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807: Autophagy and inducible 70kDa heat shock protein influences in pregnancy, parturition and postpartum
Poster Session V
ajog.org 807 Autophagy and inducible 70kDa heat shock protein influences in pregnancy, parturition and postpartum Tomi Kanninen1, Giovanni Sisti1, Dimitrios Nasioudis1, Mio Sawai1, Aswathi Jayaram2, Steven Inglis2, Steven S. Witkin1 1
Weill Cornell Medical College, New York, NY, 2Jamaica Hospital Medical Center, New York, NY
OBJECTIVE: Determine the relationship between autophagy and levels
of the 70kDa heat shock protein (hsp70) in pregnancy and parturition. STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were isolated from pregnant and non-pregnant women. A portion was tested immediately while other aliquots were incubated for 24 hours in the presence of an hsp70 inducer. PBMCs were lysed and analyzed for intracellular hsp70 and p62. Hsp70 inhibits autophagy and down-regulates pro-inflammatory immunity; p62 is a cytoplasmic protein consumed during autophagy induction. Its concentration is inversely related to the extent of autophagy. Vaginal epithelial cells were obtained from pregnant and postpartum (PP) women and similarly tested for p62 and hsp70. Clinical data was obtained after completion of testing. RESULTS: The level of autophagy was higher, and hsp70 was lower, in PBMCs from pregnant than from non-pregnant women (p<0.000). Autophagy levels in third trimester PBMCs were higher in women whose labor had to be induced or augmented than in women with spontaneous labor (p ¼ 0.044). Autophagy levels in third trimester vaginal epithelial cells was inversely proportional to the time interval from membrane rupture to delivery (p¼0.020). Autophagy levels in PP vaginal epithelial cells was inversely correlated with the time interval from a 4 cm cervical dilation to delivery (p¼0.010). Incubation of PBMCs with an hsp70 inducer resulted in elevated intracellular hsp70 levels and inhibition of autophagy. Concentrations of hsp70 and the extent of autophagy induction were highly inversely correlated in all samples (p<0.000). CONCLUSION: Autophagy, modulated by hsp70, is induced to a greater extent in PBMCs from pregnant than in non-pregnant women emphasizing their regulatory roles during gestation. The association between a reduction in autophagy, labor induction and time to delivery is consistent with evidence that autophagy inhibition contributes to parturition.
RESULTS: Among 1315 women, 46.0% (N¼612) of labors were within the green zone, 40.0% (N¼523) in yellow, and 14.0% (N¼180) in red. Compared to women in the green zone, there was a 3.7-fold (95% CI 2.35-5.84) and 10.23-fold (95% CI 6.47-16.10) increased risk of cesarean delivery among women in the yellow and red zones, respectively. Chorioamnionitis increased by 3.71-fold (95%CI 1.66-8.27) and 5.24-fold (95% CI 2.14-12.84) among women in the yellow and red zones, respectively. Apgar score <7 at 5 minutes was increased 2.11-fold (95%CI 1.12-3.95) and 2.98-fold (95%CI 6.33) in both the yellow and red zones. Partogram zones were not associated with NICU admission or EBL. CONCLUSION: We found an increase in adverse maternal and neonatal outcomes among women with active labor duration in the yellow and red partogram zones. Future prospective studies using a partogram and specific labor management protocols will help determine if the NICHD-SMFM-ACOG labor length guidelines will result in improvement in the cesarean rates without increasing other adverse outcomes.
808 The effects of contemporary partogram zone analysis for spontaneous labor on adverse maternal and neonatal outcomes Kara Hoppe1, Shani Delaney1, Melissa A. Schiff1, Thomas J. Benedetti1 1
University of Washington, Seattle, WA
OBJECTIVE: To assess the effect of a newly constructed partogram
based on the NICHD-SMFM-ACOG labor guidelines on maternal and neonatal outcomes. STUDY DESIGN: A retrospective cohort study evaluated the association between active labor partogram zones and adverse maternal and neonatal outcomes at the University of Washington from 1/2012 - 1/ 2015. Our subjects included women 18-44 years in spontaneous labor with a cephalic, singleton fetus >37 weeks gestation. Partogram zones were based on labor duration from 6-10 cm published by Zhang, et al, with green zone defined as 4 to 8 hours. The partogram was applied retrospectively to historical labor. We evaluated the association between zones and cesarean delivery, chorioamnionitis, estimated blood loss (EBL), Apgar score < 7 at 5 minutes, and admission to neonatal intensive care (NICU) unit using logistic regression to estimate odds ratios and 95% confidence intervals (CI), adjusting for parity.
809 Cell free DNA (cfDNA), the inflammatory cascade, and initiation of term labor Christina Herrera1, Jay Stoerker2, John Carlquist1, Sean Esplin1, Greg Snow3, Marc Jackson1, Nancy C. Rose1 1
University of Utah and Intermountain Healthcare, Salt Lake City, UT, Progenity Inc, Ann Arbor, MI, 3Intermountain Healthcare, Murray, UT
2
OBJECTIVE: It has been proposed that hypomethylated cfDNA acti-
vates the TLR9 receptor of the inflammatory cascade to initiate labor.
Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S421
ajog.org 807 Autophagy and inducible 70kDa heat shock protein influences in pregnancy, parturition and postpartum Tomi Kanninen1, Giovanni Sisti1, Dimitrios Nasioudis1, Mio Sawai1, Aswathi Jayaram2, Steven Inglis2, Steven S. Witkin1 1
Weill Cornell Medical College, New York, NY, 2Jamaica Hospital Medical Center, New York, NY
OBJECTIVE: Determine the relationship between autophagy and levels
of the 70kDa heat shock protein (hsp70) in pregnancy and parturition. STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were isolated from pregnant and non-pregnant women. A portion was tested immediately while other aliquots were incubated for 24 hours in the presence of an hsp70 inducer. PBMCs were lysed and analyzed for intracellular hsp70 and p62. Hsp70 inhibits autophagy and down-regulates pro-inflammatory immunity; p62 is a cytoplasmic protein consumed during autophagy induction. Its concentration is inversely related to the extent of autophagy. Vaginal epithelial cells were obtained from pregnant and postpartum (PP) women and similarly tested for p62 and hsp70. Clinical data was obtained after completion of testing. RESULTS: The level of autophagy was higher, and hsp70 was lower, in PBMCs from pregnant than from non-pregnant women (p<0.000). Autophagy levels in third trimester PBMCs were higher in women whose labor had to be induced or augmented than in women with spontaneous labor (p ¼ 0.044). Autophagy levels in third trimester vaginal epithelial cells was inversely proportional to the time interval from membrane rupture to delivery (p¼0.020). Autophagy levels in PP vaginal epithelial cells was inversely correlated with the time interval from a 4 cm cervical dilation to delivery (p¼0.010). Incubation of PBMCs with an hsp70 inducer resulted in elevated intracellular hsp70 levels and inhibition of autophagy. Concentrations of hsp70 and the extent of autophagy induction were highly inversely correlated in all samples (p<0.000). CONCLUSION: Autophagy, modulated by hsp70, is induced to a greater extent in PBMCs from pregnant than in non-pregnant women emphasizing their regulatory roles during gestation. The association between a reduction in autophagy, labor induction and time to delivery is consistent with evidence that autophagy inhibition contributes to parturition.
RESULTS: Among 1315 women, 46.0% (N¼612) of labors were within the green zone, 40.0% (N¼523) in yellow, and 14.0% (N¼180) in red. Compared to women in the green zone, there was a 3.7-fold (95% CI 2.35-5.84) and 10.23-fold (95% CI 6.47-16.10) increased risk of cesarean delivery among women in the yellow and red zones, respectively. Chorioamnionitis increased by 3.71-fold (95%CI 1.66-8.27) and 5.24-fold (95% CI 2.14-12.84) among women in the yellow and red zones, respectively. Apgar score <7 at 5 minutes was increased 2.11-fold (95%CI 1.12-3.95) and 2.98-fold (95%CI 6.33) in both the yellow and red zones. Partogram zones were not associated with NICU admission or EBL. CONCLUSION: We found an increase in adverse maternal and neonatal outcomes among women with active labor duration in the yellow and red partogram zones. Future prospective studies using a partogram and specific labor management protocols will help determine if the NICHD-SMFM-ACOG labor length guidelines will result in improvement in the cesarean rates without increasing other adverse outcomes.
808 The effects of contemporary partogram zone analysis for spontaneous labor on adverse maternal and neonatal outcomes Kara Hoppe1, Shani Delaney1, Melissa A. Schiff1, Thomas J. Benedetti1 1
University of Washington, Seattle, WA
OBJECTIVE: To assess the effect of a newly constructed partogram
based on the NICHD-SMFM-ACOG labor guidelines on maternal and neonatal outcomes. STUDY DESIGN: A retrospective cohort study evaluated the association between active labor partogram zones and adverse maternal and neonatal outcomes at the University of Washington from 1/2012 - 1/ 2015. Our subjects included women 18-44 years in spontaneous labor with a cephalic, singleton fetus >37 weeks gestation. Partogram zones were based on labor duration from 6-10 cm published by Zhang, et al, with green zone defined as 4 to 8 hours. The partogram was applied retrospectively to historical labor. We evaluated the association between zones and cesarean delivery, chorioamnionitis, estimated blood loss (EBL), Apgar score < 7 at 5 minutes, and admission to neonatal intensive care (NICU) unit using logistic regression to estimate odds ratios and 95% confidence intervals (CI), adjusting for parity.
809 Cell free DNA (cfDNA), the inflammatory cascade, and initiation of term labor Christina Herrera1, Jay Stoerker2, John Carlquist1, Sean Esplin1, Greg Snow3, Marc Jackson1, Nancy C. Rose1 1
University of Utah and Intermountain Healthcare, Salt Lake City, UT, Progenity Inc, Ann Arbor, MI, 3Intermountain Healthcare, Murray, UT
2
OBJECTIVE: It has been proposed that hypomethylated cfDNA acti-
vates the TLR9 receptor of the inflammatory cascade to initiate labor.
Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S421