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777: Low maternal middle cerebral artery (MMCA) doppler resistance indices can predict future development of preeclampsia
Poster Session V
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
link between IDO, vascular tone, and the maternal adaptation to elevated sFLT-1, we investigated changes of key analytes in maternal sera. STUDY DESIGN: Gestationally age-matched control and preeclamptic sera were obtained from the IRB approved University of New Mexico Maternal Bank. IDO activity was determined by a colorimetric assay. Other effector proteins were measured using a multiplex protein array or ELISA. Statistical analysis was performed utilizing either a 2 tail Student T test or 2 way ANOVA with ␣ ⫽ 0.05. RESULTS: After 24 weeks, IDO activity (p⬍0.001) and sFLT-1 (p⬍0.001) levels are higher in preeclamptic sera than in control sera. In contrast, IL-4 was higher in control sera versus preeclamptic sera after 24 weeks (p⬍0.006). TRAIL was higher in the control sera in comparison to the preeclamptic sera especially early in pregnancy (⬍24 weeks) (p⫽0.017). CONCLUSIONS: In contrast to the placenta, IDO activity is higher in preeclamptic sera after 24 weeks. Because endothelial IDO leads to vasodilation through kynurenine, elevated serum IDO activity may represent a maternal adaptation to the hypertensive sFLT-1 environment in preeclampsia. In addition, TRAIL has been shown to be antiangiogenic. A decrease in TRAIL in preeclamptic sera may represent an early feedback mechanism to prevent excess anti-angiogenesis. The decrease in IL4 in preeclamptic sera correlates well with the known increase in soluble IL4 receptor in preeclampsia. Because IL4 increases oxidative stress, reduced IL4 may represent maternal compensation for the oxidative preeclamptic environment. TRAIL and IL4 each have tolerogenic effects. Therefore, their reduction in preeclampsia may be representative of the increased maternal immune response to the fetus. These data support further molecular investigation into the maternal adaptive mechanisms of these immuno-vasoactive analytes in preeclampsia.
775 The impact of magnesium sulfate therapy on angiogenic proteins in preeclampsia Mary Vadnais1, Sarosh Rana2, Ananth Karumanchi3, Michele R. Hacker4 1
Beth Israel Deaconess Medical Center, Boston, MA, 2BIDMC, Boston, MA, 3BIDMC/Harvard Medical School, Boston, MA, 4Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA
OBJECTIVE: To determine if intravenous magnesium sulfate affects levels of angiogenic proteins, specifically placental growth factor (PLGF) and soluble fms-like tyrosine kinase-1 (sFlt1), in patients with preeclampsia. STUDY DESIGN: This prospective cohort study compared two groups diagnosed with preeclampsia, as defined by ACOG criteria. One group received magnesium for seizure prophylaxis; the other did not receive magnesium. Serum samples were collected at the time of diagnosis or before initiating magnesium and 24 hours later. Concentrations of PLGF and sFlt1 were analyzed with ELISA, and the change over 24 hours was compared between the groups with adjustment for gestational age. Medians and interquartile ranges are presented. RESULTS: There was no statistically significant difference between the group treated with magnesium (n⫽37) and the group that did not receive magnesium (n⫽45) with respect to age, BMI, gestational age at enrollment, gravidity, smoking, insurance type, race, ethnicity or marital status. Women given magnesium were more likely to have severe preeclampsia, treatment with steroids and higher blood pressure (all p ⱕ0.02). Although not statistically significant, women who received magnesium had a larger increase in sFlt1 (p⫽0.49) and a larger decrease in PLGF (p⫽0.56) than women without magnesium. The median increase in sFlt1 was 2730 pg/mL (-1299 –5337) and 481 pg/mL (-1112–5041) in women receiving magnesium and women not receiving magnesium, respectively. The median decrease in PLGF was 27 pg/mL (-55–1) in women receiving magnesium and 18 pg/mL (-51– 6) in women not receiving magnesium. Results were similar when restricting to women with mild preeclampsia and those with severe preeclampsia (all p ⬎0.15).
S304
www.AJOG.org
CONCLUSIONS: Among women with preeclampsia, magnesium did not result in a statistically significantly different change in the levels of sFlt1 and PLGF compared to no magnesium. Magnesium likely decreases the risk of seizure in patients with preeclampsia by a mechanism other than altering serum levels of these angiogenic factors.
776 Mode of delivery and neonatal outcomes in patients with eclampsia: 1990-2005 Mauro Schenone1, Jacques Samson1, Rebecca Uhlmann2, Norman Meyer1, Ramasubbareddy Dhanireddy2, Giancarlo Mari2 1
University of Tennessee Health Science Center, Memphis, TN, University of Tennessee Health Science Center, Tennessee Institute of Fetal-Maternal and Infant Health, Memphis, TN 2
OBJECTIVE: The aim of this study was to compare neonatal outcome of patients with eclampsia delivered via vaginal delivery (VD) vs. those delivered via cesarean section (CS). STUDY DESIGN: Patients who developed eclampsia before delivery were included in this study. Data were gathered from our obstetrical database on deliveries, which had a diagnosis of eclampsia listed as part of obstetrical complications and delivered in our hospital from 1990 to 2005. Patients without eclampsia were selected as a control group. Neonatal outcome included an Apgar score of ⬍ 7 at 5 minutes and/or admission to the neonatal intensive care unit (NICU). We controlled for gestational age (GA). Binary logistic regression was used in the statistical analysis. A p ⬍ .05 was used to indicate statistical significance. RESULTS: 104 patients were identified. The patients were divided into three groups: Group A, patients who underwent labor followed by CS (n ⫽ 29); Group B, patients who had an indicated CS (n ⫽ 48), Group C patients who delivered vaginally (n ⫽ 27). GA at diagnosis ranged from 24.1 to 41.0 weeks (median: 36.1 weeks) for patients in Group A, it was between 24.1 and 39.3 weeks in the patients of Group B (median: 30.7), and between 31.1 and 40.6 weeks (median: 37.1 weeks) for the patients in Group C. The neonates with an Apgar ⬍ 7 at 5 minutes were 10 in Group A, 15 in Group B, and 2 in Group C. There were 12 neonates who were admitted to the NICU in Group A, 35 in Group B, and 2 in Group C. No difference in number of cases with 5 min Apgar ⬍7 was found among the three groups. However, the admission to the NICU was higher in both, group A and B (p⬍.05). This difference remained when we corrected for GA. CONCLUSIONS: These data indicate that in patients who develop eclampsia, vaginal delivery decreases the risk of admission to the neonatal intensive care unit. Vaginal delivery, following stabilization of the patient, should be strongly considered in patients who develop eclampsia.
777 Low maternal middle cerebral artery (MMCA) doppler resistance indices can predict future development of preeclampsia Michael Belfort1, Teelkien Van Veen2, G. Lance White3, Shalece Kofford3, Janalee Allred3, Ineke R Postma4, Michael Varner5 1
HCA Healthcare and University of Utah, Salt Lake City, UT, 2University Medical Center Groningen, Groningen, AB, 3HCA Healthcare, Salt Lake City, UT, 4Department of Obstetrics & Gynecology, University Medical Center Groningen, Groningen, 5University of Utah Health Sciences Center, Salt Lake City, UT
OBJECTIVE: Failure of second wave trophoblastic invasion may cause release of vasodilator substances to improve placental perfusion. Vasodilatation in the MMCA (a 2mm diameter artery) can be detected with Doppler providing reliable maternal hemodynamic information. Decreased resistance (vasodilatation) in the MMCA in the second trimester may predict third trimester development of preeclampsia. STUDY DESIGN: 405 low risk gravidas had MMCA Transcranial Doppler (TCD) once in the second trimester (19.0⫹/-1.3 weeks, range 12 26 weeks). Maternal/neonatal outcomes were evaluated after delivery (chart review). Exclusions: chronic illness, fetal anomalies, multiple pregnancy, medications other than vitamins and thyroxine, ⬎ trace
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2011
www.AJOG.org
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
Poster Session V
proteinuria, BP ⬎ 140/90 mmHg at Doppler. BP and MCA systolic, diastolic and mean velocity were recorded, and Resistance Index (RI), Pulsatility Index (PI) and Cerebral Perfusion Pressure (CPP) were calculated using standard formulae (Belfort et al 2001). Analysis: parametric and non-parametric statistics, ROC curve analysis, p⬍0.05. RESULTS: Seven subjects (1.7%) developed preeclampsia (per ACOG) (EGA ⫽ 37.3⫹/-2.8 weeks). An RI ⬍0.54 and PI ⬍0.81 were clinically useful in predicting subsequent preeclampsia (Positive Likelihood Ratio (⫹LR) ⫽ 11.8 (RI), 12.3 (PI); Negative LR (-LR) ⫽ 0.15 (RI), 0.15 (PI)). Positive Predictive Values for RI and PI were 0.17 and 0.19, Negative Predictive Values were 0.99 and 0.99 respectively. Sensitivity/Specificity were 0.86/0.93 (RI) and 0.86/0.93 (PI). Areas under the ROC curves (Figure) for MMCA RI and PI were 0.93⫹/-0.04 and 0.93⫹/-0.04. Although MAP and MCA diastolic velocity showed some promise, both were less reliable predictors of preeclampsia than RI and PI. CONCLUSIONS: TCD indices of low MMCA resistance in the second trimester are highly predictive of the subsequent development of preeclampsia in a low risk, ethnically homogenous population. This indicator may be the most reliable predictor yet identified, and if confirmed in a more diverse ethnic population, may provide an important prenatal screening test for preeclampsia.
Age (years)
Normal (n ⴝ 398)
Preeclamptic (n ⴝ 7)
P
778 Trisomy 13 and placental sFlt-1 expression
28 ⫹/- 5
29 ⫹/- 6
0.6
Michelle Silasi1, Sarosh Rana1 , Camille Powe2, Bruce Cohen1, Kee- Hak Lim1, Ananth Karumanchi1, Isaac Stillman1
..........................................................................................................................................................................................
White Race (%) 91% 100% .......................................................................................................................................................................................... Weight (lbs)
155 ⫹/- 30
164 ⫹/- 36
0.6
..........................................................................................................................................................................................
Gravidity 2 [1-12] 2 [1-5] .......................................................................................................................................................................................... Gestational Age at 19 ⫹/- 1.3 19 ⫹/- 1.5 0.5 TCD (wks) .......................................................................................................................................................................................... Systolic BP (mmHg)
110 ⫹/- 10
115 ⫹/- 10
0.2
..........................................................................................................................................................................................
Diastolic BP (mmHg) 69 ⫹/- 7 76 ⫹/- 8 0.06 .......................................................................................................................................................................................... MAP (mmHg) 83 ⫹/- 7 89 ⫹/- 7 0.04* .......................................................................................................................................................................................... MCA systolic velocity
93⫹/-19
99⫹/-26
0.5
..........................................................................................................................................................................................
MCA diastolic velocity 37⫹/-8 48⫹/-12 0.046* .......................................................................................................................................................................................... MCA Resistance 0.60 ⫹/- 0.05 0.51 ⫹/- 0.05 0.002* Index (RI) .......................................................................................................................................................................................... MCA Pulsatility Index 1.00 ⫹/- 0.15 0.75 ⫹/- 0.11 0.001* (PI) ..........................................................................................................................................................................................
1
BIDMC/Harvard Medical School, Boston, MA, Massachussetts General Hospital, Boston, MA
2
OBJECTIVE: Trisomy 13 is associated with an increased risk of preeclampsia, and similarly shows angiogenic dysfunction in the maternal serum. The placenta has been implicated as the source of the dysfunction in preeclampsia. The purpose of this study is to demonstrate the expression of sFlt-1 in Trisomy 13 placentas using immunohistochemistry methods and to compare this expression to Trisomy 21 and euploid placentas. STUDY DESIGN: This is a retrospective case-control study analyzing placentas from patients receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA, over the past 10 years. Paraffinembedded placental blocks were stained with hematoxylin and eosin and antibodies to N-terminal region of sFlt-1 and their staining intensity was compared using a semiquantitative technique. The Kruskal Wallis test and Wilcoxon rank sum test were used for statistical analysis. RESULTS: Staining intensity for sFlt-1 from Trisomy 13 placentas was significantly more intense compared to both Trisomy 21 and euploid placentas. In the Trisomy 13 placentas, 4 stained 4⫹ (57%), 2 stained 3⫹ (28%), and one stained 2⫹ (15%). In the Trisomy 21 and euploid placentas, the majority stained 2⫹, with only 2 euploid placentas, and 1 Trisomy 21 placenta staining 3⫹. The median value was 4⫹ Trisomy 13 placentas, 2⫹ for euploid placentas, 2⫹ for Trisomy 21 placentas. The difference in staining intensity between groups was statistically significant (p⫽0.005). Statistically significant differences were seen between Trisomy 13 and Trisomy 21 placentas (p⫽0.0068), and between Trisomy 13 and euploid placentas (p⫽0.0089), but not between Trisomy 21 and euploid placentas (p⫽0.617). CONCLUSIONS: Our study demonstrates that Trisomy 13 placentas express a greater level of sFlt-1 protein when compared to euploid and Trisomy 21 placentas. Taken together with prior work that serum levels of sFlt-1 is elevated patients with trisomy 13 pregnanies, strengthens the hypothesis that increased incidence of preeclampsia in pregnancies complicated by Trisomy 13 is secondary to placental upregulation of sFlt-1.
Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology
S305
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
link between IDO, vascular tone, and the maternal adaptation to elevated sFLT-1, we investigated changes of key analytes in maternal sera. STUDY DESIGN: Gestationally age-matched control and preeclamptic sera were obtained from the IRB approved University of New Mexico Maternal Bank. IDO activity was determined by a colorimetric assay. Other effector proteins were measured using a multiplex protein array or ELISA. Statistical analysis was performed utilizing either a 2 tail Student T test or 2 way ANOVA with ␣ ⫽ 0.05. RESULTS: After 24 weeks, IDO activity (p⬍0.001) and sFLT-1 (p⬍0.001) levels are higher in preeclamptic sera than in control sera. In contrast, IL-4 was higher in control sera versus preeclamptic sera after 24 weeks (p⬍0.006). TRAIL was higher in the control sera in comparison to the preeclamptic sera especially early in pregnancy (⬍24 weeks) (p⫽0.017). CONCLUSIONS: In contrast to the placenta, IDO activity is higher in preeclamptic sera after 24 weeks. Because endothelial IDO leads to vasodilation through kynurenine, elevated serum IDO activity may represent a maternal adaptation to the hypertensive sFLT-1 environment in preeclampsia. In addition, TRAIL has been shown to be antiangiogenic. A decrease in TRAIL in preeclamptic sera may represent an early feedback mechanism to prevent excess anti-angiogenesis. The decrease in IL4 in preeclamptic sera correlates well with the known increase in soluble IL4 receptor in preeclampsia. Because IL4 increases oxidative stress, reduced IL4 may represent maternal compensation for the oxidative preeclamptic environment. TRAIL and IL4 each have tolerogenic effects. Therefore, their reduction in preeclampsia may be representative of the increased maternal immune response to the fetus. These data support further molecular investigation into the maternal adaptive mechanisms of these immuno-vasoactive analytes in preeclampsia.
775 The impact of magnesium sulfate therapy on angiogenic proteins in preeclampsia Mary Vadnais1, Sarosh Rana2, Ananth Karumanchi3, Michele R. Hacker4 1
Beth Israel Deaconess Medical Center, Boston, MA, 2BIDMC, Boston, MA, 3BIDMC/Harvard Medical School, Boston, MA, 4Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA
OBJECTIVE: To determine if intravenous magnesium sulfate affects levels of angiogenic proteins, specifically placental growth factor (PLGF) and soluble fms-like tyrosine kinase-1 (sFlt1), in patients with preeclampsia. STUDY DESIGN: This prospective cohort study compared two groups diagnosed with preeclampsia, as defined by ACOG criteria. One group received magnesium for seizure prophylaxis; the other did not receive magnesium. Serum samples were collected at the time of diagnosis or before initiating magnesium and 24 hours later. Concentrations of PLGF and sFlt1 were analyzed with ELISA, and the change over 24 hours was compared between the groups with adjustment for gestational age. Medians and interquartile ranges are presented. RESULTS: There was no statistically significant difference between the group treated with magnesium (n⫽37) and the group that did not receive magnesium (n⫽45) with respect to age, BMI, gestational age at enrollment, gravidity, smoking, insurance type, race, ethnicity or marital status. Women given magnesium were more likely to have severe preeclampsia, treatment with steroids and higher blood pressure (all p ⱕ0.02). Although not statistically significant, women who received magnesium had a larger increase in sFlt1 (p⫽0.49) and a larger decrease in PLGF (p⫽0.56) than women without magnesium. The median increase in sFlt1 was 2730 pg/mL (-1299 –5337) and 481 pg/mL (-1112–5041) in women receiving magnesium and women not receiving magnesium, respectively. The median decrease in PLGF was 27 pg/mL (-55–1) in women receiving magnesium and 18 pg/mL (-51– 6) in women not receiving magnesium. Results were similar when restricting to women with mild preeclampsia and those with severe preeclampsia (all p ⬎0.15).
S304
www.AJOG.org
CONCLUSIONS: Among women with preeclampsia, magnesium did not result in a statistically significantly different change in the levels of sFlt1 and PLGF compared to no magnesium. Magnesium likely decreases the risk of seizure in patients with preeclampsia by a mechanism other than altering serum levels of these angiogenic factors.
776 Mode of delivery and neonatal outcomes in patients with eclampsia: 1990-2005 Mauro Schenone1, Jacques Samson1, Rebecca Uhlmann2, Norman Meyer1, Ramasubbareddy Dhanireddy2, Giancarlo Mari2 1
University of Tennessee Health Science Center, Memphis, TN, University of Tennessee Health Science Center, Tennessee Institute of Fetal-Maternal and Infant Health, Memphis, TN 2
OBJECTIVE: The aim of this study was to compare neonatal outcome of patients with eclampsia delivered via vaginal delivery (VD) vs. those delivered via cesarean section (CS). STUDY DESIGN: Patients who developed eclampsia before delivery were included in this study. Data were gathered from our obstetrical database on deliveries, which had a diagnosis of eclampsia listed as part of obstetrical complications and delivered in our hospital from 1990 to 2005. Patients without eclampsia were selected as a control group. Neonatal outcome included an Apgar score of ⬍ 7 at 5 minutes and/or admission to the neonatal intensive care unit (NICU). We controlled for gestational age (GA). Binary logistic regression was used in the statistical analysis. A p ⬍ .05 was used to indicate statistical significance. RESULTS: 104 patients were identified. The patients were divided into three groups: Group A, patients who underwent labor followed by CS (n ⫽ 29); Group B, patients who had an indicated CS (n ⫽ 48), Group C patients who delivered vaginally (n ⫽ 27). GA at diagnosis ranged from 24.1 to 41.0 weeks (median: 36.1 weeks) for patients in Group A, it was between 24.1 and 39.3 weeks in the patients of Group B (median: 30.7), and between 31.1 and 40.6 weeks (median: 37.1 weeks) for the patients in Group C. The neonates with an Apgar ⬍ 7 at 5 minutes were 10 in Group A, 15 in Group B, and 2 in Group C. There were 12 neonates who were admitted to the NICU in Group A, 35 in Group B, and 2 in Group C. No difference in number of cases with 5 min Apgar ⬍7 was found among the three groups. However, the admission to the NICU was higher in both, group A and B (p⬍.05). This difference remained when we corrected for GA. CONCLUSIONS: These data indicate that in patients who develop eclampsia, vaginal delivery decreases the risk of admission to the neonatal intensive care unit. Vaginal delivery, following stabilization of the patient, should be strongly considered in patients who develop eclampsia.
777 Low maternal middle cerebral artery (MMCA) doppler resistance indices can predict future development of preeclampsia Michael Belfort1, Teelkien Van Veen2, G. Lance White3, Shalece Kofford3, Janalee Allred3, Ineke R Postma4, Michael Varner5 1
HCA Healthcare and University of Utah, Salt Lake City, UT, 2University Medical Center Groningen, Groningen, AB, 3HCA Healthcare, Salt Lake City, UT, 4Department of Obstetrics & Gynecology, University Medical Center Groningen, Groningen, 5University of Utah Health Sciences Center, Salt Lake City, UT
OBJECTIVE: Failure of second wave trophoblastic invasion may cause release of vasodilator substances to improve placental perfusion. Vasodilatation in the MMCA (a 2mm diameter artery) can be detected with Doppler providing reliable maternal hemodynamic information. Decreased resistance (vasodilatation) in the MMCA in the second trimester may predict third trimester development of preeclampsia. STUDY DESIGN: 405 low risk gravidas had MMCA Transcranial Doppler (TCD) once in the second trimester (19.0⫹/-1.3 weeks, range 12 26 weeks). Maternal/neonatal outcomes were evaluated after delivery (chart review). Exclusions: chronic illness, fetal anomalies, multiple pregnancy, medications other than vitamins and thyroxine, ⬎ trace
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2011
www.AJOG.org
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
Poster Session V
proteinuria, BP ⬎ 140/90 mmHg at Doppler. BP and MCA systolic, diastolic and mean velocity were recorded, and Resistance Index (RI), Pulsatility Index (PI) and Cerebral Perfusion Pressure (CPP) were calculated using standard formulae (Belfort et al 2001). Analysis: parametric and non-parametric statistics, ROC curve analysis, p⬍0.05. RESULTS: Seven subjects (1.7%) developed preeclampsia (per ACOG) (EGA ⫽ 37.3⫹/-2.8 weeks). An RI ⬍0.54 and PI ⬍0.81 were clinically useful in predicting subsequent preeclampsia (Positive Likelihood Ratio (⫹LR) ⫽ 11.8 (RI), 12.3 (PI); Negative LR (-LR) ⫽ 0.15 (RI), 0.15 (PI)). Positive Predictive Values for RI and PI were 0.17 and 0.19, Negative Predictive Values were 0.99 and 0.99 respectively. Sensitivity/Specificity were 0.86/0.93 (RI) and 0.86/0.93 (PI). Areas under the ROC curves (Figure) for MMCA RI and PI were 0.93⫹/-0.04 and 0.93⫹/-0.04. Although MAP and MCA diastolic velocity showed some promise, both were less reliable predictors of preeclampsia than RI and PI. CONCLUSIONS: TCD indices of low MMCA resistance in the second trimester are highly predictive of the subsequent development of preeclampsia in a low risk, ethnically homogenous population. This indicator may be the most reliable predictor yet identified, and if confirmed in a more diverse ethnic population, may provide an important prenatal screening test for preeclampsia.
Age (years)
Normal (n ⴝ 398)
Preeclamptic (n ⴝ 7)
P
778 Trisomy 13 and placental sFlt-1 expression
28 ⫹/- 5
29 ⫹/- 6
0.6
Michelle Silasi1, Sarosh Rana1 , Camille Powe2, Bruce Cohen1, Kee- Hak Lim1, Ananth Karumanchi1, Isaac Stillman1
..........................................................................................................................................................................................
White Race (%) 91% 100% .......................................................................................................................................................................................... Weight (lbs)
155 ⫹/- 30
164 ⫹/- 36
0.6
..........................................................................................................................................................................................
Gravidity 2 [1-12] 2 [1-5] .......................................................................................................................................................................................... Gestational Age at 19 ⫹/- 1.3 19 ⫹/- 1.5 0.5 TCD (wks) .......................................................................................................................................................................................... Systolic BP (mmHg)
110 ⫹/- 10
115 ⫹/- 10
0.2
..........................................................................................................................................................................................
Diastolic BP (mmHg) 69 ⫹/- 7 76 ⫹/- 8 0.06 .......................................................................................................................................................................................... MAP (mmHg) 83 ⫹/- 7 89 ⫹/- 7 0.04* .......................................................................................................................................................................................... MCA systolic velocity
93⫹/-19
99⫹/-26
0.5
..........................................................................................................................................................................................
MCA diastolic velocity 37⫹/-8 48⫹/-12 0.046* .......................................................................................................................................................................................... MCA Resistance 0.60 ⫹/- 0.05 0.51 ⫹/- 0.05 0.002* Index (RI) .......................................................................................................................................................................................... MCA Pulsatility Index 1.00 ⫹/- 0.15 0.75 ⫹/- 0.11 0.001* (PI) ..........................................................................................................................................................................................
1
BIDMC/Harvard Medical School, Boston, MA, Massachussetts General Hospital, Boston, MA
2
OBJECTIVE: Trisomy 13 is associated with an increased risk of preeclampsia, and similarly shows angiogenic dysfunction in the maternal serum. The placenta has been implicated as the source of the dysfunction in preeclampsia. The purpose of this study is to demonstrate the expression of sFlt-1 in Trisomy 13 placentas using immunohistochemistry methods and to compare this expression to Trisomy 21 and euploid placentas. STUDY DESIGN: This is a retrospective case-control study analyzing placentas from patients receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA, over the past 10 years. Paraffinembedded placental blocks were stained with hematoxylin and eosin and antibodies to N-terminal region of sFlt-1 and their staining intensity was compared using a semiquantitative technique. The Kruskal Wallis test and Wilcoxon rank sum test were used for statistical analysis. RESULTS: Staining intensity for sFlt-1 from Trisomy 13 placentas was significantly more intense compared to both Trisomy 21 and euploid placentas. In the Trisomy 13 placentas, 4 stained 4⫹ (57%), 2 stained 3⫹ (28%), and one stained 2⫹ (15%). In the Trisomy 21 and euploid placentas, the majority stained 2⫹, with only 2 euploid placentas, and 1 Trisomy 21 placenta staining 3⫹. The median value was 4⫹ Trisomy 13 placentas, 2⫹ for euploid placentas, 2⫹ for Trisomy 21 placentas. The difference in staining intensity between groups was statistically significant (p⫽0.005). Statistically significant differences were seen between Trisomy 13 and Trisomy 21 placentas (p⫽0.0068), and between Trisomy 13 and euploid placentas (p⫽0.0089), but not between Trisomy 21 and euploid placentas (p⫽0.617). CONCLUSIONS: Our study demonstrates that Trisomy 13 placentas express a greater level of sFlt-1 protein when compared to euploid and Trisomy 21 placentas. Taken together with prior work that serum levels of sFlt-1 is elevated patients with trisomy 13 pregnanies, strengthens the hypothesis that increased incidence of preeclampsia in pregnancies complicated by Trisomy 13 is secondary to placental upregulation of sFlt-1.
Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology
S305