- Email: [email protected]
397: Cost effectiveness of open fetal surgery for fetal myelomeningocele (MMC)
www.AJOG.org
Doppler Assessment, Fetus, Prematurity
395 Isoimmunization to minor red blood cell antigens in pregnancy: management, monitoring and outcomes Sharmilee Thota1, Srinivas Ketharaju2, Carolyn Salafia3, Aleksandr Fuks4 1 Bronx-Lebanon Hospital Center, OB/GYN, Bronx, NY, 2Bronx-Lebanon Hospital Center, OB/GYN, Bronx, NY, 3New York Methodist Hospital Cornell Presbyterian, OB/GYN, Pathology, Pediatrics, Brooklyn, NY, 4Queens Hospital Center, OB/GYN, Queens, NY
OBJECTIVE: To examine fetal and neonatal outcomes of pregnancies complicated by isoimmunization to minor red blood cell (RBC) antigens and managed by serial antibody titer and MCA-peal systolic velocity (MCA-PSV) assessments. STUDY DESIGN: Retrospective cohort study of all patients isoimmunized to minor RBC antigens managed at Bronx-Lebanon Hospital Center, 2008-2011. Inclusion criteria: live singleton gestataion, presence of minor RBC antibodies, gestational age 24 0/7 - 36 0/7 weeks. Exclusion criteria: multiple gestations, Kell and major RBC antibodies, fetal malformations and chromosomal abnormalities. All patients were managed with serial antibody titer and MCA-PSV assessments. Outcome parameters were assessed: birthweight, fetal bilirubin concentration, cord gas base excess, fetal hematocrit, NICU stay duration. RESULTS: 24 patients fit study inclusion criteria. Demographic and outcome parameters are summarized in the Table below. None of the patients in the study had MCA-PSV values in the range of severe fetal anemia requiring PUBS and in-utero transfusion. None of the neonates required RBC transfusion and only 2 newborns were Coombs positive and required phototherapy. CONCLUSION: Patients with alloimmunization to minor RBC antigens and antibody titers less than critical value (1:32) do not appear to be at risk for sever fetal anemia. In those patients, serial MCA-PSV assessments do not influence management decisions and outcomes of pregnancy and forgoing such evaluation might be suitable.
Poster Session III
specifically manifested in reduced limb and truncal growth but not reduced head growth. STUDY DESIGN: 865 singleton pregnancies were prospectively followed with sequential blood sampling (10, 18, 24, 35 weeks) and 3rd trimester fetal ultrasound measurements. PlGF and sFlt levels were measured with the Abbott Architect assay. Gestational age specific Z-scores were evaluated for birth weight (BW), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD). RESULTS: PlGF and sFlt levels at weeks 10 and 18 were not associated with BW or fetal anthropometric Z-scores. At weeks 24 and 35, PlGF was positively and sFlt was negatively associated with BW Z-score (Table). At these gestations, the angiogenic markers were associated with AC and FL Z-scores but not BPD Z-scores. Linear regression, controlling for clinical covariates including the diagnosis of PE and using BW, AC and FL Z-scores as the dependent variables, demonstrated independent effects of PlGF and sFlt concentrations (R^2⫽0.09, p⬍0.0001 for all). CONCLUSION: Associations between the angiogenic markers and reduced fetal growth manifest in the 3rd trimester. Increased concentrations of sFlt and decreased concentrations of PlGF were associated with reduced limb and truncal growth but not reduced head growth.
397 Cost effectiveness of open fetal surgery for fetal myelomeningocele (MMC) Alison G. Cahill1, Rachel Pilliod2, Anthony Odibo1, Brian Shaffer2, Aaron Caughey2 1 Washington University in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO, 2Oregon Health & Science University, Department of Obstetrics and Gynecology, Portland, OR
396 Fetal growth and anthropometrics in relation to serial maternal sFlt-1 and PlGF levels A.E. Lehmann1, J.N. Robinson2, A.M. Thomas3, P.M. Doubilet4, T.F. McElrath2 1
Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, MA, Harvard Medical School, Brigham & Women’s Hospital, Division of Maternal-Fetal Medicine, Boston, MA, 3Brigham & Women’s Hospital, Division of Maternal-Fetal Medicine, Boston, MA, 4Harvard Medical School, Brigham & Women’s Hospital, Department of Radiology, Boston, MA 2
OBJECTIVE: Concentrations of the angiogenic markers placental growth factor (PlGF) and the soluble fms-like tyrosine kinase-1 (sFlt) vary greatly between otherwise normal pregnancies. The concentrations of the markers are most extreme in conditions of aberrant placentation including preeclampsia (PE). We hypothesize that 1) even absent the effect of PE, decreased PlGF and increased sFlt concentrations are associated with reduced fetal growth and 2) this reduction is
OBJECTIVE: : Given recently published evidence for efficacy of open fetal surgical repair of MMC, we aimed to estimate its cost-effectiveness compared to post-natal repair STUDY DESIGN: We constructed a decision analytic model to compare 2 strategies for the surgical treatment of antenatally diagnosed isolated myelomeningocele: 1)fetal surgical repair, or 2)post-natal repair. The model was constructed from the societal perspective for a theoretical cohort of 1000 women fulfilling the inclusion criteria for the recently published MOMS trial. We assumed delivery in either arm would be by cesarean. Clinical outcomes included: maternal transfusion, maternal pulmonary edema, preterm birth (PTB), respiratory distress syndrome (RDS), post-natal shunt, surgery for tethered cord, incontinence, non-ambulatory, moderate-severe neurodevelopmental delay. Probabilities, utilities and costs were derived from the literature. Due to the paucity of data available on the cost of fetal surgery for MMC, we estimated the cost based on the MOMS trial protocol. Strategies were compared by numbers of clinical events prevented, and costs per quality-adjusted life-years (QALYs) RESULTS: Fetal surgery for MMC was the dominant strategy (least costly and most effective) in the base-case analysis. Sensitivity analyses revealed the model to be sensitive to the number of antepartum ad-
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S185
Poster Session III
Doppler Assessment, Fetus, Prematurity
mission days required for women undergoing fetal surgery; if more than 38 days were spent in the hospital, post-natal surgery became the cheaper strategy but fetal surgery remains dominant. Fetal repair of MMC in a hypothetical cohort of 1000 women would yield 526 fewer shunts and 395 fewer non-ambulatory toddlers at age 30-months, but result in 290 additional PTBs and 18 additional cases of RDS. CONCLUSION: Fetal MMC repair is cost-effective from a societal perspective, but trades improved post-natal outcomes for higher rates of preterm birth-associated and maternal morbidities. However, given the significant investment required to initiate and maintain such programs, the most cost-effective strategy from the institutional perspective deserves further analysis
www.AJOG.org
obtained from live IUGR fetuses exhibited increased inflammation in the absence of maternal systemic inflammation. Future studies will investigate whether inflammatory cytokines in IUGR model can be modulated. Supported by Oxenhorn Family.
398 Intrauterine growth restriction is associated with enhanced amniotic fluid and placental cytokine levels in an animal model Amanda Roman1, Neeraj Desai1, Burton Rochelson1, Madhu Gupta2, Xiangying Xue2, Prodyot Chatterjee2, Christine Metz2 1 Hofstra North Shore-LIJ School of Medicine, Division of Maternal-Fetal Medicine, Manhasset, NY, 2Feinstein Institute for Medical Research, Center for Immunology and Inflammation, Manhasset, NY
OBJECTIVE: To evaluate maternal and fetal inflammatory responses using a rat model of intrauterine growth restriction (IUGR) STUDY DESIGN: Pregnant female Wistar rats (12 wks old, GD18) were anesthetized using inhaled isoflurane and underwent either bilateral uterine artery ligation (BL; n⫽6) or sham surgery (without ligation; n⫽4). Dams were euthanized 24 hrs later (GD19). For comparison, a group of control dams (C, no anesthesia, no surgery; n⫽4) were euthanized on GD19. Maternal plasma was collected; fetal plasma (pooled from the pups of a single dam), individual amniotic fluid samples, and placentas were collected from live fetal pups only (BL⫽32; sham⫽20; and C⫽22). All samples were analyzed for cytokines (IL-6, IL-1, GRO/KC, MCP-1 and TNF; sensitivity ⬍3pg/ml) using multiplex. Data was analyzed using ANOVA and t-test. RESULTS: The average fetal and placental weights were significantly lower in the BL dams when compared to sham dams (P⬍0.001); sham fetal and placental weights did not differ from control dams. The overall fetal mortality was 37% among BL rats and 0% among shams and controls (Table 1). IL-6, IL-1, TNF (P⬍0.05) and MCP-1 (P⬍0.001) levels were significantly increased in the amniotic fluids obtained from BL dams, while IL-6, IL-1, MCP-1 and GRO/KC (P⬍0.001) and TNF (P⬍0.05) were significantly increased in placental tissues obtained from the BL dams when compared to shams or controls (Fig. 1). Sham placentas did not differ significantly from control placentas. There were no significant differences in cytokines with respect to proximity to fetal demise or uterine artery ligation site. Interestingly, neither maternal nor fetal plasma showed differences in cytokine levels. CONCLUSION: Bilateral uterine artery ligation produced measurable IUGR with moderate fetal mortality. Amniotic fluid and placentas
S186
399 Stem cell markers in amniotic fluid derived cells Ashwin Jadhav1, Ross Basch2, Michael Chan1, Nikolai Strelchenko1, Zhisheng Chen1, Bruce Young1 1 New York University Medical Center, Obstetrics and Gynecology, New York, NY, 2New York University Medical Center, Pathology, New York, NY
OBJECTIVE: We sought to characterize markers of pluripotency in amniotic fluid derived cells as a non-controversial and readily available source of potentially therapeutic stem cells. STUDY DESIGN: Amniotic fluid stem cells (AFSC) express stem cell surface markers as well as transcription factors. Isolation and enrichment of the stem cell population is essential to their therapeutic potential. We studied expression of stem cell surface markers CD 117, CD 133, SSEA3, SSEA4, TRA 160, TRA 181 and CD90; as well as transcription factors OCT4, SOX2, NANOG and REX 1 by magnetic bead separation, flow cytometry analysis and PCR for transcription factors. Samples were obtained after cytogenetic analysis following routine amniocentesis for age or maternal anxiety in 10 normal patients. Cells were cultured for up to seven passages with analysis after confluence. RESULTS: There was great variation in different samples ability to express the different markers. The most prevalent marker was CD90, a mesenchymal stem cell factor; followed by SSEA4 and TRA160, both embryonic stem cell markers. The other markers were significantly present as well (SSEA3, TRA 160, TRA 181,CD90,OCT4, SOX2, NANOG and REX 1), however CD 117 and CD 133 were often undetectable or present in small amounts.
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
Doppler Assessment, Fetus, Prematurity
395 Isoimmunization to minor red blood cell antigens in pregnancy: management, monitoring and outcomes Sharmilee Thota1, Srinivas Ketharaju2, Carolyn Salafia3, Aleksandr Fuks4 1 Bronx-Lebanon Hospital Center, OB/GYN, Bronx, NY, 2Bronx-Lebanon Hospital Center, OB/GYN, Bronx, NY, 3New York Methodist Hospital Cornell Presbyterian, OB/GYN, Pathology, Pediatrics, Brooklyn, NY, 4Queens Hospital Center, OB/GYN, Queens, NY
OBJECTIVE: To examine fetal and neonatal outcomes of pregnancies complicated by isoimmunization to minor red blood cell (RBC) antigens and managed by serial antibody titer and MCA-peal systolic velocity (MCA-PSV) assessments. STUDY DESIGN: Retrospective cohort study of all patients isoimmunized to minor RBC antigens managed at Bronx-Lebanon Hospital Center, 2008-2011. Inclusion criteria: live singleton gestataion, presence of minor RBC antibodies, gestational age 24 0/7 - 36 0/7 weeks. Exclusion criteria: multiple gestations, Kell and major RBC antibodies, fetal malformations and chromosomal abnormalities. All patients were managed with serial antibody titer and MCA-PSV assessments. Outcome parameters were assessed: birthweight, fetal bilirubin concentration, cord gas base excess, fetal hematocrit, NICU stay duration. RESULTS: 24 patients fit study inclusion criteria. Demographic and outcome parameters are summarized in the Table below. None of the patients in the study had MCA-PSV values in the range of severe fetal anemia requiring PUBS and in-utero transfusion. None of the neonates required RBC transfusion and only 2 newborns were Coombs positive and required phototherapy. CONCLUSION: Patients with alloimmunization to minor RBC antigens and antibody titers less than critical value (1:32) do not appear to be at risk for sever fetal anemia. In those patients, serial MCA-PSV assessments do not influence management decisions and outcomes of pregnancy and forgoing such evaluation might be suitable.
Poster Session III
specifically manifested in reduced limb and truncal growth but not reduced head growth. STUDY DESIGN: 865 singleton pregnancies were prospectively followed with sequential blood sampling (10, 18, 24, 35 weeks) and 3rd trimester fetal ultrasound measurements. PlGF and sFlt levels were measured with the Abbott Architect assay. Gestational age specific Z-scores were evaluated for birth weight (BW), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD). RESULTS: PlGF and sFlt levels at weeks 10 and 18 were not associated with BW or fetal anthropometric Z-scores. At weeks 24 and 35, PlGF was positively and sFlt was negatively associated with BW Z-score (Table). At these gestations, the angiogenic markers were associated with AC and FL Z-scores but not BPD Z-scores. Linear regression, controlling for clinical covariates including the diagnosis of PE and using BW, AC and FL Z-scores as the dependent variables, demonstrated independent effects of PlGF and sFlt concentrations (R^2⫽0.09, p⬍0.0001 for all). CONCLUSION: Associations between the angiogenic markers and reduced fetal growth manifest in the 3rd trimester. Increased concentrations of sFlt and decreased concentrations of PlGF were associated with reduced limb and truncal growth but not reduced head growth.
397 Cost effectiveness of open fetal surgery for fetal myelomeningocele (MMC) Alison G. Cahill1, Rachel Pilliod2, Anthony Odibo1, Brian Shaffer2, Aaron Caughey2 1 Washington University in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO, 2Oregon Health & Science University, Department of Obstetrics and Gynecology, Portland, OR
396 Fetal growth and anthropometrics in relation to serial maternal sFlt-1 and PlGF levels A.E. Lehmann1, J.N. Robinson2, A.M. Thomas3, P.M. Doubilet4, T.F. McElrath2 1
Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, MA, Harvard Medical School, Brigham & Women’s Hospital, Division of Maternal-Fetal Medicine, Boston, MA, 3Brigham & Women’s Hospital, Division of Maternal-Fetal Medicine, Boston, MA, 4Harvard Medical School, Brigham & Women’s Hospital, Department of Radiology, Boston, MA 2
OBJECTIVE: Concentrations of the angiogenic markers placental growth factor (PlGF) and the soluble fms-like tyrosine kinase-1 (sFlt) vary greatly between otherwise normal pregnancies. The concentrations of the markers are most extreme in conditions of aberrant placentation including preeclampsia (PE). We hypothesize that 1) even absent the effect of PE, decreased PlGF and increased sFlt concentrations are associated with reduced fetal growth and 2) this reduction is
OBJECTIVE: : Given recently published evidence for efficacy of open fetal surgical repair of MMC, we aimed to estimate its cost-effectiveness compared to post-natal repair STUDY DESIGN: We constructed a decision analytic model to compare 2 strategies for the surgical treatment of antenatally diagnosed isolated myelomeningocele: 1)fetal surgical repair, or 2)post-natal repair. The model was constructed from the societal perspective for a theoretical cohort of 1000 women fulfilling the inclusion criteria for the recently published MOMS trial. We assumed delivery in either arm would be by cesarean. Clinical outcomes included: maternal transfusion, maternal pulmonary edema, preterm birth (PTB), respiratory distress syndrome (RDS), post-natal shunt, surgery for tethered cord, incontinence, non-ambulatory, moderate-severe neurodevelopmental delay. Probabilities, utilities and costs were derived from the literature. Due to the paucity of data available on the cost of fetal surgery for MMC, we estimated the cost based on the MOMS trial protocol. Strategies were compared by numbers of clinical events prevented, and costs per quality-adjusted life-years (QALYs) RESULTS: Fetal surgery for MMC was the dominant strategy (least costly and most effective) in the base-case analysis. Sensitivity analyses revealed the model to be sensitive to the number of antepartum ad-
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S185
Poster Session III
Doppler Assessment, Fetus, Prematurity
mission days required for women undergoing fetal surgery; if more than 38 days were spent in the hospital, post-natal surgery became the cheaper strategy but fetal surgery remains dominant. Fetal repair of MMC in a hypothetical cohort of 1000 women would yield 526 fewer shunts and 395 fewer non-ambulatory toddlers at age 30-months, but result in 290 additional PTBs and 18 additional cases of RDS. CONCLUSION: Fetal MMC repair is cost-effective from a societal perspective, but trades improved post-natal outcomes for higher rates of preterm birth-associated and maternal morbidities. However, given the significant investment required to initiate and maintain such programs, the most cost-effective strategy from the institutional perspective deserves further analysis
www.AJOG.org
obtained from live IUGR fetuses exhibited increased inflammation in the absence of maternal systemic inflammation. Future studies will investigate whether inflammatory cytokines in IUGR model can be modulated. Supported by Oxenhorn Family.
398 Intrauterine growth restriction is associated with enhanced amniotic fluid and placental cytokine levels in an animal model Amanda Roman1, Neeraj Desai1, Burton Rochelson1, Madhu Gupta2, Xiangying Xue2, Prodyot Chatterjee2, Christine Metz2 1 Hofstra North Shore-LIJ School of Medicine, Division of Maternal-Fetal Medicine, Manhasset, NY, 2Feinstein Institute for Medical Research, Center for Immunology and Inflammation, Manhasset, NY
OBJECTIVE: To evaluate maternal and fetal inflammatory responses using a rat model of intrauterine growth restriction (IUGR) STUDY DESIGN: Pregnant female Wistar rats (12 wks old, GD18) were anesthetized using inhaled isoflurane and underwent either bilateral uterine artery ligation (BL; n⫽6) or sham surgery (without ligation; n⫽4). Dams were euthanized 24 hrs later (GD19). For comparison, a group of control dams (C, no anesthesia, no surgery; n⫽4) were euthanized on GD19. Maternal plasma was collected; fetal plasma (pooled from the pups of a single dam), individual amniotic fluid samples, and placentas were collected from live fetal pups only (BL⫽32; sham⫽20; and C⫽22). All samples were analyzed for cytokines (IL-6, IL-1, GRO/KC, MCP-1 and TNF; sensitivity ⬍3pg/ml) using multiplex. Data was analyzed using ANOVA and t-test. RESULTS: The average fetal and placental weights were significantly lower in the BL dams when compared to sham dams (P⬍0.001); sham fetal and placental weights did not differ from control dams. The overall fetal mortality was 37% among BL rats and 0% among shams and controls (Table 1). IL-6, IL-1, TNF (P⬍0.05) and MCP-1 (P⬍0.001) levels were significantly increased in the amniotic fluids obtained from BL dams, while IL-6, IL-1, MCP-1 and GRO/KC (P⬍0.001) and TNF (P⬍0.05) were significantly increased in placental tissues obtained from the BL dams when compared to shams or controls (Fig. 1). Sham placentas did not differ significantly from control placentas. There were no significant differences in cytokines with respect to proximity to fetal demise or uterine artery ligation site. Interestingly, neither maternal nor fetal plasma showed differences in cytokine levels. CONCLUSION: Bilateral uterine artery ligation produced measurable IUGR with moderate fetal mortality. Amniotic fluid and placentas
S186
399 Stem cell markers in amniotic fluid derived cells Ashwin Jadhav1, Ross Basch2, Michael Chan1, Nikolai Strelchenko1, Zhisheng Chen1, Bruce Young1 1 New York University Medical Center, Obstetrics and Gynecology, New York, NY, 2New York University Medical Center, Pathology, New York, NY
OBJECTIVE: We sought to characterize markers of pluripotency in amniotic fluid derived cells as a non-controversial and readily available source of potentially therapeutic stem cells. STUDY DESIGN: Amniotic fluid stem cells (AFSC) express stem cell surface markers as well as transcription factors. Isolation and enrichment of the stem cell population is essential to their therapeutic potential. We studied expression of stem cell surface markers CD 117, CD 133, SSEA3, SSEA4, TRA 160, TRA 181 and CD90; as well as transcription factors OCT4, SOX2, NANOG and REX 1 by magnetic bead separation, flow cytometry analysis and PCR for transcription factors. Samples were obtained after cytogenetic analysis following routine amniocentesis for age or maternal anxiety in 10 normal patients. Cells were cultured for up to seven passages with analysis after confluence. RESULTS: There was great variation in different samples ability to express the different markers. The most prevalent marker was CD90, a mesenchymal stem cell factor; followed by SSEA4 and TRA160, both embryonic stem cell markers. The other markers were significantly present as well (SSEA3, TRA 160, TRA 181,CD90,OCT4, SOX2, NANOG and REX 1), however CD 117 and CD 133 were often undetectable or present in small amounts.
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012