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501: Value of magnesium sulfate < 12 hours to prevent cerebral palsy and death
Poster Session III 499 Cytokine concentrations and their association with preterm birth: comparison between serum and cervicovaginal measurements
Kristin Ashford1, John O’Brien1, Kristen McQuerry1, Janine Barnett1, Andrea McCubbin1, James Ferguson2, Jeff Ebersole1
1 University of Kentucky, Lexington, KY, 2University of Virginia, Obstetrics & Gynecology, Charlottesville, VA
OBJECTIVE: Our aim was to determine the association of cytokine values obtained at each trimester from different body fluids with the frequency of preterm birth. STUDY DESIGN: This was a primary analysis of a prospective, multicenter study of women with a singleton gestation. Maternal serum was collected each trimester. Cytokines (IL-1a, IL-1b, IL-2, IL-6, IL8, IL-10, TNFa, CRP and MMP 8) were measured using multiplex beadlyte assay on a Luminex IS-100. Statistical analysis was performed using univariate analyses. The analysis was adjusted for potential confounders including age, race, education, income, and tobacco use. RESULTS: 399 women were enrolled. 114 (29%) of the participants were smokers and 38 (9.5%) delivered preterm. Using univariate analysis, serum IL-6 (P¼ .03) in the 1st trimester; and IL-1b (P¼ .01) and MMP-8 (P¼.03) in the 3rd trimester were significantly different in groups who delivered preterm versus term. These remained significant in the adjusted analysis. The interval change of these cytokines was associated with preterm birth for IL-1b between the 2nd and 3rd trimesters. A subset of 92 patients also underwent evaluation of cytokines in cervicovaginal fluid. In the adjusted analysis, the following cytokines were significantly associated with preterm birth in each trimester: IL-10 (P¼.004, 001, .005, respectively); TNFa (P¼.001,<.001,.009, respectively); and CRP (P¼.01,.009,.01, respectively). In the 2nd and 3rd trimesters, IL-1b (P¼.03,.005, respectively) and IL-8 (P¼.05) in the 3rd trimester were also significantly associated with preterm birth. CONCLUSION: Both pro-inflammatory and anti-inflammatory cytokine concentrations vary in women who will deliver preterm versus term. Varying cytokines are associated with preterm birth in differing bodily fluids. Cervicovaginal fluid is the more descriptive source of the inflammatory milieu predicting preterm birth especially earlier in gestation when therapeutic interventions can be potentially efficacious.
500 Tobacco use alters pregnancy biomarkers reflecting tissue function
Kristin Ashford1, John O’Brien1, Janine Barnett1, Andrea McCubbin1, Kristin McQuerry1, Thomas Curry1 1
University of Kentucky, Lexington, KY
OBJECTIVE: We have previously identified associations between
tobacco exposure and cytokine concentrations in the serum and cervicovaginal fluid. Our aim was to determine the association between urinary cotinine concentration and other biomarkers reflecting tissue level pharmacodynamic changes particularly in placental function and cervical performance. STUDY DESIGN: This study was a secondary analysis of a prospective, multi-center study of pregnant women with a singleton gestation and included women with sufficient sample to allow assessment of serum progesterone concentration in the second trimester. Women on progestogen therapy (17-OHPC or vaginal progesterone) were excluded. Concentrations of progesterone and estradiol were measured using an Immulite 1000. Urine cotinine was measured using a validated assay. Analysis of variance was performed to test for associations. Multiple variable regression analysis was used to adjust for potential confounders including age, race, and BMI. RESULTS: 109 women were included at a mean gestational age of 19.9 1.5 weeks. Five patients had previously undergone cervical surgery (LEEP or cerclage) and were excluded from the analyses. Smoking
ajog.org was confirmed by objective measure in 25 of these patients (24%). Rising urinary cotinine values (100 ng/mL) were significantly associated with decreasing serum progesterone values, 60 19.5 ng/mL lower cotinine group versus 49 14.6 ng/mL with higher concentrations, P¼.024. Serum estradiol was not associated with cotinine values nor was the ratio of serum progesterone/estradiol. The cervical length in the second trimester was also associated with cotinine concentrations. Mean cervical length for smokers was 30 16 mm versus 35 12 mm for nonsmokers, P¼.023. The findings remained statistically significant in the adjusted analysis. CONCLUSION: Urinary cotinine is significantly associated with tissue dysfunction affecting placental production of progesterone and cervical length. Further evaluation of the mechanisms for these findings of tissue dysfunction is needed.
501 Value of magnesium sulfate < 12 hours to prevent cerebral palsy and death Laura Meints1, Alexandra Edwards1, Meng Liu2
1 University of Kentucky, Obstetrics & Gynecology, Lexington, KY, 2University of Kentucky, Biostatistics & Epidemiology, Lexington, KY
OBJECTIVE: Magnesium sulfate (MS) is standard of care for the prevention of moderate and severe cerebral palsy (CP), among women who are expected to deliver at less than 32 weeks gestation. Many women who are expected to deliver in this circumstance do not receive the recommended course of MS for 12 hours. Our aim is to examine whether women who are expected to deliver before 32 weeks gestation and who receive < 12 hours of MS have an increased risk of CP and death in their children. STUDY DESIGN: This study is a secondary analysis of a multi-center, randomized controlled trial. The exposure was duration of MS among women who received at least 6g of MS (< 4 hrs, 4-12 hrs, 12 hrs). The primary outcome was a composite of stillbirth or infant death by 1 year of corrected age or moderate or severe CP at or beyond 2 years of corrected age. We performed univariate and multiple logistic regression with generalized estimating equations to determine the potential association between primary outcome and duration of magnesium sulfate. These associations are reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: There were 1,065 women included in the analysis. Women who received at least 12 hours of MS were more likely to have PPROM (p < .0001), be multiparous (p ¼ .01), have a singleton gestation (p ¼ .01), and receive antenatal steroids (p ¼ 0.001). In the univariate analysis, women who received at least 12 hours of MS had decreased rate of the combined outcome (9.3%, vs 12.8% among women who received 4-12 hrs of MS and 16.3% among women who received < 4 hrs of MS). After controlling for birth weight, gestational age, tobacco use, race, and betamethasone, however, the adjusted model showed no statistically significant differences: < 4 hrs (aOR 1.57, CI 0.84 - 2.95), 4-12 hrs (aOR 1.64, 0.84 - 3.21), and 12 hrs (reference). CONCLUSION: This study showed no increase in risk for cerebral palsy and death among children of women expected to deliver preterm due to exposure time of < 12 hours of magnesium sulfate.
502 Myometrial electrical activity at labor e Is there a correlation between labor stages?
Liran Hiersch1, Eran Ashwal1, Amir Aviram1, Liat Salzer1, Eran Hadar1, Arnon Wiznitzer1, Yariv Yogev1
1 Helen Schneider Hospital for Women, Rabin Medical Center, Obstetrics and Gynecology, Petach Tikva, Israel
OBJECTIVE: To determine the association between the myometrial
electrical activity in the active and second stages of labor at term using a novel technology of electrical uterine monitor (EUM). STUDY DESIGN: A prospective observational study of 47 women with singleton pregnancy and spontaneous onset of labor at term (370/6 to 416/6 weeks of gestation) in a university-affiliated tertiary hospital. All patients were assessed using non-invasive 9-channel surface
S252 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
Kristin Ashford1, John O’Brien1, Kristen McQuerry1, Janine Barnett1, Andrea McCubbin1, James Ferguson2, Jeff Ebersole1
1 University of Kentucky, Lexington, KY, 2University of Virginia, Obstetrics & Gynecology, Charlottesville, VA
OBJECTIVE: Our aim was to determine the association of cytokine values obtained at each trimester from different body fluids with the frequency of preterm birth. STUDY DESIGN: This was a primary analysis of a prospective, multicenter study of women with a singleton gestation. Maternal serum was collected each trimester. Cytokines (IL-1a, IL-1b, IL-2, IL-6, IL8, IL-10, TNFa, CRP and MMP 8) were measured using multiplex beadlyte assay on a Luminex IS-100. Statistical analysis was performed using univariate analyses. The analysis was adjusted for potential confounders including age, race, education, income, and tobacco use. RESULTS: 399 women were enrolled. 114 (29%) of the participants were smokers and 38 (9.5%) delivered preterm. Using univariate analysis, serum IL-6 (P¼ .03) in the 1st trimester; and IL-1b (P¼ .01) and MMP-8 (P¼.03) in the 3rd trimester were significantly different in groups who delivered preterm versus term. These remained significant in the adjusted analysis. The interval change of these cytokines was associated with preterm birth for IL-1b between the 2nd and 3rd trimesters. A subset of 92 patients also underwent evaluation of cytokines in cervicovaginal fluid. In the adjusted analysis, the following cytokines were significantly associated with preterm birth in each trimester: IL-10 (P¼.004, 001, .005, respectively); TNFa (P¼.001,<.001,.009, respectively); and CRP (P¼.01,.009,.01, respectively). In the 2nd and 3rd trimesters, IL-1b (P¼.03,.005, respectively) and IL-8 (P¼.05) in the 3rd trimester were also significantly associated with preterm birth. CONCLUSION: Both pro-inflammatory and anti-inflammatory cytokine concentrations vary in women who will deliver preterm versus term. Varying cytokines are associated with preterm birth in differing bodily fluids. Cervicovaginal fluid is the more descriptive source of the inflammatory milieu predicting preterm birth especially earlier in gestation when therapeutic interventions can be potentially efficacious.
500 Tobacco use alters pregnancy biomarkers reflecting tissue function
Kristin Ashford1, John O’Brien1, Janine Barnett1, Andrea McCubbin1, Kristin McQuerry1, Thomas Curry1 1
University of Kentucky, Lexington, KY
OBJECTIVE: We have previously identified associations between
tobacco exposure and cytokine concentrations in the serum and cervicovaginal fluid. Our aim was to determine the association between urinary cotinine concentration and other biomarkers reflecting tissue level pharmacodynamic changes particularly in placental function and cervical performance. STUDY DESIGN: This study was a secondary analysis of a prospective, multi-center study of pregnant women with a singleton gestation and included women with sufficient sample to allow assessment of serum progesterone concentration in the second trimester. Women on progestogen therapy (17-OHPC or vaginal progesterone) were excluded. Concentrations of progesterone and estradiol were measured using an Immulite 1000. Urine cotinine was measured using a validated assay. Analysis of variance was performed to test for associations. Multiple variable regression analysis was used to adjust for potential confounders including age, race, and BMI. RESULTS: 109 women were included at a mean gestational age of 19.9 1.5 weeks. Five patients had previously undergone cervical surgery (LEEP or cerclage) and were excluded from the analyses. Smoking
ajog.org was confirmed by objective measure in 25 of these patients (24%). Rising urinary cotinine values (100 ng/mL) were significantly associated with decreasing serum progesterone values, 60 19.5 ng/mL lower cotinine group versus 49 14.6 ng/mL with higher concentrations, P¼.024. Serum estradiol was not associated with cotinine values nor was the ratio of serum progesterone/estradiol. The cervical length in the second trimester was also associated with cotinine concentrations. Mean cervical length for smokers was 30 16 mm versus 35 12 mm for nonsmokers, P¼.023. The findings remained statistically significant in the adjusted analysis. CONCLUSION: Urinary cotinine is significantly associated with tissue dysfunction affecting placental production of progesterone and cervical length. Further evaluation of the mechanisms for these findings of tissue dysfunction is needed.
501 Value of magnesium sulfate < 12 hours to prevent cerebral palsy and death Laura Meints1, Alexandra Edwards1, Meng Liu2
1 University of Kentucky, Obstetrics & Gynecology, Lexington, KY, 2University of Kentucky, Biostatistics & Epidemiology, Lexington, KY
OBJECTIVE: Magnesium sulfate (MS) is standard of care for the prevention of moderate and severe cerebral palsy (CP), among women who are expected to deliver at less than 32 weeks gestation. Many women who are expected to deliver in this circumstance do not receive the recommended course of MS for 12 hours. Our aim is to examine whether women who are expected to deliver before 32 weeks gestation and who receive < 12 hours of MS have an increased risk of CP and death in their children. STUDY DESIGN: This study is a secondary analysis of a multi-center, randomized controlled trial. The exposure was duration of MS among women who received at least 6g of MS (< 4 hrs, 4-12 hrs, 12 hrs). The primary outcome was a composite of stillbirth or infant death by 1 year of corrected age or moderate or severe CP at or beyond 2 years of corrected age. We performed univariate and multiple logistic regression with generalized estimating equations to determine the potential association between primary outcome and duration of magnesium sulfate. These associations are reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: There were 1,065 women included in the analysis. Women who received at least 12 hours of MS were more likely to have PPROM (p < .0001), be multiparous (p ¼ .01), have a singleton gestation (p ¼ .01), and receive antenatal steroids (p ¼ 0.001). In the univariate analysis, women who received at least 12 hours of MS had decreased rate of the combined outcome (9.3%, vs 12.8% among women who received 4-12 hrs of MS and 16.3% among women who received < 4 hrs of MS). After controlling for birth weight, gestational age, tobacco use, race, and betamethasone, however, the adjusted model showed no statistically significant differences: < 4 hrs (aOR 1.57, CI 0.84 - 2.95), 4-12 hrs (aOR 1.64, 0.84 - 3.21), and 12 hrs (reference). CONCLUSION: This study showed no increase in risk for cerebral palsy and death among children of women expected to deliver preterm due to exposure time of < 12 hours of magnesium sulfate.
502 Myometrial electrical activity at labor e Is there a correlation between labor stages?
Liran Hiersch1, Eran Ashwal1, Amir Aviram1, Liat Salzer1, Eran Hadar1, Arnon Wiznitzer1, Yariv Yogev1
1 Helen Schneider Hospital for Women, Rabin Medical Center, Obstetrics and Gynecology, Petach Tikva, Israel
OBJECTIVE: To determine the association between the myometrial
electrical activity in the active and second stages of labor at term using a novel technology of electrical uterine monitor (EUM). STUDY DESIGN: A prospective observational study of 47 women with singleton pregnancy and spontaneous onset of labor at term (370/6 to 416/6 weeks of gestation) in a university-affiliated tertiary hospital. All patients were assessed using non-invasive 9-channel surface
S252 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015