- Email: [email protected]
223: Correlation of urine protein-creatinine ratios and 24-hour urinary excretion in twin pregnancies
Poster Session I and dysregulation of angiogenesis. Since 1) urinary MMP2 and 9 have been used as biomarkers for certain cancers, 2) the pathophysiology of invasive placentation may mimic cancer pathophysiology, and 3) MMP 2 and 9 concentrations are elevated in the decidua of patients with accreta, our goal was to determine if urinary MMPs that are known to degrade major collagens could be biomarkers of invasive placentation. STUDY DESIGN: We performed a case-control study of women with suspected invasive placentation and controls comprised of women with normal placentation. Patients with suspected invasive placentation had urine samples collected at delivery. Pathology reports confirmed invasive versus normal placentation. MMP 1, 2, 7, 9 and 10 concentrations were measured using Luminex multiplex assays. MMP values were normalized to total urine protein concentration. Differences in MMP values between invasive placentation cases and controls were compared using MannWhitney U test and subsequently adjusted for maternal age through linear regression models. RESULTS: Urine samples were obtained from 23 patients with invasive placentation and 13 controls. Race, ethnicity, number of previous cesarean sections, gravidity were similar between the groups, although the mean maternal age among cases was marginally higher than controls (35.6 4.0 versus 32.5 5.1; P¼ 0.04). After linear regression to control for age, women with invasive placentation had higher urinary MMP 2 concentrations. (Figure 1) No significant differences were noted in MMP 1, 7, 9 and 10 concentrations between the groups. CONCLUSION: Urinary MMP 2 levels are elevated in women with invasive placentation and may be a potential biomarker to aid in the antepartum diagnosis of invasive placentation.
ajog.org or placebo. For this secondary analysis we included non-anomalous singleton gestations delivered between 22 0/7 -25 6/7 weeks. We excluded women with missing exposure or outcome data. The primary exposure of interest was mode of delivery. The primary outcomes were Bayley II scores <70 (mental and motor) at two years of age. Logbinomial regression was used to control for possible confounders including, gestational age at delivery, chorioamnionitis, years of maternal education, maternal BMI and original study treatment group. RESULTS: A total of 158 women met inclusion criteria. Ninety-one had a vaginal delivery and sixty-seven had a cesarean delivery. Exposure to magnesium sulfate, maternal education, chorioamnionitis, years of maternal education, and maternal BMI were similar in both groups. There was no difference in either mental or motor Bayley II scores <70 or <85 by mode of delivery in either univariable or multivariable analysis. CONCLUSION: There is no difference in Bayley II scores by mode of delivery at time of periviability. This adds to the literature supporting obstetric indications dictating mode of delivery at this gestational age. MDI and PDI by mode of delivery
*Adjusted for gestational age at delivery, chorioamnionitis, years of maternal education, maternal BMI and original study treatment group.
223 Correlation of urine protein-creatinine ratios and 24-hour urinary excretion in twin pregnancies
Sarah Osmundson1, Richard Lafayette4, Raffick Bowen2, Valerie Roque3, Natali Aziz1 1
Stanford University School of Medicine, Department of Obstetrics & Gynecology, Stanford, CA, 2Stanford University School of Medicine, Department of Pathology, Stanford, CA, 3University of California, Davis, Department of Medicine, Sacramento, CA, 4Stanford University School of Medicine, Department of Medicine, Stanford, CA
222 Mode of delivery at periviability and early childhood neurodevelopment
Sarah Obican1, Daphnie Drassinower1, Heather Levin1, Cynthia Gyamfi-Bannerman1
1 Columbia University Medical Center, Department of Obstetrics and Gynecology, New York, NY
OBJECTIVE: Little is known regarding the impact of mode of delivery in the periviable period. Even less is understood regarding the effect of mode of delivery on neurodevelopment. Our objective is to determine if the mode of delivery at time of periviability impacts Bayley II scores at two years of age. STUDY DESIGN: This is a secondary analysis of the a randomized, controlled trial of Magnesium sulfate for the prevention of cerebral palsy, a multicenter trial where women at imminent risk for delivery between 24 and 31 weeks were assigned to receive magnesium sulfate
OBJECTIVE: To compare urine protein-creatinine (UPC) ratios with 24-hour urinary protein excretion (UPE) in twin pregnancies. Accurate monitoring of proteinuria is essential in screening high-risk pregnancies for preeclampsia. STUDY DESIGN: We prospectively evaluated UPC ratios and 24-hour urinary protein excretion in non-hypertensive twin pregnancies between 24 0/7 and 36 0/7 weeks of gestation. Women with urinary tract infections, chronic hypertension, pregestational diabetes, and renal or autoimmune diseases were excluded. Collection adequacy of 24-hour collection was assessed by urinary creatinine excretion adjusted for maternal weight. Correlation between the UPC ratio and the 24-hour UPE was calculated using Pearson’s correlation coefficient. Receiver operator curves were generated to determine the optimal UPC ratio as a cut-off for proteinuria (300 mg protein/24 hours). RESULTS: UPC ratios and 24-hour urinary protein excretion were evaluated in 40 non-hypertensive twin pregnancies, of whom 19 had proteinuria. The median UPC ratio was 0.18 (IQR 0.14-0.24). UPC ratios were moderately correlated with 24-hour UPE (Pearson r¼0.62, p<0.001). The area under the receiver operator curve for proteinuria was 0.86 and the optimal UPC ratio cutoff was 0.30 (Figure). A UPC ratio of 0.30 had a sensitivity of 0.47, a specificity of 0.96, a positive predictive value of 0.88 and a negative predictive value of 0.75 for predicting proteinuria (300 mg protein/24h) in twin pregnancies. CONCLUSION: UPC ratios have a moderate correlation with 24-hour UPE in twin pregnancies. This finding differs from the reported
S124 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
Poster Session I
ajog.org higher predictive value of UPC for proteinuria in singleton pregnancies. Caution should be exercised in substituting UPC ratios for 24-hour urinary protein collections in twin pregnancies given the relatively poor positive and negative predictive value of this test.
224 Is there a correlation between chorionic villi morphology, gene expression and pregnancy outcomes?
Shilpa Chetty1, Roberta Hannibal2, Margarida Cardoso Moreira3, Julie Baker2, Mary Norton1 1 University of California, San Francisco, Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal Fetal Medicine, San Francisco, CA, 2Stanford University, Genetics, Stanford, CA, 3University of Lausanne, Switzerland, Center of Integrative Genomics, Lausanne, Switzerland
OBJECTIVE: To evaluate associations between molecular profiles and abnormal chorionic villi morphology, adverse pregnancy outcomes, and maternal demographics. STUDY DESIGN: Prospective observational study of women who had CVS performed at Lucile Packard Hospital from Feb 2012 to May 2013. CVS morphology assessment included number of buds, branching, and veins (0-3 per field for each, total score 0-9). Maternal demographics and perinatal outcome data were collected. Strand-specific RNA sequencing was performed on CVS samples. Differential gene expression analyses were conducted to identify variations in gene expression between samples with normal and abnormal CVS morphology and normal and adverse perinatal outcomes. RESULTS: 321 women underwent CVS for prenatal diagnosis between 10-13 wks gestation, and were eligible for recruitment. 154 women consented, and there was sufficient tissue after diagnostic testing to perform RNA sequencing on 60 samples. Chorionic villi samples with normal (more mature) morphology (more branches, buds, and veins; score >7)) were enriched for expression of genes involved in cell adhesion, while those with immature morphology (score <7) were enriched for expression of genes involved in blood and vascular development, as well as cell migration (p < 0.001 for all comparisons). Analysis of perinatal outcomes and gene expression was limited due to small sample size. CONCLUSION: Immature villi morphology patterns are associated with changes in RNA expression. In a prior study, we demonstrated that immature villi morphology is associated with adverse pregnancy outcomes, including gestational diabetes, preterm birth, and hypertensive disorders. In this study, we show that immature villi have distinct molecular profiles. Our data suggest that adverse birth outcomes are reflected in molecular and morphologic changes in villi early in pregnancy. Identification of altered gene expression in chorionic villi may allow early detection of obstetric complications and potential for early intervention.
225 Platelet function in intra-uterine growth restriction: altered platelet behaviour as a cause or a consequence of utero-placental disease
Sieglinde Mullers2, Naomi Burke2, Jonathan Cowman3, Morgan Kearney2, Karen Flood2, Hugh O’ Connor2, Patrick Dicker1, Elizabeth Tully2, Michael Geary2, Dermot Kenny3, Fergal Malone2 1 Royal College of Surgeons in Ireland, Department of Epidemiology and Public Health, Dublin, Ireland, 2Royal College of Surgeons in Ireland, Obstetrics and Gynecology, Dublin, Ireland, 3Royal College of Surgeons in Ireland, Cardiovascular Research Laboratory, Dublin, Ireland
OBJECTIVE: Platelet-derived products such as VEGF are currently
being trialled as a therapy for pregnancies complicated by intrauterine growth restriction (IUGR). Previous studies of platelet function in IUGR have yielded conflicting results. We sought to comprehensively evaluate platelet reactivity in IUGR using a novel platelet function assay. STUDY DESIGN: Singleton pregnancies with IUGR were recruited between 24-40 weeks’ gestation (estimated fetal weight <10th centile). A modification of light transmission aggregometry was used and dose-response curves of platelet reactivity in response to multiple agonists at differing concentrations were created. Findings were compared to healthy controls matched for gestational age with normal pregnancy outcome. A number of sub-analyses were subsequently performed to determine the significance of severity of IUGR in relation to platelet aggregation. Cases with a subsequent normal birth weight were analysed separately as a ‘small-for-gestational-age group’ (SGA). RESULTS: A total of 51 patients with EFW < 10th centile and 36 third trimester normally grown controls were recruited from 24 weeks’ gestation. Seven were excluded from analysis resulting in a total of 33 patients in the IUGR group and the remaining 11 in the SGA group. The IUGR group demonstrated significantly reduced platelet reactivity to all agonists when compared to controls (Table 1). When IUGR occurred with preeclampsia or gestational hypertension the findings were even more significant. The SGA group also demonstrated significantly reduced platelet function suggesting a potential role for platelets in promoting fetal growth. CONCLUSION: Using this novel platelet assay we have demonstrated a functional impairment of platelets in IUGR. This may reflect activation at the utero-placental interface where vascular promotion is required to improve fetal growth. Further evaluation of platelet function may aid in the development of future platelet-targeted therapies for IUGR.
Supplement to JANUARY 2015 American Journal of Obstetrics & Gynecology
S125
ajog.org or placebo. For this secondary analysis we included non-anomalous singleton gestations delivered between 22 0/7 -25 6/7 weeks. We excluded women with missing exposure or outcome data. The primary exposure of interest was mode of delivery. The primary outcomes were Bayley II scores <70 (mental and motor) at two years of age. Logbinomial regression was used to control for possible confounders including, gestational age at delivery, chorioamnionitis, years of maternal education, maternal BMI and original study treatment group. RESULTS: A total of 158 women met inclusion criteria. Ninety-one had a vaginal delivery and sixty-seven had a cesarean delivery. Exposure to magnesium sulfate, maternal education, chorioamnionitis, years of maternal education, and maternal BMI were similar in both groups. There was no difference in either mental or motor Bayley II scores <70 or <85 by mode of delivery in either univariable or multivariable analysis. CONCLUSION: There is no difference in Bayley II scores by mode of delivery at time of periviability. This adds to the literature supporting obstetric indications dictating mode of delivery at this gestational age. MDI and PDI by mode of delivery
*Adjusted for gestational age at delivery, chorioamnionitis, years of maternal education, maternal BMI and original study treatment group.
223 Correlation of urine protein-creatinine ratios and 24-hour urinary excretion in twin pregnancies
Sarah Osmundson1, Richard Lafayette4, Raffick Bowen2, Valerie Roque3, Natali Aziz1 1
Stanford University School of Medicine, Department of Obstetrics & Gynecology, Stanford, CA, 2Stanford University School of Medicine, Department of Pathology, Stanford, CA, 3University of California, Davis, Department of Medicine, Sacramento, CA, 4Stanford University School of Medicine, Department of Medicine, Stanford, CA
222 Mode of delivery at periviability and early childhood neurodevelopment
Sarah Obican1, Daphnie Drassinower1, Heather Levin1, Cynthia Gyamfi-Bannerman1
1 Columbia University Medical Center, Department of Obstetrics and Gynecology, New York, NY
OBJECTIVE: Little is known regarding the impact of mode of delivery in the periviable period. Even less is understood regarding the effect of mode of delivery on neurodevelopment. Our objective is to determine if the mode of delivery at time of periviability impacts Bayley II scores at two years of age. STUDY DESIGN: This is a secondary analysis of the a randomized, controlled trial of Magnesium sulfate for the prevention of cerebral palsy, a multicenter trial where women at imminent risk for delivery between 24 and 31 weeks were assigned to receive magnesium sulfate
OBJECTIVE: To compare urine protein-creatinine (UPC) ratios with 24-hour urinary protein excretion (UPE) in twin pregnancies. Accurate monitoring of proteinuria is essential in screening high-risk pregnancies for preeclampsia. STUDY DESIGN: We prospectively evaluated UPC ratios and 24-hour urinary protein excretion in non-hypertensive twin pregnancies between 24 0/7 and 36 0/7 weeks of gestation. Women with urinary tract infections, chronic hypertension, pregestational diabetes, and renal or autoimmune diseases were excluded. Collection adequacy of 24-hour collection was assessed by urinary creatinine excretion adjusted for maternal weight. Correlation between the UPC ratio and the 24-hour UPE was calculated using Pearson’s correlation coefficient. Receiver operator curves were generated to determine the optimal UPC ratio as a cut-off for proteinuria (300 mg protein/24 hours). RESULTS: UPC ratios and 24-hour urinary protein excretion were evaluated in 40 non-hypertensive twin pregnancies, of whom 19 had proteinuria. The median UPC ratio was 0.18 (IQR 0.14-0.24). UPC ratios were moderately correlated with 24-hour UPE (Pearson r¼0.62, p<0.001). The area under the receiver operator curve for proteinuria was 0.86 and the optimal UPC ratio cutoff was 0.30 (Figure). A UPC ratio of 0.30 had a sensitivity of 0.47, a specificity of 0.96, a positive predictive value of 0.88 and a negative predictive value of 0.75 for predicting proteinuria (300 mg protein/24h) in twin pregnancies. CONCLUSION: UPC ratios have a moderate correlation with 24-hour UPE in twin pregnancies. This finding differs from the reported
S124 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
Poster Session I
ajog.org higher predictive value of UPC for proteinuria in singleton pregnancies. Caution should be exercised in substituting UPC ratios for 24-hour urinary protein collections in twin pregnancies given the relatively poor positive and negative predictive value of this test.
224 Is there a correlation between chorionic villi morphology, gene expression and pregnancy outcomes?
Shilpa Chetty1, Roberta Hannibal2, Margarida Cardoso Moreira3, Julie Baker2, Mary Norton1 1 University of California, San Francisco, Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal Fetal Medicine, San Francisco, CA, 2Stanford University, Genetics, Stanford, CA, 3University of Lausanne, Switzerland, Center of Integrative Genomics, Lausanne, Switzerland
OBJECTIVE: To evaluate associations between molecular profiles and abnormal chorionic villi morphology, adverse pregnancy outcomes, and maternal demographics. STUDY DESIGN: Prospective observational study of women who had CVS performed at Lucile Packard Hospital from Feb 2012 to May 2013. CVS morphology assessment included number of buds, branching, and veins (0-3 per field for each, total score 0-9). Maternal demographics and perinatal outcome data were collected. Strand-specific RNA sequencing was performed on CVS samples. Differential gene expression analyses were conducted to identify variations in gene expression between samples with normal and abnormal CVS morphology and normal and adverse perinatal outcomes. RESULTS: 321 women underwent CVS for prenatal diagnosis between 10-13 wks gestation, and were eligible for recruitment. 154 women consented, and there was sufficient tissue after diagnostic testing to perform RNA sequencing on 60 samples. Chorionic villi samples with normal (more mature) morphology (more branches, buds, and veins; score >7)) were enriched for expression of genes involved in cell adhesion, while those with immature morphology (score <7) were enriched for expression of genes involved in blood and vascular development, as well as cell migration (p < 0.001 for all comparisons). Analysis of perinatal outcomes and gene expression was limited due to small sample size. CONCLUSION: Immature villi morphology patterns are associated with changes in RNA expression. In a prior study, we demonstrated that immature villi morphology is associated with adverse pregnancy outcomes, including gestational diabetes, preterm birth, and hypertensive disorders. In this study, we show that immature villi have distinct molecular profiles. Our data suggest that adverse birth outcomes are reflected in molecular and morphologic changes in villi early in pregnancy. Identification of altered gene expression in chorionic villi may allow early detection of obstetric complications and potential for early intervention.
225 Platelet function in intra-uterine growth restriction: altered platelet behaviour as a cause or a consequence of utero-placental disease
Sieglinde Mullers2, Naomi Burke2, Jonathan Cowman3, Morgan Kearney2, Karen Flood2, Hugh O’ Connor2, Patrick Dicker1, Elizabeth Tully2, Michael Geary2, Dermot Kenny3, Fergal Malone2 1 Royal College of Surgeons in Ireland, Department of Epidemiology and Public Health, Dublin, Ireland, 2Royal College of Surgeons in Ireland, Obstetrics and Gynecology, Dublin, Ireland, 3Royal College of Surgeons in Ireland, Cardiovascular Research Laboratory, Dublin, Ireland
OBJECTIVE: Platelet-derived products such as VEGF are currently
being trialled as a therapy for pregnancies complicated by intrauterine growth restriction (IUGR). Previous studies of platelet function in IUGR have yielded conflicting results. We sought to comprehensively evaluate platelet reactivity in IUGR using a novel platelet function assay. STUDY DESIGN: Singleton pregnancies with IUGR were recruited between 24-40 weeks’ gestation (estimated fetal weight <10th centile). A modification of light transmission aggregometry was used and dose-response curves of platelet reactivity in response to multiple agonists at differing concentrations were created. Findings were compared to healthy controls matched for gestational age with normal pregnancy outcome. A number of sub-analyses were subsequently performed to determine the significance of severity of IUGR in relation to platelet aggregation. Cases with a subsequent normal birth weight were analysed separately as a ‘small-for-gestational-age group’ (SGA). RESULTS: A total of 51 patients with EFW < 10th centile and 36 third trimester normally grown controls were recruited from 24 weeks’ gestation. Seven were excluded from analysis resulting in a total of 33 patients in the IUGR group and the remaining 11 in the SGA group. The IUGR group demonstrated significantly reduced platelet reactivity to all agonists when compared to controls (Table 1). When IUGR occurred with preeclampsia or gestational hypertension the findings were even more significant. The SGA group also demonstrated significantly reduced platelet function suggesting a potential role for platelets in promoting fetal growth. CONCLUSION: Using this novel platelet assay we have demonstrated a functional impairment of platelets in IUGR. This may reflect activation at the utero-placental interface where vascular promotion is required to improve fetal growth. Further evaluation of platelet function may aid in the development of future platelet-targeted therapies for IUGR.
Supplement to JANUARY 2015 American Journal of Obstetrics & Gynecology
S125