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349: Gestational prehypertension–additional category of hypertensive disease of pregnancy
www.AJOG.org
Hypertension, Diabetes, Prematurity, Physiology
Poster Session II
in the Table. When comparing 135 mg/dL vs 130 mg/dL GCT cutoff utilization 6.3% less patients tested positive at the same 100% sensitivity. CONCLUSION: In twin pregnancies universal screening for GDM is routinely performed. As the recent NIH Consensus Panel concluded (March 4-6, 2013) the current two-step approach to screening and diagnosis for gestational diabetes should be maintained. In twin pregnancies our analysis suggests optimal GCT screening cut-off to be at 135 mg/dL.
Testing characteristics of a one-hour GCT at 24-28 weeks for the diagnosis of GDM in twin pregnancies
348 Randomized trial of glyburide plus diet compared to placebo plus diet in women with gestational diabetes Mina Abbassi-Ghanavati1, Brian Casey1, Stephan Shivvers1, Carmen Tudela1, Donald McIntire1, Kenneth Leveno1 1
University of Texas Southwestern Medical Center, Obstetrics and Gynecology, Dallas, TX
OBJECTIVE: To determine if the addition of glyburide to diet ther-
apy modifies pregnancy outcome in women with gestational diabetes. STUDY DESIGN: Women with at least 2 abnormal values on a 3-hour, 100 gm oral glucose tolerance test according to NDDG criteria and fasting values less than 105 mg/dL between 24 and 30 weeks gestation were randomized to blinded glyburide or placebo study drug. All women underwent monitored diet with weekly dietary logs as well as 4 X daily capillary glucose measurements recorded in memory-based glucose meters. Starting dose for glyburide was 2.5 mg and was titrated to a maximum of 20 mg per day based on weekly maternal capillary glucose values. Target values were less than 95 mg/dL and 120 mg/dL for fasting and 2-hour postprandial glucose measurements respectively. The primary study outcome chosen based on an apriori sample size analysis, was a 200 gm birthweight decrement in infants of women treated with glyburide. The sample size estimate for this outcome was 334 randomized women. RESULTS: A total of 395 women were enrolled in this trial at a single center between September 2008 and October 2012. Twenty women were lost to followup at delivery. As shown in the figure, women treated with glyburide had a greater decline in fasting glucose values over the course of therapy. As shown in the table of selected outcomes, the difference in the mean birthweight was 33 gms (p ¼ 0.52). CONCLUSION: Though the addition of glyburide to diet therapy significantly impacted maternal glycemic control, it did not modify infant size.
349 Gestational prehypertensioneadditional category of hypertensive disease of pregnancy Vivian Adum1, Steve Buyske5, Amen Ness1, Yali Xiong3, Eliezer Holtzman4, Ed Guzman1, Ossie Geifman-Holtzman2 1
Saint Peters University Hospital, Obstetrics & Gynecology, New Brunswick, NJ, 2Drexel College of Medicine, Obstetrics & Gynecology, Philadelphia, PA, 3 Temple School of Medicine, Fels Institute, Philadelphia, PA, 4Sheba Medical Center, Tel-Aviv University, Nephrology Institute, Tel-Aviv, Israel, 5Rutgers University, Department of Statistics & Biostatistics, Piscataway, NJ
OBJECTIVE: The joint national committee on high blood pressure (JNC7) determined blood pressure of 120-139/80-89 in adults to be Prehypertension associate with increased risk of cardiovascular disease. We hypothesize that gestational prehypertension is associated with increased risk of anterpartum and peripartum complications. STUDY DESIGN: A retrospective case control study consists of pregnant patients at our clinic during the year of 2010. The study group consists of pregnant patients with blood pressure of 120-139/80-89 at <15 weeks. The control group consists of pregnant patients with blood pressure <120/80 at <15 weeks. Outcome measures included development of hypertensive disease: Gestational hypertension and/ or Preeclampsia as the primary outcome and preterm delivery (PTL), lower birth weight (LBW), APGARS & admission to NICU as a secondary outcome. Comparisons between the two groups were accomplished using Fisher exact test & two-sample t-tests for comparing birth weight means. Logistic regression was used to obtain Odd Ratios while linear regression was used for adjusting of confounding variants. RESULTS: A total of 346 patients were eligible to be included in the study with 108 cases and 111 in the control group. The outcome measures analyzed resulted in poorer results being associated with the study group compared with control as follows: 15.9% vs. 0.9% (p<0.0001) for gestational hypertension, respectively, 19.4% vs. 10% (P¼0.0043) for gestational diabetes, 12% vs. 5% (P¼0.3567) for preterm labor, 30% vs. 13 % (P¼0.0031) for admission to the NICU, 7.4 % vs. 0.9% (P¼0.001), for APGARS less than 9 at 5 minutes On
Supplement to JANUARY 2014 American Journal of Obstetrics & Gynecology
S179
Poster Session II
Hypertension, Diabetes, Prematurity, Physiology
admission mean SBP and DBP was 130 and 76 mmHg, respectively, in the study group, compared to 120 and 70 mmHg in the control group. CONCLUSION: Gestational Pre-hypertension may be a real pregnancy condition that when is recognized, physician attention, patient close monitoring during prenatal care and delivery and early intervention in patients at risk, may all promote improved pregnancy outcome.
350 Identification of biomarkers associated with defective deep placentation using proteomics Sun Min Kim1, Joong Shin Park1, Errol Norwitz3, Min Ji Kang1, Seung Mi Lee2, Joonho Lee1, Chan-Wook Park1, Byoung Jae Kim2, Jong Kwan Jun1 1
Seoul National University College of Medicine, Obstetrics and Gynecology, Seoul, Republic of Korea, 2Seoul Metropolitan Government Seoul National University Boramae Medical Center, Obstetrics and Gynecology, Seoul, Republic of Korea, 3Tufts University School of Medicine, Obstetrics and Gynecology, Boston, MA
OBJECTIVE: Defective deep placentation is an abnormal trans-
formation of spiral artery in junctional zone of myometrium. It results in significant obstetrical complications, and preeclampsia is a representative disease. We aimed to discover biomarkers associated with defective deep placentation using integrative proteomic discovery/validation tools. STUDY DESIGN: A case-control study was performed. Maternal plasma was obtained from singleton pregnant women between 16 and 21 weeks of gestation, in which deep placentation seems to be occurred in that period. Thirteen women subsequently diagnosed with preeclampsia were selected as cases and an equal number of matched women who delivered at term without complications as controls. Differential proteome profiling was conducted with the previously stored plasma using an LTQ-Velos mass spectrometer. Proteins potentially associated with deep placentation were further validated by MRM (multiple reaction monitoring) targeted proteome analysis via using an Agilent 6490 triple quadrupole mass spectrometer. RESULTS: In our proteome profiling analysis, we have identified a panel of differentially abundant proteins in the cases compared to the controls. Subsequently, MRM targeted proteome analysis resulted in four significantly up-regulated proteins(apolipoprotein C-I [P¼0.074], complement C1s subcomponent[P¼0.020], haptoglobin [P¼0.018] and alpha-1-microglobulin/bikunin precursor(AMBP) [P¼0.033]) and three down-regulated proteins (apolipoprotein M [P¼0.041], complement C5[P¼0.034], and vitronectin[P¼0.095]). CONCLUSION: In this study, we have identified proteins using proteomics with MRM technique that are differentially expressed in the maternal plasma during defective deep placentation. Here, we propose that the proteins identified may be involved in the remodeling process of the spiral arteries even before the manifestation of clinical disease. These proteins could be served as potential biomarkers, which could predict obstetrical complications associated with defective deep placentation.
351 Relationship between glyburide dose and insulin concentration in women with gestational diabetes Maisa Feghali1, Mary Hebert2, Christina Scifres1, Steve Caritis1 1
Magee Womens Hospital of UPMC. University of Pittsburgh, Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, 2 University of Washington, Department of Pharmacy and Obstetrics & Gynecology. For the for the Obstetric-fetal Pharmacology Research Units Network, Seattle, WA
OBJECTIVE: Despite the widespread use of glyburide for glycemic control in cases with gestational diabetes (GDM), limited
www.AJOG.org
information is available regarding its pharmacologic properties during pregnancy. The objective of this investigation was to characterize the relationship between glyburide and insulin concentrations. STUDY DESIGN: This was a secondary analysis from a pharmacokinetic/ pharmacodynamics study in women (n¼40) with GDM treated glyburide at doses of 1.25-7.5 twice daily (Clinical Pharmacology & Therapeutics 85:6, 2009). Following an overnight fast, each subject received her scheduled morning dose of glyburide and underwent a standardized mixed meal tolerance test 60 minutes later. Blood was obtained prior to glyburide dose and 12 additional times over the ensuing 12 hours. Samples were analyzed for glyburide, insulin, c-peptide and glucose concentrations. RESULTS: Peak concentration and the area under the curve (AUC) of glyburide increased with increasing dose. The plasma concentration of glyburide increased proportionally to the dose (y ¼ 49.654x + 18.78, R2¼ 0.948). Insulin levels following the standardized meal increased proportionally (y ¼ 11.897x + 2.6695, R2 ¼ 0.53885) to the plasma concentration of glyburide. CONCLUSION: There is proportionality between glyburide dose and plasma glyburide concentrations. An increase in plasma glyburide concentrations is associated with an increasingly more robust insulin response to a mixed meal tolerance test.
352 Cerebral autoregulation in different hypertensive disorders of pregnancy Teelkien van Veen1, Ronney Panerai2, Sina Haeri3, Jasbir Singh3, Jasvant Adusumalli3, Michael Belfort4 1 University Medical Center Groningen, Department of Obstetrics and Gynecology, Groningen, Netherlands, 2University of Leicester, Department of Cardiovascular Sciences, Leicester, United Kingdom, 3St. David’s North Austin Medical Center, Women’s Center of Texas, Austin, TX, 4Baylor College of Medicine, Department of Obstetrics and Gynecology, Houston, TX
S180 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2014
Hypertension, Diabetes, Prematurity, Physiology
Poster Session II
in the Table. When comparing 135 mg/dL vs 130 mg/dL GCT cutoff utilization 6.3% less patients tested positive at the same 100% sensitivity. CONCLUSION: In twin pregnancies universal screening for GDM is routinely performed. As the recent NIH Consensus Panel concluded (March 4-6, 2013) the current two-step approach to screening and diagnosis for gestational diabetes should be maintained. In twin pregnancies our analysis suggests optimal GCT screening cut-off to be at 135 mg/dL.
Testing characteristics of a one-hour GCT at 24-28 weeks for the diagnosis of GDM in twin pregnancies
348 Randomized trial of glyburide plus diet compared to placebo plus diet in women with gestational diabetes Mina Abbassi-Ghanavati1, Brian Casey1, Stephan Shivvers1, Carmen Tudela1, Donald McIntire1, Kenneth Leveno1 1
University of Texas Southwestern Medical Center, Obstetrics and Gynecology, Dallas, TX
OBJECTIVE: To determine if the addition of glyburide to diet ther-
apy modifies pregnancy outcome in women with gestational diabetes. STUDY DESIGN: Women with at least 2 abnormal values on a 3-hour, 100 gm oral glucose tolerance test according to NDDG criteria and fasting values less than 105 mg/dL between 24 and 30 weeks gestation were randomized to blinded glyburide or placebo study drug. All women underwent monitored diet with weekly dietary logs as well as 4 X daily capillary glucose measurements recorded in memory-based glucose meters. Starting dose for glyburide was 2.5 mg and was titrated to a maximum of 20 mg per day based on weekly maternal capillary glucose values. Target values were less than 95 mg/dL and 120 mg/dL for fasting and 2-hour postprandial glucose measurements respectively. The primary study outcome chosen based on an apriori sample size analysis, was a 200 gm birthweight decrement in infants of women treated with glyburide. The sample size estimate for this outcome was 334 randomized women. RESULTS: A total of 395 women were enrolled in this trial at a single center between September 2008 and October 2012. Twenty women were lost to followup at delivery. As shown in the figure, women treated with glyburide had a greater decline in fasting glucose values over the course of therapy. As shown in the table of selected outcomes, the difference in the mean birthweight was 33 gms (p ¼ 0.52). CONCLUSION: Though the addition of glyburide to diet therapy significantly impacted maternal glycemic control, it did not modify infant size.
349 Gestational prehypertensioneadditional category of hypertensive disease of pregnancy Vivian Adum1, Steve Buyske5, Amen Ness1, Yali Xiong3, Eliezer Holtzman4, Ed Guzman1, Ossie Geifman-Holtzman2 1
Saint Peters University Hospital, Obstetrics & Gynecology, New Brunswick, NJ, 2Drexel College of Medicine, Obstetrics & Gynecology, Philadelphia, PA, 3 Temple School of Medicine, Fels Institute, Philadelphia, PA, 4Sheba Medical Center, Tel-Aviv University, Nephrology Institute, Tel-Aviv, Israel, 5Rutgers University, Department of Statistics & Biostatistics, Piscataway, NJ
OBJECTIVE: The joint national committee on high blood pressure (JNC7) determined blood pressure of 120-139/80-89 in adults to be Prehypertension associate with increased risk of cardiovascular disease. We hypothesize that gestational prehypertension is associated with increased risk of anterpartum and peripartum complications. STUDY DESIGN: A retrospective case control study consists of pregnant patients at our clinic during the year of 2010. The study group consists of pregnant patients with blood pressure of 120-139/80-89 at <15 weeks. The control group consists of pregnant patients with blood pressure <120/80 at <15 weeks. Outcome measures included development of hypertensive disease: Gestational hypertension and/ or Preeclampsia as the primary outcome and preterm delivery (PTL), lower birth weight (LBW), APGARS & admission to NICU as a secondary outcome. Comparisons between the two groups were accomplished using Fisher exact test & two-sample t-tests for comparing birth weight means. Logistic regression was used to obtain Odd Ratios while linear regression was used for adjusting of confounding variants. RESULTS: A total of 346 patients were eligible to be included in the study with 108 cases and 111 in the control group. The outcome measures analyzed resulted in poorer results being associated with the study group compared with control as follows: 15.9% vs. 0.9% (p<0.0001) for gestational hypertension, respectively, 19.4% vs. 10% (P¼0.0043) for gestational diabetes, 12% vs. 5% (P¼0.3567) for preterm labor, 30% vs. 13 % (P¼0.0031) for admission to the NICU, 7.4 % vs. 0.9% (P¼0.001), for APGARS less than 9 at 5 minutes On
Supplement to JANUARY 2014 American Journal of Obstetrics & Gynecology
S179
Poster Session II
Hypertension, Diabetes, Prematurity, Physiology
admission mean SBP and DBP was 130 and 76 mmHg, respectively, in the study group, compared to 120 and 70 mmHg in the control group. CONCLUSION: Gestational Pre-hypertension may be a real pregnancy condition that when is recognized, physician attention, patient close monitoring during prenatal care and delivery and early intervention in patients at risk, may all promote improved pregnancy outcome.
350 Identification of biomarkers associated with defective deep placentation using proteomics Sun Min Kim1, Joong Shin Park1, Errol Norwitz3, Min Ji Kang1, Seung Mi Lee2, Joonho Lee1, Chan-Wook Park1, Byoung Jae Kim2, Jong Kwan Jun1 1
Seoul National University College of Medicine, Obstetrics and Gynecology, Seoul, Republic of Korea, 2Seoul Metropolitan Government Seoul National University Boramae Medical Center, Obstetrics and Gynecology, Seoul, Republic of Korea, 3Tufts University School of Medicine, Obstetrics and Gynecology, Boston, MA
OBJECTIVE: Defective deep placentation is an abnormal trans-
formation of spiral artery in junctional zone of myometrium. It results in significant obstetrical complications, and preeclampsia is a representative disease. We aimed to discover biomarkers associated with defective deep placentation using integrative proteomic discovery/validation tools. STUDY DESIGN: A case-control study was performed. Maternal plasma was obtained from singleton pregnant women between 16 and 21 weeks of gestation, in which deep placentation seems to be occurred in that period. Thirteen women subsequently diagnosed with preeclampsia were selected as cases and an equal number of matched women who delivered at term without complications as controls. Differential proteome profiling was conducted with the previously stored plasma using an LTQ-Velos mass spectrometer. Proteins potentially associated with deep placentation were further validated by MRM (multiple reaction monitoring) targeted proteome analysis via using an Agilent 6490 triple quadrupole mass spectrometer. RESULTS: In our proteome profiling analysis, we have identified a panel of differentially abundant proteins in the cases compared to the controls. Subsequently, MRM targeted proteome analysis resulted in four significantly up-regulated proteins(apolipoprotein C-I [P¼0.074], complement C1s subcomponent[P¼0.020], haptoglobin [P¼0.018] and alpha-1-microglobulin/bikunin precursor(AMBP) [P¼0.033]) and three down-regulated proteins (apolipoprotein M [P¼0.041], complement C5[P¼0.034], and vitronectin[P¼0.095]). CONCLUSION: In this study, we have identified proteins using proteomics with MRM technique that are differentially expressed in the maternal plasma during defective deep placentation. Here, we propose that the proteins identified may be involved in the remodeling process of the spiral arteries even before the manifestation of clinical disease. These proteins could be served as potential biomarkers, which could predict obstetrical complications associated with defective deep placentation.
351 Relationship between glyburide dose and insulin concentration in women with gestational diabetes Maisa Feghali1, Mary Hebert2, Christina Scifres1, Steve Caritis1 1
Magee Womens Hospital of UPMC. University of Pittsburgh, Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, 2 University of Washington, Department of Pharmacy and Obstetrics & Gynecology. For the for the Obstetric-fetal Pharmacology Research Units Network, Seattle, WA
OBJECTIVE: Despite the widespread use of glyburide for glycemic control in cases with gestational diabetes (GDM), limited
www.AJOG.org
information is available regarding its pharmacologic properties during pregnancy. The objective of this investigation was to characterize the relationship between glyburide and insulin concentrations. STUDY DESIGN: This was a secondary analysis from a pharmacokinetic/ pharmacodynamics study in women (n¼40) with GDM treated glyburide at doses of 1.25-7.5 twice daily (Clinical Pharmacology & Therapeutics 85:6, 2009). Following an overnight fast, each subject received her scheduled morning dose of glyburide and underwent a standardized mixed meal tolerance test 60 minutes later. Blood was obtained prior to glyburide dose and 12 additional times over the ensuing 12 hours. Samples were analyzed for glyburide, insulin, c-peptide and glucose concentrations. RESULTS: Peak concentration and the area under the curve (AUC) of glyburide increased with increasing dose. The plasma concentration of glyburide increased proportionally to the dose (y ¼ 49.654x + 18.78, R2¼ 0.948). Insulin levels following the standardized meal increased proportionally (y ¼ 11.897x + 2.6695, R2 ¼ 0.53885) to the plasma concentration of glyburide. CONCLUSION: There is proportionality between glyburide dose and plasma glyburide concentrations. An increase in plasma glyburide concentrations is associated with an increasingly more robust insulin response to a mixed meal tolerance test.
352 Cerebral autoregulation in different hypertensive disorders of pregnancy Teelkien van Veen1, Ronney Panerai2, Sina Haeri3, Jasbir Singh3, Jasvant Adusumalli3, Michael Belfort4 1 University Medical Center Groningen, Department of Obstetrics and Gynecology, Groningen, Netherlands, 2University of Leicester, Department of Cardiovascular Sciences, Leicester, United Kingdom, 3St. David’s North Austin Medical Center, Women’s Center of Texas, Austin, TX, 4Baylor College of Medicine, Department of Obstetrics and Gynecology, Houston, TX
S180 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2014