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Low cardiac output in pregnancy and risk of intrauterine growth restriction
S94 SMFM Abstracts
December 2003 Am J Obstet Gynecol
105
AMNIOTIC FLUID CYTOKINEIN IS ASSOCIATED WITH AMNIOTIC APOPTOSIS AND INJURY IN INTRA-AMNIOTIC INFECTION CHAURDONG HSU1, STEPHANIE HONG1, HASSAN HARIRAH2, 1New York Medical College-Westchester Medical Center, Obstetrics and Gynecology, Valhalla, NY 2University of Texas Medical Branch at Galveston, Galveston, TX OBJECTIVE: Fas-FasL (apoptosis markers) and thrombomodulin (TM) have been previously localized on fetal amnion. We determined whether amniotic fluid cytokine (IL-6) was associated with fetal amniotic apoptosis (FasFasL) and injury (TM) in intra-amniotic infection (IAI). We measured amniotic fluid (AF) IL-6, soluble Fas (sFas), FasL (sFasL), and TM (sTM) in patients with and without IAI. STUDY DESIGN: Sixty-two singleton pregnant women were studied. Twenty-five patients had IAI and 37 were healthy pregnant women. IAI was defined as the presence of a positive AF culture. AF was tested for leukocytes, IL6, sFas, sFasL, and sTM. Student t test and Pearson correlation coefficient were used for statistical analyses. RESULTS: There were no significant differences in maternal age, gestational age, parity, or race between patients with and without IAI. AF IL-6 (56.9 ± 7.8 vs 6.8 ± 1.6 ng/mL, P < 0.0001), sFasL (0.56 ± 0.06 vs 0.24 ± 0.01 ng/mL, P < 0.0001), sFas (6.0 ± 0.7 vs 2.7 ± 0.2 U/mL, P = 0.0002), sTM (77.2 ± 8.0 vs 36.5 ± 6.6 ng/mL, P = 0.0002), and leukocytes (1560 ± 335 vs 69 ± 2 cell/mm3, P < 0.0001) were significantly higher in patients with IAI than those without IAI. AF IL-6, sFas, sFasL, and sTM were positively correlated (IL-6/ sFas: r = 0.6, P = 0.0001, IL-6/sFas: r = 0.6, P < 0.0001, IL-6/sTM: r = 0.5, P = 0.0003, sTM/sFas: 0.4, P = 0.003, TM/sFasL: 0.4, P = 0.003, sFas/sFasL: r = 0.7, P < 0.0001). AF leukocytes were positively correlated with AF IL-6, sFasL, sFas, and sTM. CONCLUSION: Our data suggest that elevated AF cytokine, IL-6, is associated with an increase of amniotic apoptosis and injury occurring in IAI. Although fetal amnion is one of the sources for the elevated amniotic fluid IL-6, sFas, and sTM, amniotic fluid leukocytes may be another source for the observation.
107
EFFECTS OF REPEATED STEROID DOSING PROTOCOLS IN A RAT MODEL OF PREECLAMPSIA CARL ROSE1, WILLIAM BENNETT1, BRAD THIGPEN1, KATHY COCKRELL2, JOHN MORRISON1, JAMES MARTIN, JR1, JOEY GRANGER3, 1University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, MS 2University of Mississippi Medical Center, Physiology, Jackson, MS 3University of Mississippi Medical Center, Physiology and Biophysics, Jackson, MS OBJECTIVE: To determine the effects of high- and low-dose steroids on maternal and fetal parameters in a RUPP (reduced uterine perfusion pressure) model of preeclampsia. STUDY DESIGN: The RUPP model was utilized to experimentally induce preeclampsia in timed-pregnant Sprague-Dawley rats. Laparotomy was performed on day 15 of a 22-day gestation to establish fetal counts, and animals were randomly assigned to either immediate closure or RUPP procedure (calibrated occlusion of infra-renal aorta and ovarian arteries). RUPP and sham groups were then assigned to high-dose dexamethasone (DEX, 400 mg/kg/d), low-dose DEX (80 mg/kg/d), or saline control protocol. Carotid catheters were placed on day 18, and blood pressure, pup and placental weights were determined at time of sacrifice on day 19. Statistical analysis was performed using one-way analysis of variance (ANOVA) with means compared using the Tukey-Kramer multiple comparisons test. RESULTS: Rats undergoing the RUPP procedure demonstrated higher blood pressures and reduced pup survival compared to matched controls. Lowdose DEX significantly reduced blood pressure in the RUPP-treated rats, but neither DEX treatment protocol improved fetal survival or birthweight. Highdose DEX reduced placental weights in both RUPP and control groups and fetal weights in sham surgery rats. CONCLUSION: Low-dose DEX reduced blood pressure without affecting fetal survival or birthweight in a rat model of preeclampsia. High-dose DEX proved detrimental to fetal birthweight and placental mass without significantly affecting fetal outcome. The findings from this study suggest that repeated low doses of DEX may prevent the maternal hypertension associated with reduced uterine perfusion in the pregnant rat, whereas higher dosages appears to exacerbate fetal growth restriction and reduce placental mass.
106
LOW CARDIAC OUTPUT IN PREGNANCY AND RISK OF INTRAUTERINE GROWTH RESTRICTION JEFFREY RIDGEWAY1, DARCY CARR1, THOMAS EASTERLING1, 1University of Washington Medical Center, Seattle, WA OBJECTIVE: To determine the relationship between decreased cardiac output during pregnancy and risk of intrauterine growth restriction (IUGR) at delivery. STUDY DESIGN: A retrospective review of patients at risk for preeclampsia who were seen in an outpatient hypertension consult clinic between 1993 and 2002 was performed. Entry criteria included singleton gestation, delivery of a viable infant, and available information about infant gestational age and weight at delivery. Hemodynamic parameters were measured at each visit using noninvasive testing that has been previously validated in pregnancy. Cardiac output (CO) was categorized as low if measured below the mean for gestational age or high if measured above the mean for gestational age. IUGR was defined as a birth weight less than 10% for gestational age. Rates of low CO were then compared with rates of IUGR using chi-square or Fisher’s exact test as appropriate. RESULTS: 651 pregnancies met inclusion criteria for the study. IUGR was noted in 17% of all pregnancies studied. Low CO at any point in pregnancy was significantly associated with an increased risk of IUGR (P < 0.05). When analyzed at two-week intervals, a significant risk for development of IUGR was noted in patients with a low CO at 16-18 weeks (P < 0.05), 26-28 weeks (P < 0.05), 30-32 weeks (P < 0.05), 32-34 weeks (P < 0.05), and 34-36 weeks (P = 0.05). CONCLUSION: Low cardiac output during pregnancy is significantly associated with an increased risk of IUGR. Careful monitoring and control of cardiac output during critical periods of pregnancy may decrease the risk of IUGR at delivery.
108
ADJUNCTIVE INTRAVENOUS DEXAMETHASONE IN PATIENTS WITH SEVERE PREECLAMPSIA NOT COMPLICATED BY HELLP SYNDROME P. SCOTT BARRILLEAUX1, JAMES MARTIN, JR2, CHAD KLAUSER3, LAURA BUFKIN3, WARREN MAY4, 1University of Mississippi Medical Center, Ob/ Gyn Div. of MFM, Jackson, MS 2University of Mississippi Medical Center, Graduate Medical Education, Jackson, MS 3University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, MS 4University of Mississippi Medical Center, Preventive Medicine, Jackson, MS OBJECTIVE: To determine the benefit of adjunctive intravenous dexamethasone for patients with severe preeclampsia without HELLP syndrome. STUDY DESIGN: A prospective, placebo-controlled randomized trial comparing postpartum intravenous dexamethasone (Group 1 = 86; 10 mg-10 mg-5 mg-5 mg doses q12h) versus saline (Group 2 = 89) with severe preeclampsia. T-tests for continuous variables and chi-square tests for categorical variables were utilized. Repeated-measures ANOVA was used to compare groups for post-delivery parameters. RESULTS: Demographics were similar including a mean gestational age of 33 weeks. group 1 exhibited less headache, visual changes, oliguria, eclampsia (2.3% vs 9.0%) and fewer returns to the recovery room for intensive monitoring and blood pressure control (5.8% vs 10.1%) but lacked statistical significance. similarly, changes in platelet count (p = .008), ldh (p = .077), and AST (.015) laboratory values as reflectors of vessel wall-circulating cell interaction were more normalized at 48 hours post partum in Group 1. However, no statistically significant differences at 48 hours post partum were noted between groups regarding mean arterial pressure changes, antihypertensive needs, and urine output. Length of hospitalization was overall not shortened. CONCLUSION: Statistically significant improvements were observed in several parameters during the first 24 hours in the treatment group but not at 48 hours. There was no evidence that these differences translated clinically into lessened disease severity or duration.
December 2003 Am J Obstet Gynecol
105
AMNIOTIC FLUID CYTOKINEIN IS ASSOCIATED WITH AMNIOTIC APOPTOSIS AND INJURY IN INTRA-AMNIOTIC INFECTION CHAURDONG HSU1, STEPHANIE HONG1, HASSAN HARIRAH2, 1New York Medical College-Westchester Medical Center, Obstetrics and Gynecology, Valhalla, NY 2University of Texas Medical Branch at Galveston, Galveston, TX OBJECTIVE: Fas-FasL (apoptosis markers) and thrombomodulin (TM) have been previously localized on fetal amnion. We determined whether amniotic fluid cytokine (IL-6) was associated with fetal amniotic apoptosis (FasFasL) and injury (TM) in intra-amniotic infection (IAI). We measured amniotic fluid (AF) IL-6, soluble Fas (sFas), FasL (sFasL), and TM (sTM) in patients with and without IAI. STUDY DESIGN: Sixty-two singleton pregnant women were studied. Twenty-five patients had IAI and 37 were healthy pregnant women. IAI was defined as the presence of a positive AF culture. AF was tested for leukocytes, IL6, sFas, sFasL, and sTM. Student t test and Pearson correlation coefficient were used for statistical analyses. RESULTS: There were no significant differences in maternal age, gestational age, parity, or race between patients with and without IAI. AF IL-6 (56.9 ± 7.8 vs 6.8 ± 1.6 ng/mL, P < 0.0001), sFasL (0.56 ± 0.06 vs 0.24 ± 0.01 ng/mL, P < 0.0001), sFas (6.0 ± 0.7 vs 2.7 ± 0.2 U/mL, P = 0.0002), sTM (77.2 ± 8.0 vs 36.5 ± 6.6 ng/mL, P = 0.0002), and leukocytes (1560 ± 335 vs 69 ± 2 cell/mm3, P < 0.0001) were significantly higher in patients with IAI than those without IAI. AF IL-6, sFas, sFasL, and sTM were positively correlated (IL-6/ sFas: r = 0.6, P = 0.0001, IL-6/sFas: r = 0.6, P < 0.0001, IL-6/sTM: r = 0.5, P = 0.0003, sTM/sFas: 0.4, P = 0.003, TM/sFasL: 0.4, P = 0.003, sFas/sFasL: r = 0.7, P < 0.0001). AF leukocytes were positively correlated with AF IL-6, sFasL, sFas, and sTM. CONCLUSION: Our data suggest that elevated AF cytokine, IL-6, is associated with an increase of amniotic apoptosis and injury occurring in IAI. Although fetal amnion is one of the sources for the elevated amniotic fluid IL-6, sFas, and sTM, amniotic fluid leukocytes may be another source for the observation.
107
EFFECTS OF REPEATED STEROID DOSING PROTOCOLS IN A RAT MODEL OF PREECLAMPSIA CARL ROSE1, WILLIAM BENNETT1, BRAD THIGPEN1, KATHY COCKRELL2, JOHN MORRISON1, JAMES MARTIN, JR1, JOEY GRANGER3, 1University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, MS 2University of Mississippi Medical Center, Physiology, Jackson, MS 3University of Mississippi Medical Center, Physiology and Biophysics, Jackson, MS OBJECTIVE: To determine the effects of high- and low-dose steroids on maternal and fetal parameters in a RUPP (reduced uterine perfusion pressure) model of preeclampsia. STUDY DESIGN: The RUPP model was utilized to experimentally induce preeclampsia in timed-pregnant Sprague-Dawley rats. Laparotomy was performed on day 15 of a 22-day gestation to establish fetal counts, and animals were randomly assigned to either immediate closure or RUPP procedure (calibrated occlusion of infra-renal aorta and ovarian arteries). RUPP and sham groups were then assigned to high-dose dexamethasone (DEX, 400 mg/kg/d), low-dose DEX (80 mg/kg/d), or saline control protocol. Carotid catheters were placed on day 18, and blood pressure, pup and placental weights were determined at time of sacrifice on day 19. Statistical analysis was performed using one-way analysis of variance (ANOVA) with means compared using the Tukey-Kramer multiple comparisons test. RESULTS: Rats undergoing the RUPP procedure demonstrated higher blood pressures and reduced pup survival compared to matched controls. Lowdose DEX significantly reduced blood pressure in the RUPP-treated rats, but neither DEX treatment protocol improved fetal survival or birthweight. Highdose DEX reduced placental weights in both RUPP and control groups and fetal weights in sham surgery rats. CONCLUSION: Low-dose DEX reduced blood pressure without affecting fetal survival or birthweight in a rat model of preeclampsia. High-dose DEX proved detrimental to fetal birthweight and placental mass without significantly affecting fetal outcome. The findings from this study suggest that repeated low doses of DEX may prevent the maternal hypertension associated with reduced uterine perfusion in the pregnant rat, whereas higher dosages appears to exacerbate fetal growth restriction and reduce placental mass.
106
LOW CARDIAC OUTPUT IN PREGNANCY AND RISK OF INTRAUTERINE GROWTH RESTRICTION JEFFREY RIDGEWAY1, DARCY CARR1, THOMAS EASTERLING1, 1University of Washington Medical Center, Seattle, WA OBJECTIVE: To determine the relationship between decreased cardiac output during pregnancy and risk of intrauterine growth restriction (IUGR) at delivery. STUDY DESIGN: A retrospective review of patients at risk for preeclampsia who were seen in an outpatient hypertension consult clinic between 1993 and 2002 was performed. Entry criteria included singleton gestation, delivery of a viable infant, and available information about infant gestational age and weight at delivery. Hemodynamic parameters were measured at each visit using noninvasive testing that has been previously validated in pregnancy. Cardiac output (CO) was categorized as low if measured below the mean for gestational age or high if measured above the mean for gestational age. IUGR was defined as a birth weight less than 10% for gestational age. Rates of low CO were then compared with rates of IUGR using chi-square or Fisher’s exact test as appropriate. RESULTS: 651 pregnancies met inclusion criteria for the study. IUGR was noted in 17% of all pregnancies studied. Low CO at any point in pregnancy was significantly associated with an increased risk of IUGR (P < 0.05). When analyzed at two-week intervals, a significant risk for development of IUGR was noted in patients with a low CO at 16-18 weeks (P < 0.05), 26-28 weeks (P < 0.05), 30-32 weeks (P < 0.05), 32-34 weeks (P < 0.05), and 34-36 weeks (P = 0.05). CONCLUSION: Low cardiac output during pregnancy is significantly associated with an increased risk of IUGR. Careful monitoring and control of cardiac output during critical periods of pregnancy may decrease the risk of IUGR at delivery.
108
ADJUNCTIVE INTRAVENOUS DEXAMETHASONE IN PATIENTS WITH SEVERE PREECLAMPSIA NOT COMPLICATED BY HELLP SYNDROME P. SCOTT BARRILLEAUX1, JAMES MARTIN, JR2, CHAD KLAUSER3, LAURA BUFKIN3, WARREN MAY4, 1University of Mississippi Medical Center, Ob/ Gyn Div. of MFM, Jackson, MS 2University of Mississippi Medical Center, Graduate Medical Education, Jackson, MS 3University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, MS 4University of Mississippi Medical Center, Preventive Medicine, Jackson, MS OBJECTIVE: To determine the benefit of adjunctive intravenous dexamethasone for patients with severe preeclampsia without HELLP syndrome. STUDY DESIGN: A prospective, placebo-controlled randomized trial comparing postpartum intravenous dexamethasone (Group 1 = 86; 10 mg-10 mg-5 mg-5 mg doses q12h) versus saline (Group 2 = 89) with severe preeclampsia. T-tests for continuous variables and chi-square tests for categorical variables were utilized. Repeated-measures ANOVA was used to compare groups for post-delivery parameters. RESULTS: Demographics were similar including a mean gestational age of 33 weeks. group 1 exhibited less headache, visual changes, oliguria, eclampsia (2.3% vs 9.0%) and fewer returns to the recovery room for intensive monitoring and blood pressure control (5.8% vs 10.1%) but lacked statistical significance. similarly, changes in platelet count (p = .008), ldh (p = .077), and AST (.015) laboratory values as reflectors of vessel wall-circulating cell interaction were more normalized at 48 hours post partum in Group 1. However, no statistically significant differences at 48 hours post partum were noted between groups regarding mean arterial pressure changes, antihypertensive needs, and urine output. Length of hospitalization was overall not shortened. CONCLUSION: Statistically significant improvements were observed in several parameters during the first 24 hours in the treatment group but not at 48 hours. There was no evidence that these differences translated clinically into lessened disease severity or duration.