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571: Can placental vascular lesions predict reccurence of preeclampsia?
Poster Session IV
ajog.org 569 First-trimester maternal abdominal adiposity and dysglycemia in mid-pregnancy Leanne R. De Souza1, Howard Berger1, Ravi Retnakaran1, Jonathon L. Maguire1, Avery B. Nathens1, Philip W. Connelly1, Joel G. Ray1 1
St Michael’s Hospital, Toronto, ON, Canada
OBJECTIVE: Small studies suggest that abdominal adiposity measured
in early pregnancy can predict gestational diabetes mellitus (GDM). We assessed the association between first-trimester abdominal adiposity and markers of dysglycemia and insulin resistance in the second-trimester of pregnancy in a large and diverse cohort of women. STUDY DESIGN: In a prospective cohort of 485 women, subcutaneous (SAT), visceral (VAT) and total (TAT) adipose tissue depth were measured by ultrasonography at 11-14 weeks’ gestation. A standardized 2-hour 75-g oral glucose tolerance test (OGTT) was completed at 24-28 weeks’ gestation. Area under the glucose curve (AUC-glucose) was calculated from the 0, 1 and 2-hour glucose measures. Insulin resistance was estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) and the OGTT-derived Insulin Sensitivity Index (ISIOGTT). RESULTS: Upon adjusting for maternal age, parity, ethnicity, family history of type 2 diabetes, first-trimester body mass index (BMI) and change in BMI from 11-14 weeks to 24-28 weeks gestation, VAT and TAT explained 15% (95% CI 0.09 to 0.21) of the variance in AUCglucose beyond pregnancy BMI. VAT and TAT depth each explained 34% (95% CI 0.27 to 0.41) and 35% (95% CI 0.28 to 0.42) of the variance in HOMA-IR respectively, compared to 24% variance described by first-trimester BMI (95% CI 0.17 to 0.31). For ISIOGTT, the model variance values were 28% (95% CI 0.21 to 0.35) and 31% (95% CI 0.34 to 0.38) for VAT and TAT respectively compared to the variance of 15% (95% CI 0.09 to 0.21) described by the firsttrimester BMI model. The highest quartile of VAT conferred a 3.2 (95% CI 1.1 to 9.9) higher odds of having impaired fasting glucose or gestational impaired glucose tolerance or GDM compared to the lower 3 quartiles (95% CI 1.4 to 11.4). TAT was similarly observed as an independent determinant of dysglycemia with a 2.7 (95% CI 1.0 to 7.5) greater odds of IFG or GIGT or GDM or dysglycemia in the highest quartile than in the lower 3 quartiles (95% CI 1.1 to 8.1). CONCLUSION: Elevated maternal abdominal adipose tissue depth, measured at the time of routine first-trimester ultrasonography, may contribute to the development of dysglycemia in mid-gestation and confers a greater risk of developing dysglycemia in mid-gestation than first-trimester BMI alone.
570 What is the impact of fetal sex on maternal glucose metabolism? Edward H. Springel1, Erica K. Berggren1, Larraine Huston-Presley1, Patrick M. Catalano1 1
MetroHealth Medical Center / Case Western Reserve University, Cleveland, OH
OBJECTIVE: Recent investigations have had conflicting results
regarding the impact of gender on maternal glucose metabolism, in particular an increased risk of gestational diabetes. Our objective was to determine if fetal sex is associated with differences in maternal plasma markers of glucose metabolism and inflammation in pregnant women. STUDY DESIGN: We performed a secondary analysis of data collected prospectively as part of an ongoing NIH-sponsored study on fetal growth. 472 mother-infant pairs were available for analysis (250
male and 222 female). All blood samples were collected in the fasting state before scheduled cesarean delivery at term (> 37 weeks). Statistical comparisons were performed using Kruskal-Wallis and Chisquared tests as appropriate. RESULTS: Median and interquartile range fasting plasma concentrations of analytes were compared in mothers of male versus female fetuses: insulin (17.9[12.9-23.14] v 18.6[12.3-25.5] mIU/L, p¼0.7); glucose (78.3[72.0-83.5] v 77.9[70.0-83.7] mg/dL, p¼0.6); HOMA-IR (3.43[2.35-4.75] v 3.60[2.25-5.00] p¼0.8). Further, no significant differences were identified in maternal leptin, free fatty acid, triglyceride, adiponectin, resistin, estradiol, progesterone, TNF, C-Reactive Protein, or IL-6 concentrations. There was no significant difference in gestational weight gain between groups (15.0[10.3-15.7] v 13.6[8.6-19.1] lbs, p¼0.07) or pre-gravid BMI (30.1[24.3-37.6] v 30.4[24.6-37.6] kg/m2, p¼0.6. Our cohort included 58 mothers with diabetes, including 34 with GDM. Pregestational diabetics were no more likely to have male fetuses (RR 0.81, 95%CI 0.51-1.31, p¼0.4). Mothers of male fetuses were no more likely to have been diagnosed with GDM (RR 1.00, 95%CI 0.93-1.04). CONCLUSION: We did not identify any marker of maternal glucose metabolism or inflammation in maternal serum that was related to fetal sex. No relationship between fetal sex, pre-gravid BMI, gestational weight gain, or relative risk for development of GDM was identified.
571 Can placental vascular lesions predict reccurence of preeclampsia? Eran Weiner1, Noa Rymer-Haskel1, Ehud Grinstein1, Ohad Feldstein1, Yossi Mizrachi1, Letizia Schreiber1, Jacob Bar1, Michal Kovo1 1
Wolfson Medical Center, Holon, Israel
OBJECTIVE: To investigate the association between placental vascular
lesions in an initial pregnancy with preeclampsia (PE), and recurrence of PE in subsequent pregnancies. STUDY DESIGN: According to departmental protocol, during 2008-2014, placentas from every PE patients, were sent to histopathology examination. PE was diagnosed according to ACOG criteria. This cohort of PE patients were followed for their subsequent pregnancy and were divided into those who developed recurrent PE in the subsequent pregnancy (Re-PE group) and those who did not developed recurrent PE (No Re-PE group). Maternal characteristics and placental pathology reports, of the initial pregnancies, were compared between the two groups. Placental lesions were classified to lesions of maternal vascular supply consistent with maternal malperfusion and lesions of fetal vascular supply consistent with fetal thrombo-occlusive disease. Multivariate logistic regression was used to control for potential known potential confounders for PE recurrence. RESULTS: Out of 372 PE patients, 94 included in the Re-PE group and 113 in the No Re-PE group. Maternal age and gestational age at delivery were similar between the Re-PE and the No Re-PE groups, 315.8vs. 31.36.0 years, respectively, p¼0.3, and 35.92.7 vs. 36.42.9 weeks, respectively, p¼0.204. Placentas from the Re-PE group had higher rate of maternal vascular supply lesions and fetal vascular supply lesions, as compared to placentas from the No-PE group, 94.7% vs. 57.5%, respectively, p<0.001, and 57.4% vs. 16.8% respectively, p<0.001. By logistic regression analysis, composite maternal and fetal vascular supply lesions were found to be independently associated
Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S307
Poster Session IV
ajog.org
with Re-PE, OR¼15.2, 95% CI¼ 5.5-42.1, p<0.001, and OR¼6.7, 95% CI¼ 3.4-13.1, p<0.001 respectively. CONCLUSION: Placental maternal and fetal vascular lesions are independently associated with increased risk for recurrence of PE. In cases with preeclampsia, placental histopathology results should be used for patient counseling and prophylaxis considerations for their following pregnancies.
572 Detection and confirmation of early gestation, serum lipidomic biomarkers for preeclampsia Steven W. Graves1, Swati Anand1, Sydney Young1, Dennis H. Tolley1, Michael S. Esplin2,3, Mary D’Alton4 1 Brigham Young University, Provo, UT, 2University of Utah Medical School, Salt Lake City, UT, 3Intermountain Health Care, Murray, UT, 4Columbia University College of Physicians and Surgeons, New York City, NY
OBJECTIVE: The early diagnosis of preeclampsia (PE) remains elusive.
Nonetheless, many studies demonstrate biochemical alternations early in gestation in women who develop PE. This suggests that biomarkers might be found in pregnant women at risk for PE. Among biomolecules emerging as being important in physiology and disease are lipids. Consequently, two lipidomic studies were undertaken to find predictive serum biomarkers for PE. STUDY DESIGN: Shotgun lipidomic studies were performed to find predictive serum lipid biomarkers for PE comparing pregnant women at 12-14 wks having uncomplicated pregnancies (controls) or having later PE (cases). The discovery study included sera from 27 controls and 29 cases. Lipids were extracted using organic solvents and analyzed by direct infusion into a time-of-flight mass spectrometer (MS). Peaks with apparent differences were selected, their abundances determined and statistical differences tested. Statistically different lipids were reevaluated in a confirmatory study having 43 controls and 37 cases. Multi-marker panels were developed using confirmed biomarkers and chemical characterization of these same lipids was performed by tandem MS. RESULTS: The initial study detected 45 statistically significant PE biomarkers. When the 45 were retested in a second, confirmatory set of different sera, 23 continued to be statistically significant. The best single marker had a p-value of 8x10-5. Five multi-marker panels had AUCs >0.85, the best providing 91% sensitivity at 82% specificity. See figure. Twenty one of the 23 validated markers were chemically classified, with 18 identified. Six of these were closely related oxidized unsaturated triglycerides found increased in controls, perhaps due to higher oxygen exposure. CONCLUSION: This shotgun serum lipidomics approach found many reproducible candidate PE biomarkers. Developed panels of serum lipid biomarkers appeared able to identify most women at risk for PE in a given pregnancy at 12-14 weeks gestation.
573 Choosing between bad, worse and worst: What is the preferred mode of delivery for failure of the second stage of labor? Michal Kirshenbaum1, Moshe Berg2, Salim Kees1, Shali Mazaki-Tovi1, Orit Moran1, Anat Kalter1, Israel Hendler1 1
Sheba medical center, Ramat Gan, Israel, 2Tel Aviv University, Tel Aviv, Israel
OBJECTIVE: To determine the neonatal and maternal outcome as
compared between vacuum, forceps or cesarean delivery during the second stage of labor. STUDY DESIGN: Retrospective cohort study in a tertiary center over a 2 year period. Study population included 3 groups of patients with failure of the second stage of labor: 1. Patients delivered by forceps; 2. by vacuum; and 3. by Cesarean section. Maternal and neonatal composite outcome for each mode of delivery was compared. Neonatal composite outcome included 5 minutes Apgar score<7, cephalohematoma, subgaleal hematoma, facial nerve palsy, artificial ventilation and/ or neonatal intensive care unit admission. Maternal composite outcome included 3rd /4th grade perineal tear, postpartum hemorrhage, fever and/ or post-partum hospitalization of more than 5 days. Non-parametric statistics were used for analysis as well as logisted regression. RESULTS: 547 patients were included in the analysis: 150 were delivered by forceps (FD), 200 by vacuum (VD) and 197 by cesarean deliveries (CD) during second stage of labor. The most common indications for FD and VD were non reassuring fetal monitoring (63% and 66.5% respectively) and prolonged second stage (38.5% and 28.9% respectively) whereas the most common indication for CD was suspected cephalo-pelvic disproportion. Gestational age at delivery was comparable among the 3 groups. The rate of composite outcome was significantly higher in the VD group (27%) compared to FD (14.7%) or CD (9.7%) (p<0.001). There was no difference in the rate of maternal composite outcome among the 3 groups. Multivariate regression analysis revealed that mode of delivery and height of fetal head were significantly and independently associated with neonatal composite outcome after adjusting for maternal age,
S308 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016
ajog.org 569 First-trimester maternal abdominal adiposity and dysglycemia in mid-pregnancy Leanne R. De Souza1, Howard Berger1, Ravi Retnakaran1, Jonathon L. Maguire1, Avery B. Nathens1, Philip W. Connelly1, Joel G. Ray1 1
St Michael’s Hospital, Toronto, ON, Canada
OBJECTIVE: Small studies suggest that abdominal adiposity measured
in early pregnancy can predict gestational diabetes mellitus (GDM). We assessed the association between first-trimester abdominal adiposity and markers of dysglycemia and insulin resistance in the second-trimester of pregnancy in a large and diverse cohort of women. STUDY DESIGN: In a prospective cohort of 485 women, subcutaneous (SAT), visceral (VAT) and total (TAT) adipose tissue depth were measured by ultrasonography at 11-14 weeks’ gestation. A standardized 2-hour 75-g oral glucose tolerance test (OGTT) was completed at 24-28 weeks’ gestation. Area under the glucose curve (AUC-glucose) was calculated from the 0, 1 and 2-hour glucose measures. Insulin resistance was estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) and the OGTT-derived Insulin Sensitivity Index (ISIOGTT). RESULTS: Upon adjusting for maternal age, parity, ethnicity, family history of type 2 diabetes, first-trimester body mass index (BMI) and change in BMI from 11-14 weeks to 24-28 weeks gestation, VAT and TAT explained 15% (95% CI 0.09 to 0.21) of the variance in AUCglucose beyond pregnancy BMI. VAT and TAT depth each explained 34% (95% CI 0.27 to 0.41) and 35% (95% CI 0.28 to 0.42) of the variance in HOMA-IR respectively, compared to 24% variance described by first-trimester BMI (95% CI 0.17 to 0.31). For ISIOGTT, the model variance values were 28% (95% CI 0.21 to 0.35) and 31% (95% CI 0.34 to 0.38) for VAT and TAT respectively compared to the variance of 15% (95% CI 0.09 to 0.21) described by the firsttrimester BMI model. The highest quartile of VAT conferred a 3.2 (95% CI 1.1 to 9.9) higher odds of having impaired fasting glucose or gestational impaired glucose tolerance or GDM compared to the lower 3 quartiles (95% CI 1.4 to 11.4). TAT was similarly observed as an independent determinant of dysglycemia with a 2.7 (95% CI 1.0 to 7.5) greater odds of IFG or GIGT or GDM or dysglycemia in the highest quartile than in the lower 3 quartiles (95% CI 1.1 to 8.1). CONCLUSION: Elevated maternal abdominal adipose tissue depth, measured at the time of routine first-trimester ultrasonography, may contribute to the development of dysglycemia in mid-gestation and confers a greater risk of developing dysglycemia in mid-gestation than first-trimester BMI alone.
570 What is the impact of fetal sex on maternal glucose metabolism? Edward H. Springel1, Erica K. Berggren1, Larraine Huston-Presley1, Patrick M. Catalano1 1
MetroHealth Medical Center / Case Western Reserve University, Cleveland, OH
OBJECTIVE: Recent investigations have had conflicting results
regarding the impact of gender on maternal glucose metabolism, in particular an increased risk of gestational diabetes. Our objective was to determine if fetal sex is associated with differences in maternal plasma markers of glucose metabolism and inflammation in pregnant women. STUDY DESIGN: We performed a secondary analysis of data collected prospectively as part of an ongoing NIH-sponsored study on fetal growth. 472 mother-infant pairs were available for analysis (250
male and 222 female). All blood samples were collected in the fasting state before scheduled cesarean delivery at term (> 37 weeks). Statistical comparisons were performed using Kruskal-Wallis and Chisquared tests as appropriate. RESULTS: Median and interquartile range fasting plasma concentrations of analytes were compared in mothers of male versus female fetuses: insulin (17.9[12.9-23.14] v 18.6[12.3-25.5] mIU/L, p¼0.7); glucose (78.3[72.0-83.5] v 77.9[70.0-83.7] mg/dL, p¼0.6); HOMA-IR (3.43[2.35-4.75] v 3.60[2.25-5.00] p¼0.8). Further, no significant differences were identified in maternal leptin, free fatty acid, triglyceride, adiponectin, resistin, estradiol, progesterone, TNF, C-Reactive Protein, or IL-6 concentrations. There was no significant difference in gestational weight gain between groups (15.0[10.3-15.7] v 13.6[8.6-19.1] lbs, p¼0.07) or pre-gravid BMI (30.1[24.3-37.6] v 30.4[24.6-37.6] kg/m2, p¼0.6. Our cohort included 58 mothers with diabetes, including 34 with GDM. Pregestational diabetics were no more likely to have male fetuses (RR 0.81, 95%CI 0.51-1.31, p¼0.4). Mothers of male fetuses were no more likely to have been diagnosed with GDM (RR 1.00, 95%CI 0.93-1.04). CONCLUSION: We did not identify any marker of maternal glucose metabolism or inflammation in maternal serum that was related to fetal sex. No relationship between fetal sex, pre-gravid BMI, gestational weight gain, or relative risk for development of GDM was identified.
571 Can placental vascular lesions predict reccurence of preeclampsia? Eran Weiner1, Noa Rymer-Haskel1, Ehud Grinstein1, Ohad Feldstein1, Yossi Mizrachi1, Letizia Schreiber1, Jacob Bar1, Michal Kovo1 1
Wolfson Medical Center, Holon, Israel
OBJECTIVE: To investigate the association between placental vascular
lesions in an initial pregnancy with preeclampsia (PE), and recurrence of PE in subsequent pregnancies. STUDY DESIGN: According to departmental protocol, during 2008-2014, placentas from every PE patients, were sent to histopathology examination. PE was diagnosed according to ACOG criteria. This cohort of PE patients were followed for their subsequent pregnancy and were divided into those who developed recurrent PE in the subsequent pregnancy (Re-PE group) and those who did not developed recurrent PE (No Re-PE group). Maternal characteristics and placental pathology reports, of the initial pregnancies, were compared between the two groups. Placental lesions were classified to lesions of maternal vascular supply consistent with maternal malperfusion and lesions of fetal vascular supply consistent with fetal thrombo-occlusive disease. Multivariate logistic regression was used to control for potential known potential confounders for PE recurrence. RESULTS: Out of 372 PE patients, 94 included in the Re-PE group and 113 in the No Re-PE group. Maternal age and gestational age at delivery were similar between the Re-PE and the No Re-PE groups, 315.8vs. 31.36.0 years, respectively, p¼0.3, and 35.92.7 vs. 36.42.9 weeks, respectively, p¼0.204. Placentas from the Re-PE group had higher rate of maternal vascular supply lesions and fetal vascular supply lesions, as compared to placentas from the No-PE group, 94.7% vs. 57.5%, respectively, p<0.001, and 57.4% vs. 16.8% respectively, p<0.001. By logistic regression analysis, composite maternal and fetal vascular supply lesions were found to be independently associated
Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S307
Poster Session IV
ajog.org
with Re-PE, OR¼15.2, 95% CI¼ 5.5-42.1, p<0.001, and OR¼6.7, 95% CI¼ 3.4-13.1, p<0.001 respectively. CONCLUSION: Placental maternal and fetal vascular lesions are independently associated with increased risk for recurrence of PE. In cases with preeclampsia, placental histopathology results should be used for patient counseling and prophylaxis considerations for their following pregnancies.
572 Detection and confirmation of early gestation, serum lipidomic biomarkers for preeclampsia Steven W. Graves1, Swati Anand1, Sydney Young1, Dennis H. Tolley1, Michael S. Esplin2,3, Mary D’Alton4 1 Brigham Young University, Provo, UT, 2University of Utah Medical School, Salt Lake City, UT, 3Intermountain Health Care, Murray, UT, 4Columbia University College of Physicians and Surgeons, New York City, NY
OBJECTIVE: The early diagnosis of preeclampsia (PE) remains elusive.
Nonetheless, many studies demonstrate biochemical alternations early in gestation in women who develop PE. This suggests that biomarkers might be found in pregnant women at risk for PE. Among biomolecules emerging as being important in physiology and disease are lipids. Consequently, two lipidomic studies were undertaken to find predictive serum biomarkers for PE. STUDY DESIGN: Shotgun lipidomic studies were performed to find predictive serum lipid biomarkers for PE comparing pregnant women at 12-14 wks having uncomplicated pregnancies (controls) or having later PE (cases). The discovery study included sera from 27 controls and 29 cases. Lipids were extracted using organic solvents and analyzed by direct infusion into a time-of-flight mass spectrometer (MS). Peaks with apparent differences were selected, their abundances determined and statistical differences tested. Statistically different lipids were reevaluated in a confirmatory study having 43 controls and 37 cases. Multi-marker panels were developed using confirmed biomarkers and chemical characterization of these same lipids was performed by tandem MS. RESULTS: The initial study detected 45 statistically significant PE biomarkers. When the 45 were retested in a second, confirmatory set of different sera, 23 continued to be statistically significant. The best single marker had a p-value of 8x10-5. Five multi-marker panels had AUCs >0.85, the best providing 91% sensitivity at 82% specificity. See figure. Twenty one of the 23 validated markers were chemically classified, with 18 identified. Six of these were closely related oxidized unsaturated triglycerides found increased in controls, perhaps due to higher oxygen exposure. CONCLUSION: This shotgun serum lipidomics approach found many reproducible candidate PE biomarkers. Developed panels of serum lipid biomarkers appeared able to identify most women at risk for PE in a given pregnancy at 12-14 weeks gestation.
573 Choosing between bad, worse and worst: What is the preferred mode of delivery for failure of the second stage of labor? Michal Kirshenbaum1, Moshe Berg2, Salim Kees1, Shali Mazaki-Tovi1, Orit Moran1, Anat Kalter1, Israel Hendler1 1
Sheba medical center, Ramat Gan, Israel, 2Tel Aviv University, Tel Aviv, Israel
OBJECTIVE: To determine the neonatal and maternal outcome as
compared between vacuum, forceps or cesarean delivery during the second stage of labor. STUDY DESIGN: Retrospective cohort study in a tertiary center over a 2 year period. Study population included 3 groups of patients with failure of the second stage of labor: 1. Patients delivered by forceps; 2. by vacuum; and 3. by Cesarean section. Maternal and neonatal composite outcome for each mode of delivery was compared. Neonatal composite outcome included 5 minutes Apgar score<7, cephalohematoma, subgaleal hematoma, facial nerve palsy, artificial ventilation and/ or neonatal intensive care unit admission. Maternal composite outcome included 3rd /4th grade perineal tear, postpartum hemorrhage, fever and/ or post-partum hospitalization of more than 5 days. Non-parametric statistics were used for analysis as well as logisted regression. RESULTS: 547 patients were included in the analysis: 150 were delivered by forceps (FD), 200 by vacuum (VD) and 197 by cesarean deliveries (CD) during second stage of labor. The most common indications for FD and VD were non reassuring fetal monitoring (63% and 66.5% respectively) and prolonged second stage (38.5% and 28.9% respectively) whereas the most common indication for CD was suspected cephalo-pelvic disproportion. Gestational age at delivery was comparable among the 3 groups. The rate of composite outcome was significantly higher in the VD group (27%) compared to FD (14.7%) or CD (9.7%) (p<0.001). There was no difference in the rate of maternal composite outcome among the 3 groups. Multivariate regression analysis revealed that mode of delivery and height of fetal head were significantly and independently associated with neonatal composite outcome after adjusting for maternal age,
S308 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016