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Placental adenoviral-mediated gene transfer: gene therapy model for intrauterine growth restriction
Maternal and Fetal Outcomes in Women Requiring Antepartum Mechanical Ventilation Michael B. Schneider, MD University of Tennessee Health Sciences Center, Memphis, TN
Thomas S. Ivester, MD, William C. Mabie, MD, Jeffery C. Livingston, MD, Risa Ramsey, RN, and Kelly A. Bennett, MD OBJECTIVE: To study maternal and fetal outcomes in women requiring antepartum mechanical ventilation. STUDY DESIGN: A retrospective cohort study using data from the perinatal database at the University of Tennessee, Memphis from January 1, 1992 to December 31, 2001. The cohort included all pregnant women admitted to the intensive care unit who received mechanical ventilation. Categoric data were analyzed with a 2 or Fisher test, and continuous data by the Student t test. RESULTS: During the study period, 45,306 deliveries were identified. 53 patients delivered while receiving ventilator support. Of these, 25 delivered within 48 hours (47.1%), with 41 delivering preterm (77.4%). The most common indication for delivery was nonreassuring fetal heart rate: 31 in the cesarean and two in the vaginal group (P ⬍ .001). There were nine (17.0%) maternal deaths: seven in the cesarean group and two in the vaginal group (P ⫽ .70). Maternal mortality rates did not differ between delivery within 48 hours or delayed delivery after 48 hours (P ⫽ .47; odds ratio 0.50; 95% confidence interval 0.11, 2.2). There were 17 neonatal deaths (32.1%): ten in the cesarean group and seven in the vaginal group (P ⫽ .31). CONCLUSIONS: Antepartum mechanical ventilation is associated with high rates of maternal and neonatal mortality, but these were not significantly affected by timing or route of delivery.
DESIGN: A descriptive study of pregnant women with a history of stroke. Charts were reviewed from 1990 to 2002. The inclusion criterion was a history of nonobstetric stroke or stroke documented during pregnancy or postpartum. The data were analyzed for the antenatal management strategies and recurrence risk. RESULTS: There were 23 study patients with a total of 35 subsequent pregnancies analyzed. Associated risk factors of the stroke were multiple: thrombophilia (five), sickle cell disease (three), heart malformations (three), hypertension (three), oral contraceptive use (two), A-V malformations (two), head trauma (one), meningitis (one), endocarditis (one), and idiopathic (two). Eleven pregnancies (five with thrombophilia) received prophylactic anticoagulation. Two of the pregnancies in women with pregnancy-related strokes were anticoagulated (one heparin, one heparin plus aspirin). Nine of the pregnancies in women with stroke before pregnancy were anticoagulated (five heparin, three aspirin, one heparin plus aspirin). Twenty-four pregnancies did not receive prophylactic anticoagulation. Overall, there were 19 term deliveries, seven preterm, five miscarriages, one IUFD, and three SGA infants. Three are currently pregnant. There were no recurrent thrombotic episodes during pregnancy or postpartum. Maternal complications included admission to the ICU (one). CONCLUSIONS: In a large case series, women with a history of stroke were found to have a low risk of recurrent stroke (0%) or other pregnancy complications. This information is useful for the prepregnancy counseling of such individuals. The need for prophylactic anticoagulation cannot be answered by this study.
Placental Adenoviral-Mediated Gene Transfer: Gene Therapy Model for Intrauterine Growth Restriction Anna B. Katz The Children’s Hospital of Philadelphia, Philadelphia, PA
Maternal and Perinatal Outcome in Women With a History of Stroke
Sundeep G. Keswani, MD, Philip W. Zoltick, MD, Mark P. Johnson, MD, and Timothy M. Crombleholme, MD
Andrea C. Hinton, MD, Julie Moldenhauer, MD, A. Hammoud, MD, John Barton, MD, and Baha M. Sibai, MD
OBJECTIVE: Gene therapy is a novel approach to treat IUGR by inducing placental growth as a means to enhance fetal development. We hypothesize that adenoviral-mediated overexpression of growth factor transgenes may enhance placental growth. To evaluate the feasibility of intraplacental gene transfer we used a naturally occurring rabbit model of IUGR. To assess the efficiency and toxicity of placental injection we used a serotype-5 replication-incompetent adenoviral vector with a -galactosidase reporter gene.
OBJECTIVE: To determine recurrence risk and pregnancy outcome in women with a history of stroke.
METHODS: Intraplacental injections of 1 ⫻ 108 (n ⫽ 6) or 1 ⫻ 109 (n ⫽ 12) plaque-forming units (PFUs) of Ad-LacZ were
Kristin H. Coppage, MD University of Cincinnati, Cincinnati, OH
VOL. 101, NO. 4 (SUPPLEMENT), APRIL 2003
TUESDAY POSTERS
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performed in NZ-White rabbits at the first and third uterine horn positions at E21. Injected and adjacent noninjected (negative control) fetuses and placentas were harvested at the 48 – 60-hour time point for peak transgene expression. Efficiency of gene transfer was evaluated histologically by X-gal staining and toxicity by fetal and maternal survival. RESULTS: Survival was 100% in both dams and fetuses. There were no histological changes in injected placentas. -gal expression was observed in zero of six placentas treated with 1 ⫻ 108 PFUs, but was observed in 11 of 12 (92%) placentas treated with 1 ⫻ 109 PFUs. Transgene expression was localized to injection site with a mean X-gal–positive cross-sectional area of 8.6% ⫾ 9.7% (range 1–29%). CONCLUSION: Intraplacental adenoviral-mediated gene transfer is well tolerated, resulting in highly efficient, localized placental transgene expression. A threshold dose of 1 ⫻ 109 PFUs is required for efficient gene transfer. Adenoviral-mediated placental gene transfer is a feasible strategy to evaluate proof of concept for gene transfer to alter placental growth as a potential therapy for IUGR.
greatest stressors. Stress was relieved in all women by ultrasounds, family members staying in the room, cable television, and Internet access. Routine beauty maintenance, massage, physical therapy, and continued contact with referring physicians were also cited as stress alleviators. CONCLUSIONS: After maternal-fetal transfer, prolonged antepartum hospitalization is associated with stress that may be alleviatd by access to the outside world via television and the Internet, liberal visitation, access to health and beauty maintenance, and ongoing contact with the referring physician.
Method of Delivery Affects Neonatal Mortality in Very LowBirth-Weight Singleton Infants Alex Befeler, MD St. Louis University School of Medicine, St. Louis, MO
Maternal Stressors During Prolonged Antepartum Hospitalization Nora M. Doyle, MD, MPH University of Texas Health Science Center at Houston, Houston, TX
Manju Monga, MD, Lisa Hollier, MD, MPH, and Marcia Kerr, RN OBJECTIVE: To identify stressors for women requiring prolonged antepartum hospitalization after maternal-fetal transfer to a tertiary care center. STUDY DESIGN: Using a modified version of the previously validated Antepartum Hospital Stressors Inventory(AHSI), all women transferred to our university-based maternal-fetal service between May 2000 and June 2002 and hospitalized for more than 1 month completed a semistructured interview. The AHSI uses Likert scales to evaluate environment, health factors, communication with health care providers, family separation, self-image, and emotional and family status issues as stressors. RESULTS: Nine consecutive women met inclusion criteria and all agreed to participate. Median maternal age was 27 (19 –33), and gestational age at transfer was 25 weeks (20 –31). Parity ranged from 0 to 3 and educational level ranged from grade 2 to graduate degrees. The women were from white, Hispanic, and Asian racial-ethnic backgrounds; all were married. Median distance from transferring hospital was 20 miles(10 –275 miles). All patients reported separation from family, sleeping alone, anxiety about the pregnancy and the infant’s health, boredom, and eating hospital meals as the
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Brenda Grossman, MD, Jaye M. Shyken, MD, and Terry L. Leet, PhD OBJECTIVE: The impact of method of delivery on the survival of very low birth weight (VLBW) infants is unclear. This study compared neonatal mortality rates of VLBW infants by delivery route. METHODS: A population-based cohort study was conducted using data from linked birth-death certificates and birth defect files for all VLBW Missouri-born infants during 1993–1999. The study population included all resident singleton infants weighing 500 –1499 g without lethal congenital anomalies (N ⫽ 4643). Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to measure the strength of association for method of delivery and neonatal mortality for infants weighing 500 –749, 750 –999, 1000 –1249, or 1250 –1499 g. RESULTS: VLBW infants born by cesarean delivery were less likely to die (215 of 2389) than those delivered vaginally (444 of 2254) during the neonatal period (OR 0.46; CI 0.39, 0.53). Cesarean delivery for breech presentation greatly reduced the mortality risk for VLBW infants weighing 500 – 749 g (0.23; 0.08, 0.64) and 750 –999 g (0.28; 0.07, 1.16). The protective effect was less for nonbreech infants weighing 500 – 749 g (0.41; 0.28, 0.59) and 750 –999 g (0.64; 0.40, 1.0). Further adjustment by estimated gestational age less than 24 weeks or 24 weeks or more reduced the protective effect for 500 –999-g infants. There was no difference in mortality risk by method of delivery for VLBW infants weighing 1000 –1499 g. CONCLUSION: Cesarean delivery reduces the risk of neonatal mortality for infants weighing 500 –999 g at birth, but this effect is modified by breech presentation and gestational age.
OBSTETRICS & GYNECOLOGY
Thomas S. Ivester, MD, William C. Mabie, MD, Jeffery C. Livingston, MD, Risa Ramsey, RN, and Kelly A. Bennett, MD OBJECTIVE: To study maternal and fetal outcomes in women requiring antepartum mechanical ventilation. STUDY DESIGN: A retrospective cohort study using data from the perinatal database at the University of Tennessee, Memphis from January 1, 1992 to December 31, 2001. The cohort included all pregnant women admitted to the intensive care unit who received mechanical ventilation. Categoric data were analyzed with a 2 or Fisher test, and continuous data by the Student t test. RESULTS: During the study period, 45,306 deliveries were identified. 53 patients delivered while receiving ventilator support. Of these, 25 delivered within 48 hours (47.1%), with 41 delivering preterm (77.4%). The most common indication for delivery was nonreassuring fetal heart rate: 31 in the cesarean and two in the vaginal group (P ⬍ .001). There were nine (17.0%) maternal deaths: seven in the cesarean group and two in the vaginal group (P ⫽ .70). Maternal mortality rates did not differ between delivery within 48 hours or delayed delivery after 48 hours (P ⫽ .47; odds ratio 0.50; 95% confidence interval 0.11, 2.2). There were 17 neonatal deaths (32.1%): ten in the cesarean group and seven in the vaginal group (P ⫽ .31). CONCLUSIONS: Antepartum mechanical ventilation is associated with high rates of maternal and neonatal mortality, but these were not significantly affected by timing or route of delivery.
DESIGN: A descriptive study of pregnant women with a history of stroke. Charts were reviewed from 1990 to 2002. The inclusion criterion was a history of nonobstetric stroke or stroke documented during pregnancy or postpartum. The data were analyzed for the antenatal management strategies and recurrence risk. RESULTS: There were 23 study patients with a total of 35 subsequent pregnancies analyzed. Associated risk factors of the stroke were multiple: thrombophilia (five), sickle cell disease (three), heart malformations (three), hypertension (three), oral contraceptive use (two), A-V malformations (two), head trauma (one), meningitis (one), endocarditis (one), and idiopathic (two). Eleven pregnancies (five with thrombophilia) received prophylactic anticoagulation. Two of the pregnancies in women with pregnancy-related strokes were anticoagulated (one heparin, one heparin plus aspirin). Nine of the pregnancies in women with stroke before pregnancy were anticoagulated (five heparin, three aspirin, one heparin plus aspirin). Twenty-four pregnancies did not receive prophylactic anticoagulation. Overall, there were 19 term deliveries, seven preterm, five miscarriages, one IUFD, and three SGA infants. Three are currently pregnant. There were no recurrent thrombotic episodes during pregnancy or postpartum. Maternal complications included admission to the ICU (one). CONCLUSIONS: In a large case series, women with a history of stroke were found to have a low risk of recurrent stroke (0%) or other pregnancy complications. This information is useful for the prepregnancy counseling of such individuals. The need for prophylactic anticoagulation cannot be answered by this study.
Placental Adenoviral-Mediated Gene Transfer: Gene Therapy Model for Intrauterine Growth Restriction Anna B. Katz The Children’s Hospital of Philadelphia, Philadelphia, PA
Maternal and Perinatal Outcome in Women With a History of Stroke
Sundeep G. Keswani, MD, Philip W. Zoltick, MD, Mark P. Johnson, MD, and Timothy M. Crombleholme, MD
Andrea C. Hinton, MD, Julie Moldenhauer, MD, A. Hammoud, MD, John Barton, MD, and Baha M. Sibai, MD
OBJECTIVE: Gene therapy is a novel approach to treat IUGR by inducing placental growth as a means to enhance fetal development. We hypothesize that adenoviral-mediated overexpression of growth factor transgenes may enhance placental growth. To evaluate the feasibility of intraplacental gene transfer we used a naturally occurring rabbit model of IUGR. To assess the efficiency and toxicity of placental injection we used a serotype-5 replication-incompetent adenoviral vector with a -galactosidase reporter gene.
OBJECTIVE: To determine recurrence risk and pregnancy outcome in women with a history of stroke.
METHODS: Intraplacental injections of 1 ⫻ 108 (n ⫽ 6) or 1 ⫻ 109 (n ⫽ 12) plaque-forming units (PFUs) of Ad-LacZ were
Kristin H. Coppage, MD University of Cincinnati, Cincinnati, OH
VOL. 101, NO. 4 (SUPPLEMENT), APRIL 2003
TUESDAY POSTERS
69S
performed in NZ-White rabbits at the first and third uterine horn positions at E21. Injected and adjacent noninjected (negative control) fetuses and placentas were harvested at the 48 – 60-hour time point for peak transgene expression. Efficiency of gene transfer was evaluated histologically by X-gal staining and toxicity by fetal and maternal survival. RESULTS: Survival was 100% in both dams and fetuses. There were no histological changes in injected placentas. -gal expression was observed in zero of six placentas treated with 1 ⫻ 108 PFUs, but was observed in 11 of 12 (92%) placentas treated with 1 ⫻ 109 PFUs. Transgene expression was localized to injection site with a mean X-gal–positive cross-sectional area of 8.6% ⫾ 9.7% (range 1–29%). CONCLUSION: Intraplacental adenoviral-mediated gene transfer is well tolerated, resulting in highly efficient, localized placental transgene expression. A threshold dose of 1 ⫻ 109 PFUs is required for efficient gene transfer. Adenoviral-mediated placental gene transfer is a feasible strategy to evaluate proof of concept for gene transfer to alter placental growth as a potential therapy for IUGR.
greatest stressors. Stress was relieved in all women by ultrasounds, family members staying in the room, cable television, and Internet access. Routine beauty maintenance, massage, physical therapy, and continued contact with referring physicians were also cited as stress alleviators. CONCLUSIONS: After maternal-fetal transfer, prolonged antepartum hospitalization is associated with stress that may be alleviatd by access to the outside world via television and the Internet, liberal visitation, access to health and beauty maintenance, and ongoing contact with the referring physician.
Method of Delivery Affects Neonatal Mortality in Very LowBirth-Weight Singleton Infants Alex Befeler, MD St. Louis University School of Medicine, St. Louis, MO
Maternal Stressors During Prolonged Antepartum Hospitalization Nora M. Doyle, MD, MPH University of Texas Health Science Center at Houston, Houston, TX
Manju Monga, MD, Lisa Hollier, MD, MPH, and Marcia Kerr, RN OBJECTIVE: To identify stressors for women requiring prolonged antepartum hospitalization after maternal-fetal transfer to a tertiary care center. STUDY DESIGN: Using a modified version of the previously validated Antepartum Hospital Stressors Inventory(AHSI), all women transferred to our university-based maternal-fetal service between May 2000 and June 2002 and hospitalized for more than 1 month completed a semistructured interview. The AHSI uses Likert scales to evaluate environment, health factors, communication with health care providers, family separation, self-image, and emotional and family status issues as stressors. RESULTS: Nine consecutive women met inclusion criteria and all agreed to participate. Median maternal age was 27 (19 –33), and gestational age at transfer was 25 weeks (20 –31). Parity ranged from 0 to 3 and educational level ranged from grade 2 to graduate degrees. The women were from white, Hispanic, and Asian racial-ethnic backgrounds; all were married. Median distance from transferring hospital was 20 miles(10 –275 miles). All patients reported separation from family, sleeping alone, anxiety about the pregnancy and the infant’s health, boredom, and eating hospital meals as the
70S
TUESDAY POSTERS
Brenda Grossman, MD, Jaye M. Shyken, MD, and Terry L. Leet, PhD OBJECTIVE: The impact of method of delivery on the survival of very low birth weight (VLBW) infants is unclear. This study compared neonatal mortality rates of VLBW infants by delivery route. METHODS: A population-based cohort study was conducted using data from linked birth-death certificates and birth defect files for all VLBW Missouri-born infants during 1993–1999. The study population included all resident singleton infants weighing 500 –1499 g without lethal congenital anomalies (N ⫽ 4643). Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to measure the strength of association for method of delivery and neonatal mortality for infants weighing 500 –749, 750 –999, 1000 –1249, or 1250 –1499 g. RESULTS: VLBW infants born by cesarean delivery were less likely to die (215 of 2389) than those delivered vaginally (444 of 2254) during the neonatal period (OR 0.46; CI 0.39, 0.53). Cesarean delivery for breech presentation greatly reduced the mortality risk for VLBW infants weighing 500 – 749 g (0.23; 0.08, 0.64) and 750 –999 g (0.28; 0.07, 1.16). The protective effect was less for nonbreech infants weighing 500 – 749 g (0.41; 0.28, 0.59) and 750 –999 g (0.64; 0.40, 1.0). Further adjustment by estimated gestational age less than 24 weeks or 24 weeks or more reduced the protective effect for 500 –999-g infants. There was no difference in mortality risk by method of delivery for VLBW infants weighing 1000 –1499 g. CONCLUSION: Cesarean delivery reduces the risk of neonatal mortality for infants weighing 500 –999 g at birth, but this effect is modified by breech presentation and gestational age.
OBSTETRICS & GYNECOLOGY