effect of pregnancy on postnatal growth in offspring of endothelial nitric oxide synthase knockout...

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97 EFFECT OF PREGNANCY ON POSTNATAL GROWTH IN OFFSPRING OF ENDOTHELIAL NITRIC OXIDE SYNTHASE KNOCKOUT MICE MONICA LONGO 1 , JOSJE LANGENVELD 2 , VENU JAIN 1 , GARY HANKINS 1 , GAR- LAND ANDERSON 1 , ROBERT GARFIELD 1 , GEORGE SAADE 1 , 1 University of Texas Medical Branch, Dept. of Obstetrics & Gynecology, Galveston, TX 2 Maastricht University Medical Center, Dept. of Obstetrics & Gynecology, Maastricht, Netherlands OBJECTIVE: Previously we demonstrated that postnatal growth in heterozygous offspring of transgenic mice with a single disrupted allele of endothelial nitric oxide synthase gene (NOS3) depends on the parental source (male or female) of the disrupted allele. Our objective in the current study was to assess the role of gravidity in the fetal programming of growth in these transgenic mice. STUDY DESIGN: Litters of homozygous NOS3 knockout (C57BL/6J- NOS3 ÿ/ÿKO ), maternally derived heterozygous (NOS3 +/ÿmat ) and paternally derived heterozygous (NOS3 +/ÿpat ) female mice were studied. Those litters were obtained from two groups of breeder mice: G1 (gravidity 0-2) and G2 (gravidity 5-9). These pups were weighted on day 1 post partum and weekly for 5 weeks. One-way ANOVA and Newman-Keuls post hoc tests were used for statistical analysis (significance: P < 0.05). RESULTS: Postnatal weight increased linearly in both groups. In litters born to G1 mothers, the weights of NOS3 ÿ/ÿKO and NOS3 +/ÿmat female litters remained significantly lower compared with NOS3 +/ÿpat , while in the litters born from G2, NOS3 ÿ/ÿKO , NOS3 +/ÿmat , and NOS3 +/ÿpat did not show any significant differences. CONCLUSION: These data support the role of abnormal uterine environment in fetal programming of postnatal growth. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional NOS3 and prevent fetal programming of postnatal growth. Given the effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy. 98 THE MATERNAL AND FETAL PRESENTATION IN SEVERE PRE- ECLAMPSIA AMONG DIFFERENT ETHNIC GROUPS ODICIE FIELDER 1 , KEITH WILLIAMS 1 , 1 Yale University, Obstetrics & Gynecology, New Haven, CT OBJECTIVE: To identify differences in the maternal and fetal presentation with coexisting medical problems among different ethnic groups with severe preeclampsia. STUDY DESIGN: The data of 169 women who met the criteria for severe preeclampsia (NHBPEP working group 2001) were obtained from the medical records of Y-NHH from December 1997, then until April 2002. From the prenatal charts we obtained from each ethnic group, pre-pregnancy weight, incidence of eclampsia, gestational diabetes, HELLP syndrome, chronic hypertension, DIC, IUGR, and renal dysfunction. We initially reviewed all ethnic groups, but as there were only 5 Oriental and 3 Native American patients, these ethnic groups were removed from further analysis. Comparison of the outcomes between the three remaining ethnic groups of white, black, and Hispanic was done using chi-squared analysis for proportions and ANOVA for continuous data RESULTS: We analyzed 111 white, 41 black, and 17 patients diagnosed with severe preeclampsia. Among white preeclamptic patients the incidence of twins and HELLP syndrome was higher (Table). Black preeclamptic patients had a higher pre-pregnancy weight and incidence of eclampsia, chronic hyperten- sion, and DIC. The Hispanic population behaved similarly to the white population except for a higher incidence of eclampsia (Table I). CONCLUSION: Preeclampsia is related to end-stage vascular dysfunction, which may be aggravated by different medical conditions. The aggravating factors differ among ethnic groups. 99 EFFECTS OF MAGNESIUM SULFATE ON PROSTACYCLIN AND THROMBOXANE IN WOMEN WITH SEVERE PREECLAMPSIA YUPING WANG 1 , LISA PHILIBERT 2 , YANPING ZHANG 2 , YANG GU 2 , KERRY TYNES 2 , DAVID F. LEWIS 2 , 1 Louisiana State University Health Sciences Center, Shreveport, LA 2 Louisiana State University Health Sciences Center, Obstetrics and Gynecology, Shreveport, LA OBJECTIVE: To study effects of MgSO 4 on vasoactivator prostacyclin (PGI2) and thromboxane A2 (TXA2) in women with severe preeclampsia (SPE). STUDY DESIGN: Women with SPE were randomized into two groups, A: Patients continuously received MgSO 4 through 24 h post partum; B: MgSO 4 was discontinued when urinary output was of $100 cc/hr for 2 consecutive hours. Patient demographic data were collected. Venous blood was drawn at time of MgSO 4 administration and 24 h post partum. Plasma levels of 6-keto PGF1a and TXB2, stable metabolites of PGI2 and TXA2, were measured by enzyme-linked immunoassay (EIA). Data are presented as mean ± SE, and analyzed by t-test or ANOVA. RESULTS: A total of 26 patients were recruited, with 15 in group A and 11 in group B. There were no differences for demographic data between the two groups including maternal age, GA, delivery mode, systolic and diastolic blood pressures at admission, 12 and 24 h post partum. Platelet counts were all in normal range at enrollment. The duration for MgSO 4 administration was 10.7 hours, on average, post partum in group B. Maternal blood pressure returned to normal or close to normal levels in both groups at 24 h post partum. TXB2 levels were no different between group A and group B at administration, 31 ± 3 vs 29 ± 9 ng/mL, and 24 h post partum, 26 ± 6 vs 28 ± 6 ng/mL, respectively. 6- keto PGF1a levels were significantly decreased 24 h post partum compared to those at enrollment in both groups, A: 103 ± 15 vs 157 ± 23 ng/mL; B: 126 ± 18 vs 164 ± 21 ng/mL, P < 0.05, respectively, but not different between the groups. The ratio of 6-keto PGF1a and TXB2 was no different at admission and 24 h post partum, 6.33 ± 0.91 vs 6.86 ± 1.46, P = 0.74, respectively. CONCLUSION: Administration of MgSO 4 does not affect PGI2 and TXA2 levels in the maternal circulation in women with PE before and after delivery. We speculate that a higher level of PGI2 before delivery may reflect compensatory effects to offset increased maternal blood pressure during pregnancy. 100 ELEVATED ENDOTHELIAL MICROPARTICLES (EMP): PREECLAMPSIA (PE) VS GESTATIONAL HYPERTENSION (GH) VICTOR HUGO GONZA- LEZ-QUINTERO 1 , LOREN SMARKUSKY 1 , JOAQUIN JIMENEZ 2 , LUCIA MAURO 2 , WENCHE JY 2 , CARL SODERLAND 3 , MARY O’SULLIVAN 4 , YEON AHN 2 , 1 University of Miami, Obstetrics/Gynecology, Miami, FL 2 University of Miami, Department of Medicine, Miami, FL 3 Applied Cell Biology Research Institute, Kirkland, WA 4 University of Miami, Obstetrics and Gynecology, Miami, FL OBJECTIVE: EMP have been found to be elevated in women with PE. However, their role in distinguishing PE from GH remains to be elucidated. The objectives of this study were to (1) compare EMP levels among patients with PE, GH, and healthy pregnant controls (HPC); (2) evaluate the effect of HPC, PE, and GH plasma on the release of EMP by renal microvascular endothelial cells (RMVEC). STUDY DESIGN: A prospective study was conducted on 52 women with PE, 20 with GH, and 38 HPC recruited from our university hospital during the period of July 2002 to February 2003. EMP were measured by flow cytometry using antibodies against CD31, CD42b, and CD62E RESULTS: CD31+/42bÿ EMP were 10497 ± 5145 counts/mL in PE vs 6768 ± 1810 counts/mL in GH (P < 0.01). In HPC CD31+/42bÿ were 6119 ± 3592 counts/mL. CD62E+ counts were1930 ± 966 in PE, vs 822 ± 150 counts/mL in GH (P < 0.01). In HPC CD62E+ were 712 ± 160 counts/mL. Incubation of RMVEC with PE plasma resulted in a rise in CD31+ and CD62E+ EMP as compared to GH and HPC. We found a positive correlation between plasma EMP and the mean arterial pressure and proteinuria among pre- eclamptic women. CONCLUSION: EMP levels are higher in PE than in GH and HPC. A soluble factor present in PE plasma induces EC injury. The measurement of EMP may be useful as a screening tool for PE in pregnant women. Preeclampsia presentation White Black Hispanic Sig Pre preg. Wt 171+40 193+65 144+53 .01 Eclampsia 5% 20% 12% .029 Twins 13% 0% 6% .038 Gest. Diabetes 10% 10% 6% NS HELLP 46% 27% 18% .008 Chr. Hyp. 8% 24% 12% .026 DIC 4% 20% 6% .012 IUGR 24% 37% 35% NS Abn Renal 13% 12% 12% NS December 2003 Am J Obstet Gynecol S92 SMFM Abstracts

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Page 1: Effect of pregnancy on postnatal growth in offspring of endothelial nitric oxide synthase knockout mice

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99 EFFECTS OF MAGNESIUM SULFATE ON PROSTACYCLIN ANDTHROMBOXANE IN WOMEN WITH SEVERE PREECLAMPSIA YUPINGWANG1, LISA PHILIBERT2, YANPING ZHANG2, YANG GU2, KERRYTYNES2, DAVID F. LEWIS2, 1Louisiana State University Health SciencesCenter, Shreveport, LA 2Louisiana State University Health Sciences Center,Obstetrics and Gynecology, Shreveport, LA

OBJECTIVE: To study effects of MgSO4 on vasoactivator prostacyclin(PGI2) and thromboxane A2 (TXA2) in women with severe preeclampsia(SPE).

STUDY DESIGN: Women with SPE were randomized into two groups, A:Patients continuously receivedMgSO4 through 24 h post partum; B: MgSO4 wasdiscontinued when urinary output was of $100 cc/hr for 2 consecutive hours.Patient demographic data were collected. Venous blood was drawn at time ofMgSO4 administration and 24 h post partum. Plasma levels of 6-keto PGF1a andTXB2, stable metabolites of PGI2 and TXA2, were measured by enzyme-linkedimmunoassay (EIA). Data are presented as mean ± SE, and analyzed by t-test orANOVA.

RESULTS: A total of 26 patients were recruited, with 15 in group A and 11 ingroup B. There were no differences for demographic data between the twogroups including maternal age, GA, delivery mode, systolic and diastolic bloodpressures at admission, 12 and 24 h post partum. Platelet counts were all innormal range at enrollment. The duration for MgSO4 administration was 10.7hours, on average, post partum in group B.Maternal blood pressure returned tonormal or close to normal levels in both groups at 24 h post partum. TXB2 levelswere no different between group A and group B at administration, 31 ± 3 vs29 ± 9 ng/mL, and 24 h post partum, 26 ± 6 vs 28 ± 6 ng/mL, respectively. 6-keto PGF1a levels were significantly decreased 24 h post partum compared tothose at enrollment in both groups, A: 103 ± 15 vs 157 ± 23 ng/mL; B:126 ± 18 vs 164 ± 21 ng/mL, P < 0.05, respectively, but not different betweenthe groups. The ratio of 6-keto PGF1a and TXB2 was no different at admissionand 24 h post partum, 6.33 ± 0.91 vs 6.86 ± 1.46, P = 0.74, respectively.

December 2003Am J Obstet Gynecol

S92 SMFM Abstracts

EFFECT OF PREGNANCY ON POSTNATAL GROWTH IN OFFSPRING OFENDOTHELIAL NITRIC OXIDE SYNTHASE KNOCKOUT MICE MONICALONGO1, JOSJE LANGENVELD2, VENU JAIN1, GARY HANKINS1, GAR-LAND ANDERSON1, ROBERT GARFIELD1, GEORGE SAADE1, 1Universityof Texas Medical Branch, Dept. of Obstetrics & Gynecology, Galveston, TX2Maastricht University Medical Center, Dept. of Obstetrics & Gynecology,Maastricht, Netherlands

OBJECTIVE: Previously we demonstrated that postnatal growth inheterozygous offspring of transgenic mice with a single disrupted allele ofendothelial nitric oxide synthase gene (NOS3) depends on the parental source(male or female) of the disrupted allele. Our objective in the current study wasto assess the role of gravidity in the fetal programming of growth in thesetransgenic mice.

STUDY DESIGN: Litters of homozygous NOS3 knockout (C57BL/6J-NOS3�/�KO), maternally derived heterozygous (NOS3+/�mat) and paternallyderived heterozygous (NOS3+/�pat) femalemice were studied. Those litters wereobtained from two groups of breeder mice: G1 (gravidity 0-2) and G2 (gravidity5-9). These pups were weighted on day 1 post partum and weekly for 5 weeks.One-way ANOVA and Newman-Keuls post hoc tests were used for statisticalanalysis (significance: P < 0.05).

RESULTS: Postnatal weight increased linearly in both groups. In litters bornto G1 mothers, the weights of NOS3�/�KO and NOS3+/�mat female littersremained significantly lower compared with NOS3+/�pat, while in the littersborn from G2, NOS3�/�KO, NOS3+/�mat, and NOS3+/�pat did not show anysignificant differences.

CONCLUSION: These data support the role of abnormal uterineenvironment in fetal programming of postnatal growth. Successive pregnanciesmay lead to maternal uterine adaptations that bypass the lack of a functionalNOS3 and prevent fetal programming of postnatal growth. Given the effect ofparity on the risk of preeclampsia, similar mechanisms may be operative inhuman pregnancy.

THE MATERNAL AND FETAL PRESENTATION IN SEVERE PRE-ECLAMPSIA AMONG DIFFERENT ETHNIC GROUPS ODICIE FIELDER1,KEITH WILLIAMS1, 1Yale University, Obstetrics & Gynecology, New Haven,CT

OBJECTIVE: To identify differences in the maternal and fetal presentationwith coexisting medical problems among different ethnic groups with severepreeclampsia.

STUDY DESIGN: The data of 169 women who met the criteria for severepreeclampsia (NHBPEP working group 2001) were obtained from the medicalrecords of Y-NHH from December 1997, then until April 2002. From theprenatal charts we obtained from each ethnic group, pre-pregnancy weight,incidence of eclampsia, gestational diabetes, HELLP syndrome, chronichypertension, DIC, IUGR, and renal dysfunction. We initially reviewed allethnic groups, but as there were only 5 Oriental and 3 Native American patients,these ethnic groups were removed from further analysis. Comparison of theoutcomes between the three remaining ethnic groups of white, black, andHispanic was done using chi-squared analysis for proportions and ANOVA forcontinuous data

RESULTS: We analyzed 111 white, 41 black, and 17 patients diagnosed withsevere preeclampsia. Among white preeclamptic patients the incidence of twinsand HELLP syndrome was higher (Table). Black preeclamptic patients hada higher pre-pregnancy weight and incidence of eclampsia, chronic hyperten-sion, and DIC. The Hispanic population behaved similarly to the whitepopulation except for a higher incidence of eclampsia (Table I).

CONCLUSION: Preeclampsia is related to end-stage vascular dysfunction,which may be aggravated by different medical conditions. The aggravatingfactors differ among ethnic groups.

CONCLUSION: Administration of MgSO4 does not affect PGI2 and TXA2levels in thematernal circulation in women with PE before and after delivery.Wespeculate that a higher level of PGI2 before delivery may reflect compensatoryeffects to offset increased maternal blood pressure during pregnancy.

100 ELEVATED ENDOTHELIAL MICROPARTICLES (EMP): PREECLAMPSIA(PE) VS GESTATIONAL HYPERTENSION (GH) VICTOR HUGO GONZA-LEZ-QUINTERO1, LOREN SMARKUSKY1, JOAQUIN JIMENEZ2, LUCIAMAURO2, WENCHE JY2, CARL SODERLAND3, MARY O’SULLIVAN4, YEONAHN2, 1University of Miami, Obstetrics/Gynecology, Miami, FL 2Universityof Miami, Department of Medicine, Miami, FL 3Applied Cell BiologyResearch Institute, Kirkland, WA 4University of Miami, Obstetrics andGynecology, Miami, FL

OBJECTIVE: EMP have been found to be elevated in women with PE.However, their role in distinguishing PE fromGH remains to be elucidated. Theobjectives of this study were to (1) compare EMP levels among patients with PE,GH, and healthy pregnant controls (HPC); (2) evaluate the effect of HPC, PE,and GH plasma on the release of EMP by renal microvascular endothelial cells(RMVEC).

STUDY DESIGN: A prospective study was conducted on 52 women with PE,20 with GH, and 38 HPC recruited from our university hospital during theperiod of July 2002 to February 2003. EMP were measured by flow cytometryusing antibodies against CD31, CD42b, and CD62E

RESULTS: CD31+/42b� EMP were 10497 ± 5145 counts/mL in PE vs6768 ± 1810 counts/mL in GH (P < 0.01). In HPC CD31+/42b� were6119 ± 3592 counts/mL. CD62E+ counts were1930 ± 966 in PE, vs 822 ± 150counts/mL in GH (P < 0.01). In HPC CD62E+ were 712 ± 160 counts/mL.Incubation of RMVEC with PE plasma resulted in a rise in CD31+ and CD62E+EMP as compared to GH and HPC. We found a positive correlation betweenplasma EMP and the mean arterial pressure and proteinuria among pre-eclamptic women.

CONCLUSION:EMP levels are higher in PE than inGHandHPC. A solublefactor present in PEplasma induces EC injury. Themeasurement of EMPmay beuseful as a screening tool for PE in pregnant women.

Preeclampsia presentation

White Black Hispanic Sig

Pre preg. Wt 171+40 193+65 144+53 .01Eclampsia 5% 20% 12% .029Twins 13% 0% 6% .038Gest. Diabetes 10% 10% 6% NSHELLP 46% 27% 18% .008Chr. Hyp. 8% 24% 12% .026DIC 4% 20% 6% .012IUGR 24% 37% 35% NSAbn Renal 13% 12% 12% NS