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Maternal echocardiogram findings in pregnant patients with chronic hypertension
S40 SMFM Abstracts 105
106
VALIDATION AND QUANTITATION OF PROTEOMIC BIOMARKERS FOR SEVERE PREECLAMPSIA IN CEREBROSPINAL FLUID ERROL NORWITZ1, LAWRENCE TSEN2, JOONG-SHIN PARK1, PATRICIA FITZPATRICK3, DAVID DORFMAN3, CATALIN BUHIMSCHI1, GEORGE SAADE4, CHARLES LOCKWOOD1, IRINA BUHIMSCHI1, 1Yale University, Ob./Gyn. & Reprod Sci., New Haven, Connecticut, 2Harvard University, Obstetric Anesthesia, Boston, Massachusetts, 3Harvard University, Pathology, Boston, Massachusetts, 4University of Texas Medical Branch at Galveston, Obstetrics & Gynecology, Galveston, Texas OBJECTIVE: We previously demonstrated that proteomic analysis of cerebrospinal fluid (CSF) using SELDI-TOF mass spectrometry can accurately distinguish patients with severe preeclampsia (sPE) from both mild preeclampsia (mPE) and normotensive controls (CRL) based on the presence or absence of four discriminatory protein peaks. The current study was designed to validate these biomarkers. STUDY DESIGN: CSF was collected at the time of spinal anesthesia from women with sPE (n = 7), mPE (n = 8), and CRL (n = 7). SELDI-TOF mass spectrometry in-gel tryptic digest, on-chip immunoassays, ELISA, and spectral analysis of CSF were performed on the blinded CSF samples. RESULTS: We identified the discriminatory protein biomarkers as the glycated and non-glycated isoforms of hemoglobin a- and b-chains. ELISA confirmed that levels of hemoglobin were significantly higher in the CSF of women with sPE compared with mPE and CRL (mean [95% CI]: 6.0 [3.6-8.4] vs 0.2 [-0.2-0.5] vs 0 [0-0] mg/mL; P ! .001; Figure). These levels indicate a concentration of approximately 100nM free hemoglobin in CSF of women with sPE. Direct spectrophotometry confirmed the presence of free oxyhemoglobin (414 nm max. absorbance) in CSF of women with sPE, but not in mPE or CRL. Comparisons with quantitative standards suggest that a hemoglobin equivalent of 280 lysed RBC/mL enters CSF in women with sPE. These small numbers effectively exclude a bloody tap. The changes in hemoglobin concentration are not associated with changes in CSF total protein concentration among the groups (P = .256). CONCLUSION: sPE (but not mPE) is characterized by micro-hemorrhage into CSF. These observations may have important diagnostic and/or therapeutic implications for diagnosis and management of women with preeclampsia.
107
MATERNAL ECHOCARDIOGRAM FINDINGS IN PREGNANT PATIENTS WITH CHRONIC HYPERTENSION JULIE GAINER1, JAMES A. ALEXANDER1, DONALD MCINTIRE1, KENNETH LEVENO1, 1University of Texas Southwestern Medical Center at Dallas, Obstetrics and Gynecology, Dallas, Texas OBJECTIVE: To evaluate the role of echocardiogram in pregnant patients with chronic hypertension controlled by medication. STUDY DESIGN: From 1/1998 to 4/2004, all chronic hypertensive women requiring medication were referred to and followed in a single specialty clinic staffed by MFM faculty and fellows. An echocardiogram study was performed during the antepartum period. For this study, pregnancy outcomes were compared in those women who had echocardiogram findings associated with chronic hypertension to those women who had a normal study. RESULTS: 87 women were available for analysis. 47 (54%) had an echocardiogram finding commonly associated with chronic hypertension. The most common findings included concentric left ventricular hypertrophy, dilitation of the left atrium, impaired relaxation of the mitral valve, or a combination of these findings. Demographics were similar between the two groups. The mean maternal age was 32.0 G 6.4, and 32% of the cohort was nulliparous. Other medical conditions including diabetes, renal disease, and pulmonary disease were common in women with and without echocardiogram findings, however, there was no signicant difference between the groups. Pregnancy outcomes were similar in both groups including gestational age at delivery (36.7 weeks G 3.6), development of superimposed preeclampsia, heart failure, and length of hospital stay. CONCLUSION: Pregnant women with chronic hypertension requiring medication commonly have underlying heart lesions associated with hypertension as identified by echocardiogram. Women with abnormal echocardiogram findings were not at increased risk for adverse pregnancy outcomes.
108
OUTCOMES OF PREGNANCIES DIAGNOSED WITH GESTATIONAL HYPERTENSION WHO DEVELOP SUBJECTIVE SYMPTOMS OF PREECLAMPSIA THADDEUS WATERS1, ANTHONY SCISCIONE1, DEBBIE RHEA2, GARY STANZIANO2, NIKI ISTWAN2, 1Drexel University College of Medicine, Obstetrics and Gynecology, Philadelphia, Pennsylvania, 2Matria Healthcare, Marietta, Georgia OBJECTIVE: We sought to evaluate the outcomes in women who have the diagnosis of gestational hypertension (GHTN) and develop subjective symptoms of preeclampsia. STUDY DESIGN: This is a case-cohort study of women enrolled in an outpatient management and surveillance program for GHTN between 1/99 and 11/03. GHTN was defined as hypertension without proteinuria or other signs of preeclampsia. Outpatient surveillance included nursing assessment (blood pressure, weight and urine protein) and assesment of subjective symptoms (presence of headache, epigastric pain, or visual disturbances). Maternal demographics, antepartum complications, and neonatal outcomes were compared using the Mann-Whitney U, Fisher’s Exact and Student t test. RESULTS: A total of 735 patients were evaluated. There was no difference in maternal age, tobacco use, gravidity, marital status, systolic blood pressure, or diastolic blood pressure between the groups. Outcome data is shown in Table 1. CONCLUSION: Except for an increased risk of cesarean delivery there is no difference in neonatal or maternal outcomes in women with gestational hypertension with and without subjective symptoms of preeclampsia. Outcomes Outcome
No Sx (N = 510)
Reported Sx (N = 225)
P value
HELLP Abruption Abnormal FHR Thrombocytopenia Oliguria DIC Maternal Death Cesarean Delivery Birthweight (g) Neonatal Death (#) NICU Admission
0.6% 0.2% 2.9% 0.8% 0.2% 0 0 40.8% 3119 +/- 634 1 15.0%
2.2% 0.9% 1.9% 2.4% 0 0 0 55.6% 3060 +/- 695 1 19.6%
.06 .223 .606 .138 1.0 — — ! .001 .254 .52 .130
VASCULAR DYSFUNCTION IN PREECLAMPSIA ASSESSED BY BRACHIAL ARTERY ULTRASOUND INNA LANDRES1, MARIA SMALL2, SAMUEL RAMSAWAK3, ADESH SUIRJUSINGH4, KEITH WILLIAMS1, 1Yale University, Obstetrics & Gynecology, New Haven, Connecticut, 2Yale University, OB/GYN, New Haven, Connecticut, 3University of the West Indies, Obstetrics and Gynecology, Mount Hope, Trinidad and Tobago, 4University of the West Indies, Obstetrics and Gynecology, Mount Hope, Port of Spain, Trinidad and Tobago OBJECTIVE: This study compared vascular changes in the brachial artery between normotensive and preeclamptic women to assess differences in vascular reactivity and their timing in brachial artery flow mediated vascular dilation (FMVD) between the groups. STUDY DESIGN: This was a matched case controlled study of 12 preeclamptic vs 24 normotensive pregnant women conducted at three hospitals in two geographic settings; (1) Yale-New Haven Hospital in New Haven CT, (2) Mount Hope Maternity and (3) Port of Spain General Hospital in Port of Spain, Trinidad. Patients were matched for gestational age, maternal age and ethnicity. FMVD of the brachial artery was measured every 15 seconds post cuff-release for an initial 90s and then repeated at 120s (7 measurements). We assessed the degree and timing of maximum dilation in each patient. Student t tests and chi square analysis was done as necessary. RESULTS: Brachial Artery flow mediated vascular dilation (FMVD) was significantly reduced in women with preeclampsia compared with matched controls at each time point after 15s. Individual maximum end-diastolic dilation (EDD max) represents the best measurement of the difference in FMVD between the two groups( 4.5% G 2.7 in preeclamptics vs 9.8% G 4.0 in controls) (P ! .0002). There was a trend towards an earlier maximum EDD in the preeclamptic group (51s G 14) vs controls (61s G 26), P = .211. CONCLUSION: We confirmed a significant impairment in endothelial cell function in preeclamptic women by using ultrasound to detect brachial artery dilation. Care should be exercised in the interpretation of the FMVD as the timing of the maximun end- diastolic dilation which is the best measure of endothelial dysfunction may vary from patient to patient.
106
VALIDATION AND QUANTITATION OF PROTEOMIC BIOMARKERS FOR SEVERE PREECLAMPSIA IN CEREBROSPINAL FLUID ERROL NORWITZ1, LAWRENCE TSEN2, JOONG-SHIN PARK1, PATRICIA FITZPATRICK3, DAVID DORFMAN3, CATALIN BUHIMSCHI1, GEORGE SAADE4, CHARLES LOCKWOOD1, IRINA BUHIMSCHI1, 1Yale University, Ob./Gyn. & Reprod Sci., New Haven, Connecticut, 2Harvard University, Obstetric Anesthesia, Boston, Massachusetts, 3Harvard University, Pathology, Boston, Massachusetts, 4University of Texas Medical Branch at Galveston, Obstetrics & Gynecology, Galveston, Texas OBJECTIVE: We previously demonstrated that proteomic analysis of cerebrospinal fluid (CSF) using SELDI-TOF mass spectrometry can accurately distinguish patients with severe preeclampsia (sPE) from both mild preeclampsia (mPE) and normotensive controls (CRL) based on the presence or absence of four discriminatory protein peaks. The current study was designed to validate these biomarkers. STUDY DESIGN: CSF was collected at the time of spinal anesthesia from women with sPE (n = 7), mPE (n = 8), and CRL (n = 7). SELDI-TOF mass spectrometry in-gel tryptic digest, on-chip immunoassays, ELISA, and spectral analysis of CSF were performed on the blinded CSF samples. RESULTS: We identified the discriminatory protein biomarkers as the glycated and non-glycated isoforms of hemoglobin a- and b-chains. ELISA confirmed that levels of hemoglobin were significantly higher in the CSF of women with sPE compared with mPE and CRL (mean [95% CI]: 6.0 [3.6-8.4] vs 0.2 [-0.2-0.5] vs 0 [0-0] mg/mL; P ! .001; Figure). These levels indicate a concentration of approximately 100nM free hemoglobin in CSF of women with sPE. Direct spectrophotometry confirmed the presence of free oxyhemoglobin (414 nm max. absorbance) in CSF of women with sPE, but not in mPE or CRL. Comparisons with quantitative standards suggest that a hemoglobin equivalent of 280 lysed RBC/mL enters CSF in women with sPE. These small numbers effectively exclude a bloody tap. The changes in hemoglobin concentration are not associated with changes in CSF total protein concentration among the groups (P = .256). CONCLUSION: sPE (but not mPE) is characterized by micro-hemorrhage into CSF. These observations may have important diagnostic and/or therapeutic implications for diagnosis and management of women with preeclampsia.
107
MATERNAL ECHOCARDIOGRAM FINDINGS IN PREGNANT PATIENTS WITH CHRONIC HYPERTENSION JULIE GAINER1, JAMES A. ALEXANDER1, DONALD MCINTIRE1, KENNETH LEVENO1, 1University of Texas Southwestern Medical Center at Dallas, Obstetrics and Gynecology, Dallas, Texas OBJECTIVE: To evaluate the role of echocardiogram in pregnant patients with chronic hypertension controlled by medication. STUDY DESIGN: From 1/1998 to 4/2004, all chronic hypertensive women requiring medication were referred to and followed in a single specialty clinic staffed by MFM faculty and fellows. An echocardiogram study was performed during the antepartum period. For this study, pregnancy outcomes were compared in those women who had echocardiogram findings associated with chronic hypertension to those women who had a normal study. RESULTS: 87 women were available for analysis. 47 (54%) had an echocardiogram finding commonly associated with chronic hypertension. The most common findings included concentric left ventricular hypertrophy, dilitation of the left atrium, impaired relaxation of the mitral valve, or a combination of these findings. Demographics were similar between the two groups. The mean maternal age was 32.0 G 6.4, and 32% of the cohort was nulliparous. Other medical conditions including diabetes, renal disease, and pulmonary disease were common in women with and without echocardiogram findings, however, there was no signicant difference between the groups. Pregnancy outcomes were similar in both groups including gestational age at delivery (36.7 weeks G 3.6), development of superimposed preeclampsia, heart failure, and length of hospital stay. CONCLUSION: Pregnant women with chronic hypertension requiring medication commonly have underlying heart lesions associated with hypertension as identified by echocardiogram. Women with abnormal echocardiogram findings were not at increased risk for adverse pregnancy outcomes.
108
OUTCOMES OF PREGNANCIES DIAGNOSED WITH GESTATIONAL HYPERTENSION WHO DEVELOP SUBJECTIVE SYMPTOMS OF PREECLAMPSIA THADDEUS WATERS1, ANTHONY SCISCIONE1, DEBBIE RHEA2, GARY STANZIANO2, NIKI ISTWAN2, 1Drexel University College of Medicine, Obstetrics and Gynecology, Philadelphia, Pennsylvania, 2Matria Healthcare, Marietta, Georgia OBJECTIVE: We sought to evaluate the outcomes in women who have the diagnosis of gestational hypertension (GHTN) and develop subjective symptoms of preeclampsia. STUDY DESIGN: This is a case-cohort study of women enrolled in an outpatient management and surveillance program for GHTN between 1/99 and 11/03. GHTN was defined as hypertension without proteinuria or other signs of preeclampsia. Outpatient surveillance included nursing assessment (blood pressure, weight and urine protein) and assesment of subjective symptoms (presence of headache, epigastric pain, or visual disturbances). Maternal demographics, antepartum complications, and neonatal outcomes were compared using the Mann-Whitney U, Fisher’s Exact and Student t test. RESULTS: A total of 735 patients were evaluated. There was no difference in maternal age, tobacco use, gravidity, marital status, systolic blood pressure, or diastolic blood pressure between the groups. Outcome data is shown in Table 1. CONCLUSION: Except for an increased risk of cesarean delivery there is no difference in neonatal or maternal outcomes in women with gestational hypertension with and without subjective symptoms of preeclampsia. Outcomes Outcome
No Sx (N = 510)
Reported Sx (N = 225)
P value
HELLP Abruption Abnormal FHR Thrombocytopenia Oliguria DIC Maternal Death Cesarean Delivery Birthweight (g) Neonatal Death (#) NICU Admission
0.6% 0.2% 2.9% 0.8% 0.2% 0 0 40.8% 3119 +/- 634 1 15.0%
2.2% 0.9% 1.9% 2.4% 0 0 0 55.6% 3060 +/- 695 1 19.6%
.06 .223 .606 .138 1.0 — — ! .001 .254 .52 .130
VASCULAR DYSFUNCTION IN PREECLAMPSIA ASSESSED BY BRACHIAL ARTERY ULTRASOUND INNA LANDRES1, MARIA SMALL2, SAMUEL RAMSAWAK3, ADESH SUIRJUSINGH4, KEITH WILLIAMS1, 1Yale University, Obstetrics & Gynecology, New Haven, Connecticut, 2Yale University, OB/GYN, New Haven, Connecticut, 3University of the West Indies, Obstetrics and Gynecology, Mount Hope, Trinidad and Tobago, 4University of the West Indies, Obstetrics and Gynecology, Mount Hope, Port of Spain, Trinidad and Tobago OBJECTIVE: This study compared vascular changes in the brachial artery between normotensive and preeclamptic women to assess differences in vascular reactivity and their timing in brachial artery flow mediated vascular dilation (FMVD) between the groups. STUDY DESIGN: This was a matched case controlled study of 12 preeclamptic vs 24 normotensive pregnant women conducted at three hospitals in two geographic settings; (1) Yale-New Haven Hospital in New Haven CT, (2) Mount Hope Maternity and (3) Port of Spain General Hospital in Port of Spain, Trinidad. Patients were matched for gestational age, maternal age and ethnicity. FMVD of the brachial artery was measured every 15 seconds post cuff-release for an initial 90s and then repeated at 120s (7 measurements). We assessed the degree and timing of maximum dilation in each patient. Student t tests and chi square analysis was done as necessary. RESULTS: Brachial Artery flow mediated vascular dilation (FMVD) was significantly reduced in women with preeclampsia compared with matched controls at each time point after 15s. Individual maximum end-diastolic dilation (EDD max) represents the best measurement of the difference in FMVD between the two groups( 4.5% G 2.7 in preeclamptics vs 9.8% G 4.0 in controls) (P ! .0002). There was a trend towards an earlier maximum EDD in the preeclamptic group (51s G 14) vs controls (61s G 26), P = .211. CONCLUSION: We confirmed a significant impairment in endothelial cell function in preeclamptic women by using ultrasound to detect brachial artery dilation. Care should be exercised in the interpretation of the FMVD as the timing of the maximun end- diastolic dilation which is the best measure of endothelial dysfunction may vary from patient to patient.