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to 33 times in the L0 neonates. (the PD formation after AAPH was notdifferent 1155 vs 1146 it may be since AAPH is very strong radicalgenerator but the difference was that base line of the two were 10 and34 so the control neonates can increased by much more times than theother group)CONCLUSIONS: Prenatal maternal exposure to LPS increases baseline

xidative stress in the neonates and decreases the response to AAPH-nduced stress. These results suggest that maternal inflammation dur-ng the antenatal period may induces long term sequelae in the off-pring which may predispose to adult disease. The basal CRP levels ofhe groups were 3.21�2.2 and 10.1�4.1 for the neonates of the salinend LPS treated dams respectively.

232 Transport of opiates by P-glycoprotein expressedn preparations of human placental inside-out vesicles

Sarah Hemauer1, Svetlana Patrikeeva1, Tatiana Nanovskaya1,ary D.V. Hankins1, Mahmoud S. Ahmed1

1The University of Texas Medical Branch, Galveston, TXOBJECTIVE: The use of methadone (MT) or buprenorphine (BUP) forreatment of the pregnant opiate-dependent patient improves mater-al and neonatal outcome. However, both medications are associatedith development of neonatal abstinence syndrome (NAS). The inci-ence and intensity of NAS should correlate with the concentration ofhe opiate in the fetal circulation which is regulated by the placenta.he function of human placental P-glycoprotein (P-gp) is the extru-

ion of its substrates from the feto-placental unit to the maternal cir-ulation. Previously, we demonstrated that MT, BUP, and morphineMR) inhibit P-gp transport of its prototypic substrate paclitaxel in-icating opiate/P-gp interactions. The goal of this investigation was toetermine the transport kinetics of [3H]-MT, [3H]-BUP, and [3H]-R by placental P-gp.

STUDY DESIGN: Opiate interaction with P-gp was determined by theirtimulation of ATP hydrolysis by human P-gp expressing mem-ranes. ATP-dependent transport of [3H]-MT, [3H]-BUP, and [3H]-

MR was determined by inside-out brush border membrane vesiclesprepared from human placental tissue (n � 60). Specific transport ofeach opiate was calculated from the difference in its transfer in pres-ence and absence of 600 �M verapamil.RESULTS: The three opiates stimulated ATP hydrolysis by P-gp ex-

ressing membranes. The transport of MT and MR by placental P-gpas saturable and revealed the following kinetics parameters: [3H]-

MT Kt: 300 � 100 nM and Vmax 4.3 � 0.6 pmol/mg protein min;[3H]-MR Kt: 226 � 200 nM, and Vmax: 3.6 � 2.4 pmol/mg protein-

in. Verapamil did not inhibit the uptake of [3H]-BUP by inside-outvesicles, indicating that it is not transported by P-gp.CONCLUSIONS: The data demonstrate that placental P-gp is involved inegulating the maternal-to-fetal transfer of MT and MR.

233 T Lymphocyte induced AT1-AAs causeypertension in response to placental ischemia

Sarah Richards1, Kedra Wallace1, Abram Weimer1,ushpinder Dhillon1, Gerd Wallukat2, Katrin Wenzel2,

ames N Martin Jr1, Ralf Dechend2, Babbette LaMarca1

1University of Mississippi Medical Center, Jackson, MS,2Max-Delbruck-Center for Molecular Medicine, BerlineOBJECTIVE: We have shown that hypertension in rats with chronic

lacental ischemia (RUPP) is associated with elevated TNF-� andIL-6, AT1-AA and most recently, CD4�T cells; all of which are ele-vated in preclamptic women. However, it is unknown if CD4�T cellsincrease blood pressure or stimulate the AT1-AA in response to pla-cental ischemia. Therefore, we hypothesize that RUPP, reduced uter-ine perfusion pressure, induced CD4�Tcells increase blood pressurevia AT1-AA.STUDY DESIGN: To answer this question, CD4�Tcells were magneti-ally separated using anti-CD4 labeled beads from spleens of RUPPnd normal pregnant rats (NP) on day 19 of gestation. Following

entrifugation, 106cells/100 �l saline were injected intraperitoneally t

S100 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2

nto NP rats at day 13 of gestation. To determine a role for AT1-AA toediate RUPP CD4�Tcell induced hypertension, rats were treated

or AT1 receptor blockade with Losartan 10 mg/kg/day. On day 18,rterial catheters were inserted, and on day 19 blood pressure (MAP)as analyzed; serum collected for AT1-AA analysis.

RESULTS: MAP increased from 104�/-2 mmHg NP to 124�/-2mHg in RUPP rats (P�0.001) and to 118�/-1mmHg inP�RUPPCD4�T cells (P�0.001) but did not change inP�NPCD4�T cells (109 �/- 3.4 mmHg). Circulating AT1-AA in-

reased from 0.22�/-0.1 beats per minute in NP�NPCD4�Tcellreated rats to 23�/-0.7 (P�0.001) beats per minute inP�RUPPCD4�Tcell treated rats. Furthermore, this hypertensive

esponse to CD4�T lymphocytes from RUPP rats was blocked bydministration of Losartan, (102�/-4 mmHg).

CONCLUSIONS: CD4�T lymphocytes activated in response to placentalschemia induce hypertension via AT1-AA in pregnant rats.

234 Differential effects of maternal lipids on fetal growthn normal weight and overweight/obese women

Uma Perni1, Vinod Misra1, Anjel Vahratian2, Marjorie Treadwell11University of Michigan Medical Center, Ann Arbor, MI,2University of Michigan Medical School, Ann Arbor, MIOBJECTIVE: The objective of this study is to estimate the influence ofhe components of maternal lipid profiles on sonographically esti-

ated fetal weight (EFW) measured serially during pregnancy inverweight/obese and normal weight women.

STUDY DESIGN: We prospectively followed a cohort of 143 gravidas atfive time points during gestation. Maternal serum levels of triglycer-ides (TG), high density lipoprotein cholesterol (HDL-C), and lowdensity lipoprotein cholesterol (LDL-C) were measured at 10-14, 16-20, 22-26, and 32-36 weeks. Gestational age was confirmed at 6-10weeks and an estimated fetal weight was obtained at each visit after 16weeks. The effects of each lipid component on future EFW were ana-lyzed using linear regression models. Analyses were then performedafter stratification by maternal prepregnancy body mass index (BMI).RESULTS: We found a significant (p�0.05) inverse association be-ween EFW at 32-36 weeks and HDL-C at all preceding time pointsut not with EFW performed earlier in gestiation. A 1gm/dL increase

n HDL-C at 10-14 was associated with a 6.2 gm decrease in EFW at2-36 weeks. In overweight/obese gravidas (BMI � 26, N�58), wegain observed a significant inverse association between EFW at 32-36eeks and HDL-C in early pregnancy. A 1gm/dL increase in HDL-C at0-14 weeks was associated with a 9.1 gram increase in EFW at 32-36eeks. However, in normal BMI women (BMI � 26, N�85), onlyDL-C measured at 22-26 weeks was associated with EFW at 32-36eeks. A significant positive association was also found in overweight/bese women between EFW at 32-36 weeks and TG measured at 22-26eeks (p�0.03). There was no association between EFW and LDL-C

n either group.CONCLUSIONS: Reduced levels of HDL-C and increased triglycerideevels in early pregnancy are significantly associated with increasedetal growth mainly in overweight/obese women. The impact of

DL-C and triglycerides on the increased fetal growth associated withncreasing maternal BMI seems to be an effect manifested in the earlyhird trimester.

235 Placental fetal thrombotic vasculopathy changesn intrauterine fetal death do not appear to beelated to maternal thrombophilia

Fenna Beeksma1, Jan Jaap Erwich2, Yee Khong1

1SA Pathology at Womens and Childrens Hospital, North Adelaide,2University Medical Centre of Groningen, GroningenOBJECTIVE: Following intrauterine fetal demise (IUFD), the placentaletal vessels undergo regressive changes. These changes are virtuallyndistinguishable from lesions that are the result of fetal vascular

hrombosis. This study investigated the relation between maternal

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