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Placenta growth factor (PIGF) levels in women with preeclampsia and intrauterine growth restriction: is PIGF a marker for fetal well-being?
S166 SMFM Abstracts
December 2003 Am J Obstet Gynecol
384
TOCOLYSIS DUE TO THE COX-2 INHIBITOR, MELOXICAM, IS NOT ASSOCIATED WITH REDUCED EXPRESSION OF COX-2 AND COX-1 PROTEIN IN FETAL KIDNEY, LUNG, SMALL INTESTINE, ADRENAL GLAND, HEART, LIVER, AND BRAIN OF SHEEP IN PRETERM LABOR VALERIJA RAC1, STEPHEN LYE2, 1Mount Sinai Hospital Toronto, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada 2Mount Sinai Hospital Toronto, Ob/Gyn, Toronto, Ontario, Canada OBJECTIVE: Preterm birth occurs in 5%-10 % of all pregnancies and is associated with considerable neonatal mortality and morbidity. Labor in sheep is caused by increased production of prostaglandins in uterine and placental tissues by inducible COX-2 isoform. Our previous studies have shown that tocolysis with the specific COX-2 inhibitor meloxicam (MEL) blocks COX-2 protein expression in intrauterine tissues while leaving placental COX-2 expression unchanged. Recent studies have shown that the COX-2 isoform is constitutively expressed in many fetal tissues and some fetal side effects of indomethacin are caused by the inhibition of COX protein expression. We wanted to determine whether meloxicam administration induced changes in COX protein expression in different fetal tissues. STUDY DESIGN: On day 127 of gestation, preterm labor was induced in chronically catheterized sheep by maternal administration of RU486. Animals were randomized to receive maternal infusions of saline (n = 12) or MEL (n = 12). Infusion of saline/drug continued until delivery or for 48 hours when the animals were euthanized and tissue samples were collected. Western blot analysis was used to compare COX-1 and COX-2 protein levels in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain. RESULTS: (a) MEL administration was not associated with any change in COX-2 protein expression in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain in saline- and MEL-treated sheep. (b) COX-1 protein expression in these fetal tissues was not significantly different in MEL-treated animals compared to saline-treated animals. CONCLUSION: These studies indicate that meloxicam, at the dose used, did not block COX-1 and COX-2 protein expression in fetal tissues and this might contribute to the absence of fetal complications associated with tocolysis using meloxicam.
386
THE OPTIMAL DOSING STRATEGY FOR CORTICOSTEROIDS TO PREVENT RDS: A DECISION ANALYSIS KIM BOGGESS1, JENNIFER BAILIT2, BRIAN MERCER2, MENDEL SINGER3, VALERIE PARISI1, 1University of North Carolina at Chapel Hill, Obstetrics/Gynecology, Chapel Hill, NC 2Case Western Reserve University, Reproductive Biology, Cleveland, OH 3 Case Western Reserve University, Epidemiology and Biostatistics, Cleveland, OH OBJECTIVE: Antenatal steroids (ACS) before preterm birth (PTB) are highly effective in reducing infant morbidity and mortality. As weekly steroids are not recommended, the optimal timing of ACS continues to be studied. Our purpose was to evaluate alternative strategies of ACS administration. STUDY DESIGN: We performed a decision analysis to test 3 strategies: ACS for every pregnant woman (ALL), ACS for women at clinical risk for PTB (RSK), and ACS for symptomatic women (SX). For this analysis, we chose respiratory distress syndrome (RDS) as the primary outcome. Included in the model were: risk of PTB at each week ± risk factors, risk of RDS ± ACS, probability of symptoms and of PTB before ACS if symptomatic, and duration of ACS effect. Baseline estimates and ranges for key variables were obtained by MEDLINE search. A Monte Carlo simulation was performed using 10,000 pregnancies. Sensitivity analysis was performed for frequency of risk factors (2%-100%), risk of PTB if symptomatic (50%-75%), probability of PTB before ACS (5%-40%). The model was tested varying gestational age (24-30) at ACS administration (ALL & RSK) RESULTS: The ALL performed best (1.1%, 1.7%, 1.9% RDS for ALL, RSK, SX). As the percent of women with risk factors increased, the effectiveness of all strategies decreased. However, the RSK strategy was relatively more effective and the SX strategy was less effective as the percent of women with a risk factor for PTB increased (3.5%, 3.5%, 5.9% RDS for ALL, RSK, SX) in a high-risk population. Further assessing routine ACS in high-risk women, we found increased RDS with ACS with advancing gestational age at administration (3.5%, 3.8%, 4.4%, 4.9% at 24, 26, 28, 30 weeks.) CONCLUSION: Routine single-course ACS is more effective in preventing RDS than ACS for symptoms only. The optimal time for ACS in high-risk women is 24 weeks. We recommend confirmation of this decision analysis by a randomized clinical trial.
385
COMPARING NEONATAL OUTCOMES USING DIFFERENT BETAMETHASONE DOSING REGIMENS DAVID HAAS1, WILLIAM MCCULLOUGH2, CARA OLSEN3, DANIEL SHIAU2, JOHN RICHARD4, EMORY FRY2, MICHAEL MCNAMARA4, 1Naval Hospital Camp Lejeune, NC, OB/GYN, Jacksonville, NC 2Naval Medical Center, San Diego, Pediatrics, San Diego, CA 3 USUHS, Biostatistics, Bethesda, MD 4Naval Medical Center, San Diego, OBGYN, San Diego, CA OBJECTIVE: Antenatal corticosteroids are used to improve neonatal outcomes when preterm delivery is expected. The current standard regimen for betamethasone is two 12-milligram injections, 24 hours apart. We sought to determine if there is a difference in neonatal outcomes when dosing betamethasone every 12 hours or every 24 hours for anticipated preterm delivery. STUDY DESIGN: A retrospective review of all birth records of infants delivered at less than 36 weeks gestation from January 1, 1996, to July 1, 2000. Maternal and neonatal charts were reviewed. The deliveries were separated into three groups: those not receiving antenatal corticosteroids, those who received betamethasone 12 hours apart, and those who received the standard 24-hour dosing. Demographic, obstetric, and neonatal variables were compared between the groups. RESULTS: There were 909 deliveries analyzed. When comparing the two betamethasone groups, a statistically significant difference was only found for antibiotic and surfactant use. For all other variables and outcomes, including neonatal death, chronic lung disease, respiratory distress syndrome, intraventricular hemorrhage, intubation, and hospital days, there was no difference. Both betamethasone groups had better outcomes than the group not receiving steroids for most variables except for no difference found in neonatal death, necrotizing enterocolitis, or 1-minute Apgar score. The outcomes are also compared by gestational age ranges. CONCLUSION: Outcomes using a 12-hour dosing schedule of betamethasone seem to be similar to the standard 24-hour regimen and should be considered as an alternative way to deliver antenatal corticosteroids.
387
PLACENTA GROWTH FACTOR (PIGF) LEVELS IN WOMEN WITH PREECLAMPSIA AND INTRAUTERINE GROWTH RESTRICTION: IS PIGF A MARKER FOR FETAL WELL-BEING? DIETMAR SCHLEMBACH1, RUTH SENGENBERGER2, WENZEL WALLNER2, BRITTA MEURER2, MATTHIAS W. BECKMANN2, ROBERT E. GARFIELD1, 1University of Texas Medical Branch, Department of Obstetrics & Gynecology, Galveston, TX 2Friedrich Alexander University of Erlangen-Nuremberg, Department of Obstetrics & Gynecology, Erlangen, Germany OBJECTIVE: PlGF is a potent angiogenic factor of the VEGF family that is produced exclusively by the placenta. In normal pregnancy (NP) maternal PlGF levels increase with gestation, and in preeclampsia (PE) and intrauterine growth restriction (IUGR) a decrease of PlGF occurs. Whether PlGF can predict pregnancy complications is still in discussion. Purpose of this study was to examine if PlGF levels in women with PE and IUGR at the time of the disease are correlated with clinical features such as placental (PW) and fetal weight (FBW) and Doppler ultrasound parameters. STUDY DESIGN: Serum PlGF levels were measured in 16 women with PE, 15 women with IUGR, and 16 women with NP by ELISA. All women were delivered by cesarean section to avoid a possible hypoxic effect of labor. RESULTS: PlGF were significantly lower in PE (62.92 ± 31.40 pg/mL; P = .001) and IUGR (48.44 ± 41.63 pg/mL; P < .001) compared to NP (245.74 ± 217.42 pg/mL). This significance was also detectable when comparing women at similar gestational age. No difference could be found between PE and IUGR. PlGF was significantly correlated with PW in PE (r = .684, P = .004) and IUGR (r = .547, P = .035), as well as FBW (PE: r = .810, P < .001; IUGR: r = .724, P = .002). Additionally, a significant negative correlation between maternal PlGF levels and pulsatility index in umbilical artery could be found (PE: r = .738, P = .002; IUGR: r = .607, P = .016). PlGF levels were significantly correlated with uterine artery PI only in PE (r = .765, P = .002). CONCLUSION: PlGF is a highly specific marker for estimating the presence and the severity of PE and IUGR. Estimates of levels of PIGF in pregnant women might be used to predict and treat women with these conditions. Furthermore, maternal PlGF could be useful to predict fetal well-being and therefore for planning the management of these pregnancies. (Supported by W. Sander Stiftung, Munich.)
December 2003 Am J Obstet Gynecol
384
TOCOLYSIS DUE TO THE COX-2 INHIBITOR, MELOXICAM, IS NOT ASSOCIATED WITH REDUCED EXPRESSION OF COX-2 AND COX-1 PROTEIN IN FETAL KIDNEY, LUNG, SMALL INTESTINE, ADRENAL GLAND, HEART, LIVER, AND BRAIN OF SHEEP IN PRETERM LABOR VALERIJA RAC1, STEPHEN LYE2, 1Mount Sinai Hospital Toronto, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada 2Mount Sinai Hospital Toronto, Ob/Gyn, Toronto, Ontario, Canada OBJECTIVE: Preterm birth occurs in 5%-10 % of all pregnancies and is associated with considerable neonatal mortality and morbidity. Labor in sheep is caused by increased production of prostaglandins in uterine and placental tissues by inducible COX-2 isoform. Our previous studies have shown that tocolysis with the specific COX-2 inhibitor meloxicam (MEL) blocks COX-2 protein expression in intrauterine tissues while leaving placental COX-2 expression unchanged. Recent studies have shown that the COX-2 isoform is constitutively expressed in many fetal tissues and some fetal side effects of indomethacin are caused by the inhibition of COX protein expression. We wanted to determine whether meloxicam administration induced changes in COX protein expression in different fetal tissues. STUDY DESIGN: On day 127 of gestation, preterm labor was induced in chronically catheterized sheep by maternal administration of RU486. Animals were randomized to receive maternal infusions of saline (n = 12) or MEL (n = 12). Infusion of saline/drug continued until delivery or for 48 hours when the animals were euthanized and tissue samples were collected. Western blot analysis was used to compare COX-1 and COX-2 protein levels in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain. RESULTS: (a) MEL administration was not associated with any change in COX-2 protein expression in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain in saline- and MEL-treated sheep. (b) COX-1 protein expression in these fetal tissues was not significantly different in MEL-treated animals compared to saline-treated animals. CONCLUSION: These studies indicate that meloxicam, at the dose used, did not block COX-1 and COX-2 protein expression in fetal tissues and this might contribute to the absence of fetal complications associated with tocolysis using meloxicam.
386
THE OPTIMAL DOSING STRATEGY FOR CORTICOSTEROIDS TO PREVENT RDS: A DECISION ANALYSIS KIM BOGGESS1, JENNIFER BAILIT2, BRIAN MERCER2, MENDEL SINGER3, VALERIE PARISI1, 1University of North Carolina at Chapel Hill, Obstetrics/Gynecology, Chapel Hill, NC 2Case Western Reserve University, Reproductive Biology, Cleveland, OH 3 Case Western Reserve University, Epidemiology and Biostatistics, Cleveland, OH OBJECTIVE: Antenatal steroids (ACS) before preterm birth (PTB) are highly effective in reducing infant morbidity and mortality. As weekly steroids are not recommended, the optimal timing of ACS continues to be studied. Our purpose was to evaluate alternative strategies of ACS administration. STUDY DESIGN: We performed a decision analysis to test 3 strategies: ACS for every pregnant woman (ALL), ACS for women at clinical risk for PTB (RSK), and ACS for symptomatic women (SX). For this analysis, we chose respiratory distress syndrome (RDS) as the primary outcome. Included in the model were: risk of PTB at each week ± risk factors, risk of RDS ± ACS, probability of symptoms and of PTB before ACS if symptomatic, and duration of ACS effect. Baseline estimates and ranges for key variables were obtained by MEDLINE search. A Monte Carlo simulation was performed using 10,000 pregnancies. Sensitivity analysis was performed for frequency of risk factors (2%-100%), risk of PTB if symptomatic (50%-75%), probability of PTB before ACS (5%-40%). The model was tested varying gestational age (24-30) at ACS administration (ALL & RSK) RESULTS: The ALL performed best (1.1%, 1.7%, 1.9% RDS for ALL, RSK, SX). As the percent of women with risk factors increased, the effectiveness of all strategies decreased. However, the RSK strategy was relatively more effective and the SX strategy was less effective as the percent of women with a risk factor for PTB increased (3.5%, 3.5%, 5.9% RDS for ALL, RSK, SX) in a high-risk population. Further assessing routine ACS in high-risk women, we found increased RDS with ACS with advancing gestational age at administration (3.5%, 3.8%, 4.4%, 4.9% at 24, 26, 28, 30 weeks.) CONCLUSION: Routine single-course ACS is more effective in preventing RDS than ACS for symptoms only. The optimal time for ACS in high-risk women is 24 weeks. We recommend confirmation of this decision analysis by a randomized clinical trial.
385
COMPARING NEONATAL OUTCOMES USING DIFFERENT BETAMETHASONE DOSING REGIMENS DAVID HAAS1, WILLIAM MCCULLOUGH2, CARA OLSEN3, DANIEL SHIAU2, JOHN RICHARD4, EMORY FRY2, MICHAEL MCNAMARA4, 1Naval Hospital Camp Lejeune, NC, OB/GYN, Jacksonville, NC 2Naval Medical Center, San Diego, Pediatrics, San Diego, CA 3 USUHS, Biostatistics, Bethesda, MD 4Naval Medical Center, San Diego, OBGYN, San Diego, CA OBJECTIVE: Antenatal corticosteroids are used to improve neonatal outcomes when preterm delivery is expected. The current standard regimen for betamethasone is two 12-milligram injections, 24 hours apart. We sought to determine if there is a difference in neonatal outcomes when dosing betamethasone every 12 hours or every 24 hours for anticipated preterm delivery. STUDY DESIGN: A retrospective review of all birth records of infants delivered at less than 36 weeks gestation from January 1, 1996, to July 1, 2000. Maternal and neonatal charts were reviewed. The deliveries were separated into three groups: those not receiving antenatal corticosteroids, those who received betamethasone 12 hours apart, and those who received the standard 24-hour dosing. Demographic, obstetric, and neonatal variables were compared between the groups. RESULTS: There were 909 deliveries analyzed. When comparing the two betamethasone groups, a statistically significant difference was only found for antibiotic and surfactant use. For all other variables and outcomes, including neonatal death, chronic lung disease, respiratory distress syndrome, intraventricular hemorrhage, intubation, and hospital days, there was no difference. Both betamethasone groups had better outcomes than the group not receiving steroids for most variables except for no difference found in neonatal death, necrotizing enterocolitis, or 1-minute Apgar score. The outcomes are also compared by gestational age ranges. CONCLUSION: Outcomes using a 12-hour dosing schedule of betamethasone seem to be similar to the standard 24-hour regimen and should be considered as an alternative way to deliver antenatal corticosteroids.
387
PLACENTA GROWTH FACTOR (PIGF) LEVELS IN WOMEN WITH PREECLAMPSIA AND INTRAUTERINE GROWTH RESTRICTION: IS PIGF A MARKER FOR FETAL WELL-BEING? DIETMAR SCHLEMBACH1, RUTH SENGENBERGER2, WENZEL WALLNER2, BRITTA MEURER2, MATTHIAS W. BECKMANN2, ROBERT E. GARFIELD1, 1University of Texas Medical Branch, Department of Obstetrics & Gynecology, Galveston, TX 2Friedrich Alexander University of Erlangen-Nuremberg, Department of Obstetrics & Gynecology, Erlangen, Germany OBJECTIVE: PlGF is a potent angiogenic factor of the VEGF family that is produced exclusively by the placenta. In normal pregnancy (NP) maternal PlGF levels increase with gestation, and in preeclampsia (PE) and intrauterine growth restriction (IUGR) a decrease of PlGF occurs. Whether PlGF can predict pregnancy complications is still in discussion. Purpose of this study was to examine if PlGF levels in women with PE and IUGR at the time of the disease are correlated with clinical features such as placental (PW) and fetal weight (FBW) and Doppler ultrasound parameters. STUDY DESIGN: Serum PlGF levels were measured in 16 women with PE, 15 women with IUGR, and 16 women with NP by ELISA. All women were delivered by cesarean section to avoid a possible hypoxic effect of labor. RESULTS: PlGF were significantly lower in PE (62.92 ± 31.40 pg/mL; P = .001) and IUGR (48.44 ± 41.63 pg/mL; P < .001) compared to NP (245.74 ± 217.42 pg/mL). This significance was also detectable when comparing women at similar gestational age. No difference could be found between PE and IUGR. PlGF was significantly correlated with PW in PE (r = .684, P = .004) and IUGR (r = .547, P = .035), as well as FBW (PE: r = .810, P < .001; IUGR: r = .724, P = .002). Additionally, a significant negative correlation between maternal PlGF levels and pulsatility index in umbilical artery could be found (PE: r = .738, P = .002; IUGR: r = .607, P = .016). PlGF levels were significantly correlated with uterine artery PI only in PE (r = .765, P = .002). CONCLUSION: PlGF is a highly specific marker for estimating the presence and the severity of PE and IUGR. Estimates of levels of PIGF in pregnant women might be used to predict and treat women with these conditions. Furthermore, maternal PlGF could be useful to predict fetal well-being and therefore for planning the management of these pregnancies. (Supported by W. Sander Stiftung, Munich.)