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494: Antenatal intra-abdominal bowel dilation in the prediction of postnatal bowel atresia in fetuses with gastroschisis
Poster Session III
Doppler Assessment, Fetus, Prematurity
492 Plasma proteomic profiles in preterm labor (PTL) and preterm premature rupture of membranes (PPROM) Joyce Sung1, John Whitin2, Qing Yang3, Ashima Madan4, Yasser El-Sayed1 1 Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Stanford, CA, 2Stanford University, Pediatrics, Stanford, CA, 3Hunan Agricultural University, School of Veterinary Medicine, Changsha City, Hunan Province, China, 4Healthy Start Pediatrics, Pediatrics, Mountain View, CA
OBJECTIVE: To compare plasma proteomic profiles of patients presenting with PTL and/or PPROM to those presenting with term labor. STUDY DESIGN: Plasma was prospectively collected from women at the time of presentation with (1) PTL between 24-34 weeks gestation and subsequent preterm delivery, (2) PPROM between 24-34 weeks and preterm delivery, and (3) term labor between 37-42 weeks. Samples were analyzed by surface-enhanced laser desorption/ionization timeof-flight mass spectrometry (SELDI-TOF MS) using ProteinChip arrays. We compared SELDI-TOF MS profiles for PTL vs. term labor; PPROM vs. term labor; PTL⫹PPROM vs. term labor; and PTL vs. PPROM. RESULTS: 8 patients presented with PTL, 7 with PPROM, and 18 with term labor. There were no significant differences in maternal age, race, or education level between the three groups. Mean gestational age at delivery was significantly less in PTL (32.8 weeks) and PPROM (31.9 weeks) patients, when compared to term labor patients (39.1 weeks). A total of 1274 SELDI mass spectra peaks were analyzed. The number of peaks significantly different at p⬍0.05 using the Mann-Whitney U test ranged from 34-64 for the different comparisons (see table). False Discovery Rate (FDR) analysis was then used to control for multiple hypothesis testing. When analyzing 1274 peaks, 62 peaks would be expected at significance of p⬍0.05. In addition, for all of the above comparisons, none of the seemingly significantly different peaks met the threshold of validity of a local FDR of ⬍5%. CONCLUSION: No differences in plasma proteomic profiles were seen between PTL, PPROM, and term labor patients at the time of presentation. Possible explanations include: 1) differences exist in other compartments (e.g. amniotic fluid) that are not seen in plasma; 2) both term labor and PTL/PPROM may involve similar proteomic changes, regardless of gestational age at presentation; and 3) the methods used here detect 200 of the most abundant plasma proteins, but differences may exist in less abundant proteins (e.g. cytokines).
www.AJOG.org
STUDY DESIGN: Retrospective analysis of a cohort of women with prior
SPTB enrolled in outpatient 17P administration program at ⬍27 weeks gestation. Maternal characteristics, obstetric history and rates of recurrent SPTB were compared between women of African-American (AA) vs. Caucasian descent using 2 and multivariable logistic regression at two-tailed ␣⫽0.05. Primary study outcome was the rate of recurrent SPTB ⬍34 weeks. RESULTS: Of 7,108 women meeting inclusion criteria, 1,913 (26.9%) were AA. Rates of recurrent SPTB ⬍34 weeks were 13.0% and 6.8% for AA vs. Caucasian women, respectively (p⬍0.001). Among women starting 17P at 16-20.9 vs. 21-26.9 weeks, rates of recurrent SPTB at ⬍37 weeks (27.9 vs. 29.6%), and ⬍34 weeks (8.2 vs. 9.3%) were similar. On univariate analysis, significant differences were observed in maternal characteristics, social factors and obstetric history between races. Risk factors associated with SPTB ⬍34 weeks for women receiving 17P in multivariable analysis are presented in the Table. CONCLUSION: Women of AA descent have higher rates of SPTB during treatment with 17P as compared to Caucasian women. African American race, obstetric history and social factors influence rates of recurrent SPTB in women receiving 17P.
494 Antenatal intra-abdominal bowel dilation in the prediction of postnatal bowel atresia in fetuses with gastroschisis Katherine Goetzinger1, Methodius Tuuli1, Ryan Longman1, Kristina Huster1, Anthony Odibo1, Alison Cahill1 1 Washington University in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO
493 Effectiveness of 17␣-hydroxyprogesterone for prevention of preterm birth in AfricanAmerican vs Caucasian women Julia Timofeev1, Jasbir Singh1, Niki Istwan2, Debbie Rhea2, Rita Driggers1 1 Washington Hospital Center, Obstetrics and Gynecology, Washington, DC, 2Alere Health, Department of Clinical Research, Atlanta, GA
OBJECTIVE: To determine if the rates of recurrent spontaneous preterm birth (SPTB) differ according to maternal race in women receiving compounded 17␣-hydroxyprogesterone caproate (17P).
S224
OBJECTIVE: Given the dramatic difference in postnatal hospital course in the setting of bowel atresia with gastroschisis, we aimed to estimate the association between antenatal intra-abdominal bowel dilation (IABD) and postnatal small bowel atresia in gastroschisis and to evaluate its predictive ability. STUDY DESIGN: A retrospective cohort study of singleton gestations with an antenatal diagnosis of gastroschisis seen in our ultrasound unit from 2001-2010. Stored images were reviewed, blind to postnatal outcomes, from the last ultrasound exam before delivery, and the transverse diameter of the largest dilated loop of intra-abdominal small bowel measured. Previously published definitions of IABD including ⬎6mm, ⬎10mm, and ⬎14mm were evaluated for association with the primary outcome of bowel atresia. Secondary outcomes included neonatal intensive care unit (NICU) length of stay, necrotizing enterocolitis (NEC), time to complete closure, time on total parenteral nutrition (TPN), and time to initial and full enteral feeding. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: Of 94 consecutive live births with gastroschisis, 39 (41.5%) had IABD at their last ultrasound. The range of IABD was 7mm75mm. There were 14 (14.9%) cases of bowel atresia. There was no
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
www.AJOG.org
Doppler Assessment, Fetus, Prematurity
significant association between IABD and bowel atresia when thresholds of ⬎6mm and ⬎10mm were used to define IABD; however, there was a significantly increased risk of bowel atresia with IABD⬎14mm (28.6% v. 9.1%, RR 3.1, 95% CI 1.2-8.2). Sensitivity, specificity, PPV, and NPV for IABD⬎14mm and bowel atresia were 57.1%, 75.0%, 28.6%, and 90.9%, respectively. The AUC for IABD and bowel atresia was 0.73 (95% CI 0.57-0.89). CONCLUSION: IABD⬎14mm is associated with an increased risk for bowel atresia; however, the PPV remains low due to the rarity of the finding. Given the high NPV, patients can be counseled that in the absence of this finding, the risk of postnatal bowel atresia is low for their neonate with gastroschisis.
495 Withdrawn 496 Cervico-vaginal soluble FMS-like tyrosine kinase-1 (sFlt-1) and risk of preterm birth (PTB) Katherine H. Campbell1, Catalin S. Buhimschi1, Unzila A. Ali1, Asif Ahmed2, Irina A. Buhimschi1
Poster Session III
497 Silvestat sodium hydrate suppresses premature cervical ripening in a rabbit preterm delivery model Katsufumi Otsuki1, Maki Sawada1, Hiroshi Chiba1, Mayumi Tokunaka1, Hajime Ota1, Masaaki Nagatsuka1, Takashi Okai1 1
Showa University, Obstetrics and Gynecology, Tokyo, Japan
OBJECTIVE: Sivelestat sodium hydrae (Elaspol) is known to selectively
hinder elastase released from neutrophils in patients with acute lung injury. To investigate the effect of Sivelestat Sodium Hydrate on cervical ripening using a rabbit model, in which preterm labor was induced by bacterial endotoxin lipopolysaccharide (LPS). STUDY DESIGN: Timed pregnant rabbits (New Zealand White, 3 to 4 kg, day 14) were randomly assigned to the following treatment groups; group A: control (n ⫽ 4), group B: LPS ⫹ Elaspol (n ⫽ 4), group C: LPS ⫹ Urinary Trypsin Inhibitor (UTI) (n ⫽ 4), and group D: LPS-induced. Pregnant rabbits were pretreated with 10 micrograms of Elaspol in group B, 10ng of UTI in group C and not in group A. A hundred ng of LPS was given to them for 3 days (day14⬃16) in all groups. Drugs were administered as a vaginal suppository. On day 18, after rabbits were anesthetized with intramuscular ketamine hydrochloride (20mg / kg) and diazepam (4mg / kg), Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution for histological study with standard Hematoxylin/eosin staining. The other was used for an extension test to assess the grade of ripening. The length of extension was measured after cervical tissue of 5mm length was loaded by 5.8g. Expression of MMP(matrix metalloproteinase) in the cervix was evaluated by Western blot. RESULTS: Histological study showed remarkably loose and edematous connective tissue in group D cervices. Cervical tissues in group B was not different from group A and C (Figure). Extension length were 1.7 1.0mm, 2.0 1.0mm, 3.3 1.9mm and 6.0 2.7mm in group A, B, C and D, respectively. MMP production in cervix in group B and C had a tendency to become low although group B and C did not admit a significant difference in comparison with group D. CONCLUSION: These results suggest that Elaspol inhibits cervical maturation induced by LPS in a rabbit model and may have a potential to prevent preterm delivery caused by cervical infection and ripening.
1 Yale University, Ob/Gyn & Reprod Sci., New Haven, CT, 2University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom
OBJECTIVE: During pregnancy the human cervix undergoes profound enzymatic and angiogenic transformations. Compelling data suggests that VEGF is decreased in cervico-vaginal secretions of women at risk for PTB. The mechanism responsible for this observation is unknown. Given that the interplay between VEGF and its antagonist sFlt-1 regulates angiogenic homeostasis, we tested the hypothesis that the lower VEGF results from an upregulation of sFlt-1 in cervico-vaginal secretions of women with threatened PTB. STUDY DESIGN: We conducted an observational prospective cohort study on cervical fluid samples of 96 pregnant women (GA: 28 [25-31] wks) who presented for either a routine prenatal visit (n⫽51) or for evaluation of threatened PTB (n⫽45). Samples were collected under a standard protocol. Cervical length (CL) was assessed by transvaginal ultrasound. Dilation was evaluated by digital exam, performed after biological sample collection. sFlt-1 levels were measured by ELISA. Exclusion criteria were ruptured membranes, vaginal bleeding and active labor. Results were analyzed with and without normalization for total protein. RESULTS: 1) 42 (44%) women had a short cervix (CL240 pg/mL had a sensitivity, specificity, (⫹)LR and (-)LR of 88%, 95%, 18.4 and 0.1, respectively, in predicting PTB within 7 days. CONCLUSION: Increased sFlt-1 levels may explain the lower concentrations of VEGF in the cervico-vaginal secretions of women at increased risk of PTB. Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S225
Doppler Assessment, Fetus, Prematurity
492 Plasma proteomic profiles in preterm labor (PTL) and preterm premature rupture of membranes (PPROM) Joyce Sung1, John Whitin2, Qing Yang3, Ashima Madan4, Yasser El-Sayed1 1 Stanford University School of Medicine/Lucile Salter Packard Children’s Hospital, Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Stanford, CA, 2Stanford University, Pediatrics, Stanford, CA, 3Hunan Agricultural University, School of Veterinary Medicine, Changsha City, Hunan Province, China, 4Healthy Start Pediatrics, Pediatrics, Mountain View, CA
OBJECTIVE: To compare plasma proteomic profiles of patients presenting with PTL and/or PPROM to those presenting with term labor. STUDY DESIGN: Plasma was prospectively collected from women at the time of presentation with (1) PTL between 24-34 weeks gestation and subsequent preterm delivery, (2) PPROM between 24-34 weeks and preterm delivery, and (3) term labor between 37-42 weeks. Samples were analyzed by surface-enhanced laser desorption/ionization timeof-flight mass spectrometry (SELDI-TOF MS) using ProteinChip arrays. We compared SELDI-TOF MS profiles for PTL vs. term labor; PPROM vs. term labor; PTL⫹PPROM vs. term labor; and PTL vs. PPROM. RESULTS: 8 patients presented with PTL, 7 with PPROM, and 18 with term labor. There were no significant differences in maternal age, race, or education level between the three groups. Mean gestational age at delivery was significantly less in PTL (32.8 weeks) and PPROM (31.9 weeks) patients, when compared to term labor patients (39.1 weeks). A total of 1274 SELDI mass spectra peaks were analyzed. The number of peaks significantly different at p⬍0.05 using the Mann-Whitney U test ranged from 34-64 for the different comparisons (see table). False Discovery Rate (FDR) analysis was then used to control for multiple hypothesis testing. When analyzing 1274 peaks, 62 peaks would be expected at significance of p⬍0.05. In addition, for all of the above comparisons, none of the seemingly significantly different peaks met the threshold of validity of a local FDR of ⬍5%. CONCLUSION: No differences in plasma proteomic profiles were seen between PTL, PPROM, and term labor patients at the time of presentation. Possible explanations include: 1) differences exist in other compartments (e.g. amniotic fluid) that are not seen in plasma; 2) both term labor and PTL/PPROM may involve similar proteomic changes, regardless of gestational age at presentation; and 3) the methods used here detect 200 of the most abundant plasma proteins, but differences may exist in less abundant proteins (e.g. cytokines).
www.AJOG.org
STUDY DESIGN: Retrospective analysis of a cohort of women with prior
SPTB enrolled in outpatient 17P administration program at ⬍27 weeks gestation. Maternal characteristics, obstetric history and rates of recurrent SPTB were compared between women of African-American (AA) vs. Caucasian descent using 2 and multivariable logistic regression at two-tailed ␣⫽0.05. Primary study outcome was the rate of recurrent SPTB ⬍34 weeks. RESULTS: Of 7,108 women meeting inclusion criteria, 1,913 (26.9%) were AA. Rates of recurrent SPTB ⬍34 weeks were 13.0% and 6.8% for AA vs. Caucasian women, respectively (p⬍0.001). Among women starting 17P at 16-20.9 vs. 21-26.9 weeks, rates of recurrent SPTB at ⬍37 weeks (27.9 vs. 29.6%), and ⬍34 weeks (8.2 vs. 9.3%) were similar. On univariate analysis, significant differences were observed in maternal characteristics, social factors and obstetric history between races. Risk factors associated with SPTB ⬍34 weeks for women receiving 17P in multivariable analysis are presented in the Table. CONCLUSION: Women of AA descent have higher rates of SPTB during treatment with 17P as compared to Caucasian women. African American race, obstetric history and social factors influence rates of recurrent SPTB in women receiving 17P.
494 Antenatal intra-abdominal bowel dilation in the prediction of postnatal bowel atresia in fetuses with gastroschisis Katherine Goetzinger1, Methodius Tuuli1, Ryan Longman1, Kristina Huster1, Anthony Odibo1, Alison Cahill1 1 Washington University in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO
493 Effectiveness of 17␣-hydroxyprogesterone for prevention of preterm birth in AfricanAmerican vs Caucasian women Julia Timofeev1, Jasbir Singh1, Niki Istwan2, Debbie Rhea2, Rita Driggers1 1 Washington Hospital Center, Obstetrics and Gynecology, Washington, DC, 2Alere Health, Department of Clinical Research, Atlanta, GA
OBJECTIVE: To determine if the rates of recurrent spontaneous preterm birth (SPTB) differ according to maternal race in women receiving compounded 17␣-hydroxyprogesterone caproate (17P).
S224
OBJECTIVE: Given the dramatic difference in postnatal hospital course in the setting of bowel atresia with gastroschisis, we aimed to estimate the association between antenatal intra-abdominal bowel dilation (IABD) and postnatal small bowel atresia in gastroschisis and to evaluate its predictive ability. STUDY DESIGN: A retrospective cohort study of singleton gestations with an antenatal diagnosis of gastroschisis seen in our ultrasound unit from 2001-2010. Stored images were reviewed, blind to postnatal outcomes, from the last ultrasound exam before delivery, and the transverse diameter of the largest dilated loop of intra-abdominal small bowel measured. Previously published definitions of IABD including ⬎6mm, ⬎10mm, and ⬎14mm were evaluated for association with the primary outcome of bowel atresia. Secondary outcomes included neonatal intensive care unit (NICU) length of stay, necrotizing enterocolitis (NEC), time to complete closure, time on total parenteral nutrition (TPN), and time to initial and full enteral feeding. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: Of 94 consecutive live births with gastroschisis, 39 (41.5%) had IABD at their last ultrasound. The range of IABD was 7mm75mm. There were 14 (14.9%) cases of bowel atresia. There was no
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
www.AJOG.org
Doppler Assessment, Fetus, Prematurity
significant association between IABD and bowel atresia when thresholds of ⬎6mm and ⬎10mm were used to define IABD; however, there was a significantly increased risk of bowel atresia with IABD⬎14mm (28.6% v. 9.1%, RR 3.1, 95% CI 1.2-8.2). Sensitivity, specificity, PPV, and NPV for IABD⬎14mm and bowel atresia were 57.1%, 75.0%, 28.6%, and 90.9%, respectively. The AUC for IABD and bowel atresia was 0.73 (95% CI 0.57-0.89). CONCLUSION: IABD⬎14mm is associated with an increased risk for bowel atresia; however, the PPV remains low due to the rarity of the finding. Given the high NPV, patients can be counseled that in the absence of this finding, the risk of postnatal bowel atresia is low for their neonate with gastroschisis.
495 Withdrawn 496 Cervico-vaginal soluble FMS-like tyrosine kinase-1 (sFlt-1) and risk of preterm birth (PTB) Katherine H. Campbell1, Catalin S. Buhimschi1, Unzila A. Ali1, Asif Ahmed2, Irina A. Buhimschi1
Poster Session III
497 Silvestat sodium hydrate suppresses premature cervical ripening in a rabbit preterm delivery model Katsufumi Otsuki1, Maki Sawada1, Hiroshi Chiba1, Mayumi Tokunaka1, Hajime Ota1, Masaaki Nagatsuka1, Takashi Okai1 1
Showa University, Obstetrics and Gynecology, Tokyo, Japan
OBJECTIVE: Sivelestat sodium hydrae (Elaspol) is known to selectively
hinder elastase released from neutrophils in patients with acute lung injury. To investigate the effect of Sivelestat Sodium Hydrate on cervical ripening using a rabbit model, in which preterm labor was induced by bacterial endotoxin lipopolysaccharide (LPS). STUDY DESIGN: Timed pregnant rabbits (New Zealand White, 3 to 4 kg, day 14) were randomly assigned to the following treatment groups; group A: control (n ⫽ 4), group B: LPS ⫹ Elaspol (n ⫽ 4), group C: LPS ⫹ Urinary Trypsin Inhibitor (UTI) (n ⫽ 4), and group D: LPS-induced. Pregnant rabbits were pretreated with 10 micrograms of Elaspol in group B, 10ng of UTI in group C and not in group A. A hundred ng of LPS was given to them for 3 days (day14⬃16) in all groups. Drugs were administered as a vaginal suppository. On day 18, after rabbits were anesthetized with intramuscular ketamine hydrochloride (20mg / kg) and diazepam (4mg / kg), Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution for histological study with standard Hematoxylin/eosin staining. The other was used for an extension test to assess the grade of ripening. The length of extension was measured after cervical tissue of 5mm length was loaded by 5.8g. Expression of MMP(matrix metalloproteinase) in the cervix was evaluated by Western blot. RESULTS: Histological study showed remarkably loose and edematous connective tissue in group D cervices. Cervical tissues in group B was not different from group A and C (Figure). Extension length were 1.7 1.0mm, 2.0 1.0mm, 3.3 1.9mm and 6.0 2.7mm in group A, B, C and D, respectively. MMP production in cervix in group B and C had a tendency to become low although group B and C did not admit a significant difference in comparison with group D. CONCLUSION: These results suggest that Elaspol inhibits cervical maturation induced by LPS in a rabbit model and may have a potential to prevent preterm delivery caused by cervical infection and ripening.
1 Yale University, Ob/Gyn & Reprod Sci., New Haven, CT, 2University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom
OBJECTIVE: During pregnancy the human cervix undergoes profound enzymatic and angiogenic transformations. Compelling data suggests that VEGF is decreased in cervico-vaginal secretions of women at risk for PTB. The mechanism responsible for this observation is unknown. Given that the interplay between VEGF and its antagonist sFlt-1 regulates angiogenic homeostasis, we tested the hypothesis that the lower VEGF results from an upregulation of sFlt-1 in cervico-vaginal secretions of women with threatened PTB. STUDY DESIGN: We conducted an observational prospective cohort study on cervical fluid samples of 96 pregnant women (GA: 28 [25-31] wks) who presented for either a routine prenatal visit (n⫽51) or for evaluation of threatened PTB (n⫽45). Samples were collected under a standard protocol. Cervical length (CL) was assessed by transvaginal ultrasound. Dilation was evaluated by digital exam, performed after biological sample collection. sFlt-1 levels were measured by ELISA. Exclusion criteria were ruptured membranes, vaginal bleeding and active labor. Results were analyzed with and without normalization for total protein. RESULTS: 1) 42 (44%) women had a short cervix (CL240 pg/mL had a sensitivity, specificity, (⫹)LR and (-)LR of 88%, 95%, 18.4 and 0.1, respectively, in predicting PTB within 7 days. CONCLUSION: Increased sFlt-1 levels may explain the lower concentrations of VEGF in the cervico-vaginal secretions of women at increased risk of PTB. Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S225