innate immune mechanisms in peripartum cardiomyopathy

1
320 FETAL GROWTH TEMPORAL TRENDS IN PREGNANCIES COMPLI- CATED BY LUPUS J. PATRICIA DHAR 1 , LYNETTE ESSENMACHER 2 , JOEL AGER 2 , ROBERT SOKOL 3 , 1 Wayne State University School of Medicine, Internal Medicine/Rheumatology, Detroit, MI 2 Wayne State University, Center for Health Care Effectiveness Research, Detroit, MI 3 Wayne State University, Obstetrics/Gynecology, Detroit, MI OBJECTIVE: The objective of this study was to evaluate whether fetal growth has improved or gestational duration has increased over time. We hypothesized improved outcomes that might be attributable to advances in lupus in- tervention. STUDY DESIGN: A cohort analysis of pregnancy outcomes from 1985-2002 in women with lupus was performed at our center. The Wayne State University Lupus Registry was linked to the Wayne State University Perinatal Database to obtain all pregnancies in women with lupus delivered at our institution. The control population consisted of demographically similar non-lupus pregnancies from the Wayne State University Perinatal Database RESULTS: There were 473 singleton deliveries in 327 women with lupus delivered at our institution. To ensure statistical independence, we calculated the mean birth weight and gestational age in the first pregnancy per parturient delivered at our center, leaving us with 327 pregnancies in 327 women with lupus (first pregnancy group). The control group consisted of 78,905 deliveries at our center during the same period. The mean birthweight and gestational age for the first pregnancy group was significantly decreased (2790 grams and 36 weeks, respectively) compared to the control group (P < 0.0001). Gestational age and birthweight did not significantly change over time. However, when birthweight percentiles over time were analyzed, a statistically significant increase in fetal growth was seen (r = ÿ0.098, r 2 = 0.10, P = 0.041). CONCLUSION: Fetal growth in pregnancies complicated by lupus improved over the 18 years of this study. Because there were no major changes in the characteristics of the sample, we speculate that this improvement might reflect advancing technology of care and improved intervention, as originally hypothesized, most notably aggressive thrombophilia assessments and treat- ment, as well as concurrent rheumatologic care during pregnancy. Any change in ‘‘spontaneous’’ gestational duration over time might be hidden by changes in obstetric intervention. 321 THE MFMU CESAREAN REGISTRY: RISK OF UTERINE RUPTURE WITH A TRIAL OF LABOR IN WOMEN WITH MULTIPLE AND SINGLE PRIOR CESAREAN DELIVERY MARK LANDON 1 , 1 for the NICHD MFMU Network, Bethesda, MD OBJECTIVE: To determine and compare success rates of trial of labor (TOL) and uterine rupture in women with single versus multiple prior cesarean deliveries (CDs). STUDY DESIGN: Prospective 4-year (1999-2002) observational study at 19 academic medical centers of singleton gestations and prior cesarean delivery. Records were reviewed by trained research nurses. Maternal and perinatal outcomes were compared between women with single versus multiple prior CDs. RESULTS: 17,931 women attempted vaginal birth after cesarean (VBAC); 16,934 (94.5%) had one prior CD, whereas 995 (5.5%) had multiple prior CDs. Higher VBAC success rate was observed in women with one prior CD (73.7%) vs women with multiple prior CDs (65.7%) (P < 0.0001). Uterine rupture occurred in 140 cases (0.78%). Multiple prior CDs were associated with higher uterine rupture rate 14/995 (1.4%) versus single prior CD 126/16,936 (0.74%) (P = 0.02). Induction and oxytocin augmentation increased risk of uterine rupture after controlling for single vs multiple prior CDs (P < 0.0001). Maternal morbidity was increased in women with multiple prior CDs (see Table). CONCLUSION: The risk for uterine rupture is significantly elevated in women with multiple prior CDs undergoing TOL. Additional increased risks for these women include hysterectomy and blood transfusion. 322 FREE T 4 (FT 4 ) LEVELS MAY NOT BE ACCURATE FOR THE DETECTION OF HYPOTHYROIDISM IN PREGNANT WOMEN ANTHONY SCISCIONE 1 , ROBYN GRAY 1 , PAT WILSON 2 , 1 Christiana Hospital, Newark, DE 2 Chris- tiana Hospital, Pathology, Newark, DE OBJECTIVE: Thyroid disease is one of the most common endocrinologic abnormalities in pregnancy. FT 4 and thyroid-stimulating hormone (TSH) levels are often used for its diagnosis. Determination of FT 4 by equilibrium dialysis (FT4e) is considered the gold standard. However, due to cost and ease of use, FT 4 by competitive immunoassay (FT4i) is most commonly used. This test has not been validated in pregnant women. We sought to compare the accuracy of FT 4 e and FT 4 i in pregnant women. STUDY DESIGN: Women who had FT 4 and TSH levels ordered by their physicians were included. After consent, they had serum levels for TSH, FT 4 e, and FT 4 i drawn. Maternal demographic data, gestational age, diagnosis of thyroid disease, and obstetrical and medical data were collected. The symptoms and clinical diagnosis were recorded. Chi-square, Student t-test, and Pearson correlation were used where appropriate. RESULTS: Twenty-five women were entered at various gestational ages. Established normative values were used for each thyroid test. 3 of 25 (12%) of FT 4 e versus 8 of 25 (32%) of FT 4 i were abnormal (P < 0.01). All abnormal values were low. Sensitivity was 100%, with specificity of 48.4%, positive predictive value of 40%, and a negative predictive value of 100% for FT 4 i. Correlation between FT 4 e and FT 4 i revealed an R value of 0.76. The FT 4 i was falsely decreased in 25% of women. CONCLUSION: Free T 4 by competitive immunoassay may be falsely decreased in pregnant women. New cutoffs should be considered in pregnancy. 323 INNATE IMMUNE MECHANISMS IN PERIPARTUM CARDIOMYOPATHY JANE ELLIS 1 , BRUCE SUNDSTROM 2 , HUGH RANDALL 1 , JAMES FETT 3 , AFTAB ANSARI 2 , 1 Emory University, Gyn/OB, Atlanta, GA 2 Emory Univer- sity, Department of Pathology and Laboratory Medicine, Atlanta, GA 3 Hospital Albert Schweitzer, Department of Adult and Tropical Medicine, Deschapelles, Haiti OBJECTIVE: Peripartum cardiomyopathy (PPCM) is a rare but devastating disorder of unknown etiology affecting women in the immediate antepartum to 5-month postpartum period. In central Haiti a high occurrence of PPCM has emerged that is associated with elevated plasma levels of cardiac-specific autoantibodies, thus providing a unique opportunity to study potential underlying autoimmune etiologies associated with this disease. The objective of this study was to characterize differences in innate immune activation potential between PPCM and control subjects by measuring plasma-induced maturation of human cord blood–derived progenitor dendritic cells. STUDY DESIGN: CD34 + cord blood stem cells (CBSCs) were isolated from cord blood by positive selection with immunomagnetic beads; then cultured in vitro in medium supplemented with granulocyte-monocyte colony-stimulating factor plus 25% v/v plasma collected from healthy Haitian women (n = 12), PPCM subjects (n = 12), or laboratory controls (n = 3) for 7 days; then counted and placed in replicate co-cultures with 100,000 responder lymphocytes in a standard 96-hour mixed lymphocyte reaction assay. Proliferative responses to matured cord blood dendritic cells (CBDCs) were determined by measuring incorporated [3H]-thymidine. Plasma levels of pro-brain natriuretic peptide (pro-BNP) and C-reactive protein (CRP) were measured by ELISA to characterize levels of cardiac dysfunction and immune activation. RESULTS: Pro-BNP and CRP levels were significantly elevated (P < 0.0005) in PPCM patients. While plasma from both Haitian PPCM patients (7 of 12) and controls (7 of 12) induced CBDC maturation, the level of maturation was significantly greater in Haitian control vs PPCM plasma (P < 0.04). CONCLUSION: Clinical evidence of cardiac dysfunction in PPCM correlated inversely with significant differences in innate immune activation potential. These data support an autoimmune etiology and represent a clinical profile that may have predictive value in early detection and prognosis of PPCM. Multiple vs single prior cesarean deliveries Multiple CDs N (%) Single CD N (%) RR (95% CI) P Uterine rupture 14/995 (1.4) 126/16934 (0.74) 1.89 (1.09-3.27) 0.0209 Endometritis 31/995 (3.1) 487/16395 (2.9) 1.08 (0.76-1.55) 0.6606 Maternal death 0/995 (0.00) 3/16934 (0.02) 1.00 Hysterectomy 7/995 (0.7) 34/16934 (0.20) 3.50 (1.56-7.88) 0.0068 Transfusion 32/995 (3.2) 275/16935 (1.6) 1.98 (1.38-2.84) 0.0002 Term NICU admit 77/674 (11.4) 1320/14619 (9.0) 1.27 (1.02-1.57) 0.0349 Term intrapartum stillbirth 1/679 (0.15) 6/14657 (0.04) 3.60 (0.43-29.84) 0.2717 Term neonatal death 1/674 (0.15) 11/14619 (0.08) 1.97 (0.25-15.25) 0.4179 Volume 189, Number 6 Am J Obstet Gynecol SMFM Abstracts S149

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Page 1: Innate immune mechanisms in peripartum cardiomyopathy

320 FETAL GROWTH TEMPORAL TRENDS IN PREGNANCIES COMPLI-CATED BY LUPUS J. PATRICIA DHAR1, LYNETTE ESSENMACHER2, JOELAGER2, ROBERT SOKOL3, 1Wayne State University School of Medicine,Internal Medicine/Rheumatology, Detroit, MI 2Wayne State University,Center for Health Care Effectiveness Research, Detroit, MI 3Wayne StateUniversity, Obstetrics/Gynecology, Detroit, MI

OBJECTIVE:The objective of this study was to evaluate whether fetal growthhas improved or gestational duration has increased over time. We hypothesizedimproved outcomes that might be attributable to advances in lupus in-tervention.

STUDY DESIGN: A cohort analysis of pregnancy outcomes from 1985-2002in women with lupus was performed at our center. The Wayne State UniversityLupus Registry was linked to the Wayne State University Perinatal Database toobtain all pregnancies in women with lupus delivered at our institution. Thecontrol population consisted of demographically similar non-lupus pregnanciesfrom the Wayne State University Perinatal Database

RESULTS: There were 473 singleton deliveries in 327 women with lupusdelivered at our institution. To ensure statistical independence, we calculatedthe mean birth weight and gestational age in the first pregnancy per parturientdelivered at our center, leaving us with 327 pregnancies in 327 womenwith lupus(first pregnancy group). The control group consisted of 78,905 deliveries at ourcenter during the same period. The mean birthweight and gestational age forthe first pregnancy group was significantly decreased (2790 grams and 36 weeks,respectively) compared to the control group (P < 0.0001). Gestational age andbirthweight did not significantly change over time. However, when birthweightpercentiles over time were analyzed, a statistically significant increase in fetalgrowth was seen (r = �0.098, r2 = 0.10, P = 0.041).

CONCLUSION: Fetal growth in pregnancies complicated by lupusimproved over the 18 years of this study. Because there were no major changesin the characteristics of the sample, we speculate that this improvement mightreflect advancing technology of care and improved intervention, as originallyhypothesized, most notably aggressive thrombophilia assessments and treat-ment, as well as concurrent rheumatologic care during pregnancy. Any changein ‘‘spontaneous’’ gestational duration over timemight be hidden by changes inobstetric intervention.

321 THE MFMU CESAREAN REGISTRY: RISK OF UTERINE RUPTURE WITHA TRIAL OF LABOR IN WOMEN WITH MULTIPLE AND SINGLE PRIORCESAREAN DELIVERY MARK LANDON1, 1for the NICHD MFMU Network,Bethesda, MD

OBJECTIVE: To determine and compare success rates of trial of labor(TOL) and uterine rupture in women with single versus multiple prior cesareandeliveries (CDs).

STUDY DESIGN: Prospective 4-year (1999-2002) observational study at 19academic medical centers of singleton gestations and prior cesarean delivery.Records were reviewed by trained research nurses. Maternal and perinataloutcomes were compared between womenwith single versusmultiple prior CDs.

RESULTS: 17,931 women attempted vaginal birth after cesarean (VBAC);16,934 (94.5%) had one prior CD, whereas 995 (5.5%) had multiple prior CDs.Higher VBAC success rate was observed in women with one prior CD (73.7%) vswomen with multiple prior CDs (65.7%) (P < 0.0001). Uterine rupture occurredin 140 cases (0.78%). Multiple prior CDs were associated with higher uterinerupture rate 14/995 (1.4%) versus single prior CD 126/16,936 (0.74%)(P = 0.02). Induction and oxytocin augmentation increased risk of uterinerupture after controlling for single vs multiple prior CDs (P < 0.0001). Maternalmorbidity was increased in women with multiple prior CDs (see Table).

CONCLUSION: The risk for uterine rupture is significantly elevated inwomen with multiple prior CDs undergoing TOL. Additional increased risks forthese women include hysterectomy and blood transfusion.

322 FREE T4 (FT4) LEVELS MAY NOT BE ACCURATE FOR THE DETECTIONOF HYPOTHYROIDISM IN PREGNANT WOMEN ANTHONY SCISCIONE1,ROBYN GRAY1, PAT WILSON2, 1Christiana Hospital, Newark, DE 2Chris-tiana Hospital, Pathology, Newark, DE

OBJECTIVE: Thyroid disease is one of the most common endocrinologicabnormalities in pregnancy. FT4 and thyroid-stimulating hormone (TSH) levelsare often used for its diagnosis. Determination of FT4 by equilibrium dialysis(FT4e) is considered the gold standard. However, due to cost and ease of use,FT4 by competitive immunoassay (FT4i) is most commonly used. This test hasnot been validated in pregnant women. We sought to compare the accuracy ofFT4e and FT4i in pregnant women.

STUDY DESIGN: Women who had FT4 and TSH levels ordered by theirphysicians were included. After consent, they had serum levels for TSH, FT4e,and FT4i drawn. Maternal demographic data, gestational age, diagnosis ofthyroid disease, and obstetrical and medical data were collected. The symptomsand clinical diagnosis were recorded. Chi-square, Student t-test, and Pearsoncorrelation were used where appropriate.

RESULTS: Twenty-five women were entered at various gestational ages.Established normative values were used for each thyroid test. 3 of 25 (12%) ofFT4e versus 8 of 25 (32%) of FT4i were abnormal (P < 0.01). All abnormal valueswere low. Sensitivity was 100%, with specificity of 48.4%, positive predictive valueof 40%, and a negative predictive value of 100% for FT4i. Correlation betweenFT4e and FT4i revealed an R value of 0.76. The FT4i was falsely decreased in 25%of women.

CONCLUSION: Free T4 by competitive immunoassay may be falselydecreased in pregnant women. New cutoffs should be considered in pregnancy.

323

Multiple vs single prior cesarean deliveries

Multiple CDsN (%)

Single CDN (%)

RR(95% CI) P

Uterine rupture 14/995 (1.4) 126/16934(0.74)

1.89(1.09-3.27)

0.0209

Endometritis 31/995 (3.1) 487/16395(2.9)

1.08(0.76-1.55)

0.6606

Maternal death 0/995 (0.00) 3/16934(0.02)

— 1.00

Hysterectomy 7/995 (0.7) 34/16934(0.20)

3.50(1.56-7.88)

0.0068

Transfusion 32/995 (3.2) 275/16935(1.6)

1.98(1.38-2.84)

0.0002

Term NICU admit 77/674 (11.4) 1320/14619(9.0)

1.27(1.02-1.57)

0.0349

Term intrapartumstillbirth

1/679 (0.15) 6/14657(0.04)

3.60(0.43-29.84)

0.2717

Term neonatal death 1/674 (0.15) 11/14619(0.08)

1.97(0.25-15.25)

0.4179

Volume 189, Number 6Am J Obstet Gynecol

SMFM Abstracts S149

INNATE IMMUNE MECHANISMS IN PERIPARTUM CARDIOMYOPATHYJANE ELLIS1, BRUCE SUNDSTROM2, HUGH RANDALL1, JAMES FETT3,AFTAB ANSARI2, 1Emory University, Gyn/OB, Atlanta, GA 2Emory Univer-sity, Department of Pathology and Laboratory Medicine, Atlanta, GA3Hospital Albert Schweitzer, Department of Adult and Tropical Medicine,Deschapelles, Haiti

OBJECTIVE: Peripartum cardiomyopathy (PPCM) is a rare but devastatingdisorder of unknown etiology affecting women in the immediate antepartum to5-month postpartum period. In central Haiti a high occurrence of PPCM hasemerged that is associated with elevated plasma levels of cardiac-specificautoantibodies, thus providing a unique opportunity to study potentialunderlying autoimmune etiologies associated with this disease. The objectiveof this study was to characterize differences in innate immune activationpotential between PPCM and control subjects by measuring plasma-inducedmaturation of human cord blood–derived progenitor dendritic cells.

STUDY DESIGN: CD34+ cord blood stem cells (CBSCs) were isolated fromcord blood by positive selection with immunomagnetic beads; then cultured invitro in medium supplemented with granulocyte-monocyte colony-stimulatingfactor plus 25% v/v plasma collected from healthy Haitian women (n = 12),PPCM subjects (n = 12), or laboratory controls (n = 3) for 7 days; then countedand placed in replicate co-cultures with 100,000 responder lymphocytes ina standard 96-hour mixed lymphocyte reaction assay. Proliferative responses tomatured cord blood dendritic cells (CBDCs) were determined by measuringincorporated [3H]-thymidine. Plasma levels of pro-brain natriuretic peptide(pro-BNP) and C-reactive protein (CRP) were measured by ELISA tocharacterize levels of cardiac dysfunction and immune activation.

RESULTS: Pro-BNP and CRP levels were significantly elevated (P < 0.0005)in PPCM patients. While plasma from both Haitian PPCM patients (7 of 12) andcontrols (7 of 12) induced CBDC maturation, the level of maturation wassignificantly greater in Haitian control vs PPCM plasma (P < 0.04).

CONCLUSION: Clinical evidence of cardiac dysfunction in PPCMcorrelated inversely with significant differences in innate immune activationpotential. These data support an autoimmune etiology and represent a clinicalprofile that may have predictive value in early detection and prognosis of PPCM.