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791: Outcomes associated with isolated borderline oligohydramnios between 24 and 34 weeks' gestation
SMFM Abstracts 790
IDENTIFICATION OF MULTIPLE PROTEINS IN AMNIOTIC AND CERVICAL FLUIDS BY LUMINEX XMAP TECHNOLOGY AND PREDICTION OF MICROBIAL INVASION OF THE AMNIOTIC CAVITY IN WOMEN WITH PRETERM LABOR ROSE-MARIE HOLST1, BO JACOBSSON1, HENRIK HAGBERG2, ULLA-BRITT WENNERHOLM1, KRISTIN SKOGSTRAND3, POUL THORSEN4, 1Institute for Clinical Sciences, Göteborg, Sweden, 2Institute for Clinical Sciences, Goteborg, Sweden, 3Statens Serum Institute, Department of Clinical Biochemistry, Cophenhagen S, Denmark, 4University of Aarhus, Epidemiology and Social Medicine, Aarhus, Denmark OBJECTIVE: This study was aimed to analyze the association between amniotic and cervical proteins and microbial invasion of the amniotic cavity (MIAC) in women in preterm labor (PTL) with intact membranes. STUDY DESIGN: Amniotic and cervical samples were collected in a cohort of 89 women in PTL between 23 to 33 weeks. The primary endpoint of the study was the relation between protein levels and MIAC. Multiple proteins (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, sIL-6ra, IFN-gamma, TNF-alfa, TNFbeta, MCP-1, TGF- beta, MIP-1alfa, MIP-1beta, MMP-9, TREM-1, BDNF, GMCSF, NT4, NT-3, sTNF RI, MIF, RANTES) were analyzed in both compartments by the xMAP technology which allows analysis of an array of proteins in small amounts of sample volume. Cervical length was measured by trans-vaginal ultrasound. The individual levels of each protein were compared in the two compartments and calculations were performed to find associations between different proteins, background variables and MIAC. Stepwise logistic regression was used to create prediction models. RESULTS: High levels of IL-17 (0.025 ng/mL) and MCP-1 (2.7 ng/mL) in the cervical compartment were as good to predict MIAC as the combination of high levels of amniotic IL-1beta (1.8 ng/mL) and cervical IL-17 (0.025 ng/mL). Both prediction models had the same diagnostic indices, sensitivity 81.3 %, specificity 76.7 %, positive predictive value 43.3 % and negative predictive value 94.9 %, likelihood ratio 3.5. The receiver-operating characteristic curve analysis of cervical proteins had a higher value (0.93) for area under the curve than the combination of proteins in both compartments (0.87). CONCLUSION: The prediction of MIAC using the non-invasively collected cervical proteins has the same predictive ability as a combination of proteins from both the amniotic and cervical compartments.
www.AJOG.org 793
Perinatal outcomes in diabetics versus non-diabetics stratified by race/ethnicity expressed as odds ratios and 95% confidence intervals PTD ⬍34 Prim. CD CPD CD Bwt ⬎4500 HMD
0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.821
791
OUTCOMES ASSOCIATED WITH ISOLATED BORDERLINE OLIGOHYDRAMNIOS BETWEEN 24 AND 34 WEEKS’ GESTATION AVISHAI ALKALAY1, NELLI FISHER1, KRISTEN CAPONE1, SCARLETT KARAKASH1, JACOB KOWENSKY1, PEER SAR1, FRANCINE EINSTEIN1, 1Albert Einstein College of Medicine, Bronx, New York OBJECTIVE: To evaluate obstetric and neonatal outcomes in women with isolated borderline amniotic fluid volume identified between 24-34 weeks’ gestation. STUDY DESIGN: All cases between January 2006 and December 2007 of isolated borderline oligohydramnios (defined as an AFI ⬍5th percentile for gestational age (GA) with a 2⫻2 cm pocket) between 24 and 34 weeks’ gestation were identified. Controls were matched (2:1) for clinically relevant factors, including maternal age, gestational age at ultrasound (U/S), medical conditions, and indication for U/S. Multiple gestations, fetal anomalies, estimated fetal weight ⬍10th percentile and pPROM were excluded from analysis. Detailed data extraction for obstetric and neonatal outcomes (demise, RDS, NEC, TTN, IVH, hyperbilinrubinemia, hypoglycemia, anemia, sepsis) was obtained from maternal and neonatal records. RESULTS: We identified 45 cases (Oligo) and matched them to 90 controls (Con). Pre-pregnancy BMI, parity, race, smoking, prior cesarean delivery (CD), hypertension, pre-gestational diabetes, GA at 1st visit, and GA at U/S were similar in both groups. AFI (7.3⫾1.5 vs. 15.4⫾4.2cm, p⬍0.01) was significantly lower in Oligo compared to Con. Induction rate was higher in Oligo (73.3 vs. 41.1%, p⬍0.01), but the rate of CD was similar (37.7 vs. 30.0% respectively, p⫽0.4). Oligo delivered earlier (37.1⫾3 vs. 38.8⫾1.7 wks, p⬍0.01), weighed less (2649⫾735 vs. 3146⫾636g, p⬍0.01), and had a higher frequency of neonatal complications (37.4 vs. 17.8%, p⬍0.01). Oligo that underwent induction had a higher frequency of neonatal complications when compared to Oligo cases that delivered spontaneously (48.5 vs. 8.3%, p⬍0.05). When GA at delivery was controlled for in Oligo cases, this association was no longer seen (p⫽.12). CONCLUSION: Borderline oligohydramnios between 24-34 wks even in the absence of clear etiology is associated with an increased risk of neonatal morbidity that cannot be explained by intervention or gestational age at delivery alone. Detailed prospective analysis of this important observation should be undertaken. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.822
792
WITHDRAWN 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.823
S224
PERINATAL OUTCOMES IN DIABETICS VERSUS NON-DIABETICS BY RACE/ETHNICITY TANIA ESAKOFF1, AARON CAUGHEY1, RAMOS GLADYS2, JUDITH CHUNG3, INGRID BLOCK-KURBISCH4, YVONNE CHENG4, 1University of California, San Francisco, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California, 2University of California, San Diego, California, 3University of California, Irvine, Orange, California, 4University of California, San Francisco, San Francisco, California OBJECTIVE: To determine if racial/ethnic differences exist in perinatal outcomes of patients with and without diabetes (DM). STUDY DESIGN: This is a retrospective cohort study of 62,377 pregnancies with DM and 2,047,100 pregnancies without DM in the United States. The outcomes were primary cesarean delivery (Prim. CD), cesarean delivery due to cephalopelvic disproportion (CPD CD), preterm delivery ⬍34 wks (PTD ⬍ 34), birthweight ⬎ 4500g (Bwt⬎4500) and hyaline membrane disease (HMD).These were examined among four ethnic groups: Caucasian, African American, Latina and Asian. Odds ratios and 95% confidence intervals were determined using multivariate logistic regression. RESULTS: Caucasians, African Americans and Latinas with diabetes had the highest odds of Prim. CD and CD for CPD compared to their non-diabetics counterparts. All groups are at higher odds of PTD⬍34 in the setting of diabetes except for Asians who have the same rate regardless of diabetes status. When compared to Caucasians and Asians, African Americans and Latinas who have diabetes are at higher odds of Bwt⬎4500 and have a trend towards a higher odds of HMD than their non-diabetic counterparts. CONCLUSION: Though DM itself is a risk factor for adverse perinatal outcomes, the severity of this risk appears to vary by race/ethnicity. Are these differences due to sociocultural variation or actual differences in genetics and pathophysiology? A search for mechanisms behind these differences could help guide management and counseling of these patients.
Cauc.
Af. Am.
Latina
Asian
1.2 1.1-1.3 2.0 2.0-2.1 1.9 1.8-2.0 2.5 2.4-2.6 1.7 1.6-1.9
1.3 1.2-1.4 2.0 2.0-2.1 2.1 1.9-2.2 4.5 4.1-5.1 2.3 1.9-2.7
1.3 1.1-1.4 1.9 1.8-2.0 2.3 2.1-2.4 3.7 3.4-4.1 2.4 2.1-2.9
1.1 0.8-1.3 1.5 1.4-1.6 1.5 1.3-1.6 2.8 2.3-3.4 1.8 1.2-2.3
0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.824
794
GENETIC VARIATION OF INFLAMMATORY MEDIATOR SEPS1 PROMOTER POLYMORPHISM IN MOTHER INFANT PAIRS SUZANNE PETERSON1, JANE HITTI1, KATHLEEN PAUL1, MICHAEL BAMSHAD2, 1University of Washington, Department of Obstetrics and Gynecology, Seattle, Washington, 2University of Washington, Department of Pediatrics, Seattle, Washington OBJECTIVE: The SEPS1 gene encodes selenoprotein 1, an inflammatory mediator involved in the endoplasmic reticulum stress response. The SEPS1 promoter polymorphism (⫺105 G¡A) is associated with impaired expression of SEPS1 and increased concentrations of proinflammatory cytokines. In this study, we examined the association between the (⫺105 G¡A) polymorphism, TNF-␣ production, and preterm birth (PTB) ⬍ 34 weeks. STUDY DESIGN: This secondary analysis included 231 parous women enrolled in an observational study of racial disparities in PTB, and their 157 surviving infants. Maternal whole blood samples were stimulated with lipopolysaccharide (E coli. LPS; Sigma) and TNF- concentrations quantified by enzyme immunoassay. DNA was extracted from maternal and index children buccal swabs and the SEPS1 (⫺105 G¡A) polymorphism was detected by restriction digest with BstNI. Regression models were used to examine the associations between maternal and infant SEPS1 genotypes and race, whole blood TNF- concentrations, and history of PTB in the index pregnancy using both dominant genotypic and additive allelic models. RESULTS: Of 231 women (57 African American (AA) and 164 European American (EA)), 73 (46%) had PTB in the index pregnancy. The SEPS1 (⫺105 G¡A) homozygous polymorphism, conferring an increased inflammatory response, was more common in the African American (AA) sample than the European American (EA) sample in mothers and infants (p⬍0.001 for both). After adjustment for ancestry, maternal SEPS1 (⫺105 G¡A) genotype was not associated with TNFconcentrations. Neither maternal nor infant SEPS1 (⫺105 G¡A) genotype was associated with PTB after adjustment for ancestry. CONCLUSION: The SEPS1 promoter polymorphism (⫺105 G¡A) was detected more frequently among AA compared to EA mothers and infants in this cohort, but was not associated with increased TNF- concentrations or with PTB. Given the contribution of inflammation in PTB and SEPS1 promoter (⫺105 G¡A) proinflammatory influence, this analysis warrants replication in a larger cohort of AA women with PTB. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.825
American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008
IDENTIFICATION OF MULTIPLE PROTEINS IN AMNIOTIC AND CERVICAL FLUIDS BY LUMINEX XMAP TECHNOLOGY AND PREDICTION OF MICROBIAL INVASION OF THE AMNIOTIC CAVITY IN WOMEN WITH PRETERM LABOR ROSE-MARIE HOLST1, BO JACOBSSON1, HENRIK HAGBERG2, ULLA-BRITT WENNERHOLM1, KRISTIN SKOGSTRAND3, POUL THORSEN4, 1Institute for Clinical Sciences, Göteborg, Sweden, 2Institute for Clinical Sciences, Goteborg, Sweden, 3Statens Serum Institute, Department of Clinical Biochemistry, Cophenhagen S, Denmark, 4University of Aarhus, Epidemiology and Social Medicine, Aarhus, Denmark OBJECTIVE: This study was aimed to analyze the association between amniotic and cervical proteins and microbial invasion of the amniotic cavity (MIAC) in women in preterm labor (PTL) with intact membranes. STUDY DESIGN: Amniotic and cervical samples were collected in a cohort of 89 women in PTL between 23 to 33 weeks. The primary endpoint of the study was the relation between protein levels and MIAC. Multiple proteins (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, sIL-6ra, IFN-gamma, TNF-alfa, TNFbeta, MCP-1, TGF- beta, MIP-1alfa, MIP-1beta, MMP-9, TREM-1, BDNF, GMCSF, NT4, NT-3, sTNF RI, MIF, RANTES) were analyzed in both compartments by the xMAP technology which allows analysis of an array of proteins in small amounts of sample volume. Cervical length was measured by trans-vaginal ultrasound. The individual levels of each protein were compared in the two compartments and calculations were performed to find associations between different proteins, background variables and MIAC. Stepwise logistic regression was used to create prediction models. RESULTS: High levels of IL-17 (0.025 ng/mL) and MCP-1 (2.7 ng/mL) in the cervical compartment were as good to predict MIAC as the combination of high levels of amniotic IL-1beta (1.8 ng/mL) and cervical IL-17 (0.025 ng/mL). Both prediction models had the same diagnostic indices, sensitivity 81.3 %, specificity 76.7 %, positive predictive value 43.3 % and negative predictive value 94.9 %, likelihood ratio 3.5. The receiver-operating characteristic curve analysis of cervical proteins had a higher value (0.93) for area under the curve than the combination of proteins in both compartments (0.87). CONCLUSION: The prediction of MIAC using the non-invasively collected cervical proteins has the same predictive ability as a combination of proteins from both the amniotic and cervical compartments.
www.AJOG.org 793
Perinatal outcomes in diabetics versus non-diabetics stratified by race/ethnicity expressed as odds ratios and 95% confidence intervals PTD ⬍34 Prim. CD CPD CD Bwt ⬎4500 HMD
0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.821
791
OUTCOMES ASSOCIATED WITH ISOLATED BORDERLINE OLIGOHYDRAMNIOS BETWEEN 24 AND 34 WEEKS’ GESTATION AVISHAI ALKALAY1, NELLI FISHER1, KRISTEN CAPONE1, SCARLETT KARAKASH1, JACOB KOWENSKY1, PEER SAR1, FRANCINE EINSTEIN1, 1Albert Einstein College of Medicine, Bronx, New York OBJECTIVE: To evaluate obstetric and neonatal outcomes in women with isolated borderline amniotic fluid volume identified between 24-34 weeks’ gestation. STUDY DESIGN: All cases between January 2006 and December 2007 of isolated borderline oligohydramnios (defined as an AFI ⬍5th percentile for gestational age (GA) with a 2⫻2 cm pocket) between 24 and 34 weeks’ gestation were identified. Controls were matched (2:1) for clinically relevant factors, including maternal age, gestational age at ultrasound (U/S), medical conditions, and indication for U/S. Multiple gestations, fetal anomalies, estimated fetal weight ⬍10th percentile and pPROM were excluded from analysis. Detailed data extraction for obstetric and neonatal outcomes (demise, RDS, NEC, TTN, IVH, hyperbilinrubinemia, hypoglycemia, anemia, sepsis) was obtained from maternal and neonatal records. RESULTS: We identified 45 cases (Oligo) and matched them to 90 controls (Con). Pre-pregnancy BMI, parity, race, smoking, prior cesarean delivery (CD), hypertension, pre-gestational diabetes, GA at 1st visit, and GA at U/S were similar in both groups. AFI (7.3⫾1.5 vs. 15.4⫾4.2cm, p⬍0.01) was significantly lower in Oligo compared to Con. Induction rate was higher in Oligo (73.3 vs. 41.1%, p⬍0.01), but the rate of CD was similar (37.7 vs. 30.0% respectively, p⫽0.4). Oligo delivered earlier (37.1⫾3 vs. 38.8⫾1.7 wks, p⬍0.01), weighed less (2649⫾735 vs. 3146⫾636g, p⬍0.01), and had a higher frequency of neonatal complications (37.4 vs. 17.8%, p⬍0.01). Oligo that underwent induction had a higher frequency of neonatal complications when compared to Oligo cases that delivered spontaneously (48.5 vs. 8.3%, p⬍0.05). When GA at delivery was controlled for in Oligo cases, this association was no longer seen (p⫽.12). CONCLUSION: Borderline oligohydramnios between 24-34 wks even in the absence of clear etiology is associated with an increased risk of neonatal morbidity that cannot be explained by intervention or gestational age at delivery alone. Detailed prospective analysis of this important observation should be undertaken. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.822
792
WITHDRAWN 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.823
S224
PERINATAL OUTCOMES IN DIABETICS VERSUS NON-DIABETICS BY RACE/ETHNICITY TANIA ESAKOFF1, AARON CAUGHEY1, RAMOS GLADYS2, JUDITH CHUNG3, INGRID BLOCK-KURBISCH4, YVONNE CHENG4, 1University of California, San Francisco, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California, 2University of California, San Diego, California, 3University of California, Irvine, Orange, California, 4University of California, San Francisco, San Francisco, California OBJECTIVE: To determine if racial/ethnic differences exist in perinatal outcomes of patients with and without diabetes (DM). STUDY DESIGN: This is a retrospective cohort study of 62,377 pregnancies with DM and 2,047,100 pregnancies without DM in the United States. The outcomes were primary cesarean delivery (Prim. CD), cesarean delivery due to cephalopelvic disproportion (CPD CD), preterm delivery ⬍34 wks (PTD ⬍ 34), birthweight ⬎ 4500g (Bwt⬎4500) and hyaline membrane disease (HMD).These were examined among four ethnic groups: Caucasian, African American, Latina and Asian. Odds ratios and 95% confidence intervals were determined using multivariate logistic regression. RESULTS: Caucasians, African Americans and Latinas with diabetes had the highest odds of Prim. CD and CD for CPD compared to their non-diabetics counterparts. All groups are at higher odds of PTD⬍34 in the setting of diabetes except for Asians who have the same rate regardless of diabetes status. When compared to Caucasians and Asians, African Americans and Latinas who have diabetes are at higher odds of Bwt⬎4500 and have a trend towards a higher odds of HMD than their non-diabetic counterparts. CONCLUSION: Though DM itself is a risk factor for adverse perinatal outcomes, the severity of this risk appears to vary by race/ethnicity. Are these differences due to sociocultural variation or actual differences in genetics and pathophysiology? A search for mechanisms behind these differences could help guide management and counseling of these patients.
Cauc.
Af. Am.
Latina
Asian
1.2 1.1-1.3 2.0 2.0-2.1 1.9 1.8-2.0 2.5 2.4-2.6 1.7 1.6-1.9
1.3 1.2-1.4 2.0 2.0-2.1 2.1 1.9-2.2 4.5 4.1-5.1 2.3 1.9-2.7
1.3 1.1-1.4 1.9 1.8-2.0 2.3 2.1-2.4 3.7 3.4-4.1 2.4 2.1-2.9
1.1 0.8-1.3 1.5 1.4-1.6 1.5 1.3-1.6 2.8 2.3-3.4 1.8 1.2-2.3
0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.824
794
GENETIC VARIATION OF INFLAMMATORY MEDIATOR SEPS1 PROMOTER POLYMORPHISM IN MOTHER INFANT PAIRS SUZANNE PETERSON1, JANE HITTI1, KATHLEEN PAUL1, MICHAEL BAMSHAD2, 1University of Washington, Department of Obstetrics and Gynecology, Seattle, Washington, 2University of Washington, Department of Pediatrics, Seattle, Washington OBJECTIVE: The SEPS1 gene encodes selenoprotein 1, an inflammatory mediator involved in the endoplasmic reticulum stress response. The SEPS1 promoter polymorphism (⫺105 G¡A) is associated with impaired expression of SEPS1 and increased concentrations of proinflammatory cytokines. In this study, we examined the association between the (⫺105 G¡A) polymorphism, TNF-␣ production, and preterm birth (PTB) ⬍ 34 weeks. STUDY DESIGN: This secondary analysis included 231 parous women enrolled in an observational study of racial disparities in PTB, and their 157 surviving infants. Maternal whole blood samples were stimulated with lipopolysaccharide (E coli. LPS; Sigma) and TNF- concentrations quantified by enzyme immunoassay. DNA was extracted from maternal and index children buccal swabs and the SEPS1 (⫺105 G¡A) polymorphism was detected by restriction digest with BstNI. Regression models were used to examine the associations between maternal and infant SEPS1 genotypes and race, whole blood TNF- concentrations, and history of PTB in the index pregnancy using both dominant genotypic and additive allelic models. RESULTS: Of 231 women (57 African American (AA) and 164 European American (EA)), 73 (46%) had PTB in the index pregnancy. The SEPS1 (⫺105 G¡A) homozygous polymorphism, conferring an increased inflammatory response, was more common in the African American (AA) sample than the European American (EA) sample in mothers and infants (p⬍0.001 for both). After adjustment for ancestry, maternal SEPS1 (⫺105 G¡A) genotype was not associated with TNFconcentrations. Neither maternal nor infant SEPS1 (⫺105 G¡A) genotype was associated with PTB after adjustment for ancestry. CONCLUSION: The SEPS1 promoter polymorphism (⫺105 G¡A) was detected more frequently among AA compared to EA mothers and infants in this cohort, but was not associated with increased TNF- concentrations or with PTB. Given the contribution of inflammation in PTB and SEPS1 promoter (⫺105 G¡A) proinflammatory influence, this analysis warrants replication in a larger cohort of AA women with PTB. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.825
American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008