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Adipocytokines in discordant twins - A paradigm for evaluation of fetal growth
SMFM Abstracts S171 598 IMPACT OF CHANGE OF MATERNAL BODY MASS INDEX BETWEEN PREGNANCIES ON THE RISK OF RECURRENT TERM LOW BIRTH WEIGHT LAURA LAFFINEUSE (F)1, AMY GOODWIN1, MARC COLLIN2, BRIAN MERCER1, 1CASE-MetroHealth Medical Center, Reproductive Biology, Maternal-Fetal Medicine, Cleveland, Ohio, 2 CASE-MetroHealth Medical Center, Pediatrics, Cleveland, Ohio OBJECTIVE: The purpose of this study was to evaluate the relationship between pre-pregnancy maternal body mass index (mBMI) and the risk of subsequent low birth weight (LBW) at term. STUDY DESIGN: This is an analysis of data from a single institution from 1996 to 2004. Data was collected by chart review at the time of discharge and maintained in an electronic database. We included only those who delivered their 1st and 2nd pregnancies at our institution, and delivered a term singleton infant in both pregnancies. Pre-pregnancy mBMI’s were calculated for the 1st and 2nd deliveries. We evaluated the impact of mBMI on birth weight (BWT) and LBW (BWT ! 2500 grams). The impact of LBW in the 1st pregnancy on the rate of subsequent LBW was also assessed. We also evaluated change in mBMI between pregnancies to determine if weight gain or oss altered the risk of subsequent LBW. A p!0.05 was considered significant. RESULTS: 1,029 women met our inclusion criteria. We found a positive correlation between BWT in the 1st and 2nd pregnancies (p! 0.0001, 2 R =0.24). Increasing mBMI was associated with increasing BWT (p!0.0001) in the first pregnancy. Women delivering a LBW infant in the 1st pregnancy were more likely to have LBW in the 2nd pregnancy (14.3 vs. 3.9%, relative risk 3.7, p = 0.02). Overall the risk of LBW in the 2nd pregnancy did not change with increasing or decreasing mBMI between pregnancies (p = 0.17). After controlling for LBW in the 1st pregnancy (p = 0.005), and pregravid mBMI (p = 0.06), risk of LBW in the 2nd pregnancy was not altered by change in mBMI (ANOVA, p = 0.36). CONCLUSION: Though LBW at term is associated with low mBMI and a prior LBW delivery, change in mBMI between pregnancies does not alter this risk.
600 ADIPOCYTOKINES IN DISCORDANT TWINS - A PARADIGM FOR EVALUATION OF FETAL GROWTH SHALI MAZAKI TOVI1, HANNAH KANETY2, CLARA PARIENTE2, RINA HEMI2, EYAL SCHIFF3, EYAL SIVAN4, 1Sheba Medical Center, Rishon Letzion, Israel, 2Institute of Endocrinology, Sheba medical center, Tel-Hashomer, Israel, 3Sheba Medical Center, Tel H Ashomer, Israel, 4Sheba Medical Center, Tel Aviv University, Obstetrics and Gynecology, Ramat-Gan, Israel OBJECTIVE: Severely discordant twins are a unique model which enables the investigation of aberrant intrauterine fetal growth. Adiponectin is a novel adipocytokine produced abundantly and exclusively in adipose tissue. In singletons, cord blood adiponectin is positively correlated with birth weight. Thus, it may have a role in intrauterine fetal growth. The aim of this study was to evaluate adiponectin and leptin levels in bichorionic, biamniotic twins with and without growth discordance. STUDY DESIGN: Twenty nine couples of twins were included in this study. Of them, 14 were with severe growth discordancy (range 25-52%) - in all of them the smaller twin was severely growth restricted (mean percentage 3.5 G 0.9) and the co-twin was appropriate for gestational age (AGA) (mean percentage 35.7 G 18.2). The additional 15 control twins were accordant (range 0.8-13%, both AGA) and matched for gestational age and maternal age, weight, gravity and parity. Adiponectin and leptin were determined in cord blood using RIA kits (Linco Research, Inc., St. Charles, MO). RESULTS: A positive correlation was found between adiponectin and both birth weight and gestational age in all twins (r = 0.4 p ! 0.002 and r = 0.3 p ! 0.002, respectively). Mean adiponectin was significantly lower in IUGR fetuses of the discordant twins as compared with their co-twin (27.1 vs. 38.2 mg/ml respectively, p ! 0.03). Leptin levels were also lower in the IUGR twins but the difference did not reach a statistical significance (2.5 vs. 3.7 ng/ml, p ! 0.09). Conversely, in the control group there were no differences in mean adiponectin (29.6 vs. 32.0 mg/ml) and leptin levels (3.1 vs. 3.6 ng/ml). CONCLUSION: This paradigm of discordance twins may point to a key role of adiponectin in intrauterine fetal growth. Moreover, since adiponectin has profound insulin-sensitizing and anti-atherogenic effects, the low adiponectin levels found in the IUGR twins may provide a link between abnormal growth in utero and the high prevalence of adulthood metabolic syndrome in IUGR newborns (Barker hypothesis).
599 IN-UTERO PROGRAMMING OF VASCULAR FUNCTION IN TRANSGENIC MICE LACKING LOW DENSITY LIPOPROTEIN RECEPTOR JOSJE LANGENVELD1, MONICA LONGO2, FANGXIAN LU2, YURI VEDERNIKOV2, EGLE BYTAUTIENE2, GARLAND ANDERSON2, SAADE GEORGE2, 1Maxima Medical center, Obstestrics and Gynecology, Veldhoven, Netherlands, Netherlands, 2University of Texas Medical Branch at Galveston, Obstetrics and Gynecology, Galveston, Texas OBJECTIVE: The lack of low density lipoprotein receptors (LDLR) leads to hypercholesterolemia and atherosclerosis which has been shown to start during fetal life. However, the role of the intrauterine environment on its pathogenesis remains unknown. Our aim was to examine the effect of maternal hypercholesterolemia on fetal vascular function using mice lacking LDL receptor. STUDY DESIGN: Homozygous LDL receptor knockout mice (B6.129S7Ldlrtm1Her, LDLRÿ/ÿKO) and their wild type controls (C57BL/6J, LDLRC/ CWT ) were cross-bred to produce four litters: LDLRÿ/ÿKO, heterozygous maternally-derived (LDLRC/ÿMat, paternally-derived (LDLRC/ÿPat) and LDLRC/CWT. Female and male offspring were sacrificed (10-12 weeks/age, n = 5-10/group) and carotid arteries were mounted in wire myograph for vascular studies. Contractile vascular function was tested using phenylephrine (PE 10ÿ10-10ÿ5 M) Ca2C (0.05-5.0 mM) in Ca2C-free high-KC solution and serotonin (10ÿ10-10ÿ5 M). One-way ANOVA and Newman-Keuls post-hoc test was used for statistical analysis. RESULTS: The dose-responses to PE was significantly higher in LDLRÿ/ÿKO and LDLRC/ÿMat male offspring compared with LDLRC/CWT and LDLRC/ÿPat (maximal effect in %: LDLRÿ/ÿKO 102.9G12.17, LDLRC/ÿMat 80.2G6 vs. LDLRC/CWT 40.70G4 and LDLRC/ÿPat 56.7G8.1, p!0.05). In females, responses to PE were significantly increased only in the LDLRÿ/ÿKO offspring compared with the other groups (maximal effect in %: LDLR ÿ/ÿKO 102.7G11.69, LDLRC/ÿMat 74.4G9.2 vs. LDLRC/CWT 61.5G3.8 and LDLRC/ÿPat 64.8G8.0, p!0.05). Maximal Ca2C contraction was higher in LDLRÿ/ÿKO male and female offspring compared with the other groups. Serotonin response didn’t differ between the groups. CONCLUSION: Lack of LDLR leads to abnormal vascular function in later life independently of gender. The heterozygous offspring also present some degree of vascular dysfunction that appears to depend on maternal LDLR status, implicating a possible role for the uterine environment in determining disease in later in life.
601 ADIPONECTIN LEVELS THROUGHOUT THE PREGNANCY SHALI MAZAKI TOVI1, CLARA PARIENTE2, RINA HEMI2, EYAL SCHIFF3, HANNAH KANETY2, EYAL SIVAN3, 1Sheba Medical Center, Rishon Letzion, Israel, 2Institute of Endocrinology, Sheba medical center, Tel-Hashomer, Israel, 3Sheba Medical Center, Obstetrics & Gynecology, Tel-Hashomer, Israel OBJECTIVE: Adiponectin is a novel adipocytokine produced abundantly and exclusively in adipose tissue. This hormone has profound insulinsensitizing properties. Pregnancy is a unique situation in which there is a physiological increase in insulin resistance. Despite the importance of adiponectin in regulation of insulin sensitivity, little is known about the role of this hormone during pregnancy. The aim of this study is to evaluate adiponectin levels during the pregnancy and immediate postpartum period. STUDY DESIGN: Twenty healthy pregnant women in first trimester (mean gestational age 10.5 G 1.9 weeks) 20 patients in second trimester (19.3 G 4.9 weeks) and 20 patients in third trimester (39.3 G 0.8 weeks) were included in the study. In addition, 20 patients 4 days postpartum were included in the study. Patients were matched for age, pre conceptional BMI, gravity and parity. Blood sample were tested for adiponectin and leptin levels using RIA kits (Linco Research, Inc., St. Charles, MO). RESULTS: There were no significant differences between adiponectin levels in first (13.3 G 4.2 mg/ml) second (12.6 G 4.4 mg/ml) and third trimester (11.2 G 3.7 mg/ml). However, postpartum adiponectin levels (8.8 G 2.1 mg/ml) were significantly lower as compared with first (p ! 0.0001) second (p ! 0.004) and third trimester (p ! 0.02). Leptin levels in second (23.6 G 11.7 ng/ml) and third trimester (30.2 G 13.4 mg/ml) were higher (p ! 0.02 and p ! 0.0001 respectively) as compared with postpartum levels(16.0 G 13.2 mg/ml). Leptin levels in first trimester (21.2 G 12.2 ng/ml) were significantly lower as compared with third trimester (p ! 0.01). CONCLUSION: The significantly higher levels of adiponectin during pregnancy as compared with postpartum may imply that adiponectin has a role in the regulation of insulin resistance along pregnancy. The gradual decrease (although not statistically significant) in adiponectin levels throughout the pregnancy support this hypothesis, as the negative correlation between adiponectin and insulin resistance is well established.
600 ADIPOCYTOKINES IN DISCORDANT TWINS - A PARADIGM FOR EVALUATION OF FETAL GROWTH SHALI MAZAKI TOVI1, HANNAH KANETY2, CLARA PARIENTE2, RINA HEMI2, EYAL SCHIFF3, EYAL SIVAN4, 1Sheba Medical Center, Rishon Letzion, Israel, 2Institute of Endocrinology, Sheba medical center, Tel-Hashomer, Israel, 3Sheba Medical Center, Tel H Ashomer, Israel, 4Sheba Medical Center, Tel Aviv University, Obstetrics and Gynecology, Ramat-Gan, Israel OBJECTIVE: Severely discordant twins are a unique model which enables the investigation of aberrant intrauterine fetal growth. Adiponectin is a novel adipocytokine produced abundantly and exclusively in adipose tissue. In singletons, cord blood adiponectin is positively correlated with birth weight. Thus, it may have a role in intrauterine fetal growth. The aim of this study was to evaluate adiponectin and leptin levels in bichorionic, biamniotic twins with and without growth discordance. STUDY DESIGN: Twenty nine couples of twins were included in this study. Of them, 14 were with severe growth discordancy (range 25-52%) - in all of them the smaller twin was severely growth restricted (mean percentage 3.5 G 0.9) and the co-twin was appropriate for gestational age (AGA) (mean percentage 35.7 G 18.2). The additional 15 control twins were accordant (range 0.8-13%, both AGA) and matched for gestational age and maternal age, weight, gravity and parity. Adiponectin and leptin were determined in cord blood using RIA kits (Linco Research, Inc., St. Charles, MO). RESULTS: A positive correlation was found between adiponectin and both birth weight and gestational age in all twins (r = 0.4 p ! 0.002 and r = 0.3 p ! 0.002, respectively). Mean adiponectin was significantly lower in IUGR fetuses of the discordant twins as compared with their co-twin (27.1 vs. 38.2 mg/ml respectively, p ! 0.03). Leptin levels were also lower in the IUGR twins but the difference did not reach a statistical significance (2.5 vs. 3.7 ng/ml, p ! 0.09). Conversely, in the control group there were no differences in mean adiponectin (29.6 vs. 32.0 mg/ml) and leptin levels (3.1 vs. 3.6 ng/ml). CONCLUSION: This paradigm of discordance twins may point to a key role of adiponectin in intrauterine fetal growth. Moreover, since adiponectin has profound insulin-sensitizing and anti-atherogenic effects, the low adiponectin levels found in the IUGR twins may provide a link between abnormal growth in utero and the high prevalence of adulthood metabolic syndrome in IUGR newborns (Barker hypothesis).
599 IN-UTERO PROGRAMMING OF VASCULAR FUNCTION IN TRANSGENIC MICE LACKING LOW DENSITY LIPOPROTEIN RECEPTOR JOSJE LANGENVELD1, MONICA LONGO2, FANGXIAN LU2, YURI VEDERNIKOV2, EGLE BYTAUTIENE2, GARLAND ANDERSON2, SAADE GEORGE2, 1Maxima Medical center, Obstestrics and Gynecology, Veldhoven, Netherlands, Netherlands, 2University of Texas Medical Branch at Galveston, Obstetrics and Gynecology, Galveston, Texas OBJECTIVE: The lack of low density lipoprotein receptors (LDLR) leads to hypercholesterolemia and atherosclerosis which has been shown to start during fetal life. However, the role of the intrauterine environment on its pathogenesis remains unknown. Our aim was to examine the effect of maternal hypercholesterolemia on fetal vascular function using mice lacking LDL receptor. STUDY DESIGN: Homozygous LDL receptor knockout mice (B6.129S7Ldlrtm1Her, LDLRÿ/ÿKO) and their wild type controls (C57BL/6J, LDLRC/ CWT ) were cross-bred to produce four litters: LDLRÿ/ÿKO, heterozygous maternally-derived (LDLRC/ÿMat, paternally-derived (LDLRC/ÿPat) and LDLRC/CWT. Female and male offspring were sacrificed (10-12 weeks/age, n = 5-10/group) and carotid arteries were mounted in wire myograph for vascular studies. Contractile vascular function was tested using phenylephrine (PE 10ÿ10-10ÿ5 M) Ca2C (0.05-5.0 mM) in Ca2C-free high-KC solution and serotonin (10ÿ10-10ÿ5 M). One-way ANOVA and Newman-Keuls post-hoc test was used for statistical analysis. RESULTS: The dose-responses to PE was significantly higher in LDLRÿ/ÿKO and LDLRC/ÿMat male offspring compared with LDLRC/CWT and LDLRC/ÿPat (maximal effect in %: LDLRÿ/ÿKO 102.9G12.17, LDLRC/ÿMat 80.2G6 vs. LDLRC/CWT 40.70G4 and LDLRC/ÿPat 56.7G8.1, p!0.05). In females, responses to PE were significantly increased only in the LDLRÿ/ÿKO offspring compared with the other groups (maximal effect in %: LDLR ÿ/ÿKO 102.7G11.69, LDLRC/ÿMat 74.4G9.2 vs. LDLRC/CWT 61.5G3.8 and LDLRC/ÿPat 64.8G8.0, p!0.05). Maximal Ca2C contraction was higher in LDLRÿ/ÿKO male and female offspring compared with the other groups. Serotonin response didn’t differ between the groups. CONCLUSION: Lack of LDLR leads to abnormal vascular function in later life independently of gender. The heterozygous offspring also present some degree of vascular dysfunction that appears to depend on maternal LDLR status, implicating a possible role for the uterine environment in determining disease in later in life.
601 ADIPONECTIN LEVELS THROUGHOUT THE PREGNANCY SHALI MAZAKI TOVI1, CLARA PARIENTE2, RINA HEMI2, EYAL SCHIFF3, HANNAH KANETY2, EYAL SIVAN3, 1Sheba Medical Center, Rishon Letzion, Israel, 2Institute of Endocrinology, Sheba medical center, Tel-Hashomer, Israel, 3Sheba Medical Center, Obstetrics & Gynecology, Tel-Hashomer, Israel OBJECTIVE: Adiponectin is a novel adipocytokine produced abundantly and exclusively in adipose tissue. This hormone has profound insulinsensitizing properties. Pregnancy is a unique situation in which there is a physiological increase in insulin resistance. Despite the importance of adiponectin in regulation of insulin sensitivity, little is known about the role of this hormone during pregnancy. The aim of this study is to evaluate adiponectin levels during the pregnancy and immediate postpartum period. STUDY DESIGN: Twenty healthy pregnant women in first trimester (mean gestational age 10.5 G 1.9 weeks) 20 patients in second trimester (19.3 G 4.9 weeks) and 20 patients in third trimester (39.3 G 0.8 weeks) were included in the study. In addition, 20 patients 4 days postpartum were included in the study. Patients were matched for age, pre conceptional BMI, gravity and parity. Blood sample were tested for adiponectin and leptin levels using RIA kits (Linco Research, Inc., St. Charles, MO). RESULTS: There were no significant differences between adiponectin levels in first (13.3 G 4.2 mg/ml) second (12.6 G 4.4 mg/ml) and third trimester (11.2 G 3.7 mg/ml). However, postpartum adiponectin levels (8.8 G 2.1 mg/ml) were significantly lower as compared with first (p ! 0.0001) second (p ! 0.004) and third trimester (p ! 0.02). Leptin levels in second (23.6 G 11.7 ng/ml) and third trimester (30.2 G 13.4 mg/ml) were higher (p ! 0.02 and p ! 0.0001 respectively) as compared with postpartum levels(16.0 G 13.2 mg/ml). Leptin levels in first trimester (21.2 G 12.2 ng/ml) were significantly lower as compared with third trimester (p ! 0.01). CONCLUSION: The significantly higher levels of adiponectin during pregnancy as compared with postpartum may imply that adiponectin has a role in the regulation of insulin resistance along pregnancy. The gradual decrease (although not statistically significant) in adiponectin levels throughout the pregnancy support this hypothesis, as the negative correlation between adiponectin and insulin resistance is well established.