CONCLUSION: Reduction of NKp46 expression in the peripheral blood and NKp30-C expression in the deciduas from patients with pre- eclampsia may be associated with impaired pregnancy-associated immune response and thus could contribute to the pathogenesis of preeclampsia. NKp46 and NKp30 levels and isoforms in peripheral blood and placenta in preeclampsia, normal pregnancies and nonpregnant patient 365 Cardiovascular and echocardiographic assessment in hypertension during pregnancy Zohar Nachum 1 , Limor Ilan-Bushari 2 , Mohamed Jabaren 2 , Yoav Turgeman 2 , Eliezer Shalev 1 , Raed Salim 1 1 Rappaport Faculty of Medicine, Technion, Ob&Gyn Department, Emek Medical Center, Afula, Haifa, Israel, 2 Emek Medical Center, Heart Institute, Afula, Israel OBJECTIVE: To assess the incidence of echocardiographic (EC) ab- normalities among pregnant women with hypertension (HTN), and to examine whether theses abnormalities predict the development of preeclampsia (PE). STUDY DESIGN: Pregnant women with HTN and a singleton preg- nancy were prospectively included. Controls were healthy pregnant women. All women underwent serial EC during pregnancy. Women were followed up until discharge after delivery. Primary outcome was the incidence of EC abnormalities, and secondary outcome was the incidence of PE. Assuming abnormal EC findings in 50% of the study group and 20% in the controls, power analysis showed that 60 and 30 women were needed in a rate of 2:1, respectively, with alpha¼0.05 and power of 80%. The study was approved by the local ethical committee and women signed informed consent before enrollment (ClinicalTrials.gov NCT 01068002). RESULTS: Ninety women were included: 61 had HTN disorder (51 had chronic HTN, 29 of them were medically treated, and 10 had gestational HTN), and 29 were healthy pregnant women. De- mographic characteristics and obstetrical history did not differ be- tween the groups. Two D and Doppler EC has revealed in both groups normal size of cardiac chambers, normal systolic left ven- tricular ejection fraction, no signs of hypertrophy, and normal flows without significant valve regurgitation. Diastolic dysfunction was found in 39 (78%) of the hypertensive group as compared with 11 (39%) of the controls (OR 3.0, 95% CI 1.2-7.5; p<0.03). PE was diagnosed in 25% of the HTN group compared to 3% of the controls (p<0.03). The incidence of PE was higher in the treated HTN group (33%) compared with the untreated group (22%), (OR 4.8, 95% CI 1.4-16.5; p< 0.01). Of the 39 women with HTN and diastolic dysfunction, 13 (34%) had PE compared to 22 (9%) women without diastolic dysfunction (OR: 5.9, 95% CI 1.2-28.3; p<0.03). CONCLUSION: HTN in pregnancy is associated with an increased incidence of diastolic dysfunction. This combination is associated with increased risk of developing PE. 366 Is glyburide use a risk factor for neonatal hyperbilirubinemia? Joseph Fitzwater 1 , Scharlene Powell 1 , Angelica Glover 1 , Joseph Biggio 1 , Lorie Harper 1 1 University of Alabama at Birmingham, Maternal-Fetal Medicine, Birmingham, AL OBJECTIVE: Glyburide is a sulfonamide used for the treatment of gestational diabetes (GDM); however, sulfonamides are discouraged in the third-trimester due to the risk of neonatal jaundice and ker- nicterus. We examined the association of glyburide use for GDM with neonatal hyperbilirubinemia. STUDY DESIGN: Retrospective cohort of singleton pregnancies complicated by GDM from 2007-2012. Exclusion criteria included fetal anomalies, major medical comorbidities, and delivery < 35 weeks. Outcomes were examined based on treatment of GDM: diet (A1), glyburide, or insulin. Primary neonatal outcomes included peak bilirubin concentration, hyperbilirubinemia (total bilirubin 95th percentile for hour of life), and use of phototherapy. This study had 85% power to detect a 2-fold difference in risk of Poster Session II Hypertension, Diabetes, Prematurity, Physiology www.AJOG.org S186 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2014
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Poster Session II Hypertension, Diabetes, Prematurity, Physiology www.AJOG.org
CONCLUSION: Reduction of NKp46 expression in the peripheral bloodand NKp30-C expression in the deciduas from patients with pre-eclampsia may be associated with impaired pregnancy-associatedimmune response and thus could contribute to the pathogenesis ofpreeclampsia.
NKp46 and NKp30 levels and isoforms in peripheralblood and placenta in preeclampsia, normalpregnancies and nonpregnant patient
S186 American Journal of Obstetrics & Gynecology Supplement to JANUARY
365
Cardiovascular and echocardiographic assessment inhypertension during pregnancyZohar Nachum1, Limor Ilan-Bushari2, Mohamed Jabaren2,Yoav Turgeman2, Eliezer Shalev1, Raed Salim1
1Rappaport Faculty of Medicine, Technion, Ob&Gyn Department, EmekMedical Center, Afula, Haifa, Israel, 2Emek Medical Center, Heart Institute,Afula, Israel
OBJECTIVE: To assess the incidence of echocardiographic (EC) ab-normalities among pregnant women with hypertension (HTN), andto examine whether theses abnormalities predict the development ofpreeclampsia (PE).STUDY DESIGN: Pregnant women with HTN and a singleton preg-nancy were prospectively included. Controls were healthy pregnantwomen. All women underwent serial EC during pregnancy. Womenwere followed up until discharge after delivery. Primary outcome wasthe incidence of EC abnormalities, and secondary outcome was theincidence of PE. Assuming abnormal EC findings in 50% of thestudy group and 20% in the controls, power analysis showed that 60and 30 women were needed in a rate of 2:1, respectively, withalpha¼0.05 and power of 80%. The study was approved by the localethical committee and women signed informed consent beforeenrollment (ClinicalTrials.gov NCT 01068002).RESULTS: Ninety women were included: 61 had HTN disorder (51had chronic HTN, 29 of them were medically treated, and 10 hadgestational HTN), and 29 were healthy pregnant women. De-mographic characteristics and obstetrical history did not differ be-tween the groups. Two D and Doppler EC has revealed in bothgroups normal size of cardiac chambers, normal systolic left ven-tricular ejection fraction, no signs of hypertrophy, and normal flowswithout significant valve regurgitation. Diastolic dysfunction wasfound in 39 (78%) of the hypertensive group as compared with 11(39%) of the controls (OR 3.0, 95% CI 1.2-7.5; p<0.03). PE wasdiagnosed in 25% of the HTN group compared to 3% of the controls(p<0.03). The incidence of PE was higher in the treated HTN group(33%) compared with the untreated group (22%), (OR 4.8, 95% CI1.4-16.5; p< 0.01). Of the 39 women with HTN and diastolicdysfunction, 13 (34%) had PE compared to 22 (9%) women withoutdiastolic dysfunction (OR: 5.9, 95% CI 1.2-28.3; p<0.03).CONCLUSION: HTN in pregnancy is associated with an increasedincidence of diastolic dysfunction. This combination is associatedwith increased risk of developing PE.
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Is glyburide use a risk factor for neonatalhyperbilirubinemia?Joseph Fitzwater1, Scharlene Powell1, Angelica Glover1,Joseph Biggio1, Lorie Harper11University of Alabama at Birmingham, Maternal-Fetal Medicine,Birmingham, AL
OBJECTIVE: Glyburide is a sulfonamide used for the treatment ofgestational diabetes (GDM); however, sulfonamides are discouragedin the third-trimester due to the risk of neonatal jaundice and ker-nicterus. We examined the association of glyburide use for GDMwith neonatal hyperbilirubinemia.STUDY DESIGN: Retrospective cohort of singleton pregnanciescomplicated by GDM from 2007-2012. Exclusion criteria includedfetal anomalies, major medical comorbidities, and delivery < 35weeks. Outcomes were examined based on treatment of GDM: diet(A1), glyburide, or insulin. Primary neonatal outcomes includedpeak bilirubin concentration, hyperbilirubinemia (total bilirubin� 95th percentile for hour of life), and use of phototherapy. Thisstudy had 85% power to detect a 2-fold difference in risk of
www.AJOG.org Hypertension, Diabetes, Prematurity, Physiology Poster Session II
hyperbilirubinemia between glyburide and A1. Groups werecompared using the t-test and chi-squared where appropriate.Backwards stepwise logistic regression was used to refine point es-timates while adjusting for confounding variables.RESULTS: 528 women with GDM were included. Although the meanpeak bilirubin was higher with glyburide, hyperbilirubinemia wasnot increased in glyburide versus A1 (11.6 vs 9.8%, adjusted oddsratio (AOR) 1.33, 95% confidence interval (CI) 0.74-2.41). Whilephototherapy use appeared to be 2-fold higher in glyburide, it wasnot significantly increased after adjustment for confounders (8.1% vs15.7%, AOR 1.3, 95% CI 0.88-1.94). The same was true forcomparing insulin (hyperbilirubinemia AOR 0.84, 95% CI 0.18-3.84, phototherapy AOR 1.46, 95% CI 0.63-3.38). Increasing dosesof glyburide did not correlate with hyperbilirubinemia or photo-therapy (AOR 1.20 (95% CI 0.20-7.29) for doses � 2.5 mg daily,1.63(95% CI 0.32-8.20) for doses � 10 mg daily).CONCLUSION: Although glyburide is in a drug class that may causeneonatal jaundice, infants exposed to glyburide in the third trimesterdo not seem to be at significantly increased risk of hyper-bilirubinemia or of requiring phototherapy prior to discharge.
367 Outcome of induction of labour in women with
gestational diabetes and comparison with general obstetricpopulationIsabella Crippa1, Clelia Callegari1, Eloisa Mariani1,Irene Cameroni1, Cristina Plevani1, Serena Mussi1,Nadia Roncaglia11MBBM Foundation, San Gerardo Hospital, University of Milano-Bicocca,Obstetrics and Gynecology, Monza, Italy
OBJECTIVE: There is controversy regarding the optimal managementof delivery in women with gestational diabetes mellitus (GDM) tominimize the risks for the fetus. The induction of labour reduces therate of stillbirth and of complications related to excessive fetalgrowth (shoulder dystocia and birth trauma), but increases the riskof caesarean section (CS). The aim of this study is to compareelective induction versus spontaneous onset of labour in pregnancyaffected by GDM.STUDY DESIGN: This is a retrospective study of women with GDMwho delivered in our Department between 01/2009 to 12/2012. In-duction of labour, according to our clinical management, was pro-posed at 38 weeks in GDM women with one or more of thefollowing conditions: poor glycemic control, fetal growth � 90�
centile, polyhydramnios, insulin or oral hypoglycemic therapy. Dataon antenatal risk factors, labour and delivery characteristics andneonatal outcome were collected.RESULTS: Among the 763 patients with GDM, 82 patients had anelective CS (11%) and were excluded from the analysis. Of theremaining 681 women, 52% had induction of labour. At univariateanalysis, as shown in the table, there was a significant difference inpre-gestational BMI, obesity and pharmacological therapy, butsimilar incidence of macrosomia and perinatal outcome. The rate of
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CS was double in the induction group vs spontaneous labour: 12%vs 6% (p¼0.01). Compared with general obstetric populationdelivered in the same period, total CS rate and CS in labour in GDMgroup was similar to general population: 19.2 % vs 19.5%; (p¼NS)for total CS and 9.5% vs 9.4% (p¼NS) for CS in labour.CONCLUSION: Frequency of induction is very high in GDM patients,but total CS rate is similar in GDM and general obstetric population.Induction of labour is associated with an increased rate of CS, but nodifferences in adverse perinatal outcome.
Comparison of spontaneous and induced labour
368 Anti-inflammatory action of metformin in trophoblasts
acts in an AMP-activated protein kinase (AMPK)-independentmannerMary Pitruzzello1, Melissa Herrin1, John Hardy1,Karen Archabald1, Christian Pettker1, Christina Han11Yale School of Medicine, Department of Obstetrics, Gynecology &Reproductive Sciences, New Haven, CT
OBJECTIVE: Our group has previously shown that hyperglycemiainduces a pro-inflammatory milieu in first trimester trophoblasts,and that metformin is effective in reversing this inflammation.Recent literature suggests that metformin exerts its anti-inflamma-tory responses in vascular smooth muscle cells via activation ofAMPK, a key sensor in maintaining metabolic homeostasis. Themechanism by which metformin exerts its effects in first trimestertrophoblasts is currently unexplored. The objective of this study wasto evaluate the effect of metformin on activation of AMPK in firsttrimester trophoblasts.STUDY DESIGN: The human first trimester extravillous trophoblastcell line (Sw-71) was cultured with media containing glucose (5 mM,normoglycemia; 10 mM, borderline hyperglycemia; or 25 mM, hy-perglycemia), and co-treated with metformin (1 or 2 mM). After 6hrs, trophoblasts were lysed for protein. Phosphorylated (p) andtotal (t) AMPK expression was determined by western blot anddensitometric analysis. Statistical significance (p<0.05) was deter-mined using one-way ANOVA with Bonferroni correction for mul-tiple comparisons.RESULTS: Excess glucose alone did not affect AMPK phosphoryla-tion. Although metformin showed a trend in increased activation ofAMPK (pAMPK:tAMPK), the difference was not statistically sig-nificant. (Figure)CONCLUSION: Metformin does not active AMPK in first trimestertrophoblasts in vitro. Alternative signaling pathways need to beexplored to better understand the anti-inflammatory actions ofmetformin on the trophoblast.
ent to JANUARY 2014 American Journal of Obstetrics & Gynecology S187
