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Increased incidence of cardiac anomalies in pregnancies complicated by gastroschisis
S162 SMFM Abstracts 570
EFFECT OF A PRIOR AMNIOCENTESIS IN PATIENTS UNDERGOING LASER THERAPY FOR TWIN-TWIN TRANSFUSION SYNDROME RAMEN CHMAIT1, CRISTINA ROSSI1, RUBEN QUINTERO1, 1Florida Institute for Fetal Diagnosis and Therapy, Tampa, Florida OBJECTIVE: To assess the implications of a previous therapeutic amniocentesis (PTA) in patients that subsequently underwent laser therapy for twin-twin transfusion syndrome (TTTS). STUDY DESIGN: All twin pregnancies that underwent laser therapy for TTTS from January 1999 through December 2003 were studied. Patients with no PTA (PTA-) were compared to those with one or more PTA’s (PTA+) in regards to demographics, operative complications, and outcome measures including gestational age at delivery and survival of at least one neonate. Statistical significance was determined if P ! .05. RESULTS: Three hundred and forty patients underwent laser therapy for TTTS during the study period. Of these, 203 (60%) were PTA- and 137 (40%) were PTA+. The median number of amniocenteses in the PTA+ group was 1 (range 1-6), with a median total volume withdrawn of 1550cc (range 100-12000). Severity of the disease was similar between the two groups in terms of Quintero stages I/II and stages III/IV. On average, the PTA- group underwent surgery one week earlier than the PTA+ group (20.1 vs. 21.2 weeks’ gestation, P = .0001). Placental location was anterior more often in the PTA- (49%) than in the PTA+ (36%, P = .019) group, yet amnioexchange to correct blood discolored amniotic fluid was necessary less often in the PTA- (9%) than in PTA+ (20%, P = .009) group. Gestational age at delivery was greater in the PTA- than in the PTA+ patients (32.0 vs. 30.6 weeks, P = .008), with a trend towards improved survival (89% vs. 81%, P = .0543). CONCLUSION: Therapeutic amniocentesis prior to laser therapy is associated with increased operative risk, earlier gestational age at delivery, and a trend towards lower perinatal survival. Patients with TTTS who desire laser therapy should avoid undergoing prior therapeutic amniocenteses.
572
PLACENTAL ANGIOGRAPHY OF DOUBLE SURVIVORS AND DOUBLE FETAL DEATHS AFTER LASER FOR TWIN TWIN TRANSFUSION SYNDROME (TTTS) LIESBETH LEWI1, MIEKE CANNIE2, JACQUES JANI1, VINCENT VANDECAVEYE2, STEVEN DYMARKOWSKI3, AGNES HUBER4, ROMAINE ROBYR5, EDUARD GRATACOS6, KYPROS NICOLAIDES7, KURT HECHER4, YVES VILLE5, JAN DEPREST1, 1University Hospital Gasthuisberg, Obstetrics and Gynecology, Leuven, Belgium, 2University Hospital Gasthuisberg Leuven, Radiology, Leuven, Belgium, 3University Hospital Gasthuisberg, Radiology, Leuven, Belgium, 4Universita¨tsklinikum HamburgEppendorf, Obstetrics/Gynecology, Hamburg, Germany, 5Universite´ ParisOuest Poissy France, Obstetrics and Gynecology, Poissy Cedex, France, 6 Universitat Autonoma Barcelona, Barcelona, Spain, 7King’s College Hospital, Harris Birthright Research Centre, London, United Kingdom OBJECTIVE: Placental injection study to detect residual feto-fetal anastomoses by inspection of the chorionic surface and Rx angiography in double survivors (2SURV) or death (2IUFD) after laser for TTTS. STUDY DESIGN: Single shot digital angiography (Philips DSI, 96 KV-224 mAs) was performed after injection of cord vessels with dyed barium (MicropaqueÒ) as well as digital photography (Sony Cybershot 5 Mpixel) of angioarchitecture as visible on the chorionic plate. The presence of residual anastomoses visible on the chorionic surface and angiography was determined. RESULTS: 16 consecutive placentas were examined;four from 2IUFD within 1-14 days post-laser and 12 from double survivors, delivered at median GA of 34 wks (30-38). TTTS had resolved in all 2SURV; 2 had discordant Hb at birth (8/ 19 at 30wk; 12/20 g/dL at 35wk). The former had discordant Vmax MCA 2 wks post-laser, managed by one IUT. The latter had normal Vmax MCA. In all 2IUFD, residual AV-VA anastomoses were visible on the chorionic plate, on angiography being typical shared cotyledons. In 2SURV, areas of coagulation along the equator and no visible residual anastomoses could be seen on the surface, suggesting successful bichorionisation. In contrast angiography revealed atypical anastomoses in all but one. Angiographic anastomoses were either (1) intercotyledonary capillaries not visible on the chorionic surface or (2) small paired/unpaired vessels of 0.5 mm (0-1.2) visible on the chorionic surface, going from one twin and dropping unexpectedly into cotyledonary territory of the other. CONCLUSION: In 2SURV, laser bichorionises on placental inspection but not on angiography. Anastomoses visible only on angiography did not prevent resolution of TTTS, and may account for lesser degrees of feto-fetal transfusion showing need for follow-up. In 2IUFD, residual AV-VA anastomoses remained visible on the surface, suggesting surgical failure. *Sponsored by the European Commission QLG1CT2002-01632 Eurofoetus.
571
INCREASED INCIDENCE OF CARDIAC ANOMALIES IN PREGNANCIES COMPLICATED BY GASTROSCHISIS LIZA KUNZ1, WILLIAM GILBERT1, DENA TOWNER1, 1University of California, Davis, Obstetrics & Gynecology, Sacramento, California OBJECTIVE: To determine the incidence of congential heart defects in infants with gastroschisis. STUDY DESIGN: California hospital discharge data from acute care civilian hospitals during the years 1992-1997 was searched for the diagnosis of gastroschisis repair, thus identifying 621 infants. The diagnosis of congenital cardiac defect (ICD 9-CM codes 745-747) and other demographic and pregnancy outcomes were examined. RESULTS: The overall incidence of congenital cardiac defects found in this population of neonates was 11% (69/621), compared to a background rate of 68/1000. There were 3 major structural anomalies: one case of Tetralogy of Fallot, one coarctation of the aorta, and one case of Ebstein’s anomaly. There were 12 right heart lesions: 10 defects in the pulmonary outflow tract, valve or artery, and 2 tricuspid valve abnormalities. There were 35 septation defects: 13 ventricular septal defects and 22 atrial septal defects. There were 35 cases of patent ductus arteriosus, of which 10 were in infants born at term. There were 16 infants with more than one lesion. 42 infants had only patent ductus arteriosus and/or atrial septal defects, possibly respresenting persistant fetal circulation rather than true defects. Excluding these cases, 25 infants remain, for an incidence rate of 4% which is still elevated over the backgroud rate. Analysis regarding maternal demographics, prenatal care, gestational age, length of stay, or requirement for major bowel surgeries were not significantly different between the infants with and without true structural defects. CONCLUSION: Contrary to conventional teaching that gastroschisis is an isolated anomaly, we found a cardiac anomaly rate significantly higher than that in the background population (4.0% vs 0.6-0.8%). Right sided lesions were present in nearly half of these infants, possibly suggesting a common etiology with development of the gastroschisis. Our data would suggest that detailed antepartum and post-natal echocardiographic evaluations are indicated in fetuses identified with gastroschisis.
573
IN UTERO HEMATOPOIETIC STEM CELL TRANSPLANTATION: RATIONALE FOR CONTINUED WORK TOWARD HUMAN APPLICATION SCOTT PETERSEN1, MARIYA GENDELMAN1, RICHARD JONES2, ALLEN CHEN2, KARIN BLAKEMORE1, 1Johns Hopkins University, Gynecology & Obstetrics, Baltimore, Maryland, 2Johns Hopkins University, Oncology Center, Baltimore, Maryland OBJECTIVE: The objective of this study was to ascertain disorders for which in utero hematopoietic stem cell transplantation (IUHSCT) would be feasible based upon recent improvements in postnatal HSCT treatment protocols and disease outcomes. STUDY DESIGN: We reviewed the current literature for human diseases where application of IUHSCT may be feasible. We focused our search to create a list of diseases where low levels of initial engraftment or mixed chimerism can affect a cure. We compiled cost data from human attempts at IUHSCT from our institution and reviewed cost data for non-HSCT disease treatment from the recent literature. RESULTS: Disorders amenable to IUHSCT include the hemoglobinopathies, storage disorders, and granulocyte disorders. Of these, hemoglobinopathies appear to be the best candidates for early human trials. Using ablative preparations before postnatal HSCT, 80-85% of patients with sickle cell anemia and b-thalassemia can live disease free. Approximately 10% of these patients display mixed chimerism and not full engraftment although they remain transfusion independent despite as little as 10% donor chimerism. Mortality and morbidity have been decreased with recent less ablative and non-ablative regimens that have been found to be similarly effective. These results suggest that IUHSCT might be applicable to these diseases at a cost of $10,000. This compares to an average lifetime cost for treatment of $500,000 and $1.5 million for sickle cell anemia and b-thalassemia, respectively. CONCLUSION: Potential candidates for human application of IUHSCT include b-thalassemia, sickle cell anemia, and granulocyte disorders. As advances are made in animal models, IUHSCT may become a feasible and cost-effective treatment strategy for these diseases, and potentially others. Given the impact of these diseases on the general population, research funding should continue for advancement toward human applications.
EFFECT OF A PRIOR AMNIOCENTESIS IN PATIENTS UNDERGOING LASER THERAPY FOR TWIN-TWIN TRANSFUSION SYNDROME RAMEN CHMAIT1, CRISTINA ROSSI1, RUBEN QUINTERO1, 1Florida Institute for Fetal Diagnosis and Therapy, Tampa, Florida OBJECTIVE: To assess the implications of a previous therapeutic amniocentesis (PTA) in patients that subsequently underwent laser therapy for twin-twin transfusion syndrome (TTTS). STUDY DESIGN: All twin pregnancies that underwent laser therapy for TTTS from January 1999 through December 2003 were studied. Patients with no PTA (PTA-) were compared to those with one or more PTA’s (PTA+) in regards to demographics, operative complications, and outcome measures including gestational age at delivery and survival of at least one neonate. Statistical significance was determined if P ! .05. RESULTS: Three hundred and forty patients underwent laser therapy for TTTS during the study period. Of these, 203 (60%) were PTA- and 137 (40%) were PTA+. The median number of amniocenteses in the PTA+ group was 1 (range 1-6), with a median total volume withdrawn of 1550cc (range 100-12000). Severity of the disease was similar between the two groups in terms of Quintero stages I/II and stages III/IV. On average, the PTA- group underwent surgery one week earlier than the PTA+ group (20.1 vs. 21.2 weeks’ gestation, P = .0001). Placental location was anterior more often in the PTA- (49%) than in the PTA+ (36%, P = .019) group, yet amnioexchange to correct blood discolored amniotic fluid was necessary less often in the PTA- (9%) than in PTA+ (20%, P = .009) group. Gestational age at delivery was greater in the PTA- than in the PTA+ patients (32.0 vs. 30.6 weeks, P = .008), with a trend towards improved survival (89% vs. 81%, P = .0543). CONCLUSION: Therapeutic amniocentesis prior to laser therapy is associated with increased operative risk, earlier gestational age at delivery, and a trend towards lower perinatal survival. Patients with TTTS who desire laser therapy should avoid undergoing prior therapeutic amniocenteses.
572
PLACENTAL ANGIOGRAPHY OF DOUBLE SURVIVORS AND DOUBLE FETAL DEATHS AFTER LASER FOR TWIN TWIN TRANSFUSION SYNDROME (TTTS) LIESBETH LEWI1, MIEKE CANNIE2, JACQUES JANI1, VINCENT VANDECAVEYE2, STEVEN DYMARKOWSKI3, AGNES HUBER4, ROMAINE ROBYR5, EDUARD GRATACOS6, KYPROS NICOLAIDES7, KURT HECHER4, YVES VILLE5, JAN DEPREST1, 1University Hospital Gasthuisberg, Obstetrics and Gynecology, Leuven, Belgium, 2University Hospital Gasthuisberg Leuven, Radiology, Leuven, Belgium, 3University Hospital Gasthuisberg, Radiology, Leuven, Belgium, 4Universita¨tsklinikum HamburgEppendorf, Obstetrics/Gynecology, Hamburg, Germany, 5Universite´ ParisOuest Poissy France, Obstetrics and Gynecology, Poissy Cedex, France, 6 Universitat Autonoma Barcelona, Barcelona, Spain, 7King’s College Hospital, Harris Birthright Research Centre, London, United Kingdom OBJECTIVE: Placental injection study to detect residual feto-fetal anastomoses by inspection of the chorionic surface and Rx angiography in double survivors (2SURV) or death (2IUFD) after laser for TTTS. STUDY DESIGN: Single shot digital angiography (Philips DSI, 96 KV-224 mAs) was performed after injection of cord vessels with dyed barium (MicropaqueÒ) as well as digital photography (Sony Cybershot 5 Mpixel) of angioarchitecture as visible on the chorionic plate. The presence of residual anastomoses visible on the chorionic surface and angiography was determined. RESULTS: 16 consecutive placentas were examined;four from 2IUFD within 1-14 days post-laser and 12 from double survivors, delivered at median GA of 34 wks (30-38). TTTS had resolved in all 2SURV; 2 had discordant Hb at birth (8/ 19 at 30wk; 12/20 g/dL at 35wk). The former had discordant Vmax MCA 2 wks post-laser, managed by one IUT. The latter had normal Vmax MCA. In all 2IUFD, residual AV-VA anastomoses were visible on the chorionic plate, on angiography being typical shared cotyledons. In 2SURV, areas of coagulation along the equator and no visible residual anastomoses could be seen on the surface, suggesting successful bichorionisation. In contrast angiography revealed atypical anastomoses in all but one. Angiographic anastomoses were either (1) intercotyledonary capillaries not visible on the chorionic surface or (2) small paired/unpaired vessels of 0.5 mm (0-1.2) visible on the chorionic surface, going from one twin and dropping unexpectedly into cotyledonary territory of the other. CONCLUSION: In 2SURV, laser bichorionises on placental inspection but not on angiography. Anastomoses visible only on angiography did not prevent resolution of TTTS, and may account for lesser degrees of feto-fetal transfusion showing need for follow-up. In 2IUFD, residual AV-VA anastomoses remained visible on the surface, suggesting surgical failure. *Sponsored by the European Commission QLG1CT2002-01632 Eurofoetus.
571
INCREASED INCIDENCE OF CARDIAC ANOMALIES IN PREGNANCIES COMPLICATED BY GASTROSCHISIS LIZA KUNZ1, WILLIAM GILBERT1, DENA TOWNER1, 1University of California, Davis, Obstetrics & Gynecology, Sacramento, California OBJECTIVE: To determine the incidence of congential heart defects in infants with gastroschisis. STUDY DESIGN: California hospital discharge data from acute care civilian hospitals during the years 1992-1997 was searched for the diagnosis of gastroschisis repair, thus identifying 621 infants. The diagnosis of congenital cardiac defect (ICD 9-CM codes 745-747) and other demographic and pregnancy outcomes were examined. RESULTS: The overall incidence of congenital cardiac defects found in this population of neonates was 11% (69/621), compared to a background rate of 68/1000. There were 3 major structural anomalies: one case of Tetralogy of Fallot, one coarctation of the aorta, and one case of Ebstein’s anomaly. There were 12 right heart lesions: 10 defects in the pulmonary outflow tract, valve or artery, and 2 tricuspid valve abnormalities. There were 35 septation defects: 13 ventricular septal defects and 22 atrial septal defects. There were 35 cases of patent ductus arteriosus, of which 10 were in infants born at term. There were 16 infants with more than one lesion. 42 infants had only patent ductus arteriosus and/or atrial septal defects, possibly respresenting persistant fetal circulation rather than true defects. Excluding these cases, 25 infants remain, for an incidence rate of 4% which is still elevated over the backgroud rate. Analysis regarding maternal demographics, prenatal care, gestational age, length of stay, or requirement for major bowel surgeries were not significantly different between the infants with and without true structural defects. CONCLUSION: Contrary to conventional teaching that gastroschisis is an isolated anomaly, we found a cardiac anomaly rate significantly higher than that in the background population (4.0% vs 0.6-0.8%). Right sided lesions were present in nearly half of these infants, possibly suggesting a common etiology with development of the gastroschisis. Our data would suggest that detailed antepartum and post-natal echocardiographic evaluations are indicated in fetuses identified with gastroschisis.
573
IN UTERO HEMATOPOIETIC STEM CELL TRANSPLANTATION: RATIONALE FOR CONTINUED WORK TOWARD HUMAN APPLICATION SCOTT PETERSEN1, MARIYA GENDELMAN1, RICHARD JONES2, ALLEN CHEN2, KARIN BLAKEMORE1, 1Johns Hopkins University, Gynecology & Obstetrics, Baltimore, Maryland, 2Johns Hopkins University, Oncology Center, Baltimore, Maryland OBJECTIVE: The objective of this study was to ascertain disorders for which in utero hematopoietic stem cell transplantation (IUHSCT) would be feasible based upon recent improvements in postnatal HSCT treatment protocols and disease outcomes. STUDY DESIGN: We reviewed the current literature for human diseases where application of IUHSCT may be feasible. We focused our search to create a list of diseases where low levels of initial engraftment or mixed chimerism can affect a cure. We compiled cost data from human attempts at IUHSCT from our institution and reviewed cost data for non-HSCT disease treatment from the recent literature. RESULTS: Disorders amenable to IUHSCT include the hemoglobinopathies, storage disorders, and granulocyte disorders. Of these, hemoglobinopathies appear to be the best candidates for early human trials. Using ablative preparations before postnatal HSCT, 80-85% of patients with sickle cell anemia and b-thalassemia can live disease free. Approximately 10% of these patients display mixed chimerism and not full engraftment although they remain transfusion independent despite as little as 10% donor chimerism. Mortality and morbidity have been decreased with recent less ablative and non-ablative regimens that have been found to be similarly effective. These results suggest that IUHSCT might be applicable to these diseases at a cost of $10,000. This compares to an average lifetime cost for treatment of $500,000 and $1.5 million for sickle cell anemia and b-thalassemia, respectively. CONCLUSION: Potential candidates for human application of IUHSCT include b-thalassemia, sickle cell anemia, and granulocyte disorders. As advances are made in animal models, IUHSCT may become a feasible and cost-effective treatment strategy for these diseases, and potentially others. Given the impact of these diseases on the general population, research funding should continue for advancement toward human applications.