- Email: [email protected]
Amniotic fluid nitric oxide is associated with amniotic apoptosis and injury in intra-amniotic infection
SMFM Abstracts S83
Volume 189, Number 6 Am J Obstet Gynecol 65
THE FREQUENCY AND CLINICAL SIGNIFICANCE OF INTRA-AMNIOTIC INFLAMMATION IN PATIENTS WITH PRETERM PREMATURE RUPTURE OF THE MEMBRANES SOON-SUP SHIM1, BO HYUN YOON1, ROBERTO ROMERO1, JOON-SEOK HONG1, GILJA KIM1, YOO-KYUNG SOHN1, JOONG SHIN PARK1, JONG KWAN JUN1, HEE CHUL SYN1, 1Seoul National University, Dept. of Ob/Gyn, Seoul, Korea, South Korea OBJECTIVE: A growing body of evidence indicates that fetuses exposed to intra-amniotic inflammation are at increased risk for adverse outcome, regardless of whether microbial infection can be proven in the amniotic fluid, newborn, or mother. This study was conducted to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of the membranes (PROM). STUDY DESIGN: In 194 patients with preterm PROM, amniotic fluid (AF) was retrieved, cultured for aerobic and anaerobic bacteria and mycoplasmas, and assayed for neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8). MMP-8 was used because previous studies indicated this to be a sensitive and specific index of inflammation and to be correlated with the AF white blood cell count. Intra-amniotic inflammation was defined as an elevated AF MMP-8 concentration (>23 ng/mL). Nonparametric and survival techniques were used for statistical analysis. RESULTS: (1) The overall rate of intra-amniotic inflammation was 46% (89/194), while proven intra-amniotic infection was only detected in 25% (48/ 194). (2) Intra-amniotic inflammation with a negative AF culture for microorganisms was found in 23% (45/194) and was as common as proven intra-amniotic infection. (3) Pregnancy outcome was worse in patients with intra-amniotic inflammation and a negative culture than in those without inflammation. (4) There were no differences in the interval to delivery or rate of complications between patients with intra-amniotic inflammation and a negative culture and those with proven AF infection. CONCLUSION: We conclude that intra-amniotic inflammation, regardless of culture result, is present in nearly half of patients with preterm PROM and that it is a risk factor for impending preterm delivery and adverse outcome. We propose that intra-amniotic inflammation, rather than infection, be used to classify and manage patients with preterm PROM.
67
HEMATOLOGIC INDICES AND FETAL OXYGENATION DETERMINE MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY (MCA-PSV) AHMET BASCHAT1, MICHELLE KUSH1, CHRISTOPHER HARMAN1, CARL WEINER2, 1University of Maryland at Baltimore, Obstetrics, Gynecology and Reproductive Sciences, Baltimore, MD 2University of Maryland at Baltimore, Physiology, Baltimore, MD OBJECTIVE: The claimed efficiency of the MCA-PSV to noninvasively detect fetal anemia is quite variable. We sought to determine which fetal variables are the primary determinants of the MCA-PSV. STUDY DESIGN: 114 fetuses undergoing cordocentesis for clinical indications had a CBC and umbilical venous gas measurements. The MCAPSV was measured by a standardized Doppler examination and related to two reference norms (Mari et al and Kumarnavicius et al). After conversion of gestation-dependent variables to z scores, the relationships between MCA-PSV and the pO2, HB, and O2 content, as well as HCT, WBC and nRBC counts, pH, and base deficit were tested by using correlation and regression analyses. RESULTS: The MCA-PSV correlated with absolute HB and HCT (r = ÿ0.44, P < 0.0001), pO2 (r = ÿ0.27, P < 0.05) and O2 content (r = ÿ0.43, P < 0.0001). Each contributed independently on multiple regression analysis to an elevated MCA-PSV. The resulting equation with just these variables accounted for >60% of subject variation. Deletion of these primary factors from the regression eliminated statistical significance. The 2 norms yielded similar results. CONCLUSION: HB, viscosity (represented by HCT), pO2, and oxygen content each influence the MCA-PSV of the human fetus. A change in any one of these variables could alter the MCA-PSV and diminish the reliability of fetal anemia prediction.
66
AMNIOTIC FLUID NITRIC OXIDE 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, OB/GYN, Galveston, TX OBJECTIVE: Fas-FasL (apoptosis markers) and thrombomodulin (TM) have been previously localized on fetal amnion. We determined whether amniotic fluid nitric oxide (NOx) was associated with fetal amniotic apoptosis (Fas-FasL) and injury (TM) in intra-amniotic infection (IAI). We measured amniotic fluid (AF) total nitric oxide (NOx), 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, NOx, 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 NOx (39.3 ± 2.63 vs 29.6 ± 1.86 mmol/L, P = 0.003), 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 NOx, sFas, sFasL, and sTM were positively correlated (NOx/sFas: r = 0.5, P < 0.0001, NOx/sFas: r = 0.7, P < 0.0001, NOx/sTM: r = 0.5, P = 0.0003, sTM/sFas: r = 0.4, P = 0.003, TM/ sFasL: r = 0.4, P = 0.003, sFas/sFasL: r = 0.7, P < 0.0001). AF leukocytes were also positively correlated with AF NOx, sFasL, sFas, and sTM. CONCLUSION: A significant association between AF NOx and AF sFas, sFasL, and sTM in IAI suggests that NOx may be related to fetal amniotic apoptosis and injury. Although fetal amnion is one of the sources of elevated AF NOx, sFas, sFasL, and sTM, AF leukocytes can be another source for these observations.
68
ANTIRETROVIRAL THERAPY IN PREGNANCY AND RISK OF ADVERSE PREGNANCY OUTCOME AMANDA COTTER1, ADOLFO GONZALEZ GARCIA2, LUNTHITA DUTHELY3, MARY J. O’SULLIVAN4, 1University of Miami, Dept of Ob/Gyn–MFM Division, Miami, FL 2University of Miami, Dept of Ob/Gyn–MFM Division, Miami, FL 3University of Miami, Dept Ob/ Gyn, Miami, FL 4University of Miami, Dept Ob/Gyn–MFM Division, Miami, FL OBJECTIVE: Data on pregnancy complications associated with antiretroviral therapy (ARV) are limited. Some small studies have demonstrated an increased preterm delivery (PTD) rate, but a recent U.S. multisite study did not concur with these findings. Our objective is to investigate if ARV is associated with adverse pregnancy outcome at a single site managed by MFM specialists according to strict protocols. STUDY DESIGN: Using a perinatal database, women who were diagnosed HIV positive prior to or during pregnancy with care at our immunology prenatal clinic and who delivered at JMH between 1990 and 2002, were identified. Statistical analyses were performed by using SPSS. RESULTS: The cohort comprised 968 women who received ARV during pregnancy (monotherapy in 468, combination without protease inhibitors [PI] in 356, combination with PI in 130) and 326 women who did not receive ARV. After controlling for CD4 count, stage of disease, smoking, alcohol, and illicit drugs, only combination therapy with a PI had an almost twofold increased risk of PTD compared to any other combination or no therapy (P = 0.01). The only other significant predictors of PTD were a previous history of PTD (P = 0.0001) and ARV for less than 10 weeks (P = 0.0001). There was no difference in rates of low birthweight and stillbirth regardless of therapy. CONCLUSION: As compared with no ARV, monotherapy or combination therapy, only combination therapy with a PI is associated with an increased risk of PTD. Our data indicate that protease inhibitors may play a role in PTD without increasing the risk of low birthweight or stillbirth.
Volume 189, Number 6 Am J Obstet Gynecol 65
THE FREQUENCY AND CLINICAL SIGNIFICANCE OF INTRA-AMNIOTIC INFLAMMATION IN PATIENTS WITH PRETERM PREMATURE RUPTURE OF THE MEMBRANES SOON-SUP SHIM1, BO HYUN YOON1, ROBERTO ROMERO1, JOON-SEOK HONG1, GILJA KIM1, YOO-KYUNG SOHN1, JOONG SHIN PARK1, JONG KWAN JUN1, HEE CHUL SYN1, 1Seoul National University, Dept. of Ob/Gyn, Seoul, Korea, South Korea OBJECTIVE: A growing body of evidence indicates that fetuses exposed to intra-amniotic inflammation are at increased risk for adverse outcome, regardless of whether microbial infection can be proven in the amniotic fluid, newborn, or mother. This study was conducted to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of the membranes (PROM). STUDY DESIGN: In 194 patients with preterm PROM, amniotic fluid (AF) was retrieved, cultured for aerobic and anaerobic bacteria and mycoplasmas, and assayed for neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8). MMP-8 was used because previous studies indicated this to be a sensitive and specific index of inflammation and to be correlated with the AF white blood cell count. Intra-amniotic inflammation was defined as an elevated AF MMP-8 concentration (>23 ng/mL). Nonparametric and survival techniques were used for statistical analysis. RESULTS: (1) The overall rate of intra-amniotic inflammation was 46% (89/194), while proven intra-amniotic infection was only detected in 25% (48/ 194). (2) Intra-amniotic inflammation with a negative AF culture for microorganisms was found in 23% (45/194) and was as common as proven intra-amniotic infection. (3) Pregnancy outcome was worse in patients with intra-amniotic inflammation and a negative culture than in those without inflammation. (4) There were no differences in the interval to delivery or rate of complications between patients with intra-amniotic inflammation and a negative culture and those with proven AF infection. CONCLUSION: We conclude that intra-amniotic inflammation, regardless of culture result, is present in nearly half of patients with preterm PROM and that it is a risk factor for impending preterm delivery and adverse outcome. We propose that intra-amniotic inflammation, rather than infection, be used to classify and manage patients with preterm PROM.
67
HEMATOLOGIC INDICES AND FETAL OXYGENATION DETERMINE MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY (MCA-PSV) AHMET BASCHAT1, MICHELLE KUSH1, CHRISTOPHER HARMAN1, CARL WEINER2, 1University of Maryland at Baltimore, Obstetrics, Gynecology and Reproductive Sciences, Baltimore, MD 2University of Maryland at Baltimore, Physiology, Baltimore, MD OBJECTIVE: The claimed efficiency of the MCA-PSV to noninvasively detect fetal anemia is quite variable. We sought to determine which fetal variables are the primary determinants of the MCA-PSV. STUDY DESIGN: 114 fetuses undergoing cordocentesis for clinical indications had a CBC and umbilical venous gas measurements. The MCAPSV was measured by a standardized Doppler examination and related to two reference norms (Mari et al and Kumarnavicius et al). After conversion of gestation-dependent variables to z scores, the relationships between MCA-PSV and the pO2, HB, and O2 content, as well as HCT, WBC and nRBC counts, pH, and base deficit were tested by using correlation and regression analyses. RESULTS: The MCA-PSV correlated with absolute HB and HCT (r = ÿ0.44, P < 0.0001), pO2 (r = ÿ0.27, P < 0.05) and O2 content (r = ÿ0.43, P < 0.0001). Each contributed independently on multiple regression analysis to an elevated MCA-PSV. The resulting equation with just these variables accounted for >60% of subject variation. Deletion of these primary factors from the regression eliminated statistical significance. The 2 norms yielded similar results. CONCLUSION: HB, viscosity (represented by HCT), pO2, and oxygen content each influence the MCA-PSV of the human fetus. A change in any one of these variables could alter the MCA-PSV and diminish the reliability of fetal anemia prediction.
66
AMNIOTIC FLUID NITRIC OXIDE 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, OB/GYN, Galveston, TX OBJECTIVE: Fas-FasL (apoptosis markers) and thrombomodulin (TM) have been previously localized on fetal amnion. We determined whether amniotic fluid nitric oxide (NOx) was associated with fetal amniotic apoptosis (Fas-FasL) and injury (TM) in intra-amniotic infection (IAI). We measured amniotic fluid (AF) total nitric oxide (NOx), 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, NOx, 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 NOx (39.3 ± 2.63 vs 29.6 ± 1.86 mmol/L, P = 0.003), 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 NOx, sFas, sFasL, and sTM were positively correlated (NOx/sFas: r = 0.5, P < 0.0001, NOx/sFas: r = 0.7, P < 0.0001, NOx/sTM: r = 0.5, P = 0.0003, sTM/sFas: r = 0.4, P = 0.003, TM/ sFasL: r = 0.4, P = 0.003, sFas/sFasL: r = 0.7, P < 0.0001). AF leukocytes were also positively correlated with AF NOx, sFasL, sFas, and sTM. CONCLUSION: A significant association between AF NOx and AF sFas, sFasL, and sTM in IAI suggests that NOx may be related to fetal amniotic apoptosis and injury. Although fetal amnion is one of the sources of elevated AF NOx, sFas, sFasL, and sTM, AF leukocytes can be another source for these observations.
68
ANTIRETROVIRAL THERAPY IN PREGNANCY AND RISK OF ADVERSE PREGNANCY OUTCOME AMANDA COTTER1, ADOLFO GONZALEZ GARCIA2, LUNTHITA DUTHELY3, MARY J. O’SULLIVAN4, 1University of Miami, Dept of Ob/Gyn–MFM Division, Miami, FL 2University of Miami, Dept of Ob/Gyn–MFM Division, Miami, FL 3University of Miami, Dept Ob/ Gyn, Miami, FL 4University of Miami, Dept Ob/Gyn–MFM Division, Miami, FL OBJECTIVE: Data on pregnancy complications associated with antiretroviral therapy (ARV) are limited. Some small studies have demonstrated an increased preterm delivery (PTD) rate, but a recent U.S. multisite study did not concur with these findings. Our objective is to investigate if ARV is associated with adverse pregnancy outcome at a single site managed by MFM specialists according to strict protocols. STUDY DESIGN: Using a perinatal database, women who were diagnosed HIV positive prior to or during pregnancy with care at our immunology prenatal clinic and who delivered at JMH between 1990 and 2002, were identified. Statistical analyses were performed by using SPSS. RESULTS: The cohort comprised 968 women who received ARV during pregnancy (monotherapy in 468, combination without protease inhibitors [PI] in 356, combination with PI in 130) and 326 women who did not receive ARV. After controlling for CD4 count, stage of disease, smoking, alcohol, and illicit drugs, only combination therapy with a PI had an almost twofold increased risk of PTD compared to any other combination or no therapy (P = 0.01). The only other significant predictors of PTD were a previous history of PTD (P = 0.0001) and ARV for less than 10 weeks (P = 0.0001). There was no difference in rates of low birthweight and stillbirth regardless of therapy. CONCLUSION: As compared with no ARV, monotherapy or combination therapy, only combination therapy with a PI is associated with an increased risk of PTD. Our data indicate that protease inhibitors may play a role in PTD without increasing the risk of low birthweight or stillbirth.