluminescent derivative of the encapsulated clinical isolate Escherichia coli O18:K1. Adequacy of intravenous injections was validated using in vivo bioluminescence imaging and Evans blue. Pups were treated with gentamicin (GENT), PTX, (GENT + PTX) or saline at 0, 1.5, or 4 h after Sepsis initiation, and euthanized after an additional 4 h. CFUs and cytokines were measured from blood and homogenized organ tissues. Results: GENT alone inhibited bacterial growth, IL-1β, and IL-6 production in blood and organs. Addition of PTX to GENT profoundly inhibited E. coli-induced TNF and enhanced IL-10 in blood of Newborn mice at all timepoints, whereas it primarily upregulated IL-10 production in peripheral organs (lung, spleen, brain). PTX, whether alone or adjunctive to GENT, did not increase microbial colony counts in blood and organs. Conclusion: Addition of PTX to antibiotics in murine neonatal E. coli Sepsis promoted an anti-inflammatory milieu through inhibition of plasma TNF and enhancement of IL-10 production in plasma and organs without increasing bacterial growth, supporting its utility as a potential adjunctive agent for Newborn Sepsis.
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pentoxifylline alone or in combination with gentamicin or vancomycin inhibits live microbe induced proinflammatory cytokine production in human cord blood and cord blood monocytes in vitro
Antimicrobial Agents and Chemotherapy, 2018Co-Authors: Esther M Speer, Elizabeth Diagonavarro, Lukasz S Ozog, David J Dowling, Mahnoor Raheel, Bettina C Fries, Ofer LevyAbstract:Introduction: Neonatal Sepsis and its accompanying inflammatory response contribute to substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses transcription and production of pro-inflammatory cytokines, is a candidate adjunctive therapy for Newborn Sepsis. We hypothesized that PTX decreases live microbe-induced inflammatory cytokine production in Newborn blood. Methods: Cord blood was stimulated with live microorganisms commonly encountered in Newborn Sepsis ( Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis , or Candida albicans ), and simultaneously treated with antimicrobial agents (gentamicin, vancomycin, or amphotericin B) and/or clinically relevant concentrations of PTX. Microbial colony counts were enumerated by plating, supernatant cytokines measured by multiplex assay, intracellular cytokines and signaling molecules by flow cytometry, and mRNA by qRT PCR. Results: PTX inhibited concentration-dependent E. coli -, S. aureus-, S. epidermidis- , and C. albicans -induced TNF and E. coli -induced IL-1β production in whole blood, with greater suppression of pro-inflammatory cytokines in combination with antimicrobial agents. Likewise, PTX suppressed E. coli -induced monocytic TNF and IL-1β, whereby combined PTX and gentamicin led to significantly greater reduction of TNF and IL-1β. The anti-inflammatory effect of PTX on microbe-induced pro-inflammatory cytokine production was accompanied by inhibition of TNF mRNA expression, and was achieved without suppressing the production of the anti-inflammatory IL-10. Of note, microbial colony counts in Newborn blood were not increased by PTX. Conclusion: Our findings demonstrated that PTX inhibited microbe-induced pro-inflammatory cytokine production, especially when combined with antimicrobial agents, without enhancing microbial proliferation in human cord blood in vitro , thus supporting its utility as candidate adjunctive agent for Newborn Sepsis.
Mark B Landon - One of the best experts on this subject based on the ideXlab platform.
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timing of elective repeat cesarean delivery at term and neonatal outcomes
Obstetrical & Gynecological Survey, 2009Co-Authors: Alan T N Tita, Mark B Landon, Catherine Y Spong, Yinglei Lai, Kenneth J Leveno, Michael W Varner, Atef H Moawad, Steve N Caritis, Paul J Meis, Ronald J WapnerAbstract:The risk of neonatal adverse respiratory outcomes is higher among infants delivered before 39 weeks' gestation than after 39 weeks', and among infants delivered by prelabor cesarean compared to those delivered vaginally. Thus, elective cesarean section before 39 weeks is discouraged in the absence of fetal lung maturity. This prospective study compared neonatal outcomes among infants delivered by elective cesarean delivery at 37, 38, and 39 weeks' gestation. The study cohort was pregnant women with viable singleton pregnancies undergoing repeat cesarean delivery at 19 academic medical centers. The women were delivered before onset of labor and had no medical or obstetrical indications for delivery before 39 weeks. The primary study outcome was a composite of any adverse neonatal outcome or death. Adverse outcomes included respiratory complications, admission to the neonatal intensive care unit (ICU), Newborn Sepsis, treated hypoglycemia, and hospitalization for 5 days or longer. Logistic regression models were used to calculate adjusted odds ratios for the association between neonatal outcomes and gestational age at birth relative to 39 completed weeks. Among the study cohort, 13,258 women underwent elective repeat cesarean section at term. Of these, 49.1% had the procedure at 39 weeks', and 35.8% had the procedure before 39 completed weeks' gestation (6.3% at 37 weeks and 29.5% at 38 weeks). With increasing gestational age at birth, the risk of the primary outcome decreased. Unadjusted analysis showed that the incidence of the primary outcome was 15.3% at 37 weeks, 11.0% at 38 weeks, and 8.0% at 39 weeks (P for trend <0.001). The differences remained after adjusting for variables (P for trend <0.001). The adjusted risk of individual adverse outcomes including adverse respiratory complications, admission to the neonatal ICU, Newborn Sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks, relative to births at 39 weeks' gestation. There was only 1 neonatal death, of an infant born at 39 weeks. These findings suggest that postponing elective delivery to 39 weeks might prevent a significant number of adverse neonatal outcomes or deaths, and support recommendations to delay elective delivery until 39 weeks' gestation.
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timing of elective repeat cesarean delivery at term and neonatal outcomes
The New England Journal of Medicine, 2009Co-Authors: Alan T N Tita, Mark B Landon, Catherine Y Spong, Yinglei Lai, Kenneth J Leveno, Michael W Varner, Atef H Moawad, Steve N Caritis, Paul J Meis, Ronald J WapnerAbstract:BACKGROUND Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes. METHODS We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively (i.e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, Newborn Sepsis, and admission to the neonatal intensive care unit (ICU). RESULTS Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation (6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome (adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend <0.001). The rates of adverse respiratory outcomes, mechanical ventilation, Newborn Sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks. CONCLUSIONS Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.