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Pre-eclampsia decreases placental oxygenation capacity – clinical application of a novel placental function test
SMFM Abstracts S143 458 DOSE-DEPENDENT AND TIME-COURSE EVALUATION OF SURFACTANT PROTEINS A (SP-A) AND B (SP-B) EXPRESSION IN HUMAN LUNG CELLS EXPOSED TO DEXAMETHASONE (DXM) LINDA FONSECA1, ALEX VIDAEFF2, ALCORN JOSEPH1, BISHOP KAREN1, GILSTRAP LARRY1, RAMIN SUSAN1, 1University of Texas Health Science Center at Houston, Houston, Texas, 2University of Texas Health Science Center at Houston, Obstetrics, Gynecology and Reproductive Sciences, Houston, Texas OBJECTIVE: Previous in vitro studies have shown that physiologic concentrations of corticosteroids significantly influence surfactant proteins gene expression after 48 hours of exposure. The purpose of this study was to determine if shorter exposures at lower concentrations elicit the same genomic effects on SP-A and B mRNA. STUDY DESIGN: NCI-H441 cells were exposed to varying concentrations of DXM (10-11 to 10-7 M) in combination with dibutyryl cAMP (1mM) an agent which promotes surfactant gene expression. The measured outcome was SP-A and SP-B mRNA expression at different time points in cell culture (6, 12, 24, 36 and 48 hours). The experiment was conducted three times in parallel with control, and mRNA levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Two-way ANOVA and Kruskal-Wallis test were used for statistical analysis. RESULTS: Both time and concentration significantly influenced SP-A and SP-B mRNA levels (ANOVA, P=0.01 and P=0.03, respectively for SP-A and p=0.001 and p!0.001, respectively for SP-B). When SP-A mRNA levels were considered relative to concentration alone, significant inhibition was evident at higher concentration (10-7 M) compared to control and lower concentration (10-11 M) (P=0.001 and P=0.01, respectively). Also, a dose-dependent effect of DXM on SP-B mRNA upregulation compared to control was first noticeable at 10 -9 M and maximal at 10-7 M concentration (P!0.001 and P=0.001, respectively). Analysis of time impact alone showed that the significant influence of DXM on SP-A and SP-B was not observed until 48 hours (P=0.001 and P=0.008, respectively). CONCLUSION: The dose-dependent effect of DXM on inhibition of SP-A mRNA steady-state levels and up regulation of SP-B mRNA levels does not appear to manifest earlier than 48 hours from exposure. The inhibition of SP-A mRNA expression at higher concentrations may be relevant to the human fetus. These results suggests that prenatal overexposure to corticosteroids may unfavorably impact the non-immune host defense in the lung, which is the primary role of SP-A. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.499
459 ADIPONECTIN PRODUCTION IS DECREASED IN WHITE ADIPOSE TISSUE OF OBESE PREGNANT WOMEN LAURA LAFFINEUSE1, SYLVIE HAUGUEL-DE MOUZON1, PATRICK CATALANO1, SUBHO BASU1, JUDI MINIUM1, JOAN LIPPUS1, 1CASEMetroHealth Medical Center, Cleveland, Ohio OBJECTIVE: Adipose production of adipokines is correlated with insulin resistance in obese subjects. The resulting hyperinsulinemia is the putative link between maternal obesity and increased neonatal adiposity at birth. This study evaluated the association of maternal white adipose tissue [MWAT] adiponectin production to insulin resistance and neonatal adiposity. STUDY DESIGN: Data from 15 normal [NML], 7 overweight [OW], 13 obese [OB], and 7 obese diabetic [OB DM] women at term were prospectively evaluated (mean pre-pregnancy BMI: 21.5, 28.5, 37.1, 38.1 kg/m2 respectively). Subcutaneous MWAT and fasting maternal blood were collected at elective cesarean delivery. MWAT adiponectin mRNA expression was measured by RT-PCR. Maternal plasma insulin, adiponectin, and glucose were measured. HOMA, a measure of insulin resistance, was calculated. Neonatal anthropometrics were obtained within 48 hours of birth. ANOVA and t-test were used where appropriate. RESULTS: Adiponectin mRNA expression for OB and OW women was decreased compared to NML (p!.001 for each) but not significantly for OB DM (Figure 1). There was a non significant decrease in plasma adiponectin for OB and OW groups (Figure 2). HOMA and plasma insulin were increased for all each group vs. NML (p!.02 for each). Only OB DM neonates showed an increase in % body fat vs. NML (16.1 vs 11.6 % p!.04).
CONCLUSION: Though all groups showed increased hyperinsulinemia and insulin resistance vs NML only OW and OB had decreased levels of MWAT adiponectin. The increased adiposity observed in OB DM neonates was not reflected by a decrease in MWAT adiponectin expression. Variation in maternal adiponectin did not explain the regulation of fetal adiposity. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.500
460 PRE-ECLAMPSIA DECREASES PLACENTAL OXYGENATION CAPACITY – CLINICAL APPLICATION OF A NOVEL PLACENTAL FUNCTION TEST KOJI MATSUO1, ANDREW MALINOW3, CHRISTOPHER HARMAN4, TADASHI KIMURA2, AHMET BASCHAT5, 1University of Maryland, Baltimore, Obstetrics, Gynecology & Reproductive Sciences, Baltimore, Maryland, 2Osaka University Graduate School of Medicine, Obstetrics and Gynecology, Osaka, Japan, 3University of Maryland at Baltimore, Anesthesiology, Baltimore, Maryland, 4University of Maryland at Baltimore, Obstetrics, Gynecology, and Reproductive Sciences, Baltimore, Maryland, 5University of Maryland at Baltimore, Obstetrics, Gynecology and Reproductive Sciences, Baltimore, Maryland OBJECTIVE: The placenta is the primary fetal repiratory organ. While arteriovenous (AV) O2 difference is an established test describing respiratory function in adults, this concept has not been applied to the placenta. Preeclampsia (PreE) features abnormal placentation that may impair placental gas exchange. This study aimed to evaluate placental gas exchange in PreE using umbilical AV differences for pO2 and pCO2. STUDY DESIGN: Case control study of normally grown singletons delivered by pre-labor cesarean section. AV difference for pO2 and pCO2 was calculated from paired umbilical artery (UA) – venous (UV) cord blood samples obtained at delivery. AV differences were compared between non PreE and PreE, matching for delivery gestational age (GA). RESULTS: Of 152 cases, 106 (69.7%) had PreE. GA and birthweight (BW) were similar among PreE and normal (29.6 G0.3 wks / 1478 G 84 g vs 30.6 G0.4 wks, 1618 G 79 g). Significant differences in UA and UV gases are shownlisted (Mann Whitney U). Pre-E had signifcantly lower AVO2 and CO2 differences (table). AVO2 differences correlated with UVpH, UVpO2 and UVpCO2 (Pearson’s r=0.28, 0.72 and -0.24, all p!0.005). AVCO2 difference correlated with GA, BW, UApH, UApCO2 and UVpO2. (Pearson’s r=0.21, 0.24, -0.21, 0.35 and 0.12, all p!0.01). CONCLUSION: Pre-eclampsia impairs placental gas exchange capacity: Umbilical venous return supplies the fetus with blood at a lower pH and pO2 and increased pCO2. Despite facilitation by lower pH, fetal oxygen extraction may be lower in pre-eclampsia. Notably, these fetuses maintained normal growth. The potential impacts of this novel observation require further study.
UA pH UA pO2 UA pCO2 UV pH UV pO2 UV pCO2 AVO2 difference AVCO2 difference
Non Pre-E
Pre-E
p-value
7.22 G 0.08 16.7 G 7.1 57.4 G 12.8 7.3 G 0.08 28.3 G 10.4 47.1 G 11.6 11.6 G 7.8 10.2 G 5.6
7.20 G 0.08 13.8 G 6.3 60.0 G 15.3 7.25 G 0.12 20.8 G 6.4 52.6 G 14.7 7.0 G 4.3 7.5 G 5.3
n.s. !0.05 n.s. 0.007 !0.001 0.02 !0.001 !0.001
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.502
459 ADIPONECTIN PRODUCTION IS DECREASED IN WHITE ADIPOSE TISSUE OF OBESE PREGNANT WOMEN LAURA LAFFINEUSE1, SYLVIE HAUGUEL-DE MOUZON1, PATRICK CATALANO1, SUBHO BASU1, JUDI MINIUM1, JOAN LIPPUS1, 1CASEMetroHealth Medical Center, Cleveland, Ohio OBJECTIVE: Adipose production of adipokines is correlated with insulin resistance in obese subjects. The resulting hyperinsulinemia is the putative link between maternal obesity and increased neonatal adiposity at birth. This study evaluated the association of maternal white adipose tissue [MWAT] adiponectin production to insulin resistance and neonatal adiposity. STUDY DESIGN: Data from 15 normal [NML], 7 overweight [OW], 13 obese [OB], and 7 obese diabetic [OB DM] women at term were prospectively evaluated (mean pre-pregnancy BMI: 21.5, 28.5, 37.1, 38.1 kg/m2 respectively). Subcutaneous MWAT and fasting maternal blood were collected at elective cesarean delivery. MWAT adiponectin mRNA expression was measured by RT-PCR. Maternal plasma insulin, adiponectin, and glucose were measured. HOMA, a measure of insulin resistance, was calculated. Neonatal anthropometrics were obtained within 48 hours of birth. ANOVA and t-test were used where appropriate. RESULTS: Adiponectin mRNA expression for OB and OW women was decreased compared to NML (p!.001 for each) but not significantly for OB DM (Figure 1). There was a non significant decrease in plasma adiponectin for OB and OW groups (Figure 2). HOMA and plasma insulin were increased for all each group vs. NML (p!.02 for each). Only OB DM neonates showed an increase in % body fat vs. NML (16.1 vs 11.6 % p!.04).
CONCLUSION: Though all groups showed increased hyperinsulinemia and insulin resistance vs NML only OW and OB had decreased levels of MWAT adiponectin. The increased adiposity observed in OB DM neonates was not reflected by a decrease in MWAT adiponectin expression. Variation in maternal adiponectin did not explain the regulation of fetal adiposity. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.500
460 PRE-ECLAMPSIA DECREASES PLACENTAL OXYGENATION CAPACITY – CLINICAL APPLICATION OF A NOVEL PLACENTAL FUNCTION TEST KOJI MATSUO1, ANDREW MALINOW3, CHRISTOPHER HARMAN4, TADASHI KIMURA2, AHMET BASCHAT5, 1University of Maryland, Baltimore, Obstetrics, Gynecology & Reproductive Sciences, Baltimore, Maryland, 2Osaka University Graduate School of Medicine, Obstetrics and Gynecology, Osaka, Japan, 3University of Maryland at Baltimore, Anesthesiology, Baltimore, Maryland, 4University of Maryland at Baltimore, Obstetrics, Gynecology, and Reproductive Sciences, Baltimore, Maryland, 5University of Maryland at Baltimore, Obstetrics, Gynecology and Reproductive Sciences, Baltimore, Maryland OBJECTIVE: The placenta is the primary fetal repiratory organ. While arteriovenous (AV) O2 difference is an established test describing respiratory function in adults, this concept has not been applied to the placenta. Preeclampsia (PreE) features abnormal placentation that may impair placental gas exchange. This study aimed to evaluate placental gas exchange in PreE using umbilical AV differences for pO2 and pCO2. STUDY DESIGN: Case control study of normally grown singletons delivered by pre-labor cesarean section. AV difference for pO2 and pCO2 was calculated from paired umbilical artery (UA) – venous (UV) cord blood samples obtained at delivery. AV differences were compared between non PreE and PreE, matching for delivery gestational age (GA). RESULTS: Of 152 cases, 106 (69.7%) had PreE. GA and birthweight (BW) were similar among PreE and normal (29.6 G0.3 wks / 1478 G 84 g vs 30.6 G0.4 wks, 1618 G 79 g). Significant differences in UA and UV gases are shownlisted (Mann Whitney U). Pre-E had signifcantly lower AVO2 and CO2 differences (table). AVO2 differences correlated with UVpH, UVpO2 and UVpCO2 (Pearson’s r=0.28, 0.72 and -0.24, all p!0.005). AVCO2 difference correlated with GA, BW, UApH, UApCO2 and UVpO2. (Pearson’s r=0.21, 0.24, -0.21, 0.35 and 0.12, all p!0.01). CONCLUSION: Pre-eclampsia impairs placental gas exchange capacity: Umbilical venous return supplies the fetus with blood at a lower pH and pO2 and increased pCO2. Despite facilitation by lower pH, fetal oxygen extraction may be lower in pre-eclampsia. Notably, these fetuses maintained normal growth. The potential impacts of this novel observation require further study.
UA pH UA pO2 UA pCO2 UV pH UV pO2 UV pCO2 AVO2 difference AVCO2 difference
Non Pre-E
Pre-E
p-value
7.22 G 0.08 16.7 G 7.1 57.4 G 12.8 7.3 G 0.08 28.3 G 10.4 47.1 G 11.6 11.6 G 7.8 10.2 G 5.6
7.20 G 0.08 13.8 G 6.3 60.0 G 15.3 7.25 G 0.12 20.8 G 6.4 52.6 G 14.7 7.0 G 4.3 7.5 G 5.3
n.s. !0.05 n.s. 0.007 !0.001 0.02 !0.001 !0.001
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.502