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317: Intratracheal delivery of amniotic fluid derived stem cells (AFSc) in perfluorcarbon as compared to tracheal occlusion (TO)
Poster Session II
ajog.org
* UA >95th centile or AEDF on > 2 occasions; ** Comparison with controls
317 Intratracheal delivery of amniotic fluid derived stem cells (AFSc) in perfluorcarbon as compared to tracheal occlusion (TO)
Francesca Russo1, Silvia Zia1, Julio Jimenez1, Patrice Eastwood1, Jaan Toelen1, Jan Deprest1 1
KU Leuven, Development and Regeneration, Leuven, Belgium
OBJECTIVE: Perfluoro-octyl-bromide (PFOB) and amniotic fluid derived stem cells (AFSc) can be used to modulate lung development. We assessed the compatibility of AFSc with PFOB and their effects on fetal rabbit lungs in vivo as compared to tracheal occlusion (TO). STUDY DESIGN: One clonal human AFSc population was cultured and transduced to express b-galactosidase to track cells (Zia, Pren Diagn 2014). Cells were seeded at 10000 cells/cm2 in 24 wells with 1 mL growth medium and 10 mL PFOB and incubated. Viability was evaluated at 1-4-8-24 and 48 hours with trypan blue. All experiments were done in duplicate. In the in vivo study fetuses of 6 pregnant rabbits on gestational day 28 were exposed via hysterotomy, and randomized to undergo tracheal instillation of either 1) PFOB, 2) AFSc followed by PFOB, 3) AFSc followed by TO or 4) AFSc followed by PFOB instillation and TO (n¼5 per group). Injected volume of PFOB was 1 mL and 1x106 AFSc were suspended in 70mL PBS. Fetuses were delivered by cesarean section after 48h and sacrificed. Total body X-rays documented the distribution of PFOB. The left lungs were isolated, embedded in OCT and freshly frozen. 20 sections through the entire lung surface were stained with X-Gal staining. The number of vital AFSc was counted and the mean number of viable AFSc per slide was compared. RESULTS: In vitro, cell viability was confirmed at all time points. After in vivo PFOB injection the product could be visualized over the entire lung on X-Ray. The mean number of viable AFSc was significantly higher in fetuses treated with AFSc + PFOB or AFSc + PFOB + TO compared to those treated with TO + AFSc alone. In the latter group, the number of viable cells was lower than in the other treatment groups (Figure). CONCLUSION: PFOB does not compromise AFSc viability. Instillation of AFSC in PFOB, alone or in association with TO, increases the number of AFSc in the lung. PFOB could therefore be used as a delivery method for cells to the fetal lungs obviating the need for TO.
Figure: mean number of AFSc per section in the four treatment groups. * p < 0.05 vs PFOB alone ** p < 0.001 vs PFOB alone
318 Role of genetic sonogram and NIPT after EIF detection: a cost-effectiveness analysis Francis Hacker1, Emily Griffin1, Brian Shaffer1, Aaron Caughey1
1 Oregon Health & Science University, Obstetrics and Gynecology, Portland, OR
OBJECTIVE: The recent Fetal Imaging Workshop recommends completion of targeted ultrasound (US) in fetuses with Echogenic Cardiac Foci (EIF) to detect additional findings associated with trisomy 21 (t21). Given the relatively low sensitivity of a t21 US and difficulty of achieving adequate sonographic visualization in obese women, our goal was to compare estimated outcomes and costs associated with this recommendation to that of non-invasive prenatal testing (NIPT) in women with prior aneuploidy screening. STUDY DESIGN: A decision-analytic model was constructed using TreeAge software and probabilities derived from the literature. The model compared NIPT to targeted US in women with a negative quad screen and fetal EIF identified on screening US. This was stratified by maternal age below or above 35. T21 sensitivities for US and and NIPT were assumed at 69% and 99% and examined in sensitivity analysis. Outcomes of interest were t21 diagnosis, procedure related loss, pregnancy termination, spontaneous abortion and t21 live births. Strategies were compared to generate an incremental cost-effectiveness ratio with a threshold set to $100,000 per QALY. RESULTS: The NIPT strategy in women<35 with an EIF and negative quad resulted in 13 fewer t21 births and 33.5 additional QALYS with cost savings of $10,054,118 per 10,000 pregnancies when compared to targeted ultrasound, a dominant strategy in cost-effectiveness analysis. In women35, the NIPT strategy resulted in 10 fewer t21 births and 25.9 additional QALYs with cost savings of $7,212,942 per 10,000 pregnancies, also a dominant strategy. CONCLUSION: In a population with prior negative aneuploidy screening, it’s cost effective to offer NIPT compared to targeted US when an EIF is visualized. This result was observed in women of all ages but was even more cost-effective in women<35, likely secondary to decreased sensitivity of quad screening in this group. Following a negative NIPT, in women below and above 35 there were 2.4 and 1.4 t21 live births per 1000 pregnancies.
Supplement to JANUARY 2015 American Journal of Obstetrics & Gynecology
S171
ajog.org
* UA >95th centile or AEDF on > 2 occasions; ** Comparison with controls
317 Intratracheal delivery of amniotic fluid derived stem cells (AFSc) in perfluorcarbon as compared to tracheal occlusion (TO)
Francesca Russo1, Silvia Zia1, Julio Jimenez1, Patrice Eastwood1, Jaan Toelen1, Jan Deprest1 1
KU Leuven, Development and Regeneration, Leuven, Belgium
OBJECTIVE: Perfluoro-octyl-bromide (PFOB) and amniotic fluid derived stem cells (AFSc) can be used to modulate lung development. We assessed the compatibility of AFSc with PFOB and their effects on fetal rabbit lungs in vivo as compared to tracheal occlusion (TO). STUDY DESIGN: One clonal human AFSc population was cultured and transduced to express b-galactosidase to track cells (Zia, Pren Diagn 2014). Cells were seeded at 10000 cells/cm2 in 24 wells with 1 mL growth medium and 10 mL PFOB and incubated. Viability was evaluated at 1-4-8-24 and 48 hours with trypan blue. All experiments were done in duplicate. In the in vivo study fetuses of 6 pregnant rabbits on gestational day 28 were exposed via hysterotomy, and randomized to undergo tracheal instillation of either 1) PFOB, 2) AFSc followed by PFOB, 3) AFSc followed by TO or 4) AFSc followed by PFOB instillation and TO (n¼5 per group). Injected volume of PFOB was 1 mL and 1x106 AFSc were suspended in 70mL PBS. Fetuses were delivered by cesarean section after 48h and sacrificed. Total body X-rays documented the distribution of PFOB. The left lungs were isolated, embedded in OCT and freshly frozen. 20 sections through the entire lung surface were stained with X-Gal staining. The number of vital AFSc was counted and the mean number of viable AFSc per slide was compared. RESULTS: In vitro, cell viability was confirmed at all time points. After in vivo PFOB injection the product could be visualized over the entire lung on X-Ray. The mean number of viable AFSc was significantly higher in fetuses treated with AFSc + PFOB or AFSc + PFOB + TO compared to those treated with TO + AFSc alone. In the latter group, the number of viable cells was lower than in the other treatment groups (Figure). CONCLUSION: PFOB does not compromise AFSc viability. Instillation of AFSC in PFOB, alone or in association with TO, increases the number of AFSc in the lung. PFOB could therefore be used as a delivery method for cells to the fetal lungs obviating the need for TO.
Figure: mean number of AFSc per section in the four treatment groups. * p < 0.05 vs PFOB alone ** p < 0.001 vs PFOB alone
318 Role of genetic sonogram and NIPT after EIF detection: a cost-effectiveness analysis Francis Hacker1, Emily Griffin1, Brian Shaffer1, Aaron Caughey1
1 Oregon Health & Science University, Obstetrics and Gynecology, Portland, OR
OBJECTIVE: The recent Fetal Imaging Workshop recommends completion of targeted ultrasound (US) in fetuses with Echogenic Cardiac Foci (EIF) to detect additional findings associated with trisomy 21 (t21). Given the relatively low sensitivity of a t21 US and difficulty of achieving adequate sonographic visualization in obese women, our goal was to compare estimated outcomes and costs associated with this recommendation to that of non-invasive prenatal testing (NIPT) in women with prior aneuploidy screening. STUDY DESIGN: A decision-analytic model was constructed using TreeAge software and probabilities derived from the literature. The model compared NIPT to targeted US in women with a negative quad screen and fetal EIF identified on screening US. This was stratified by maternal age below or above 35. T21 sensitivities for US and and NIPT were assumed at 69% and 99% and examined in sensitivity analysis. Outcomes of interest were t21 diagnosis, procedure related loss, pregnancy termination, spontaneous abortion and t21 live births. Strategies were compared to generate an incremental cost-effectiveness ratio with a threshold set to $100,000 per QALY. RESULTS: The NIPT strategy in women<35 with an EIF and negative quad resulted in 13 fewer t21 births and 33.5 additional QALYS with cost savings of $10,054,118 per 10,000 pregnancies when compared to targeted ultrasound, a dominant strategy in cost-effectiveness analysis. In women35, the NIPT strategy resulted in 10 fewer t21 births and 25.9 additional QALYs with cost savings of $7,212,942 per 10,000 pregnancies, also a dominant strategy. CONCLUSION: In a population with prior negative aneuploidy screening, it’s cost effective to offer NIPT compared to targeted US when an EIF is visualized. This result was observed in women of all ages but was even more cost-effective in women<35, likely secondary to decreased sensitivity of quad screening in this group. Following a negative NIPT, in women below and above 35 there were 2.4 and 1.4 t21 live births per 1000 pregnancies.
Supplement to JANUARY 2015 American Journal of Obstetrics & Gynecology
S171