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S230 SMFM Abstracts 548 FGL2 PROTHROMBINASE EXPRESSION IN GRAVID AND NON-GRAVID HUMAN MYOMETRIUM VIVIEN PAN 1, NIMA GOHARKHAYt, JUAN FELIX 2, DEBORAH WING1; 1University of Southern California, Obstetrics and Gynecology, Los Angeles, CA; 2University of Southern California, Pathology, Los Angeles, CA OBJECTIVE: fgl2 is a prothrombinase which is activated by proinflam- matory cytokines. Previous reports of the uterotonic activity of thrombin and the expression of prothrombin and fgl2 in rat myometrial tissue have lead to hypotheses of the potential roles of thrombin and fgl2 in uterine contractility. The purpose of this study was to assess the expression of fgl2 in gravid and non- gravid human myometrium. STUDY DESIGN: Myometrium was obtained from gravid women under- going cesarean section (n = 19), premenopausal (n - 10) and menopausal (n = 10) women undergoing hysterectomy, and nonpregnant women receiving 100~tg of misoprostol vaginany at least 12 hom-s prior to hysterectomy (n = 8). Total RNA was extracted and fgl2 mRNA expression was determined by reverse transcription PCR using specific oligonucleotide primers. Results are pre- sented as the ratio of the optical density of the fgl2 message to that ofbeta-actin from equal amounts of RNA. Statistical analysis was performed using independent t test and ANOVA where appropriate. RESULTS: All samples analyzed contained demonstrable quantities of fgl2 mRNA (n = 47). The highest expression levels for fgl2 were found in tissue from gravid women, followed by those treated with misoprostol, premeno- pausal non-pregnant women and menopausal women (P < .0001, ANOVA). Significantly higher levels of tgl2 mRNA expression were found in the gravid compared to the misoprostol-treated non-pregnant (P < .001), premenopausal non-pregnant (P < .001), and menopausal (P < .0001). When stratifying pregnant patients (n 19) into groups of preterm versus term and labored versus unlabored, there were no significant differences in fgl2 mRNA expression (P = .95 and P- .34, respectively). CONCLUSION: The expression of fgl2 mRNA is increased in late gestational human myometrium compared to non-pregnant samples. This implies a possible role of fgl2 in human parturition. 550 December 2001 AtnJ Obstet Gynecol MATERNAL STRESS, ENDOCRINE/IMMUNE-INFLAMMATORY PROCF~SES AND VAGINAL INFECTION IN HUMAN PREGNANCY: PRELIMINARY FINDINGS PATHIK WADHWA t, JENNIFER CULHANE 2, ALEKSANDRA CHICZ-DEMET 3, SHIRISH BARVE 4, VIRGINIA RAUH 5, KELLY FARLEY-MC- COLLUM 6, VIJAYA HOGAN7; 1University of California, Irvine, lrvine, CA; 2Thonms Jefferson University, Obstetrics and Gynecology, Philadelphia, PA; 3University of California, Irvine, Psychiatry & Hmnan Behavio~, Irvine, CA; 4University of Louisville, Medicine, Louisville, K'Y; 5Columbia University, School of Public Health, New York, NY; 6Thomas Jefferson University, Obstetrics and Gynecology, Philadelphia, PA; 7Center for Disease Control, Division of Reproductive Health, Atlanta, GA OBJECTIVE: Chronic maternal stress is a significant and independent risk factor for vaginal infection in pregnancy (Culhane et al, 2001). The aim of this study was to test the hypothesis that stress may heighten susceptibility for acquiring vaginal intection via activation of the maternal hypothalamic- pituitary-adrenal (HPA) axis and resultant immunosuppression (Wadhwa et al, 2001). STUDY DESIGN: From an on-going, longitudinal cohort study, data were examined from the first 20 enrolled subjects. This study sample comprised of urban, socially-disadvantaged pregnant women at 9.7 + 2.5 (SD) weeks gestation. Chronic maternal stress was assessed using a standardized question- naire (Cohen Perceived Stress Scale). Morning free (unbound) cortisol levels were measured in saliva by RIA. Interleukin-10 (IL-]0, an immunosuppressive cytokine) concentrations were quantified in serum by ELISA. Vaginal infection (bacterial vaginosis, BV) was assessed by Gram stain of vaginal secretion. RESULTS: The prevalence of BV was 50% (Nugent score >7). BV+ women had a greater proportion of women in the highest stress quartile than BV- women (.27 + .14 vs..22 + .15: z = -.26, P: .79; (+ SE)). Higher stress scores were positively associated with cortisol levels (r = .37, P = .10), which, in turn, were positively associated with IL-10 levels (r = .74, P = .002). Furthermore, BV+ women had approximately 80% higher mean cortisol levels (0.51 + .25 vs 0.28 + .03 g/dL (+SEM): t = -.87, P= .40) and approximately 30% higher mean baseline IL-10 levels (0.18 + .03 vs 0.14 + .02 OD units (+SEM); t = -1.23, P - .23) than BV- women. CONCLUSION: This pattern of preliminary findings supports the notion that chronic maternal stress and stress-associated hormones may he associated with systemic immunosuppression and risk for vaginal infection in human pregnancy. 549 THE EFFECTS OF FETAL ARTERIAL HYPOXIA AND ACIDEMIA ON PLA- CENTAL PRODUCTION OF ADRENOMEDULLIN BRIAN PIERCE l, CHRISTINA APODACA2, PETER NAPOLITANO t, LISA PIERCE 1, RODER- ICK HUME JR. 1, BYRON CALHOUN t, 1Madigan Army Medical Center, Tacoma, WA 2Tripler Army Medical Centel, Honolulu, HI OBJECTIVE: Control of the fetal-placental vasculature is not completely understood and much effort has been directed toward delineating which factors regulate this vascular bed. We have shown that the conditions of placental arterial hypoxia as well as acidenfia result in placental vasodilation, possibly as a protective adaptive response to improve in utero conditions. We have also shown that adrenomedullin expression is increased in the placentas of pregnancies complicated by oligohydramnios, a disease state that may benefit from fetal-placental vasodilation. Our goal is to determine whether adrenomedullin is responsible for the placental vasodilation noted during acute fetal hypoxia or fetal acidemia. STUDY DESIGN: In two separate experiments, the maternal and fetal circulation of two cotyledons from five human placentas were perfused for four hours. PART I: The fetal circulation of one cotyledon was perfused with hypoxic (pO2 < 25 mm Hg) Han~ Balanced Salt Solution (HBSS) while the fetal circulation of the other cotyledon was perfi~sed with hyperoxic (pO2 > 600 mm Hg) HBSS. PART ll: The fetal circulation of one cotyledon was perfused with acidemic (pH = 6.90) HBSS while the fetal circulation of the other cotyledon was perfused with physiologic (pH 7.35) HBSS. Fetal vein effluents were collected hourly and adrenomedullin concentrations were determined by RIA. RESULTS: Fetal artery acidemia resulted in lower placental venous adrenomedullin concentrations compared to the physiologic arterial pH with a significant difference noted at 4 hours (P ~ .05). There was no ditterence in adrenomedulliu concentration when comparing hypoxic conditions to hyperoxic conditions (P> .05). There was no significant change over time for adrenomedullin concenn'ations from baseline values for any of the conditions studied (P> .05). CONCLUSION: While fetal acidemia and fetal hypoxia may cause fetal- placental vasodilation, it appears not to be due to adrenomedullin, at least in the acute setting. 551 EFFECT OF GESTATIONAL AGE ON MATERNAL-FETAL GLUCOREGU- LATORY RESPONSE DURING THE SECOND HALF OF PREGNANCY 1N NON-HUMAN PRIMATE MODEL JOAQUIN SANTOLAYA-FORGAS 1, RA- MAKRISHNA MEHENDALE 2, LARRY BUD 2, V DANIEL CASTRACANE 3, THOMAS MYLES4; lTexas Tech University, Obstetrics and Gynecology, Amarillo, TX; 2University of Illinois at Chicago, Obstetrics and Gynecology, Chicago, IL; 3Texas Tech University, Obstetrics and Gynecology, Amarillo, TX: 4Texas Tech Unive~ity, Obstetrics and Gynecology, Amarillo, TX OBJECTIVE: In the baboon model (Ntern~ 184 says), fetal insulin (F-I) responses to regulated hyperglycemic states have been reported (Santolaya et al, SGI 2001). The aim of this study was to determine the effect of gestational age on F-I response to an acute glucose (G) infusion after maternal-fetal glycemia had been chronically maintained STUDY DESIGN: A tethered baboon model was established at 140 days gestation by placing cannulae in the maternal aorta and inferior vena cava via the femoral artery and vein. Following a hysterotomy, the fetal carotid artery was also cathetererized. A fourth cannula was placed in the amniotic cavity to monitor for labor. At 150, 155 and 165 days, after recovery from surgery and when they were on no medication, a G infusion (7.5 gin/h) via the femoral vein was started and maintained toe 20 hours. At 21h, G infusion was increased to 20 gm/h for 1 hour. Animals remained ad libitum during and between infusions. Maternal (M) and tetal (F) blood samples were obtained from the arterial lines before the lh G intusion and at 1/2h intervals to include 30 minutes post infusion during the 3 study dates. RESULTS: G: ng/dL; I: IU/mL: Mean (range) baseline M and F serum G and I before the acute G infusion were: C,-M 119.3 (106-124); C,-F 86.3 (78-92); I-M 76.6 (69-70); I-F 57 (52-65). Mean (range). Mean (range) G and I during the 20gm/h infusion were: G-M 264.1 (162-392); C-F 208 (175-278); I-M 793.8 (481-1384); I-F 174.8 (114-259). The highest F-I was seen on day 165. CONCLUSION: At any given time F-G increases parallel M-G with ~ a 30% gradient. Both the M and F responded to the acute G challenge but the M-F insulin gradient was -80%. Although F-G levels were similar during the 3 study days, F-I response increased with gestational age indicating some develop- mental competency. This data suggests that at this gestational age, F-I production is limited in hyperglycemic states. F-G clearance depends on decreases in M-G levels and gestatioual age.

549 The effects of fetal arterial hypoxia and acidemia on placental production of adrenomedullin

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S230 SMFM Abstracts

548 FGL2 PROTHROMBINASE EXPRESSION IN GRAVID AND NON-GRAVID HUMAN MYOMETRIUM VIVIEN PAN 1, NIMA GOHARKHAY t, JUAN FELIX 2, DEBORAH WING1; 1University of Southern California, Obstetrics and Gynecology, Los Angeles, CA; 2University of Southern California, Pathology, Los Angeles, CA

OBJECTIVE: fgl2 is a pro thrombinase which is activated by proinflam- matory cytokines. Previous reports of the uterotonic activity of thrombin and the expression of p ro thrombin and fgl2 in rat myometrial tissue have lead to hypotheses of the potential roles of thrombin and fgl2 in uterine contractility. The purpose of this study was to assess the expression of fgl2 in gravid and non- gravid h u m a n myometrium.

STUDY DESIGN: Myometrium was obtained from gravid women under- going cesarean section (n = 19), premenopausal (n - 10) and menopausal (n = 10) women u n d e r g o i n g hysterectomy, and n o n p r e g n a n t women receiving 100~tg of misoprostol vaginany at least 12 hom-s prior to hysterectomy (n = 8). Total RNA was extracted and fgl2 mRNA expression was determined by reverse t ranscr ipt ion PCR using specific ol igonucleot ide primers. Results are pre- sented as the ratio of the optical density of the fgl2 message to that ofbeta-actin f rom equal amounts of RNA. Statistical analysis was p e r f o r m e d using independent t test and ANOVA where appropriate.

RESULTS: All samples analyzed contained demonstrable quantities of fgl2 mRNA (n = 47). The highest expression levels for fgl2 were found in tissue f rom gravid women, followed by those t reated with misoprostol, premeno- pausal non-pregnant women and menopausal women (P < .0001, ANOVA). Significantly higher levels of tgl2 mRNA expression were found in the gravid compared to the misoprostol-treated non-pregnant (P < .001), premenopausal non -p regnan t (P < .001), and menopausa l (P < .0001). When stratifying pregnant patients (n 19) into groups of pre term versus term and labored versus un labored , there were no significant differences in fgl2 mRNA expression (P = .95 and P - .34, respectively).

CONCLUSION: The expression of fgl2 mRNA is increased in late gestational h u m a n myomet r ium compared to non-p regnan t samples. This implies a possible role of fgl2 in h u m a n parturition.

550

December 2001 AtnJ Obstet Gynecol

MATERNAL STRESS, ENDOCRINE/IMMUNE-INFLAMMATORY PROCF~SES AND VAGINAL INFECTION IN HUMAN PREGNANCY: PRELIMINARY FINDINGS PATHIK WADHWA t, JENNIFER CULHANE 2, ALEKSANDRA CHICZ-DEMET 3, SHIRISH BARVE 4, VIRGINIA RAUH 5, KELLY FARLEY-MC- COLLUM 6, VIJAYA HOGAN7; 1University of California, Irvine, lrvine, CA; 2Thonms Jefferson University, Obstetrics and Gynecology, Philadelphia, PA; 3University of California, Irvine, Psychiatry & H m n a n Behavio~, Irvine, CA; 4University of Louisville, Medicine, Louisville, K'Y; 5Columbia University, School of Public Heal th, New York, NY; 6Thomas Jefferson University, Obstetrics and Gynecology, Philadelphia, PA; 7Center for Disease Control , Division of Reproductive Health, Atlanta, GA

OBJECTIVE: Chronic maternal stress is a significant and independent risk factor for vaginal infection in pregnancy (Culhane et al, 2001). The aim of this study was to test the hypothesis that stress may he igh ten susceptibility for acqui r ing vaginal intect ion via activation of the maternal hypothalamic- pituitary-adrenal (HPA) axis and resultant immunosuppression (Wadhwa et al, 2001).

STUDY DESIGN: From an on-going, longitudinal cohor t study, data were examined from the first 20 enrolled subjects. This study sample comprised of u rban , socially-disadvantaged p r e g n a n t women at 9.7 + 2.5 (SD) weeks gestation. Chronic maternal stress was assessed using a standardized question- naire (Cohen Perceived Stress Scale). Morning free (unbound) cortisol levels were measured in saliva by RIA. Interleukin-10 (IL-]0, an immunosuppressive cytokine) concentrat ions were quantified in serum by ELISA. Vaginal infection (bacterial vaginosis, BV) was assessed by Gram stain of vaginal secretion.

RESULTS: The prevalence of BV was 50% (Nugent score >7). BV+ women had a greater p ropor t ion of women in the highest stress quartile than BV- women (.27 + .14 vs. .22 + .15: z = -.26, P : .79; (+ SE)). Higher stress scores were positively associated with cortisol levels (r = .37, P = .10), which, in turn, were positively associated with IL-10 levels (r = .74, P = .002). Furthermore, BV+ women had approximately 80% higher mean cortisol levels (0.51 + .25 vs 0.28 + .03 g / d L (+SEM): t = -.87, P = .40) and approximately 30% higher mean baseline IL-10 levels (0.18 + .03 vs 0.14 + .02 OD units (+SEM); t = -1.23, P - .23) than BV- women.

CONCLUSION: This pa t te rn of prel iminary findings supports the not ion that chronic maternal stress and stress-associated hormones may he associated with systemic immunosuppress ion and risk for vaginal infection in h u m a n pregnancy.

549 THE EFFECTS OF FETAL ARTERIAL HYPOXIA AND ACIDEMIA ON PLA- CENTAL PRODUCTION OF ADRENOMEDULLIN BRIAN PIERCE l, CHRISTINA APODACA 2, PETER NAPOLITANO t, LISA PIERCE 1, RODER- ICK HUME JR. 1, BYRON CALHOUN t, 1Madigan Army Medical Center, Tacoma, WA 2Tripler Army Medical Centel, Honolulu, HI

OBJECTIVE: Control of the fetal-placental vasculature is not completely unde r s tood a n d m u c h effort has been di rected toward del ineat ing which factors regulate this vascular bed. We have shown that the condi t ions of placental arterial hypoxia as well as acidenfia result in placental vasodilation, possibly as a protective adaptive response to improve in utero conditions. We have also shown that adrenomedul l in expression is increased in the placentas of pregnancies compl ica ted by ol igohydramnios , a disease state that may benefit f rom fetal-placental vasodilation. Our goal is to determine whether adrenomedul l in is responsible for the placental vasodilation no ted dur ing acute fetal hypoxia or fetal acidemia.

STUDY DESIGN: In two separate experiments, the maternal and fetal circulation of two cotyledons from five h u m a n placentas were perfused for four hours. PART I: The fetal circulation of one cotyledon was perfused with hypoxic (pO2 < 25 mm Hg) H a n ~ Balanced Salt Solution (HBSS) while the fetal circulation of the other cotyledon was perfi~sed with hyperoxic (pO2 > 600 m m Hg) HBSS. PART ll: The fetal c irculat ion of one cotyledon was perfused with acidemic (pH = 6.90) HBSS while the fetal circulation of the other cotyledon was perfused with physiologic (pH 7.35) HBSS. Fetal vein effluents were collected hour ly and ad renomedu l l in concent ra t ions were determined by RIA.

RESULTS: Fetal ar tery acidemia resul ted in lower placental venous adrenomedul l in concentrat ions compared to the physiologic arterial pH with a significant difference noted at 4 hours (P ~ .05). There was no ditterence in ad renomedu l l iu concen t ra t ion when compar ing hypoxic condi t ions to hyperoxic conditions (P> .05). There was no significant change over time for adrenomedul l in concenn'at ions f rom baseline values for any of the conditions studied (P> .05).

CONCLUSION: While fetal acidemia and fetal hypoxia may cause fetal- placental vasodilation, it appears not to be due to adrenomedull in, at least in the acute setting.

551 EFFECT OF GESTATIONAL AGE ON MATERNAL-FETAL GLUCOREGU- LATORY RESPONSE DURING THE SECOND HALF OF PREGNANCY 1N NON-HUMAN PRIMATE MODEL JOAQUIN SANTOLAYA-FORGAS 1, RA- MAKRISHNA MEHENDALE 2, LARRY BUD 2, V DANIEL CASTRACANE 3, THOMAS MYLES4; lTexas Tech University, Obstetr ics a n d Gynecology, Amarillo, TX; 2University of Illinois at Chicago, Obstetrics and Gynecology, Chicago, IL; 3Texas Tech University, Obstetrics and Gynecology, Amarillo, TX: 4Texas Tech Unive~ity, Obstetrics and Gynecology, Amarillo, TX

OBJECTIVE: In the baboon model (Ntern~ 184 says), fetal insulin (F-I) responses to regulated hyperglycemic states have been repor ted (Santolaya et al, SGI 2001). The aim of this study was to determine the effect of gestational age on F-I response to an acute glucose (G) infusion after maternal-fetal glycemia had been chronically maintained

STUDY DESIGN: A tethered baboon model was established at 140 days gestation by placing cannulae in the maternal aorta and inferior vena cava via the femoral artery and vein. Following a hysterotomy, the fetal carotid artery was also cathetererized. A fourth cannula was placed in the amniotic cavity to moni tor for labor. At 150, 155 and 165 days, after recovery from surgery and when they were on no medication, a G infusion (7.5 g in /h) via the femoral vein was started and maintained toe 20 hours. At 21h, G infusion was increased to 20 g m / h for 1 hour. Animals remained ad libitum dur ing and between infusions. Maternal (M) and tetal (F) blood samples were obtained from the arterial lines before the l h G intusion and at 1 /2h intervals to include 30 minutes post infusion dur ing the 3 study dates.

RESULTS: G: ng /dL; I: IU/mL: Mean (range) baseline M and F serum G and I before the acute G infusion were: C,-M 119.3 (106-124); C,-F 86.3 (78-92); I-M 76.6 (69-70); I-F 57 (52-65). Mean (range). Mean (range) G and I dur ing the 2 0 g m / h infusion were: G-M 264.1 (162-392); C-F 208 (175-278); I-M 793.8 (481-1384); I-F 174.8 (114-259). The highest F-I was seen on day 165.

CONCLUSION: At any given time F-G increases parallel M-G with ~ a 30% gradient. Both the M and F responded to the acute G challenge but the M-F insulin gradient was -80%. Although F-G levels were similar dur ing the 3 study days, F-I response increased with gestational age indicat ing some develop- menta l competency. This data suggests that at this gestational age, F-I p roduc t ion is l imited in hyperglycemic states. F-G clearance depends on decreases in M-G levels and gestatioual age.