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Dobutamine is the optimal inotrope for the fetus
S196 SMFM Abstracts 649 DOBUTAMINE IS THE OPTIMAL INOTROPE FOR THE FETUS SCOTT BAKER1, CHRISTOPHER LAM1, WALTER LUBBERS1, KENNETH CLARK2, PIROOZ EGHTESADY1, 1Children’s Hospital Medical Center of Cincinnati, Cardiothoracic Surgery, Cincinnati, Ohio, 2University of Cincinnati, Obstetrics and Gynecology, Cincinnati, Ohio OBJECTIVE: Recent clinical experience has shown significant declines in fetal cardiac output with open fetal surgery and improved fetal survival with intraoperative use of resuscitative measures. While some have looked at effects on placental function or uterine blood flow, none have evaluated the effects of commonly used inotropes on fetal cardiac output identifying the optimal agent for the fetus. STUDY DESIGN: Four ovine fetuses at gestational day 104-111 were chronically instrumented to measure maternal and fetal hemodynamics including fetal cardiac output and umbilical blood flow. Fetal dose response studies were carried out using clinically-relevant doses of milrinone (0.251 mcg/kg/min), dopamine (3-15 mcg/kg/min), dobutamine (3-15 mcg/kg/min) and epinephrine (0.02-2 mcg/kg/min). Random assignments to each infusion were carried out on separate days. Student’s t-test (2-tailed) was used to determine significance at p!0.05. RESULTS: Except milrinone, the other three inotropes increased fetal cardiac output and umbilical blood flow in a dose dependent fashion. Dobutamine had the most profound increase in fetal cardiac output (39G28%, MeanGSD) versus both dopamine (23G31%) and epinephrine (18G14%), (p!0.05 for all). These three inotropes increased umbilical blood flows up to 18%, but only dobutamine significantly decreased umbilical vascular resistance by 19G3%, (p!0.05 for all). All hemodynamics normalized 30 min after the infusions. Epinephrine infusion was associated with significant lactic acidosis and fetal hyperglycemia. Fetal gas exchange was preserved with all agents at all times. Fetal inotrope infusions did not alter maternal hemodynamics. CONCLUSION: Not all inotropes are equal for fetal support. Dobutamine may be superior because of its salutary effects on placental vascular resistance. Epinephrine may be the least optimal agent because of its metabolic effects on the fetus. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.704
650 WITHDRAWN 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.705
651 PLACENTAL-DERIVED MESENCHYMAL STEM CELL GRAFT FOR PRE- AND PERINATAL TREATMENT OF OSTEOGENESIS IMPERFECTA STEFAN MOHR1, BETTINA PORTMANN-LANZ1, RUTH SAGER1, DANIEL SURBEK1, 1University of Berne, Obstetrics and Gynecology, Berne, Switzerland OBJECTIVE: Osteogenesis imperfecta (OI) is a genetic bone disorder with different genotype and variable phenotype. Severe forms lead to prenatal bone fractures and developmental bone malformation. The aim of this study is to assess a novel a three dimensional, biodegradable stem cell-loaded patch for site-specific repair of bone defects of fetuses and newborns suffering from severe OI. STUDY DESIGN: We manufactured a three-dimensional scaffold derived from human chorionic membrane as support material for placental-derived mesenchymal stem cell (MSC) outgrowth. We used the chorionic reticular layer and removed cellular components by mechanical and enzymatical methods to free the extracellular matrix. We cultured human MSC’s derived from first trimester chorionic villi or term chorion membrane after seeding onto the acellular chorion-derived scaffold. We recently showed that placentalderived MSC’s possess a sound osteogenic differentiation potential. Differentiation to the osteogenic lineage was induced. Construct assembly and bone formation was investigated by scanning and transmission electron microscopy as well as confocal laser scanning microscopy. RESULTS: Using our technical approach, we were able to free the extracellular matrix of chorionic reticular layer from cells and obtained a bare three- dimensional collagenous structure. Seeded MSC’s did not only anchored on the scaffold but also invaded it to build a three- dimensional network. Under specific culture conditions these cells were able to form bone resp. differentiated osteogenically and expressed typical osteogenic markers. CONCLUSION: Our experiments suggest that a three-dimensional bony tissue structure can be constructed using placental-derived scaffold as well as MSC’s from first an third trimester trophoblast. This three-dimensional bone tissue engineering technique approach might allow a direct supply of fully autologous MSC’s to affected bone injured sites and might be a potential novel treatment strategy of bone lesions of fetuses and newborns affected by severe OI. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.706
652 DEVELOPMENTAL OUTCOMES OF CHILDREN WHO HAD INCREASED NUCHAL TRANSLUCENCY AND NORMAL KARYOTYPES STEPHANIE WINSOR1, JO-ANN JOHNSON2, DAVID CHITAYAT3, 1McMaster University, Maternal Fetal Medicine, Hamilton, Ontario, Canada, 2University of Calgary, Obstetrics and Gynecology, Calgary, Alberta, Canada, 3University of Toronto, Prenatal Diagnosis and Medical Genetics, Toronto, Ontario, Canada OBJECTIVE: To evaluate the developmental outcomes of children who had increased nuchal translucency (NT) and normal karyotypes. STUDY DESIGN: This was a prospective observational study of fetuses with NT of R3mm at 10-14 weeks and normal karyotypes. All had detailed ultrasound and cardiac screen and were followed at our center between May 1998 and May 2001. Newborn assessments were performed and the parents of the surviving children were re-contacted between May 2004- Aug 2006 to evaluate their communication, gross and fine motor, problem solving and personal-social skills, using the Ages and Stages Questionnaire (2nd edition Bricker et al). For children older than 60 months a Vineland Adaptive Behavioural Scale was used. RESULTS: 50 fetuses had an NT of R3mm and normal karyotypes. Thirteen had severe anomalies or fetal death. One child with Tetralogy of Fallot and mild dysmorphism is doing well. Of the remaining 36 children 20 had developmental assessment at 36- 80 months. Three had mild dysmorphic features and one had newborn seizures and all are doing well. Two of the children have severe global delay. The first child has an ASD, mild dysmorphic features and had intrauterine infection with Parvovirus B19. Her NT was 5.5 mm at 14 weeks. The second child has dysmorphic features and brain MRI showing delayed myelin maturation. Her NT was 3.8mm at 11 weeks. The rest of the children have normal development. Sixteen children were lost to follow-up. CONCLUSION: Increased NT with normal karyotypes can be associated with congenital anomalies, genetic syndromes and poor perinatal outcomes and can also be associated with developmental delay. However, the long-term developmental outcomes of the majority of the surviving children with increased NT and normal karyotypes is good. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.707
650 WITHDRAWN 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.705
651 PLACENTAL-DERIVED MESENCHYMAL STEM CELL GRAFT FOR PRE- AND PERINATAL TREATMENT OF OSTEOGENESIS IMPERFECTA STEFAN MOHR1, BETTINA PORTMANN-LANZ1, RUTH SAGER1, DANIEL SURBEK1, 1University of Berne, Obstetrics and Gynecology, Berne, Switzerland OBJECTIVE: Osteogenesis imperfecta (OI) is a genetic bone disorder with different genotype and variable phenotype. Severe forms lead to prenatal bone fractures and developmental bone malformation. The aim of this study is to assess a novel a three dimensional, biodegradable stem cell-loaded patch for site-specific repair of bone defects of fetuses and newborns suffering from severe OI. STUDY DESIGN: We manufactured a three-dimensional scaffold derived from human chorionic membrane as support material for placental-derived mesenchymal stem cell (MSC) outgrowth. We used the chorionic reticular layer and removed cellular components by mechanical and enzymatical methods to free the extracellular matrix. We cultured human MSC’s derived from first trimester chorionic villi or term chorion membrane after seeding onto the acellular chorion-derived scaffold. We recently showed that placentalderived MSC’s possess a sound osteogenic differentiation potential. Differentiation to the osteogenic lineage was induced. Construct assembly and bone formation was investigated by scanning and transmission electron microscopy as well as confocal laser scanning microscopy. RESULTS: Using our technical approach, we were able to free the extracellular matrix of chorionic reticular layer from cells and obtained a bare three- dimensional collagenous structure. Seeded MSC’s did not only anchored on the scaffold but also invaded it to build a three- dimensional network. Under specific culture conditions these cells were able to form bone resp. differentiated osteogenically and expressed typical osteogenic markers. CONCLUSION: Our experiments suggest that a three-dimensional bony tissue structure can be constructed using placental-derived scaffold as well as MSC’s from first an third trimester trophoblast. This three-dimensional bone tissue engineering technique approach might allow a direct supply of fully autologous MSC’s to affected bone injured sites and might be a potential novel treatment strategy of bone lesions of fetuses and newborns affected by severe OI. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.706
652 DEVELOPMENTAL OUTCOMES OF CHILDREN WHO HAD INCREASED NUCHAL TRANSLUCENCY AND NORMAL KARYOTYPES STEPHANIE WINSOR1, JO-ANN JOHNSON2, DAVID CHITAYAT3, 1McMaster University, Maternal Fetal Medicine, Hamilton, Ontario, Canada, 2University of Calgary, Obstetrics and Gynecology, Calgary, Alberta, Canada, 3University of Toronto, Prenatal Diagnosis and Medical Genetics, Toronto, Ontario, Canada OBJECTIVE: To evaluate the developmental outcomes of children who had increased nuchal translucency (NT) and normal karyotypes. STUDY DESIGN: This was a prospective observational study of fetuses with NT of R3mm at 10-14 weeks and normal karyotypes. All had detailed ultrasound and cardiac screen and were followed at our center between May 1998 and May 2001. Newborn assessments were performed and the parents of the surviving children were re-contacted between May 2004- Aug 2006 to evaluate their communication, gross and fine motor, problem solving and personal-social skills, using the Ages and Stages Questionnaire (2nd edition Bricker et al). For children older than 60 months a Vineland Adaptive Behavioural Scale was used. RESULTS: 50 fetuses had an NT of R3mm and normal karyotypes. Thirteen had severe anomalies or fetal death. One child with Tetralogy of Fallot and mild dysmorphism is doing well. Of the remaining 36 children 20 had developmental assessment at 36- 80 months. Three had mild dysmorphic features and one had newborn seizures and all are doing well. Two of the children have severe global delay. The first child has an ASD, mild dysmorphic features and had intrauterine infection with Parvovirus B19. Her NT was 5.5 mm at 14 weeks. The second child has dysmorphic features and brain MRI showing delayed myelin maturation. Her NT was 3.8mm at 11 weeks. The rest of the children have normal development. Sixteen children were lost to follow-up. CONCLUSION: Increased NT with normal karyotypes can be associated with congenital anomalies, genetic syndromes and poor perinatal outcomes and can also be associated with developmental delay. However, the long-term developmental outcomes of the majority of the surviving children with increased NT and normal karyotypes is good. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.707